Phase 2
N=608
Study to Examine Safety, Tolerability, and Effect on Body Weight of Metreleptin Administered in Conjunction With Pramlintide in Obese and Overweight Subjects
Overweight · Obesity
Bottom Line
View on ClinicalTrials.gov: NCT00673387 ↗Enrolled (actual)
608
Serious AEs
1.3%
Results posted
Nov 2013
Primary outcome: Primary: Least Squares (LS) Mean Percent Change in Body Weight From Baseline to Week 28 - Evaluable Population — -2.01; -5.47; -5.83; -6.85 Percentage change in kg — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- pramlintide acetate (Drug); metreleptin (Drug); placebo-P (Drug); placebo-M (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Apr 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Least Squares (LS) Mean Percent Change in Body Weight From Baseline to Week 28 - Evaluable Population |
-2.01; -5.47; -5.83; -6.85; -6.61; -6.39 | <0.0001 sig |
| SECONDARY Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population |
10; 27; 18; 27; 27; 23 | — |
| SECONDARY Mean Absolute Change From Baseline to Weeks 4, 12, 28 in Mean Trough Concentration of Total Leptin - Evaluable Population |
53.26; 31.00; 47.82; -2.36; 14.66; 49.16 | — |
| SECONDARY LS Mean Absolute Change in Body Weight From Baseline to Weeks 4, 12, and 28 - Evaluable Population |
-1.81; -2.85; -2.54; -2.94; -2.40; -2.62 | — |
| SECONDARY LS Mean Change in Waist Circumference From Baseline to Week 12 and Week 28 - Evaluable Population |
-3.03; -3.40; -3.41; -4.91; -4.29; -3.32 | 0.0404 sig |
| SECONDARY Geometric Mean of the Total Area Under the Concentration Time Curve (AUC) From Time 0 to Last Quantifiable Concentration (Tlast) for Pramlintide at Weeks 4 and 24 - Evaluable Population Receiving Pramlintide |
1862.5; 878.8; 967.5; 1788.2; 1920.1; 2060.4 | — |
| SECONDARY Geometric Mean of AUC From Time 0 to Infinity for Pramlintide at Weeks 4 and 24 - Evaluable Population Treated With Pramlintide |
2662.7; 989.3; 1240.7; 2159.0; 2311.3; 2511.4 | — |
| SECONDARY Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) for Pramlintide at Weeks 4 and 24 - Evaluable Population Receiving Pramlintide |
1759.0; 876.7; 897.3; 1783.8; 1851.3; 2096.4 | — |
| SECONDARY Least Squares (LS) Mean Absolute Change From Baseline to Week 28 in Percent of Body Fat - Evaluable Population |
-0.95; -1.77; -1.94; -2.32; -2.21; -2.21 | 0.0464 sig |
| SECONDARY LS Mean Absolute Change From Baseline to Week 28 in Total Body Fat Mass (k) - Evaluable Population |
-1.96; -4.28; -4.57; -4.98; -4.97; -5.03 | 0.0049 sig |
| SECONDARY LS Mean Absolute Change From Baseline to Week 28 in Fat-free Mass (kg) - Evaluable Population |
-0.69; -1.62; -1.80; -1.90; -1.99; -2.02 | 0.0222 sig |
| SECONDARY LS Mean Absolute Change From Baseline to Week 28 in Fasting Plasma Glucose, Total Cholesterol (TC), Triglycerides, Low Density Lipoprotein (LDL) Cholesterol, High Density Lipoprotein (HDL) Cholesterol - Evaluable Population |
-1.3; -1.8; -1.8; -2.5; -1.2; -1.0 | — |
| SECONDARY Mean Absolute Change From Baseline to Week 28 for Insulin - Evaluable Population |
1.1; -0.4; -1.6; -1.0; -2.5; -1.4 | — |
| SECONDARY Mean Absolute Change From Screening to Week 24 in Impact of Weight on Quality of Life Questionnaire-lite Version (IWQOL-Lite) Total Score - Evaluable Population |
10.52; 10.31; 11.09; 10.14; 16.15; 13.84 | — |
| SECONDARY Mean Absolute Change From Screening to Week 24 in Binge Eating Scale (BES) Total Score - Evaluable Population |
-3.0; -3.4; -4.0; -4.4; -6.6; -3.5 | — |
| SECONDARY Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population |
-9.0; -6.6; -4.0; -14.1; -19.8; -15.7 | — |
| SECONDARY Mean Absolute Change From Screening to Week 24 in Hospital Anxiety and Depression Scale (HADS) Total Scores - Evaluable Population |
0.02; 0.08; -0.56; -0.11; -0.43; -0.59 | — |
| SECONDARY Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population |
0.35; 0.39; -0.17; 0.87; -0.30; -0.21 | — |
| SECONDARY Mean Absolute Change From Screening to Week 24 in Minutes to Fall Asleep, Hours of Sleep and The Pittsburgh Sleep Quality Index (PSQI) Global Score - Evaluable Population |
-0.5; 1.3; -2.1; -4.3; -4.6; -4.3 | — |
| SECONDARY Mean Absolute Change From Screening to Week 24 in the Epworth Sleepiness Scale (ESS) Total Score - Evaluable Population |
-0.69; -0.63; 0.12; -1.32; -1.80; -1.05 | — |
| SECONDARY Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population |
4; 0; 0; 0; 0; 1 | — |
| SECONDARY Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population |
0; 8; 1; 0; 0; 0 | — |
| SECONDARY Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 28 - Intent to Treat Population |
2.4; -0.9; -3.4; -3.2; 0.4; -2.0 | — |
| SECONDARY Mean Change in Heart Rate From Baseline to Week 28 - Intent to Treat Population |
1.6; -1.3; -2.6; -1.4; -2.1; -0.5 | — |
| SECONDARY Number of Participants With Treatment-emergent Positive Anti-leptin Antibody Titers at Week 28 - Intent to Treat Population |
43; 49; 48; 42; 50; 42 | — |
| SECONDARY Mean Change From Screening to Week 28 in Electrocardiogram Parameters - Intent to Treat Population |
1.1; -0.1; 0.3; 0.1; 16.8; 4.4 | — |
| SECONDARY Mean Change From Screening to Week 28 in the Electrocardiogram Parameter of Heart Rate - Intent to Treat Population |
0.3; -2.8; -4.1; -4.7; -4.9; -1.9 | — |
Summary
A randomized, double-blind, placebo-controlled, dose-ranging study to examine the safety, tolerability and effect on body weight of a range of doses of metreleptin and pramlintide, each administered by a separate subcutaneous (SC) injection in obese and overweight subjects.
Eligibility Criteria
Inclusion Criteria
- 18 to 65 years old.
- Is obese (Body Mass Index [BMI]>=30kg/m^2 and =27kg/m^2 and 3% within 3 months prior to study.
- Has not been treated over the past 3 months or is currently treated with any of the following medications: Oral contraceptives (female subjects); Hormone replacement therapy (female subjects); Metformin for the treatment of polycystic ovary syndrome (female subjects); Antihypertensive agents; Lipid-lowering agents; Thyroid replacement therapy; selective serotonin reuptake inhibitors (SSRIs).
- Is comfortable with having repeated telephone contacts with a lifestyle counselor during the study.
- Is a nonsmoker (has not smoked for at least 6 months prior to the study).
Exclusion Criteria
- Has a medical history (e.g., morbid childhood obesity) and/or physical characteristics suggestive of genetic obesity or syndromatic obesity (e.g., Prader-Willi syndrome, Bardet-Biedl syndrome).
- Is currently enrolled or plans to enroll in a diet, weight loss, or exercise program with the specific intent of losing weight (subjects who have been following an exercise regimen resulting in stable weight maintenance for at least 2 months prior to enrollment are eligible for study inclusion)
- Has been treated over the past 2 months, is currently treated, or is expected to require or undergo treatment with *antiobesity agents (prescription or over-the-counter), *antipsychotic agents, *antiepileptic agents, *antidepressant agents, *drugs that directly affect gastrointestinal motility, *antidiabetic medications.
- Has previously received treatment with metreleptin or pramlintide in a clinical study or has received prior treatment with pramlintide (SYMLIN®).
- Has received any investigational drug within 30 days or within a period corresponding to 5 half-lives of that drug, whichever is greater, prior to this study starting.
- Has had a major surgery or a blood transfusion, or has donated blood over the past 2 months or is planning to donate blood during the study.
- Has had liposuction, abdominoplasty, or similar procedure over the past year or is planning to have such a procedure during the study.
Data sourced from ClinicalTrials.gov (NCT00673387). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.