A study to investigate the analgesic efficacy of AZD2423 compared with placebo after 28 days treatment in patients with painful diabetic polyneuropathy

Study identifier:D2600C00005

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A study to investigate the analgesic efficacy of AZD2423 compared with placebo

Medical condition

Neuropathic Pain

Phase

Phase 2

Healthy volunteers

Study drug

AZD2423, Placebo

Sex

All

Actual Enrollment

134

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 01 Sept 2010

Primary Completion Date: 01 Jun 2011

Study Completion Date: 01 Jun 2011

Study design

Allocation: Randomized
Endpoint Classification: None
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2013 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

WINNIPEG, MB, Canada

Location

Research Site

BRAMPTON, ON, Canada

Location

Research Site

ETOBICOKE, ON, Canada

Location

Research Site

MISSISSAUGA, ON, Canada

Location

Research Site

Laval, Canada

Location

Research Site

LACHINE, QC, Canada

Location

Research Site

GOODYEAR, AZ, United States

Location

Research Site

PHOENIX, AZ, United States

Arms	Assigned Interventions
Experimental: AZD2423, 150 mg Tablets, 150 mg once daily in the morning.	Drug: AZD2423 150 mg tablet
Experimental: AZD2423, 20 mg Tablets, 20 mg once daily in the morning.	Drug: AZD2423 20 mg tablet
Placebo Comparator: Placebo Tablets, placebo, once daily in the morning.	Drug: Placebo Placebo

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first participant was enrolled on 20th September 2010 and the last participant completed on 6th June 2011. A total of 20 centres in United States (US) and Canada randomised 134 participants.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study had an enrolment phase of up to 35 days (including wash-out and baseline periods), a 28-day treatment phase, and a follow-up phase of 7-14 days. Participants were randomly assigned to blinded treatment in a 1:1:1 ratio either to AZD2423 20 mg, AZD2423 150 mg or placebo.

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Participant Flow: Overall Study

	AZD2423 150 mg	AZD2423 20 mg	Placebo
STARTED	48	45	41
COMPLETED	39	38	33
NOT COMPLETED	9	7	8
Withdrawal by Subject	5	0	3
Adverse Event	2	2	2
Screen failure	1	1	0
Protocol Violation	0	1	1
Death	0	1	0
Study-specific withdrawal criteria	0	0	1
PDN worsening	0	1	0
Decrease in renal function	0	1	0
Lack of Efficacy	1	0	0
Safety, possible history of tuberculosis	0	0	1

Baseline Characteristics

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

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Baseline Measures

	AZD2423 150 mg	AZD2423 20 mg	Placebo	Total
Number of Participants [units: Participants]	48	45	41	134
Age Continuous [units: Years] Mean ± Standard Deviation	57.8 ± 6.9	59.6 ± 8.4	56.4 ± 8.4	58 ± 8
Gender, Male/Female [units: Participants]
Female	23	22	20	65
Male	25	23	21	69

Outcome Measures

1. Primary Outcome Measure: Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain score. [ Time Frame: Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28 ]

Measure Type	Primary
Measure Name	Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain score.
Measure Description	Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Average Pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10; 0=No pain, 10=Worst pain imaginable.
Time Frame	Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28
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.
Intention-to-treat set (ITT)

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Measured Values

	AZD2423 150 mg	AZD2423 20 mg	Placebo
Number of Participants Analyzed [units:participants]	46	42	39
Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain score. [units: Scores on a scale] Mean (Standard Deviation)	-1.35 (1.89)	-1.50 (1.77)	-1.61 (2.26)

No statistical analysis provided for Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Average Pain score.

2. Secondary Outcome Measure: Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain score. [ Time Frame: Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain score.
Measure Description	Last Observation Carried Forward (LOCF). Twice daily, the participants rated their Worst pain intensity during the past 12 hours on an Numerical Rating Scale (NRS) 0-10, 0=No pain, 10=Worst pain imaginable.
Time Frame	Baseline (mean of Day -5 to Day -1) to the mean of Day 24 to Day 28
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.
Intention-to-treat set (ITT)

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Measured Values

	AZD2423 150 mg	AZD2423 20 mg	Placebo
Number of Participants Analyzed [units:participants]	46	42	39
Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain score. [units: Scores on a scale] Mean (Standard Deviation)	-1.57 (1.96)	-1.66 (2.06)	-1.80 (2.48)

No statistical analysis provided for Change from baseline to Days 24-28 in Numerical Rating Scale (NRS) Worst Pain score.

3. Secondary Outcome Measure: Number of participants with at least 30% decrease from baseline in Numerical Rating Scale (NRS) Average Pain score at Day 28. [ Time Frame: Baseline (mean of Day -5 to Day -1) to Day 28 ]

Measure Type	Secondary
Measure Name	Number of participants with at least 30% decrease from baseline in Numerical Rating Scale (NRS) Average Pain score at Day 28.
Measure Description	Last Observation Carried Forward (LOCF). Numerical Rating Scale(NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)*100. Responder= NRS Average Pain score reduction ≥30% (yes/no)
Time Frame	Baseline (mean of Day -5 to Day -1) to Day 28
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.
Intention-to-treat set (ITT)

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Measured Values

	AZD2423 150 mg	AZD2423 20 mg	Placebo
Number of Participants Analyzed [units:participants]	46	42	39
Number of participants with at least 30% decrease from baseline in Numerical Rating Scale (NRS) Average Pain score at Day 28. [units: Participants]	16	19	15

No statistical analysis provided for Number of participants with at least 30% decrease from baseline in Numerical Rating Scale (NRS) Average Pain score at Day 28.

4. Secondary Outcome Measure: Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. [ Time Frame: Baseline (mean of Day -5 to Day -1) to Day 28 ]

Measure Type	Secondary
Measure Name	Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28.
Measure Description	Last Observation Carried Forward (LOCF). Numerical Rating Scale (NRS) Average Pain score reduction=(change from baseline at Day 28/baseline)*100. Responder= NRS Average Pain score reduction ≥50% (yes/no)
Time Frame	Baseline (mean of Day -5 to Day -1) to Day 28
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.
Intention-to-treat set (ITT)

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Measured Values

	AZD2423 150 mg	AZD2423 20 mg	Placebo
Number of Participants Analyzed [units:participants]	46	42	39
Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28. [units: Participants]	10	8	10

No statistical analysis provided for Number of Participants With at Least 50% Decrease From Baseline in Numerical Rating Scale (NRS) Average Pain Score at Day 28.

5. Secondary Outcome Measure: Change from baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total score. [ Time Frame: Baseline (Day 1) to Day 29 (Visit 7) ]

Measure Type	Secondary
Measure Name	Change from baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total score.
Measure Description	Last Observation carried Forward (LOCF). Scale consists of 10 Neuropathic Pain Symptom Inventory Scale (NPSI) pain symptom descriptors wiht a recall period of 24 hours. Each descriptor is rated on a Numerical Rating Scale (NRS) 0-10; 0=No (sympthom), 10=Worst (sympthom) imaginable. The NPSI Total Score was calculated as the sum of 10 of the NPSI descriptors. Range for total score 0 -100. Higher total score implicates worse symptoms.
Time Frame	Baseline (Day 1) to Day 29 (Visit 7)
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.
Intention- to- treat set (ITT)

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Measured Values

	AZD2423 150 mg	AZD2423 20 mg	Placebo
Number of Participants Analyzed [units:participants]	35	30	33
Change from baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total score. [units: Scores on a scale] Mean (Standard Deviation)	-14.63 (22.77)	-12.20 (22.84)	-7.82 (17.02)

No statistical analysis provided for Change from baseline to Day 29 in Neuropathic Pain Symptom Inventory Scale (NPSI) Total score.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	Safety analysis set

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Serious Adverse Events

AZD2423 150 mg

AZD2423 20 mg

Placebo

Total, serious adverse events

# participants affected / at risk

0/47 (0.00%)

3/44 (6.82%)

0/41 (0.00%)

Respiratory, thoracic and mediastinal disorders

Asthma¹

# participants affected / at risk

0/47 (0.00%)

1/44 (2.27%)

0/41 (0.00%)

Infections and infestations

Clostridium difficile colitis¹

# participants affected / at risk

0/47 (0.00%)

1/44 (2.27%)

0/41 (0.00%)

Cardiac disorders

Myocardial Infarction¹

# participants affected / at risk

0/47 (0.00%)

1/44 (2.27%)

0/41 (0.00%)

General disorders

Sudden cardiac death¹

# participants affected / at risk

0/47 (0.00%)

1/44 (2.27%)

0/41 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	Safety analysis set

Frequency Threshold

Threshold above which other adverse events are reported	4%

Reporting Groups

	Description
AZD2423 150 mg	tablets, 150 mg once daily in the morning
AZD2423 20 mg	tablets, 20 mg once daily in the morning
Placebo	tablets, once daily in the morning

Other Adverse Events

AZD2423 150 mg

AZD2423 20 mg

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

14/47 (29.79%)

6/44 (13.64%)

11/41 (26.83%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/47 (6.38%)

0/44 (0.00%)

1/41 (2.44%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

2/47 (4.26%)

1/44 (2.27%)

1/41 (2.44%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/47 (4.26%)

1/44 (2.27%)

1/41 (2.44%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

2/47 (4.26%)

1/44 (2.27%)

0/41 (0.00%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

2/47 (4.26%)

0/44 (0.00%)

0/41 (0.00%)

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

2/47 (4.26%)

0/44 (0.00%)

0/41 (0.00%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/47 (2.13%)

2/44 (4.55%)

3/41 (7.32%)

Musculoskeletal and connective tissue disorders

Muscle spasms¹,^†

# participants affected / at risk

0/47 (0.00%)

1/44 (2.27%)

3/41 (7.32%)

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

0/47 (0.00%)

0/44 (0.00%)

2/41 (4.88%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 10.0
2	Term from vocabulary,

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 such publication or presentation may include any of AstraZeneca’s Confidential Information without AstraZeneca’s prior written approval. AZ should have 60 days for review and can extend time until submission up to 90 days.

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
No text entered.

Results Point of Contact

Name/Title:	Heather Bryson
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=204&filename=CSR-D2600C00005.pdf
Download
CSR-D2600C00005.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Bror Jonzon

AstraZeneca R&D Södertälje

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=204&filename=CSR-D2600C00005.pdf

CSR-D2600C00005.pdf

Trial Results Summaries