Obesity
Conditions
Keywords
Pramlintide, Metreleptin, Obesity, Amylin, Takeda
Brief summary
Following screening, eligible subjects will be enrolled into a 6-week Low Calorie Diet (LCD) lead-in period. Subjects who lose at least 2% of their body weight at the end of the 6-week LCD lead-in period will be randomized to 1 of 2 treatment arms (pramlintide+metreleptin or placebo) to begin a 16-week treatment period during which the effect on body weight of treatment with pramlintide+metreleptin will be compared to placebo. Following the 16 week blinded core treatment period, subjects will discontinue study medication for a period of 12 weeks. Following the 12 week off-drug follow-up period, subjects in both groups will initiate a 12 week open-label treatment period with Pramlintide+Metreleptin. During the 12 week off-drug and 12 week open label treatment periods, subjects will continue to participate in a Lifestyle Intervention (LSI) program.
Interventions
DRUGPramlintide+Metreleptin
Group A: Subcutaneous Injection once a day (QD): Pramlintide 360 mcg+Metreleptin 5.0 mg for 1 week followed by Pramlintide 360 mcg+Metreleptin 5.0 mg twice a day (BID) for 15 weeks.
DRUGPlacebo
Group B: Subcutaneous Injection-twice a day (BID): Placebo equivalent volumes to active doses.
Sponsors
Takeda Pharmaceuticals North America, Inc.
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Is obese with a BMI ≥35 to ≤45 kg/m2. * Has stable body weight (not varying by \>5% within 3 months prior to study start). * Meets certain requirements with respect to concomitant medications. * Has not smoked or used nicotine-containing products for at least 12 months prior to study start.
Exclusion criteria
* Has not been enrolled in a weight loss program within 2 months prior to study start.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | Baseline up to Month 6 Follow-Up | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Lipids measured included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides. Lipids were measured in milligrams per deciliter (mg/dL). |
| Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population | Day 1 up to Month 6 Follow-Up | Treatment-Emergent Adverse Events are defined as those with an onset date and time on or after the first dose of randomized study medication and on or before the last dose of randomized study medication. Post-treatment Adverse Events are defined as those with an onset date after the date of last dose (imputed if not available) of randomized study medication. Participants experiencing multiple episodes of a given adverse event are counted once. |
| Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population | Baseline to Month 6 Follow Up | Participants who received metreleptin were analyzed; no placebo treated participants were analyzed. Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Leptin was measured in nanograms per milliliter (ng/mL). |
| Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Week 1 to Month 6 Follow-Up | Anti-leptin antibodies measured at Weeks 1 and 2 of drug treatment, early termination visit, and at Months 2, 4, and 6 post treatment follow-up in participants who received metreleptin. |
| Number of Participants With Neutralizing Activity to Metreleptin at Early Termination or During Post Treatment Follow-Up - Intent to Treat Population Who Received Metreleptin | Baseline to Month 6 Follow-Up | In vitro assays were conducted to determine if neutralizing activity to metreleptin developed in participants treated with at least one dose of the drug during the study. Baseline is Day 1 of the Randomization Period, prior to administration of metreleptin. |
| Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Screening to 6 Month Follow-Up | Criteria for laboratory values of potential clinical importance for obese and overweight (BMI \>= 25 kg/m\^2) participants: Platelets high (H) \>500,000/µL; low (L) \<75,000/µL. 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. Urine protein H \>= 3+ or \>= 500 mg/dL. Urine glucose H \>= 3+ or \>= 500 mg/dL. Urine ketones \>= 3+ or Large. |
| Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Screening to Month 6 Follow-Up | 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. |
| Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population | Baseline to Month 6 Follow-Up | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow-up was up to 6 months post treatment. Blood pressure included systolic and diastolic pressures measured in millimeters of mercury (mmHg). |
| Mean Change From Baseline to Month 6 Follow-Up in Heart Rate - Intent to Treat Population | Baseline up to Month 6 Follow-Up | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Heart rate was measured in beats per minute (beats/min). |
| Mean Change From Baseline to 6 Month Follow-Up in Fasting Plasma Glucose - Intent to Treat Population | Baseline to 6 Month Follow-Up | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Fasting glucose measured in milligrams per deciliter (mg/dL). |
| Mean Change From Baseline to Month 6 Follow-Up in Insulin - Intent to Treat Population | Baseline up to Month 6 Follow-Up | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Insulin measured in milliunits per liter (mU/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population | Baseline up to Month 6 Follow-Up | Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. |
Countries
United States
Participant flow
Recruitment details
5 January 2011 Lead-In Period started. 28 September 2011 last participants final visit procedure. Clinics where participants with body mass index \[BMI\] greater than, equal to (≥)35 kilogram per meter squared (kg/m\^2) and less than, equal to (≤)45 kg/m2) could be enrolled.
Pre-assignment details
6 week lead-in period:low-calorie diet (LCD); 16 week randomized treatment period: participants who lost \>=2% body weight at end of LCD were randomized to an arm. Sponsor terminated study during randomization period due to neutralizing activity to metreleptin observed in Study DFA102, NCT00673387. Safety follow-up 2, 4, 6 months post treatment.
Participants by arm
| Arm | Count |
|---|---|
| Non-Randomized Lead-in LCD 6 Week Lead-in with low calorie diet (LCD); in the last week of the 6 week LCD, self administered subcutaneous (SC) injections of placebo once a day (QD) was initiated and then followed by randomization to study drug in the Randomization period. | 141 |
| Placebo Self administered subcutaneous (SC ) injection of placebo matched to pramlintide (Placebo-P) plus placebo matched to metreleptin (Placebo-M) twice a day (BID) for 16 weeks. | 36 |
| Pramlintide + Metreleptin Self administered SC injection of pramlintide 360 µg + metreleptin 5.0 mg BID for 16 weeks | 36 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Follow-Up Post Treatment up to Month 6 | Lost to Follow-up | 0 | 5 | 1 |
| Follow-Up Post Treatment up to Month 6 | Other | 0 | 1 | 0 |
| Follow-Up Post Treatment up to Month 6 | Withdrawal by Subject | 0 | 3 | 6 |
| Non-Randomized Low Calorie Diet Lead-In | Failed to meet weight loss in Period 1 | 4 | 0 | 0 |
| Non-Randomized Low Calorie Diet Lead-In | Lost to Follow-up | 5 | 0 | 0 |
| Non-Randomized Low Calorie Diet Lead-In | Physician Decision | 1 | 0 | 0 |
| Non-Randomized Low Calorie Diet Lead-In | Protocol Violation | 1 | 0 | 0 |
| Non-Randomized Low Calorie Diet Lead-In | Sponsor terminated study | 121 | 0 | 0 |
| Non-Randomized Low Calorie Diet Lead-In | Withdrawal by Subject | 9 | 0 | 0 |
| Randomized to Treatment | Adverse Event | 0 | 1 | 1 |
| Randomized to Treatment | Sponsor terminated study | 0 | 35 | 34 |
| Randomized to Treatment | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Non-Randomized Lead-in LCD | Placebo | Pramlintide + Metreleptin | Total |
|---|---|---|---|---|
| Age, Continuous | 46.1 years STANDARD_DEVIATION 11.81 | 46.2 years STANDARD_DEVIATION 10.84 | 46.4 years STANDARD_DEVIATION 10.45 | 46.1 years STANDARD_DEVIATION 11.38 |
| Body Mass Index | 39.51 kg/m^2 STANDARD_DEVIATION 2.875 | 39.17 kg/m^2 STANDARD_DEVIATION 3.279 | 39.09 kg/m^2 STANDARD_DEVIATION 2.869 | 39.38 kg/m^2 STANDARD_DEVIATION 2.937 |
| Body Weight | 110.86 kg STANDARD_DEVIATION 13.21 | 109.10 kg STANDARD_DEVIATION 16.85 | 108.34 kg STANDARD_DEVIATION 12.032 | 110.13 kg STANDARD_DEVIATION 13.678 |
| Region of Enrollment United States | 141 participants | 36 participants | 36 participants | 213 participants |
| Sex: Female, Male Female | 106 Participants | 27 Participants | 29 Participants | 162 Participants |
| Sex: Female, Male Male | 35 Participants | 9 Participants | 7 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 36 | 14 / 36 |
| serious Total, serious adverse events | 0 / 36 | 1 / 36 |
Outcome results
Primary
Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population
Participants who received metreleptin were analyzed; no placebo treated participants were analyzed. Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Leptin was measured in nanograms per milliliter (ng/mL).
Time frame: Baseline to Month 6 Follow Up
Population: All participants who received a dose of metreleptin and provided a sample were analyzed. Number of participants analyzed for Week 2, and follow up Months 2, 4, 6 were 6, and 33, 29, 29, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population | Change from baseline to Week 2 of treatment | 223.38 ng/mL | Standard Deviation 512.088 |
| Placebo | Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population | Change from baseline to Month 2 Follow up | 15.46 ng/mL | Standard Deviation 34.885 |
| Placebo | Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population | Change from baseline to Month 4 Follow up | 20.08 ng/mL | Standard Deviation 35.732 |
| Placebo | Change From Baseline to Week 2, and to Follow up Months 2, 4, 6 in Fasting Leptin Concentration - Intent to Treat Population | Month 6 Follow up | 10.70 ng/mL | Standard Deviation 18.913 |
Primary
Mean Change From Baseline to 6 Month Follow-Up in Fasting Plasma Glucose - Intent to Treat Population
Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Fasting glucose measured in milligrams per deciliter (mg/dL).
Time frame: Baseline to 6 Month Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment. The number analyzed in the ITT included those participants who provided a laboratory measurement up to Month 6 Follow-Up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline to 6 Month Follow-Up in Fasting Plasma Glucose - Intent to Treat Population | 6.8 mg/dL | Standard Deviation 8.31 |
| Pramlintide + Metreleptin | Mean Change From Baseline to 6 Month Follow-Up in Fasting Plasma Glucose - Intent to Treat Population | -1.0 mg/dL | Standard Deviation 9.03 |
Primary
Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population
Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow-up was up to 6 months post treatment. Blood pressure included systolic and diastolic pressures measured in millimeters of mercury (mmHg).
Time frame: Baseline to Month 6 Follow-Up
Population: The intent to treat (ITT) population received at least one dose of drug treatment. The number analyzed in the ITT included those participants who provided a vital sign measurement up to 6 Months follow-up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population | Systolic Blood Pressure | 4.3 mmHg | Standard Deviation 9.4 |
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population | Diastolic Blood Pressure | 2.7 mmHg | Standard Deviation 7.4 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population | Systolic Blood Pressure | 3.1 mmHg | Standard Deviation 8.9 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Blood Pressure - Intent to Treat Population | Diastolic Blood Pressure | 2.7 mmHg | Standard Deviation 8.07 |
Primary
Mean Change From Baseline to Month 6 Follow-Up in Heart Rate - Intent to Treat Population
Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Heart rate was measured in beats per minute (beats/min).
Time frame: Baseline up to Month 6 Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment. The number analyzed in the ITT included those participants who provided a vital sign measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Heart Rate - Intent to Treat Population | 1.2 beats/min | Standard Deviation 8.85 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Heart Rate - Intent to Treat Population | 1.2 beats/min | Standard Deviation 7.98 |
Primary
Mean Change From Baseline to Month 6 Follow-Up in Insulin - Intent to Treat Population
Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Insulin measured in milliunits per liter (mU/L).
Time frame: Baseline up to Month 6 Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment. The number analyzed in the ITT included those participants who provided a laboratory measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Insulin - Intent to Treat Population | 3.41 mU/L | Standard Deviation 8.99 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Insulin - Intent to Treat Population | 3.46 mU/L | Standard Deviation 7.617 |
Primary
Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population
Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication. Lipids measured included total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides. Lipids were measured in milligrams per deciliter (mg/dL).
Time frame: Baseline up to Month 6 Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment. The number analyzed in the ITT included those participants who provided a laboratory measurement up to Month 6 Follow-Up.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | Total Cholesterol | 21.7 mg/dL | Standard Deviation 19.21 |
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | HDL cholesterol | 7.7 mg/dL | Standard Deviation 7.25 |
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | LDL cholesterol | 14.0 mg/dL | Standard Deviation 17.47 |
| Placebo | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | Triglycerides | 10.4 mg/dL | Standard Deviation 35.12 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | Triglycerides | 3.0 mg/dL | Standard Deviation 38.3 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | Total Cholesterol | 14.7 mg/dL | Standard Deviation 25.51 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | LDL cholesterol | 9.6 mg/dL | Standard Deviation 21.05 |
| Pramlintide + Metreleptin | Mean Change From Baseline to Month 6 Follow-Up in Lipids - Intent to Treat Population | HDL cholesterol | 6.6 mg/dL | Standard Deviation 7.6 |
Primary
Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population
Anti-leptin antibodies measured at Weeks 1 and 2 of drug treatment, early termination visit, and at Months 2, 4, and 6 post treatment follow-up in participants who received metreleptin.
Time frame: Week 1 to Month 6 Follow-Up
Population: All participants who received at least one dose of metreleptin and provided a sample to analyze; number analyzed (n) for Week 1, Week 2, early termination, Month 2, Month 4, Month 6 Follow-up were: n=22, 5, 35, 32, 25, 28.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Month 6 Follow-Up | 8 participants |
| Placebo | Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Week 1 | 0 participants |
| Placebo | Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Week 2 | 1 participants |
| Placebo | Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Early Termination | 9 participants |
| Placebo | Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Month 2 Follow-Up | 15 participants |
| Placebo | Number of Participants With Anti-leptin Antibodies Who Received Metreleptin - Intent to Treat Population | Month 4 Follow-Up | 10 participants |
Primary
Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population
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.
Time frame: Screening to Month 6 Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment. The number analyzed in the ITT included those participants who provided a laboratory measurement.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Creatine Kinase | 2 participants |
| Placebo | Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Urate | 0 participants |
| Placebo | Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Bilirubin | 0 participants |
| Pramlintide + Metreleptin | Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Creatine Kinase | 3 participants |
| Pramlintide + Metreleptin | Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Urate | 2 participants |
| Pramlintide + Metreleptin | Number of Participants With Chemistry Laboratory Value of Potential Clinical Importance - Intent to Treat Population | Bilirubin | 1 participants |
Primary
Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population
Criteria for laboratory values of potential clinical importance for obese and overweight (BMI \>= 25 kg/m\^2) participants: Platelets high (H) \>500,000/µL; low (L) \<75,000/µL. 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. Urine protein H \>= 3+ or \>= 500 mg/dL. Urine glucose H \>= 3+ or \>= 500 mg/dL. Urine ketones \>= 3+ or Large.
Time frame: Screening to 6 Month Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment. Number analyzed (n) in ITT included participants who provided a laboratory measurement. Hemoglobin, hematocrit n=27, 29 in placebo and pramlintide + metreleptin, respectively; urinalysis n=31, 29, in placebo and pramlintide + metreleptin, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Hematocrit | 0 participants |
| Placebo | Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Hemoglobin | 0 participants |
| Placebo | Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Glucose in Urine | 0 participants |
| Pramlintide + Metreleptin | Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Hematocrit | 1 participants |
| Pramlintide + Metreleptin | Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Hemoglobin | 1 participants |
| Pramlintide + Metreleptin | Number of Participants With Hematology and Urinalysis Laboratory Values of Potential Clinical Importance - Intent to Treat Population | Glucose in Urine | 1 participants |
Primary
Number of Participants With Neutralizing Activity to Metreleptin at Early Termination or During Post Treatment Follow-Up - Intent to Treat Population Who Received Metreleptin
In vitro assays were conducted to determine if neutralizing activity to metreleptin developed in participants treated with at least one dose of the drug during the study. Baseline is Day 1 of the Randomization Period, prior to administration of metreleptin.
Time frame: Baseline to Month 6 Follow-Up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Neutralizing Activity to Metreleptin at Early Termination or During Post Treatment Follow-Up - Intent to Treat Population Who Received Metreleptin | 0 participants |
Primary
Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population
Treatment-Emergent Adverse Events are defined as those with an onset date and time on or after the first dose of randomized study medication and on or before the last dose of randomized study medication. Post-treatment Adverse Events are defined as those with an onset date after the date of last dose (imputed if not available) of randomized study medication. Participants experiencing multiple episodes of a given adverse event are counted once.
Time frame: Day 1 up to Month 6 Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population | 6 participants |
| Pramlintide + Metreleptin | Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population | 13 participants |
| Post Treatment Placebo Arm | Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population | 13 participants |
| Post Treatment Pramlintide + Metreleptin Arm | Number of Participants With Treatment Emergent Adverse Events and Number With Post Treatment Adverse Events - Intent to Treat Population | 16 participants |
Secondary
Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population
Baseline was Day 1 measurement or the last measurement taken prior to first dose of randomized study medication, if Day 1 measure was missing. Follow up was 6 months post last dose of randomized study medication.
Time frame: Baseline up to Month 6 Follow-Up
Population: The intent to treat (ITT) population received at least one dose of randomized study treatment. The number analyzed in the ITT included those participants who provided a measurement. Number analyzed (n) for Week 1 provided above; 6 Month Follow-Up n=27, 29, in placebo and Pramlintide + Metreleptin, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population | Week 1 | -0.34 percentage of change in weight | Standard Deviation 0.924 |
| Placebo | Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population | 6 Month Follow-Up | -0.02 percentage of change in weight | Standard Deviation 6.575 |
| Pramlintide + Metreleptin | Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population | Week 1 | -0.26 percentage of change in weight | Standard Deviation 0.819 |
| Pramlintide + Metreleptin | Percent Change From Baseline to Week 1 and From Baseline to Month 6 Follow-up in Body Weight - Intent to Treat Population | 6 Month Follow-Up | -1.80 percentage of change in weight | Standard Deviation 6.063 |