EU Clinical Trial Information System (CTIS)

Brand Logo

Brand Logo Light

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.

I searched for some studies on AstraZeneca Clinical Trials, and found these studies that may also be of interest to you.
Here is the link to my search results

Official Title

Study DFA102E is an extension of Study DFA102, which included a 28-week treatment period with randomized study medication. The purpose of the extension study is to examine the long-term (up to 1 year) safety, tolerability, and effect on body weight of treatment with pramlintide and metreleptin, administered as separate subcutaneous (SC) injections, in obese and overweight subjects.

Extension Study of Protocol DFA102 to Examine the Long-Term Safety, Tolerability, and effect on Body Weight of Pramlintide Administered in Combination with Metreleptin

placebo pramlintide and placebo metreleptin twice daily

Research Site

Extension Study of Protocol DFA102 to Examine the Long-Term Safety, Tolerability, and effect on Body Weight of Pramlintide Administered in Combination with Metreleptin in Obese and Overweight Subjects

Original study DFA102 (NCT00673387) baseline refers to Visit 5 (Day 1). If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Least Squares (LS) Mean based on a repeated measures mixed model with treatment, sex, DFA102 baseline BMI category, nominal week, treatment by nominal week interaction as factors, and DFA102 baseline weight value as a covariate, with a heterogeneous compound symmetry error covariance structure within each treatment group. Stable population consists of all ITT participants (received at least one injection of treatment) who had the same treatment group assignment in Study DFA102 and Study DFA102E, ie, ITT participants who were in Study DFA102 treatment groups Placebo, Pramlintide 360 + Metreleptin 1.25, Pramlintide 360 + Metreleptin 2.5 and Pramlintide 360 + Metreleptin 5.0.

Age Continuous

Gender, Male/Female

Region of Enrollment

Baseline in the extension study was Week 28 in the original study.  If Week 28 value was missing or after the first dose in DFA102E, the last available value on or prior to Week 28 was used.

Body Weight at Baseline

Study Specific Characteristic

Baseline refers to Week 28 in original study.  If Week 28 was missing or after the first dose in DFA102E, the last available value on or prior to Week 28 was used. Body Mass Index (BMI) was measured as kilogram per meter of height squared (kg/m^2).

Body Mass Index (BMI) at Baseline

All participants who completed original study and chose to be enrolled into this extension study and were treated with study drug.

Original study DFA102 (NCT00673387) baseline refers to Visit 5 (Day 1). If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Least Squares (LS) Mean based on a repeated measures mixed model with treatment, sex, DFA102 baseline BMI category, nominal week, treatment by nominal week interaction as factors, and DFA102 baseline weight value as a covariate, with a heterogeneous compound symmetry error covariance structure within each treatment group. Stable population consists of all ITT participants (received at least one injection of treatment) who had the same treatment group assignment in Study DFA102 and Study DFA102E, ie, ITT participants who were
in Study DFA102 treatment groups Placebo, Pramlintide 360 + Metreleptin 1.25, Pramlintide 360 + Metreleptin 2.5 and  Pramlintide 360 + Metreleptin 5.0.

Treatment comparisons between each active treatment and placebo. Statistical tests performed two-sided at a significance level of α = 0.05. The null
hypothesis tested was that there is no difference between each active treatment and the placebo treatment. The primary analysis did not incorporate any adjustment for multiple comparisons.

Treatment comparisons between each active treatment and placebo. Statistical tests performed two-sided at a significance level of α = 0.05. The null hypothesis tested was that there is no difference between each active treatment and the placebo treatment. The primary analysis did not incorporate any adjustment for multiple comparisons

Enrolled and received at least 1 injection of any treatment (ITT); treatment regimens same in both DFA102/DFA102E (stable); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock); no major deviations during original study/extension.  Additional exclusions based on clinical review of the data prior database lock.

LS Mean Percent change in body weight from original Study DFA102 (NCT00673387) baseline (Day 1) at Week 52 in extension study DFA102E - Evaluable Treatment Stable Population

Week 12 (original study)

Week 28 (Baseline for Extension)

Week 36 in Extension Study

Week 44 in Extension Study

Week 52 in Extension Study

Original study DFA102 (NCT00673387) baseline refers to Visit 5 (Day 1). If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Weeks 12 and 28 were in original study (Week 28 was baseline for extension study), while Weeks 36, 44, and 52 were in the extension study. Body weight was measured in kilograms (kg).

LS mean Absolute change in body weight from original study baseline (Day 1) at Weeks 12, 28, 36, 44, and 52 - Evaluable Treatment Stable Population

DFA102 Baseline

DFA102E Baseline (Week 28)

Week 40

Week 52

Follow up post treatment

Baseline is Day 1 in original study DFA102, baseline in DFA102E is Week 28. Follow up is 3 - 28 days after the end of treatment period. As total leptin is measured, placebo arm was not included in the evaluation. Fasting total leptin is measured in nanograms per milliliter (ng/mL). The assay for measuring total plasma leptin is not specific for metreleptin and detects both endogenous leptin and exogenous metreleptin.

Enrolled and received at least 1 injection of metreleptin; treatment regimens same in both DFA102/DFA102E (stable population); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock); no major deviations during original study/extension.

Fasting total leptin concentration by visit and pooled metreleptin stable treatment by metreleptin dose - Week 52 Stable Evaluable population

Week 28 (baseline in Extension study)

Week 36 Extension study

Week 44 Extension study

Week 52 Extension study

Baseline is the baseline in the original study DFA102 (Day 1). If Day 1 value was missing or after the first dose of drug, the last available value on or prior to Day 1 was used. Waist circumference was measured in centimeters (cm). Week 52, treatment stable evaluable population: those participants who enrolled and received at least 1 injection of any treatment (ITT); treatment regimens same in both DFA102/DFA102E (stable); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock); no major deviations during original study/extension.  Additional exclusions based on clinical review of the data prior database lock.

n=number of participants with non-missing waist circumference data at this visit in each treatment group. Week 12 n=21,20,27,19; Week 28 n=21,20,26,19; Week 36 n=21,20,27,19; Week 44 n=20,20,27,19; Week 52 n=21,19,27,19.ITT population with treatment regimens same in DFA102/DFA102E; completed Week 52; no major protocol deviations in DFA102/102E.

LS mean absolute change in waist circumference from baseline in the original study to Week 52 in the extension study - Week 52 Evaluable Stable Population

Week 12 of original study

Week 28 Extension study

Baseline is Day 1 in study DFA102. If Day 1 value was missing or after the first dose of drug, the last available value on or prior to Day 1 was used. Baseline in the Extension Study was Week 28. Week 52, treatment stable evaluable population: those participants who enrolled and received at least 1 injection of any treatment (ITT); treatment regimens same in both DFA102/DFA102E (stable); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock).

n=number of participants with non-missing data at this visit in each treatment group. Week 12 n=21,20,27,19; Week 28 n=21,20,27,19; Week 36 n=21,20,27,19; Week 44 n=21,20,27,19; Week 52 n=21,20,27,19. ITT population with treatment regimens same in DFA102/DFA102E; completed Week 52; no major protocol deviations in DFA102/102E.

LS mean percent change in body weight from baseline of original study DFA102 at Week 12, and at Weeks 28, 36, 44, and 52 in the Extension study DFA102E - Week 52 Evaluable treatment Stable population

glucose

total cholesterol

triglycerides

low density lipoprotein  (LDL)

high density lipoprotein  (HDL)

Glucose, total cholesterol, triglycerides, low density lipoprotein (LDL), and high density lipoprotein (HDL) were measured in milligrams per deciliter (mg/dL). Baseline was Day 1 in original study DFA102, Week 52 was in extension study DFA102E. If Day 1 value was missing or after the first dose of drug, the last available value on or prior to Day 1 was used. Week 52, treatment stable evaluable population: those participants who enrolled and received at least 1 injection of any treatment (ITT); treatment regimens same in both DFA102/DFA102E (stable); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock).

n=number of participants with non-missing data in each treatment group by test. glucose n=20,20,27,19; total cholesterol n=21,20,27,19; triglycerides n=21,20,27,19; LDL/HDL n=21,20,27,19. ITT population with treatment regimens same in DFA102/DFA102E (stable); completed Week 52; no major protocol deviations in DFA102 or DFA102E.

LS mean absolute change from baseline in original study DFA102 to Week 52 in Extension study DFA102E for Glucose and Lipids - Week 52 Evaluable Treatment Stable Population

Total insulin was measured in micro international units per milliliter (µIU/mL). Baseline is Day 1 in original study DFA102. If Day 1 value was missing or after the first dose of drug, the last available value on or prior to Day 1 was used. Week 52, treatment stable evaluable population: those participants who enrolled and received at least 1 injection of any treatment (ITT); treatment regimens same in both DFA102/DFA102E (stable); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock).

n=number of participants with non-missing data in each treatment group. ITT population (received at least 1 injection) with treatment regimens same in DFA102/DFA102E (stable treatment); completed Week 52; no major protocol deviations in DFA102/102E.

LS mean absolute change from baseline in original study DFA102 to Week 52 in Extension study DFA102E in total insulin - Week 52 Evaluable Treatment Stable Population

Weight Loss >=5% and <10%

Weight Loss >=10% and <15%

Weight Loss >=5%

Weight Loss >=10%

Weight Loss >=15%

Baseline is Day 1 in original study DFA102. If Day 1 value was missing or after the first dose of drug, the last available value on or prior to Day 1 was used. Percent change in body weight from baseline was categorized: Change greater than (>) 0% (Body weight gain); Change less than, equal to (<=) 0 to > -5% (No body weight change or body weight loss <5%); Change <= -5% (Body weight loss greater than, equal to (>=)5%); Change <= -5% to > -10% (Body weight loss >=5% and <10%); Change <= -10% (Body weight loss ≥10%); Change <= -10% to > -15% (Body weight loss >=10% and <15%); Change <= -15% (Body weight loss >=15%).

Number analyzed with non-missing data at Week 52. Week 52 Evaluable Population: All ITT participants (received at least 1 injection);remained in the study through Week 52; complied with the protocol (per sponsor prior to database lock);no major deviations; some may have been excluded based on a clinical review of the data prior to database lock.

Number of Participants achieving at least 5%, 10%, and 15% of Body Weight Loss from Original Study DFA102 Baseline to Week 52 in Extension study DFA102E - Week 52 Evaluable Population

Baseline in extension study was Week 28; if value was missing or after the first dose in DFA102E, the last available value on or prior to Week 28 was used. Percent change in body weight from baseline was categorized: Change greater than (>) 0% (Body weight gain); Change less than, equal to (<=) 0 to > -5% (No body weight change or body weight loss <5%); Change <= -5% (Body weight loss greater than, equal to (>=)5%); Change <= -5% to > -10% (Body weight loss >=5% and <10%); Change <= -10% (Body weight loss ≥10%); Change <= -10% to > -15% (Body weight loss >=10% and <15%); Change <= -15% (Body weight loss >=15%).

Participants analyzed had non-missing data at Week 52. Week 52 Evaluable Population: ITT participants (received at least 1 injection); remained in the study through Week 52; complied with the protocol (per sponsor prior to database lock); no major deviations; some may have been excluded based on a clinical review of the data prior to database lock.

Number of Participants achieving at least 5%, 10% and 15% body weight loss from Extension study DFA102E baseline (Week 28) to Week 52 - Week 52 Evaluable Population

Frequency of Food Cravings

Strength of Food Cravings

Difficult to Control Eating

Difficult to Resist Food Cravings

Eating in Response to Food Cravings

Difficult to Control Portion Sizes

How Hungry

How Full After Meals

Thoughts of Food

How Pleasant Meals

The eating questionnaire is an exploratory measure of appetite, satiety, and perceived control over portion size using 10 items, with each response measured on a 100 mm visual analogue scale (VAS). Ranges vary from: Never to Very Often; Not at All Difficult to Extremely Difficult; Not at all Strong to Very Strong). Lower scores show improvement. The Eating Questionnaire instructed participants to rate their responses to these items over the past 7 days. Values were obtained for this questionnaire on Visit 3 in the screening period in DFA102 and at Weeks 28, 40, and 52 in DFA102E.

Enrolled and received at least 1 injection of any treatment (ITT); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock); no major deviations during original study/extension.  Additional exclusions based on clinical review of the data prior database lock.

Mean Absolute Change From original study DFA102 Screening at Week 52  in Extension study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores – Week 52 Evaluable Population

The Binge Eating Scale (BES) is a 16-item questionnaire that assesses the behavioral and cognitive correlates of binge eating, including participants' perceived self-control over eating behavior using a range of 1 to 4 with 1=positive perceptions and 4= negative perceptions. Lower scores show improvement. The minimum and maximum score for the BES instrument is 0 and 55, respectively; the higher the score the worse the outcome. Values were obtained for this questionnaire on Visit 3 in the screening period in DFA102 and at Weeks 28, 40, and 52 in DFA102E.

Mean Absolute Change From original study DFA102 Screening to Week 52 in Extension study DFA102E in Binge Eating Scale (BES) Total Score - Week 52 Evaluable Population

Change in Total Scores for Anxiety

Change in Total Scores for Depression

The HADS is a questionnaire that uses 14 items to assess both anxiety and depression over the past week. The odd numbered items constitute the anxiety subscale, and the even numbered items constitute the depression subscale. The individual response scores for each subscale component are added together to obtain the individual subscale scores. The minimum and maximum score for each subscale is 0 and 21, respectively. Lower scores show improvement. Values were obtained for this questionnaire on Visit 3 in the screening period in DFA102 and at Weeks 28, 40, and 52 in DFA102E.

Mean Absolute Change From original study DFA102 Screening to Week 52 in Extension study DFA102E in Hospital Anxiety and Depression Scale (HADS) Total Scores – Week 52 Evaluable Population

The Epworth Sleepiness Scale (ESS) is an eight-item questionnaire that assesses sleep propensity in daily situations of increasing sleepiness on a four-point scale with 0=would never doze and 3=high chance of dozing. Lower scores show improvement. Values were obtained for this questionnaire on Visit 3 in the screening period in DFA102 and at Weeks 28, 40, and 52 in DFA102E.

Mean Absolute Change From original study DFA102 Screening to Week 52 in Extension study DFA102E in the Epworth Sleepiness Scale (ESS) Total Score – Week 52 Evaluable Population

Baseline in DFA102 (Day 1)

Baseline in DFA102E (Week 28)

Follow up after end of treatment

Mean fasting plasma total leptin concentration (nanograms per milliliter; ng/mL) change from baseline over time by pooled metreleptin dose (sex, baseline BMI category, and baseline value). Baseline defined as Day 1 in DFA102 study and Week 28 in study DFA102E. If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Follow up occurred 3-28 days after end of treatment. Leptin concentrations were measured using a validated immunoenzymetric assay utilizing polyclonal capture antibody, monoclonal detection antibody, and colorimetric readout by Amylin Pharmaceuticals, Inc. Week 52 Stable Evaluable: Enrolled and received at least 1 injection of any treatment (ITT); treatment regimens same in both DFA102/DFA102E (stable); evaluable: completed Week 52; complied with protocol, (per Sponsor prior to database lock); no major deviations during original study/extension.

number (n) of participants who are Week 52 evaluable in a stable treatment sequence (received the same treatment in both DFA102 and DFA102E) and who had follow up data. Week 52 in Metreleptin 2.5 mg arm n=55 (all others n=56); Week 40 in Metreleptin 5 mg arm n=66 (all others n=68)

Total trough concentration of plasma Leptin at Baseline and at Weeks 40, 52, and end of treatment Follow up - Week 52 stable evaluable  population

Systolic Blood Pressure

Diastolic Blood Pressure

Baseline refers to Day 1 of original study DFA102. If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Blood pressure was taken while the participant was sitting and was measured in millimeters of mercury (mm Hg).

Enrolled and received at least 1 injection of any treatment; had data available.

Mean Change in Systolic and Diastolic Blood Pressure From Baseline of DFA102 at Week 52 of DFA102E - Intent to Treat Population

Baseline refers to Day 1 of original study DFA102. If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Heart rate was measured while the participant was sitting and was measured in beats per minute (bpm).

Mean Change in Heart Rate From Baseline of DFA102 at Week 52 of DFA102E - Intent to Treat Population

PR Interval

QT Interval

QTcF

A 12-Lead electrocardiogram (ECG) was obtained. The PR interval, which is the time from beginning of the P wave to the beginning of the QRS complex (Note: QRS complex is a name for the combination of 3 of the graphical deflections seen in an ECG); QRS interval, which is time from the beginning to the end of the QRS complex; QT interval (measure between Q wave and T wave in the heart's electrical cycle); and QT interval corrected for heart rate using Fridericia's formula (QTcF) were measured in milliseconds (msec).

Enrolled and received at least 1 injection of any treatment; had ECG data available at Week 52.

Mean Change From DFA102 Screening at Week 52 in study DFA102E for Electrocardiogram Parameters - Intent to Treat Population

Hematocrit

Hemoglobin

Platelet Count

Urinalysis

Baseline defined as Week 28 (first week of study DFA102E). Hematology: Hematocrit males <36%, females <30%. Hemoglobin males <12 g/dL, females <10 g/dL. White blood cell count (WBC) H >18,000/µL; L <1,500/µL. Urinalysis: Urine protein H >= 3+ or >= 500 mg/dL. Urine glucose H >= 3+ or >= 500 mg/dL. Urine ketones >= 3+ or Large. Laboratory values were obtained at Weeks 28, 36, 44, and 52. Numbers of values are cumulative across the extension

Enrolled and received at least 1 injection of any treatment; participants had laboratory data available; platelet counts: n=19 in second arm (not 20); n=20 in fourth arm (not 22); n=11 in fifth arm (not 12);

Number of Hematology or Urinalysis laboratory values of Potential Clinical Importance observed from baseline of DFA102E to Week 52 - Intent to Treat Population

alanine aminotransferase (ALT)

Bicarbonate

Creatine kinase

Calcium

Creatinine

Gamma-glutamyltransferase

Potassium

Sodium

Uric Acid

Baseline defined in study DFA102E as Week 28. Criteria for laboratory values of potential clinical importance for obese and overweight (BMI>=25 kg/m^2) participants: Total bilirubin High (H) > 2 mg/dL; Plasma or serum glucose fasting or non-fasting H > 200 mg/dL, low (L) < 60 mg/dL; Albumin L <2.5 g/dL; Creatine kinase H > 3*Upper limit of Normal (ULN); Sodium L <130 milliequivalents per liter (mEq/L), H > 150 mEq/L; potassium L<3.0 mEq/L, H> 5.5 mEq/L;bicarbonate L<18 mEq/L, H>35 mEq/L;calcium L <8mg/dL, H> 11 mg/dL; triglycerides H> 500 mg/dL; Cholesterol L < 100 mg/dL, H > 350 mg/dL; Alkaline phosphatase H > 3*ULN; Gamma-glutamyltransferase H>3*ULN; creatinine males > 1.6 mg/dL, females > 1.4 mg/dL; alanine aminotransferase H > 3*ULN; aspartate aminotransferase H > 3*ULN; urea nitrogen H > 45 mg/dL; uric acid males > 10.0 mg/dL, females > 8.0 mg/dL; Phosphorus L < 1.0 mg/dL H > 6.0 mg/dL. Laboratory values obtained at Weeks 28, 36, 44, and 52; number of values a

All Enrolled participants who received at least one injection of any study medication in Study DFA102E; had laboratory data available. Number analyzed presented above is at Week 52; Number analyzed at Week 28: N= 31, 35, 36, 28, 13, 14, 13, 29, 37, 37.

Number of chemistry laboratory values of Potential Clinical Importance observed from DFA102E baseline to Week 52 - Intent to Treat Population

Baseline refers to Day 1. If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Follow up occurred on Days 3 - 28 after treatment ended. Serum titer determinations for antibodies to metreleptin were made using a validated electrochemical luminescence (ECLA) bridging assay. Antibody titers were assessed according to the following dilutions: 0, 5, 25, 125, 625, 3125, 15625, and 78125. Participants were considered to have a positive titer to treatment-emergent antibodies to metreleptin at a given visit if they had a titer >=5 following a negative or missing titer at baseline or if they had a titer that had increased by at least 2 dilutions from a detectable level at baseline.

N for Week 52 presented above. For Follow up: N=18,58,68,11,7,8.

Number of Participants With Treatment Emergent Positive Anti-leptin Antibody Titers at Week 52 and at Follow up by Metreleptin Dose - Intent to Treat Population

Overall Study

DFA102 participants assigned to: placebo, 360mcg pramlintide+1.25mg metreleptin, 360mcg pram+2.5mg metre, or 360mcg pram+5.0mg metre did not change treatment in  extension (stable groups). All other groups transitioned to 360mcg pram + 1.25, 2.5 or 5.0mg metre. 274 enrolled in extension and 273 were treated.

Arms	Assigned Interventions
Placebo Comparator: 1	Drug: Placebo placebo pramlintide and placebo metreleptin twice daily
Experimental: 2 Pramlintide and 1.25mg Metreleptin	Drug: Pramlintide and Metreleptin Subcutaneous injection, twice daily Other Name: Symlin
Experimental: 3 Pramlintide and 2.5mg Metreleptin	Drug: Pramlintide and Metreleptin Subcutaneous injection, twice daily Other Name: Symlin
Experimental: 4 Pramlintide and 5.0mg Metreleptin	Drug: Pramlintide and Metreleptin Subcutaneous injection, twice daily Other Name: Symlin

Extension Study of Protocol DFA102 to Examine the Long-Term Safety, Tolerability, and effect on Body Weight of Pramlintide Administered in Combination with Metreleptin

Official Title

Medical condition

Phase

Healthy volunteers

Study drug

Sex

Actual Enrollment

Study type

Age

Date

Study design

Verification:

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Documents available

Trial Results Summaries

Contacts

Contact

Investigators

Principal Investigator