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

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

Time frame · Original Study Baseline to Week 52

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.

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

Time frame · Original baseline to Week 52

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).

Fasting Total Leptin Concentration by Visit and Pooled Metreleptin Stable Treatment by Metreleptin Dose - Week 52 Stable Evaluable Population

Time frame · Original Study Baseline to Extension Week 52 and follow up

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.

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

Time frame · Baseline to Week 52

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.

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

Time frame · Baseline to Week 52

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).

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

Time frame · Baseline (Day 1) to Week 52

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).

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

Time frame · Baseline to Week 52

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).

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

Time frame · Baseline (Day 1) to Week 52

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 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

Time frame · Baseline (Week 28) to Week 52

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%).

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

Time frame · Screening to Week 52

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.

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

Time frame · Screening to Week 52

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.