A first-in-human study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of AZD2373 after single dose administration in healthy male subjects of African ancestry.

Study identifier:D6800C00001

ClinicalTrials.gov identifier:NCT04269031

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I, First-in-Human, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD2373 following Single Ascending Dose Administrations to Healthy Male Subjects of African Ancestry

Medical condition

Healthy Volunteers

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD2373 subcutaneous injection, Placebo

Sex

Male

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 13 Feb 2020

Primary Completion Date: 31 Aug 2021

Study Completion Date: 31 Aug 2021

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Aug 2023 by AstraZeneca

Collaborators

Parexel International

Inclusion and exclusion criteria

No locations available

Arms	Assigned Interventions
Experimental: Cohort 1 On Day 1, randomized subjects will receive a subcutaneous (SC) injection of AZD2373 dose 1 (6 subjects) or matching placebo (2 subjects).	Drug: AZD2373 subcutaneous injection Randomised subjects will receive a single ascending dose of AZD2373 by SC injection (dose 1, dose 2, dose 3, dose 4, dose 5 and dose 6). Drug: Placebo Randomised subjects will receive a single ascending dose of placebo (saline solution) by SC injection.
Experimental: Cohort 2 On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 2 (6 subjects) or matching placebo (2 subjects).	Drug: AZD2373 subcutaneous injection Randomised subjects will receive a single ascending dose of AZD2373 by SC injection (dose 1, dose 2, dose 3, dose 4, dose 5 and dose 6). Drug: Placebo Randomised subjects will receive a single ascending dose of placebo (saline solution) by SC injection.
Experimental: Cohort 3 On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 3 (6 subjects) or matching placebo (2 subjects).	Drug: AZD2373 subcutaneous injection Randomised subjects will receive a single ascending dose of AZD2373 by SC injection (dose 1, dose 2, dose 3, dose 4, dose 5 and dose 6). Drug: Placebo Randomised subjects will receive a single ascending dose of placebo (saline solution) by SC injection.
Experimental: Cohort 4 On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 4 (6 subjects) or matching placebo (2 subjects).	Drug: AZD2373 subcutaneous injection Randomised subjects will receive a single ascending dose of AZD2373 by SC injection (dose 1, dose 2, dose 3, dose 4, dose 5 and dose 6). Drug: Placebo Randomised subjects will receive a single ascending dose of placebo (saline solution) by SC injection.
Experimental: Cohort 5 On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 5 (6 subjects) or matching placebo (2 subjects).	Drug: AZD2373 subcutaneous injection Randomised subjects will receive a single ascending dose of AZD2373 by SC injection (dose 1, dose 2, dose 3, dose 4, dose 5 and dose 6). Drug: Placebo Randomised subjects will receive a single ascending dose of placebo (saline solution) by SC injection.
Experimental: Cohort 6 On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 6 (6 subjects) or matching placebo (2 subjects).	Drug: AZD2373 subcutaneous injection Randomised subjects will receive a single ascending dose of AZD2373 by SC injection (dose 1, dose 2, dose 3, dose 4, dose 5 and dose 6). Drug: Placebo Randomised subjects will receive a single ascending dose of placebo (saline solution) by SC injection.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled in this study from 13 February 2020 to 31 August 2021.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. All the study assessments were performed as per schedule of assessment.

Reporting Groups

	Description
Pooled Placebo	Participants received a single dose of placebo by SC injection, on Day 1.
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Participant Flow: Overall Study

	Pooled Placebo	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
STARTED	9	6	5	6	5
COMPLETED	8	6	5	6	5
NOT COMPLETED	1	0	0	0	0
Adverse Event	1	0	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The randomized set consisted of all participants randomized into the study.

Reporting Groups

	Description
Pooled Placebo	Participants received a single dose of placebo by SC injection, on Day 1.
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Baseline Measures

	Pooled Placebo	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4	Total
Number of Participants [units: Participants]	9	6	5	6	5	31
Age Continuous [units: Years] Mean ± Standard Deviation
Pooled Placebo	34.4 ± 9.7					34.4 ± 9.7
AZD2373		32.7 ± 9.2	29.4 ± 9.6	33.0 ± 11.5	40.8 ± 12.7	33.9 ± 10.8
Sex: Female, Male [units: ]
Female	0	0	0	0	0	0
Male	9	6	5	6	5	31
Race (NIH/OMB) [units: ]
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	9	6	5	6	5	31
White	0	0	0	0	0	0
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0
Ethnicity (NIH/OMB) [units: ]
Hispanic or Latino	0	0	0	0	0	0
Not Hispanic or Latino	9	6	5	6	5	31
Unknown or Not Reported	0	0	0	0	0	0

Outcome Measures

1. Primary Outcome Measure: Number of participants with treatment-emergent adverse events (TEAEs) [ Time Frame: Day 1 to final Follow-up Visit (Week 10 post dose) or Early termination (approx. 1.6 Years) ]

Measure Type	Primary
Measure Name	Number of participants with treatment-emergent adverse events (TEAEs)
Measure Description	The adverse events as a variable of safety and tolerability of SC single ascending dose (SAD) administrations of AZD2373 were assessed.
Time Frame	Day 1 to final Follow-up Visit (Week 10 post dose) or Early termination (approx. 1.6 Years)
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all participants who received at least 1 dose of investigational medicinal product (IMP).

Reporting Groups

	Description
Pooled Placebo	Participants received a single dose of placebo by SC injection, on Day 1.
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	Pooled Placebo	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	9	6	5	6	5
Number of participants with treatment-emergent adverse events (TEAEs) [units: Participants]
Any TEAE	4	1	3	3	4
Any TEAE with outcome = death	0	0	0	0	0
Any serious TEAE (including events with outcome = death)	0	0	0	0	0
Any TEAE leading to discontinuation of IMP	0	0	0	0	0
Any TEAE leading to withdrawal from study	0	0	0	0	0

No statistical analysis provided for Number of participants with treatment-emergent adverse events (TEAEs)

2. Secondary Outcome Measure: Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) of AZD2373
Measure Description	The pharmacokinetics (PK) (AUC) of AZD2373 following SC Single ascending dose (SAD) administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) of AZD2373 [units: hoursnanograms per milliliter (hng/mL)] Geometric Mean (Geometric Coefficient of Variation)	1505 (12.59%)	5688 (28.99%)	11740 (23.47%)	29550 (22.84%)

Statistical Analysis 1 for Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) of AZD2373

Groups^[1]	All groups
Method^[3]	Regression, Linear
Slope^[5]	1.066
Standard Error of the mean	± 0.04820
90% Confidence Interval	( 0.9827 to 1.149 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Area under the plasma concentration curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2373
Measure Description	The PK (AUClast) of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Area under the plasma concentration curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2373 [units: hoursnanograms per milliliter (hng/mL)] Geometric Mean (Geometric Coefficient of Variation)	1497 (12.63%)	5567 (29.16%)	11600 (23.21%)	29150 (23.40%)

Statistical Analysis 1 for Area under the plasma concentration curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2373

Groups^[1]	All groups
Method^[3]	Regression, Linear
Slope^[5]	1.064
Standard Error of the mean	± 0.04806
90% Confidence Interval	( 0.9809 to 1.147 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Area under the plasma concentration-time curve from time zero to 72 hours after dosing [AUC(0-72)] of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from time zero to 72 hours after dosing [AUC(0-72)] of AZD2373
Measure Description	The PK AUC(0-72) of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Area under the plasma concentration-time curve from time zero to 72 hours after dosing [AUC(0-72)] of AZD2373 [units: hoursnanograms per milliliter (hng/mL)] Geometric Mean (Geometric Coefficient of Variation)	1504 (12.55%)	5446 (28.59%)	11230 (23.30%)	28030 (22.52%)

Statistical Analysis 1 for Area under the plasma concentration-time curve from time zero to 72 hours after dosing [AUC(0-72)] of AZD2373

Groups^[1]	All groups
Method^[3]	Regression, Linear
Slope^[5]	1.047
Standard Error of the mean	± 0.04739
90% Confidence Interval	( 0.9656 to 1.129 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC (0-48)] of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC (0-48)] of AZD2373
Measure Description	The PK AUC(0-48) of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC (0-48)] of AZD2373 [units: hoursnanograms per milliliter (hng/mL)] Geometric Mean (Geometric Coefficient of Variation)	1500 (12.44%)	5405 (28.61%)	11140 (23.49%)	27860 (22.57%)

Statistical Analysis 1 for Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC (0-48)] of AZD2373

Groups^[1]	All groups
Method^[3]	Regression, Linear
Slope^[5]	1.046
Standard Error of the mean	± 0.04750
90% Confidence Interval	( 0.9639 to 1.128 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Observed maximum plasma concentration (Cmax) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Observed maximum plasma concentration (Cmax) of AZD2373
Measure Description	The PK Cmax of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Observed maximum plasma concentration (Cmax) of AZD2373 [units: Nanograms per milliliter (ng/ml)] Geometric Mean (Geometric Coefficient of Variation)	292.1 (25.08%)	1057 (31.20%)	1629 (33.08%)	4095 (24.85%)

Statistical Analysis 1 for Observed maximum plasma concentration (Cmax) of AZD2373

Groups^[1]	All groups
Method^[3]	Regression, Linear
Slope^[5]	0.9218
Standard Error of the mean	± 0.06518
90% Confidence Interval	( 0.8094 to 1.034 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD2373
Measure Description	The PK tmax of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD2373 [units: hours (h)] Median (Full Range)	2.00 (2.00 to 2.50)	2.03 (1.50 to 4.00)	2.08 (1.98 to 3.00)	3.00 (2.08 to 3.00)

No statistical analysis provided for Time to reach peak or maximum observed concentration or response following drug administration (tmax) of AZD2373

8. Secondary Outcome Measure: Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz) of AZD2373
Measure Description	The PK t½λz of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz) of AZD2373 [units: hour (h)] Median (Full Range)	5.294 (2.71 to 9.34)	106.6 (27.5 to 191)	130 (91.2 to 210)	283.9 (188 to 490)

No statistical analysis provided for Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz) of AZD2373

9. Secondary Outcome Measure: Apparent total body clearance of drug from plasma after extravascular administration [CL/F] of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Apparent total body clearance of drug from plasma after extravascular administration [CL/F] of AZD2373
Measure Description	The PK CL/F of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Apparent total body clearance of drug from plasma after extravascular administration [CL/F] of AZD2373 [units: liter/hour (L/h)] Geometric Mean (Geometric Coefficient of Variation)	6.643 (12.59%)	5.274 (28.99%)	6.386 (23.47%)	5.077 (22.84%)

No statistical analysis provided for Apparent total body clearance of drug from plasma after extravascular administration [CL/F] of AZD2373

10. Secondary Outcome Measure: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD2373
Measure Description	The PK Vz/F of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD2373 [units: Liter (L)] Geometric Mean (Geometric Coefficient of Variation)	48.84 (54.98%)	732.3 (75.08%)	1281 (12.98%)	2273 (42.45%)

No statistical analysis provided for Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of AZD2373

11. Secondary Outcome Measure: Mean residence time of the unchanged drug in the systemic circulation (MRT) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Mean residence time of the unchanged drug in the systemic circulation (MRT) of AZD2373
Measure Description	The PK MRT of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Mean residence time of the unchanged drug in the systemic circulation (MRT) of AZD2373 [units: Hour (h)] Geometric Mean (Geometric Coefficient of Variation)	5.074 (13.17%)	14.88 (72.35%)	18.92 (15.87%)	32.78 (54.31%)

No statistical analysis provided for Mean residence time of the unchanged drug in the systemic circulation (MRT) of AZD2373

12. Secondary Outcome Measure: Terminal elimination rate constant (λz) of AZD2373 [ Time Frame: Visit 2 to final Follow-up Visit (Week 10 post last dose) ]

Measure Type	Secondary
Measure Name	Terminal elimination rate constant (λz) of AZD2373
Measure Description	The PK (λz) of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Visit 2 to final Follow-up Visit (Week 10 post last dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Terminal elimination rate constant (λz) of AZD2373 [units: 1/hour (1/h)] Geometric Mean (Geometric Coefficient of Variation)	0.1360 (59.37%)	0.007202 (88.43%)	0.004983 (32.45%)	0.002233 (37.80%)

No statistical analysis provided for Terminal elimination rate constant (λz) of AZD2373

13. Secondary Outcome Measure: Time of the last quantifiable concentration [tlast Ae(0-last)] of AZD2373 [ Time Frame: Visit 2 to final Follow-up Visit (Week 10 post last dose) ]

Measure Type	Secondary
Measure Name	Time of the last quantifiable concentration [tlast Ae(0-last)] of AZD2373
Measure Description	The PK [tlast Ae(0-last)] of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Visit 2 to final Follow-up Visit (Week 10 post last dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Time of the last quantifiable concentration [tlast Ae(0-last)] of AZD2373 [units: Hour (h)] Median (Full Range)	36.07 (24.05 to 48.22)	218.38 (71.85 to 316.07)	336.78 (312.35 to 504.62)	695.58 (504.47 to 1680.37)

No statistical analysis provided for Time of the last quantifiable concentration [tlast Ae(0-last)] of AZD2373

14. Secondary Outcome Measure: Cumulative fraction (%) of dose excreted unchanged into the urine from time zero to the last measured time point [fe(0-last)] of AZD2373 [ Time Frame: Visit 2 to final Follow-up Visit (Week 10 post last dose) ]

Measure Type	Secondary
Measure Name	Cumulative fraction (%) of dose excreted unchanged into the urine from time zero to the last measured time point [fe(0-last)] of AZD2373
Measure Description	The PK [fe(0-last)] of AZD2373 following SC SAD administrations of AZD2373 was determined. This was estimated by dividing Ae(0-last) by dose.
Time Frame	Visit 2 to final Follow-up Visit (Week 10 post last dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Cumulative fraction (%) of dose excreted unchanged into the urine from time zero to the last measured time point [fe(0-last)] of AZD2373 [units: Percentage (%)] Geometric Mean (Geometric Coefficient of Variation)	0.7208 (42.05%)	0.9757 (17.25%)	1.713 (75.44%)	2.958 (22.00%)

No statistical analysis provided for Cumulative fraction (%) of dose excreted unchanged into the urine from time zero to the last measured time point [fe(0-last)] of AZD2373

15. Secondary Outcome Measure: Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)] of AZD2373 [ Time Frame: Visit 2 to final Follow-up Visit (Week 10 post last dose) ]

Measure Type	Secondary
Measure Name	Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)] of AZD2373
Measure Description	The PK [Ae(t1-t2)] of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Visit 2 to final Follow-up Visit (Week 10 post last dose)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)] of AZD2373 [units: milligrams (mg)] Geometric Mean (Geometric Coefficient of Variation)	0.004001 (223.7%)	0.05337 (99.60%)	0.06794 (689.2%)	0.5546 (332.4%)

No statistical analysis provided for Amount of analyte excreted into the urine from time t1 to t2 [Ae(t1-t2)] of AZD2373

16. Secondary Outcome Measure: Fraction of dose excreted unchanged into the urine from time t1 to t2 [fe(t1-t2)] of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Fraction of dose excreted unchanged into the urine from time t1 to t2 [fe(t1-t2)] of AZD2373
Measure Description	The PK [fe(t1-t2)] of AZD2373 following SC SAD administrations of AZD2373 was determined.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Fraction of dose excreted unchanged into the urine from time t1 to t2 [fe(t1-t2)] of AZD2373 [units: Percentage (%)] Geometric Mean (Geometric Coefficient of Variation)	0.004001 (223.7%)	0.05337 (99.60%)	0.06794 (689.2%)	0.5546 (332.4%)

No statistical analysis provided for Fraction of dose excreted unchanged into the urine from time t1 to t2 [fe(t1-t2)] of AZD2373

17. Secondary Outcome Measure: Renal clearance of drug from plasma (CLR) of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Renal clearance of drug from plasma (CLR) of AZD2373
Measure Description	The PK (CLR) of AZD2373 following SC SAD administrations of AZD2373 was characterized. This was estimated by dividing Ae(0-t) by AUC(0-t) where the 0-t interval is the same for both Ae and AUC (CLR)
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PK analysis set consisted of all subjects in the safety analysis set who received AZD2373 who had evaluable PK data.

Reporting Groups

	Description
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	6	5	6	5
Renal clearance of drug from plasma (CLR) of AZD2373 [units: liter/hour (L/h)] Geometric Mean (Geometric Coefficient of Variation)	0.04792 (42.25%)	0.05375 (27.15%)	0.1144 (56.98%)	0.002233 (37.80%)

No statistical analysis provided for Renal clearance of drug from plasma (CLR) of AZD2373

18. Secondary Outcome Measure: Apolipoprotein L1 (APOL1) concentrations of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Apolipoprotein L1 (APOL1) concentrations of AZD2373
Measure Description	The effect of SC SAD administrations of AZD2373 on plasma concentrations of APOL1 protein was assessed.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The pharmacodynamic (PD) analysis set consisted of all subjects in the safety analysis set, who had at least the baseline (Day 1, pre-dose) and one post dose measurement of APOL1 protein plasma concentration.

Reporting Groups

	Description
Pooled Placebo	Participants received a single dose of placebo by SC injection, on Day 1.
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	Pooled Placebo	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	9	6	5	6	5
Apolipoprotein L1 (APOL1) concentrations of AZD2373 [units: microgram/milliliter (ug/mL)] Mean (Standard Deviation)
Day 1, pre-dose	58.19 (3.59)	59.23 (13.50)	53.40 (7.44)	46.47 (9.47)	50.18 (16.16)
Day 1, 2 hours post dose	64.01 (11.74)	61.18 (15.56)	53.48 (8.33)	49.10 (9.46)	49.26 (17.16)
Day 7	61.71 (5.39)	59.02 (13.35)	53.00 (7.77)	43.78 (10.36)	45.32 (14.57)
Day 10	58.66 (10.75)	51.17 (15.22)	52.52 (6.98)	42.23 (10.01)	45.96 (14.95)
Day 14	62.41 (12.62)	51.45 (14.11)	52.78 (8.10)	42.28 (11.18)	38.32 (9.24)
Day 21	61.69 (9.44)	40.92 (7.48)	54.56 (7.28)	42.43 (9.86)	45.44 (17.44)
Day 28	64.05 (9.38)	45.04 (11.53)	50.50 (6.26)	41.15 (9.43)	45.88 (16.75)
Day 35	61.98 (8.52)	52.20 (16.66)	49.30 (7.50)	41.02 (8.96)	42.66 (16.40)
Day 42	63.83 (12.67)	53.18 (13.33)	50.04 (7.90)	41.20 (10.73)	46.56 (18.74)
Day 56	65.38 (4.13)	48.30 (13.07)	54.94 (5.44)	43.23 (10.24)	45.04 (19.99)

No statistical analysis provided for Apolipoprotein L1 (APOL1) concentrations of AZD2373

19. Secondary Outcome Measure: Change from baseline in APOL1 concentrations of AZD2373 [ Time Frame: Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years). ]

Measure Type	Secondary
Measure Name	Change from baseline in APOL1 concentrations of AZD2373
Measure Description	The effect of SC SAD administrations of AZD2373 on plasma concentrations of APOL1 protein was assessed.
Time Frame	Pre-dose and Post-dose on Days 1 to 4 until final Follow-up Visit (Week 10 post last dose) or early termination visit (approx 1.6 years).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The PD analysis set consisted of all subjects in the safety analysis set, who had at least the baseline (Day 1, pre-dose) and one post dose measurement of APOL1 protein plasma concentration.

Reporting Groups

	Description
Pooled Placebo	Participants received a single dose of placebo by SC injection, on Day 1.
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Measured Values

	Pooled Placebo	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Number of Participants Analyzed [units:participants]	9	6	5	6	5
Change from baseline in APOL1 concentrations of AZD2373 [units: microgram/milliliter (ug/mL)] Mean (Standard Deviation)
Day 1, pre-dose	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Day 1, 2 hours post dose	5.83 (9.39)	1.95 (2.40)	0.08 (2.98)	2.63 (3.03)	-0.92 (3.38)
Day 7	3.53 (4.34)	-0.22 (3.56)	-0.40 (2.87)	-2.68 (4.08)	-4.86 (7.54)
Day 10	0.47 (9.09)	-8.07 (5.68)	-0.88 (5.43)	-4.23 (7.74)	-4.22 (5.34)
Day 14	4.23 (11.74)	-7.78 (7.49)	-0.62 (5.39)	-4.18 (8.00)	-11.86 (7.71)
Day 21	3.66 (9.53)	-16.76 (9.53)	1.16 (3.57)	-4.03 (7.62)	-4.74 (6.15)
Day 28	5.87 (8.46)	-12.64 (4.84)	-2.90 (3.13)	-5.32 (7.64)	-4.30 (4.34)
Day 35	3.80 (5.73)	-5.48 (6.44)	-4.10 (3.75)	-5.45 (7.29)	-7.52 (6.02)
Day 42	5.65 (14.08)	-4.50 (7.56)	-3.36 (2.66)	-5.27 (9.04)	-3.62 (7.14)
Day 56	7.20 (5.11)	-9.38 (9.75)	1.54 (3.49)	-3.23 (9.47)	-5.14 (8.97)

No statistical analysis provided for Change from baseline in APOL1 concentrations of AZD2373

Serious Adverse Events

Time Frame	Day 1 to final Follow-up Visit (Week 10 post dose) or Early termination (approx. 1.6 Years).
Additional Description	Safety analysis set is included and it consisted of all participants who received at least 1 dose of IMP.

Reporting Groups

	Description
Pooled Placebo	Participants received a single dose of placebo by SC injection, on Day 1.
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Serious Adverse Events

	Pooled Placebo	AZD2373 Dose 1	AZD2373 Dose 2	AZD2373 Dose 3	AZD2373 Dose 4
Total, serious adverse events
# participants affected / at risk	0/8 (0.00%)	0/6 (0.00%)	0/5 (0.00%)	0/6 (0.00%)	0/5 (0.00%)

Other Adverse Events

Time Frame	Day 1 to final Follow-up Visit (Week 10 post dose) or Early termination (approx. 1.6 Years).
Additional Description	Safety analysis set is included and it consisted of all participants who received at least 1 dose of IMP.

Frequency Threshold

Threshold above which other adverse events are reported	0%

Reporting Groups

	Description
Pooled Placebo	Participants received a single dose of placebo by SC injection, on Day 1.
AZD2373 Dose 1	Participants received a single ascending dose of AZD2373 (dose 1) by SC injection, on Day 1.
AZD2373 Dose 2	Participants received a single ascending dose of AZD2373 (dose 2) by SC injection, on Day 1.
AZD2373 Dose 3	Participants received a single ascending dose of AZD2373 (dose 3) by SC injection, on Day 1.
AZD2373 Dose 4	Participants received a single ascending dose of AZD2373 (dose 4) by SC injection, on Day 1.

Other Adverse Events

Pooled Placebo

AZD2373 Dose 1

AZD2373 Dose 2

AZD2373 Dose 3

AZD2373 Dose 4

Total, other (not including serious) adverse events

# participants affected / at risk

4/8 (50.00%)

1/6 (16.67%)

3/5 (60.00%)

3/6 (50.00%)

4/5 (80.00%)

General disorders

Injection site rash¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

2/6 (33.33%)

4/5 (80.00%)

# events

General disorders

Application site dermatitis¹

# participants affected / at risk

3/8 (37.50%)

1/6 (16.67%)

1/5 (20.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

General disorders

Injection site swelling¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

0/6 (0.00%)

3/5 (60.00%)

# events

General disorders

Injection site bruising¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

General disorders

Injection site erythema¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

General disorders

Injection site pain¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

General disorders

Injection site pruritus¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

General disorders

Vessel puncture site bruise¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Nervous system disorders

Dysgeusia¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

1/6 (16.67%)

0/5 (0.00%)

# events

Nervous system disorders

Headache¹

# participants affected / at risk

0/8 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

0/6 (0.00%)

1/5 (20.00%)

# events

Cardiac disorders

Ventricular tachycardia¹

# participants affected / at risk

1/8 (12.50%)

0/6 (0.00%)

1/5 (20.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Gastrointestinal disorders

Abdominal pain lower¹

# participants affected / at risk

1/8 (12.50%)

0/6 (0.00%)

0/5 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

Injury, poisoning and procedural complications

Contusion¹

# participants affected / at risk

1/8 (12.50%)

0/6 (0.00%)

0/5 (0.00%)

0/6 (0.00%)

0/5 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 23.0.

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca AB
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

CSR_synospis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Ronald Goldwater

Parexel Early Phase Clinical Unit Baltimore

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

CSR_synospis

Trial Results Summaries