Trial Outcomes & Findings for Study to Examine Safety, Tolerability, and Effect on Body Weight of Metreleptin Administered in Conjunction With Pramlintide in Obese and Overweight Subjects (NCT NCT00673387)

NCT ID: NCT00673387

Last Updated: 2015-04-15

Results Overview

Body weight was measured in kilogram (kg). Baseline is defined as Day 1. If Day 1 was missing or after the first dose date of randomized treatment, the last available value prior to Day 1 was used. Drug Randomization stratified by sex and 3 categories baseline BMI (12 arms); 3 treatment arms combined for summaries as single placebo treatment group; 3 combined for summaries as single pramlintide monotherapy treatment group (total: 8 treatment groups).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 636 participants
• Primary outcome timeframe: Baseline to Week 28
• Results posted on: 2015-04-15

Participant Flow

First participant dosed/lead in: 06 May 2008; last participant's final visit: 07 April 2009. Study conducted in 42 clinics in participants who were either obese (body mass index (BMI) greater than, equal to (>=) 30 kg/m^2 and less than equal to (<=) 45 kg/m^2) or overweight (>= 27 kg/m^2 and < 30 kg/m^2).

Participants enrolled, not randomized /treated (28): withdrew consent (10), adverse event (1), investigator decision (7), protocol violation (4), lost to follow up (5), administrative (1). 1 Week Lead-in Period: all arms received placebo matched to metreleptin and matched to pramlintide, BID (single blind); 28 week double blind Treatment Period.

Participant milestones

Measure	Placebo Self administered twice a day (BID) for 28 weeks, subcutaneous (SC) placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).	Pramlintide 360 mcg Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).
Overall Study STARTED	75	77	72	75	78	78	78	75
Overall Study COMPLETED	46	54	41	49	48	44	48	40
Overall Study NOT COMPLETED	29	23	31	26	30	34	30	35

Reasons for withdrawal

Measure	Placebo Self administered twice a day (BID) for 28 weeks, subcutaneous (SC) placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).	Pramlintide 360 mcg Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).
Overall Study Withdrawal by Subject	15	16	20	16	18	21	15	21
Overall Study Adverse Event	3	1	5	2	6	2	5	5
Overall Study Physician Decision	0	0	0	0	0	5	1	1
Overall Study Protocol Violation	3	0	1	2	0	1	1	3
Overall Study Lost to Follow-up	8	6	5	6	6	5	8	5

Baseline Characteristics

Study to Examine Safety, Tolerability, and Effect on Body Weight of Metreleptin Administered in Conjunction With Pramlintide in Obese and Overweight Subjects

Baseline characteristics by cohort

Measure	Placebo n=75 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).	Pramlintide 360 mcg n=77 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=72 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg.	Pramlintide 360 mcg + Metreleptin 1.25 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Total n=608 Participants Total of all reporting groups
Age, Continuous	41.9 years STANDARD_DEVIATION 11.35 • n=5 Participants	42.0 years STANDARD_DEVIATION 11.42 • n=7 Participants	45.9 years STANDARD_DEVIATION 10.92 • n=5 Participants	45.8 years STANDARD_DEVIATION 10.80 • n=4 Participants	46.8 years STANDARD_DEVIATION 10.54 • n=21 Participants	44.4 years STANDARD_DEVIATION 10.87 • n=10 Participants	45.2 years STANDARD_DEVIATION 10.07 • n=115 Participants	44.7 years STANDARD_DEVIATION 11.32 • n=24 Participants	44.6 years STANDARD_DEVIATION 10.98 • n=42 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	54 Participants n=7 Participants	53 Participants n=5 Participants	53 Participants n=4 Participants	54 Participants n=21 Participants	54 Participants n=10 Participants	55 Participants n=115 Participants	52 Participants n=24 Participants	428 Participants n=42 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	23 Participants n=7 Participants	19 Participants n=5 Participants	22 Participants n=4 Participants	24 Participants n=21 Participants	24 Participants n=10 Participants	23 Participants n=115 Participants	23 Participants n=24 Participants	180 Participants n=42 Participants
Region of Enrollment United States	75 participants n=5 Participants	77 participants n=7 Participants	72 participants n=5 Participants	75 participants n=4 Participants	78 participants n=21 Participants	78 participants n=10 Participants	78 participants n=115 Participants	75 participants n=24 Participants	608 participants n=42 Participants
Body Mass Index	36.88 (kg/m^2) STANDARD_DEVIATION 4.473 • n=5 Participants	36.93 (kg/m^2) STANDARD_DEVIATION 4.389 • n=7 Participants	36.62 (kg/m^2) STANDARD_DEVIATION 4.478 • n=5 Participants	36.88 (kg/m^2) STANDARD_DEVIATION 4.336 • n=4 Participants	36.65 (kg/m^2) STANDARD_DEVIATION 4.379 • n=21 Participants	36.80 (kg/m^2) STANDARD_DEVIATION 4.260 • n=10 Participants	36.96 (kg/m^2) STANDARD_DEVIATION 4.406 • n=115 Participants	36.68 (kg/m^2) STANDARD_DEVIATION 4.504 • n=24 Participants	36.80 (kg/m^2) STANDARD_DEVIATION 4.379 • n=42 Participants

PRIMARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population includes all intent to treat participants (received at least one dose of randomized treatment) who had adequate exposure to treatment and complied with the protocol as assessed prior to database lock and unblinding.

Body weight was measured in kilogram (kg). Baseline is defined as Day 1. If Day 1 was missing or after the first dose date of randomized treatment, the last available value prior to Day 1 was used. Drug Randomization stratified by sex and 3 categories baseline BMI (12 arms); 3 treatment arms combined for summaries as single placebo treatment group; 3 combined for summaries as single pramlintide monotherapy treatment group (total: 8 treatment groups).

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=47 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Least Squares (LS) Mean Percent Change in Body Weight From Baseline to Week 28 - Evaluable Population	-5.47 Percentage change in kg Interval -7.19 to -3.76	-5.83 Percentage change in kg Interval -7.72 to -3.95	-6.85 Percentage change in kg Interval -8.61 to -5.08	-6.61 Percentage change in kg Interval -8.41 to -4.82	-6.39 Percentage change in kg Interval -8.18 to -4.59	-6.98 Percentage change in kg Interval -8.79 to -5.17	-7.02 Percentage change in kg Interval -8.94 to -5.1	-2.01 Percentage change in kg Interval -3.76 to -0.26

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population includes all intent to treat participants (received at least one dose of randomized treatment) who had adequate exposure to treatment and complied with the protocol as assessed prior to database lock and unblinding.

Baseline refers to Day 1. If Day 1 value is missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 is used.

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=47 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population Weight Loss >=5% and <10%	14 participants	6 participants	14 participants	15 participants	15 participants	15 participants	12 participants	7 participants
Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population No Weight Change or Weight Loss <5%	17 participants	16 participants	16 participants	11 participants	17 participants	12 participants	10 participants	20 participants
Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population Weight Loss >=5%	27 participants	18 participants	27 participants	27 participants	23 participants	29 participants	25 participants	10 participants
Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population Weight Loss >=10%	13 participants	12 participants	13 participants	12 participants	8 participants	14 participants	13 participants	3 participants
Number of Participants Achieving at Least 5% and at Least 10% Body Weight Loss From Baseline to Week 28 - Evaluable Population Weight Gain	7 participants	7 participants	4 participants	8 participants	5 participants	4 participants	3 participants	17 participants

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Number analyzed (n) at baseline above. Week 4: n=41 45,46, 45, 45, 38; Week 8: n=41,45,46,44,45,37; Week 12: n=41, 46, 46, 45,45,38; Week 16: n=41,47,46,45,45,38; Week 20: n=41, 45,45,45,45,38; Week 24: n=40, 43, 46, 42, 44,38; Week 28: n=41, 45, 45, 44, 43, 36. Leptin concentration for placebo and pramlintide plus placebo groups not presented.

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. If Day 1 value is missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 is used. Evaluable population: all participants who received at least one dose of randomized treatment, had adequate exposure to treatment and complied with the protocol as assessed prior to database lock and unblinding. Leptin concentrations measured using a validated immunoenzymetric assay utilizing polyclonal capture antibody, monoclonal detection antibody, and colorimetric readout by Amylin Pharmaceuticals, Inc.

Outcome measures

Measure	Pramlintide 360 mcg n=47 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=38 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=41 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Absolute Change From Baseline to Weeks 4, 12, 28 in Mean Trough Concentration of Total Leptin - Evaluable Population Change from baseline at Week 4	31.00 ng/mL Standard Deviation 73.953	47.82 ng/mL Standard Deviation 76.469	-2.36 ng/mL Standard Deviation 16.918	14.66 ng/mL Standard Deviation 48.212	49.16 ng/mL Standard Deviation 70.881	—	—	53.26 ng/mL Standard Deviation 64.542
Mean Absolute Change From Baseline to Weeks 4, 12, 28 in Mean Trough Concentration of Total Leptin - Evaluable Population Change from baseline at Week 12	167.62 ng/mL Standard Deviation 147.512	353.61 ng/mL Standard Deviation 265.727	53.76 ng/mL Standard Deviation 68.627	165.65 ng/mL Standard Deviation 173.851	399.74 ng/mL Standard Deviation 378.120	—	—	386.48 ng/mL Standard Deviation 408.472
Mean Absolute Change From Baseline to Weeks 4, 12, 28 in Mean Trough Concentration of Total Leptin - Evaluable Population Change from baseline at Week 28	373.64 ng/mL Standard Deviation 465.511	487.17 ng/mL Standard Deviation 625.071	105.96 ng/mL Standard Deviation 143.680	266.02 ng/mL Standard Deviation 210.412	393.06 ng/mL Standard Deviation 381.428	—	—	557.22 ng/mL Standard Deviation 604.617

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population includes all intent to treat participants (received at least one dose of randomized treatment) who had adequate exposure to treatment and complied with the protocol as assessed prior to database lock and unblinding.

Least Squares (LS) mean absolute change in Body weight was measured in kilograms (kg). Baseline is defined as Day 1. If Day 1 was missing or after the first dose date of randomized treatment, the last available value prior to Day 1 was used.

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=47 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
LS Mean Absolute Change in Body Weight From Baseline to Weeks 4, 12, and 28 - Evaluable Population Change at Week 4	-2.85 kg Interval -3.41 to -2.29	-2.54 kg Interval -3.15 to -1.92	-2.94 kg Interval -3.51 to -2.36	-2.40 kg Interval -2.99 to -1.82	-2.62 kg Interval -3.21 to -2.04	-3.21 kg Interval -3.8 to -2.62	-3.32 kg Interval -3.95 to -2.69	-1.81 kg Interval -2.38 to -1.24
LS Mean Absolute Change in Body Weight From Baseline to Weeks 4, 12, and 28 - Evaluable Population Change at Week 12	-4.90 kg Interval -5.97 to -3.83	-5.13 kg Interval -6.31 to -3.95	-5.52 kg Interval -6.63 to -4.42	-4.53 kg Interval -5.65 to -4.41	-5.52 kg Interval -6.64 to -4.4	-5.88 kg Interval -7.02 to -4.75	-6.12 kg Interval -7.32 to -4.92	-3.39 kg Interval -4.5 to -2.28
LS Mean Absolute Change in Body Weight From Baseline to Weeks 4, 12, and 28 - Evaluable Population Change at Week 28	-5.66 kg Interval -7.4 to -3.92	-6.18 kg Interval -8.1 to -4.27	-6.96 kg Interval -8.75 to -5.17	-6.55 kg Interval -8.38 to -4.72	-6.38 kg Interval -8.2 to -4.56	-7.18 kg Interval -9.03 to -5.34	-6.97 kg Interval -8.92 to -5.02	-2.04 kg Interval -3.82 to -0.26

SECONDARY outcome

Timeframe: Baseline to Weeks 12 and Week 28

Population: Participants who received at least 1 dose of randomized treatment and who had adequate exposure to treatment and complied with the protocol as assessed prior to database lock/unblinding. Numbers (n) analyzed Week 12 n=45,51,41,47,45,45,45,38 in each treatment group respectively; Week 28 n= 44, 51, 41, 46, 45, 44, 43, 38 in each group, respectively.

Waist circumference was measured at baseline (Day 1), Weeks 12, 28 (or at early termination) in centimeters (cm).

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=45 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
LS Mean Change in Waist Circumference From Baseline to Week 12 and Week 28 - Evaluable Population Change at Week 12	-3.40 cm Standard Error 0.799	-3.41 cm Standard Error 0.895	-4.91 cm Standard Error 0.846	-4.29 cm Standard Error 0.876	-3.32 cm Standard Error 0.853	-4.63 cm Standard Error 0.855	-5.23 cm Standard Error 0.916	-3.03 cm Standard Error 0.851
LS Mean Change in Waist Circumference From Baseline to Week 12 and Week 28 - Evaluable Population Change at Week 28	-3.95 cm Standard Error 0.965	-3.86 cm Standard Error 1.081	-5.48 cm Standard Error 1.032	-5.75 cm Standard Error 1.058	-4.70 cm Standard Error 1.043	-5.52 cm Standard Error 1.057	-6.53 cm Standard Error 1.107	-2.54 cm Standard Error 1.038

SECONDARY outcome

Timeframe: Week 4 and Week 24

Population: Evaluable population: participants received at least one dose of randomized treatment, had adequate exposure to treatment and complied with the protocol as assessed prior to database lock and unblinding. Number (n) analyzed at Week 4:n=46, 40,41, 40,40,33 in each arm respectively;Week 24:n=48, 38, 44, 40, 35, 36.

Assessment of AUC was over a period of 2 hours following pramlintide administration. AUC (0 to time of last quantifiable concentration (-tlast). For AUC calculation, concentration at -5 min will be considered as 0 h concentration if quantifiable, otherwise, t=0 h. AUC measured as picograms*hour/milliliter (pg*h/mL). Pramlintide concentrations measured using a colorimetric immunoenzymetric assay employing monoclonal antibodies against pramlintide for both capture and detection.

Outcome measures

Measure	Pramlintide 360 mcg n=40 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=44 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=36 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=48 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
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 Week 4 AUC (0-tlast)	878.8 pg*h/mL Standard Error 87.34	967.5 pg*h/mL Standard Error 68.59	1788.2 pg*h/mL Standard Error 165.32	1920.1 pg*h/mL Standard Error 143.54	2060.4 pg*h/mL Standard Error 168.92	—	—	1862.5 pg*h/mL Standard Error 176.83
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 Week 24 AUC (0-tlast)	1033.8 pg*h/mL Standard Error 102.19	953.7 pg*h/mL Standard Error 76.19	1536.3 pg*h/mL Standard Error 103.90	1990.2 pg*h/mL Standard Error 160.49	1915.3 pg*h/mL Standard Error 158.77	—	—	1968.4 pg*h/mL Standard Error 135.60

SECONDARY outcome

Timeframe: Weeks 4 and 24

Population: Evaluable population: participants received at least one dose of randomized treatment, had adequate exposure to treatment and complied with the protocol as assessed prior to database lock and unblinding. Number (n) analyzed at Week 4: n=39,36,37,36,35,31 in each arm, respectively; Week 24 n=46, 35, 42, 39, 33, 35 in each arm, respectively.

Assessment of AUC was over a period of 2 hours following pramlintide administration. Area under the concentration curve (AUC) time 0 to infinity (-inf). For AUC calculations, concentration at -5 min will be considered as 0 h concentration if quantifiable. AUC measured in picograms*hour/milliliter (pg*h/mL).

Outcome measures

Measure	Pramlintide 360 mcg n=36 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=42 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=39 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=35 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=35 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Geometric Mean of AUC From Time 0 to Infinity for Pramlintide at Weeks 4 and 24 - Evaluable Population Treated With Pramlintide Week 4 AUC (0-inf)	989.3 pg*h/mL Standard Error 96.05	1240.7 pg*h/mL Standard Error 106.08	2159.0 pg*h/mL Standard Error 238.45	2311.3 pg*h/mL Standard Error 211.63	2511.4 pg*h/mL Standard Error 241.16	—	—	2662.7 pg*h/mL Standard Error 230.34
Geometric Mean of AUC From Time 0 to Infinity for Pramlintide at Weeks 4 and 24 - Evaluable Population Treated With Pramlintide Week 24 AUC (0-inf)	1175.1 pg*h/mL Standard Error 116.89	1216.7 pg*h/mL Standard Error 102.07	1907.5 pg*h/mL Standard Error 153.91	2411.8 pg*h/mL Standard Error 218.29	2349.3 pg*h/mL Standard Error 210.77	—	—	2499.5 pg*h/mL Standard Error 215.51

SECONDARY outcome

Timeframe: Week 4 and Week 24

Population: Evaluable population: participants received at least one dose of randomized treatment, had adequate exposure to treatment and complied with the protocol as assessed prior to database lock and unblinding. Number (n) analyzed at Week 4 n=46,40,41,40,40,33 in each arm, respectively; Week 24 n=48,38, 44,40,35,36 in each arm, respectively.

Assessment of Cmax was over a period of 2 hours following pramlintide administration at Weeks 4 and 24. Cmax was measured as picograms/milliliter (pg/mL).

Outcome measures

Measure	Pramlintide 360 mcg n=40 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=44 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=36 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=48 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) for Pramlintide at Weeks 4 and 24 - Evaluable Population Receiving Pramlintide Week 24 Cmax	1048.1 pg/mL Standard Error 76.86	925.5 pg/mL Standard Error 64.16	1573.5 pg/mL Standard Error 100.69	2032.0 pg/mL Standard Error 152.70	1972.2 pg/mL Standard Error 159.33	—	—	1985.8 pg/mL Standard Error 118.31
Geometric Mean of the Maximum Observed Plasma Concentration (Cmax) for Pramlintide at Weeks 4 and 24 - Evaluable Population Receiving Pramlintide Week 4 Cmax	876.7 pg/mL Standard Error 77.37	897.3 pg/mL Standard Error 51.16	1783.8 pg/mL Standard Error 144.34	1851.3 pg/mL Standard Error 118.87	2096.4 pg/mL Standard Error 149.65	—	—	1759.0 pg/mL Standard Error 168.40

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Number analyzed (n) were of evaluable participants with valid DEXA scan at Week 28.

Parameters of body composition were measured with a Dual Energy X-ray absorptiometry (DEXA) scan and reported as a percent (%). Data from the first valid DEXA scan obtained no later than 7 days after the first randomized dose was considered as valid baseline values; data from the last valid DEXA scan obtained no later than 10 days after last clinical visit or no later than 14 days after last dose of randomized study medication was considered as valid study termination values. Absolute change from baseline was defined as percent body fat at Week 28 - percent body fat at baseline.

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=42 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=39 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=35 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=36 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Least Squares (LS) Mean Absolute Change From Baseline to Week 28 in Percent of Body Fat - Evaluable Population	-1.77 percentage of body fat Standard Error 0.421	-1.94 percentage of body fat Standard Error 0.492	-2.32 percentage of body fat Standard Error 0.480	-2.21 percentage of body fat Standard Error 0.475	-2.21 percentage of body fat Standard Error 0.497	-1.56 percentage of body fat Standard Error 0.482	-2.46 percentage of body fat Standard Error 0.515	-0.95 percentage of body fat Standard Error 0.501

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Number analyzed (n) were of evaluable participants with valid DEXA scan at Week 28.

Parameters of body composition were measured with a Dual Energy X-ray absorptiometry (DEXA) scan. Data from the first valid DEXA scan obtained no later than 7 days after the first randomized dose was considered as valid baseline values; data from the last valid DEXA scan obtained no later than 10 days after last clinical visit or no later than 14 days after last dose of randomized study medication was considered as valid study termination values. Body fat mass was measured in kilogram (k).

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=42 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=39 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=35 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=36 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
LS Mean Absolute Change From Baseline to Week 28 in Total Body Fat Mass (k) - Evaluable Population	-4.28 kg Standard Error 0.661	-4.57 kg Standard Error 0.763	-4.98 kg Standard Error 0.746	-4.97 kg Standard Error 0.734	-5.03 kg Standard Error 0.755	-4.35 kg Standard Error 0.748	-5.51 kg Standard Error 0.792	-1.96 kg Standard Error 0.0779

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Number analyzed (n) were of evaluable participants with valid DEXA scan at Week 28.

Parameters of body composition were measured with a Dual Energy X-ray Absorptiometry (DEXA) scan. Data from the first valid DEXA scan obtained no later than 7 days after the first randomized dose was considered as valid baseline values; data from the last valid DEXA scan obtained no later than 10 days after last clinical visit or no later than 14 days after last dose of randomized study medication was considered as valid study termination values. Fat-free mass were measured in kilogram (k).

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=42 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=39 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=40 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=35 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=36 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
LS Mean Absolute Change From Baseline to Week 28 in Fat-free Mass (kg) - Evaluable Population	-1.62 kg Standard Error 0.337	-1.80 kg Standard Error 0.389	-1.90 kg Standard Error 0.377	-1.99 kg Standard Error 0.373	-2.02 kg Standard Error 0.391	-2.11 kg Standard Error 0.380	-2.29 kg Standard Error 0.399	-0.69 kg Standard Error 0.393

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population: received at least one dose of randomized treatment, had adequate exposure to treatment, complied with the protocol as assessed prior to database lock and unblinding. Number analyzed (n) presented above for TC, LDL and HDL cholesterol. Glucose n= 43, 50, 41, 46, 45, 43,44,36; Triglycerides n= 44,50,41,46,45,44,44.38.

Baseline refers to Visit 5 (Day 1). If Day 1 value is missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 is used. Fasting samples were obtained at baseline, Weeks 4, 12, and 28. All parameters were measured in milligrams per deciliter (mg/dL).

Outcome measures

Measure	Pramlintide 360 mcg n=50 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=39 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=37 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=44 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
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 Fasting Plasma Glucose	-1.8 mg/dL Standard Error 1.25	-1.8 mg/dL Standard Error 1.39	-2.5 mg/dL Standard Error 1.32	-1.2 mg/dL Standard Error 1.34	-1.0 mg/dL Standard Error 1.36	-1.7 mg/dL Standard Error 1.35	-1.3 mg/dL Standard Error 1.47	-1.3 mg/dL Standard Error 1.35
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 Triglycerides	-8.6 mg/dL Standard Error 7.73	-13.0 mg/dL Standard Error 8.66	-1.4 mg/dL Standard Error 8.17	-10.9 mg/dL Standard Error 8.29	11.1 mg/dL Standard Error 8.34	-9.2 mg/dL Standard Error 8.35	0.9 mg/dL Standard Error 8.86	-0.1 mg/dL Standard Error 8.25
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 Total Cholesterol	-7.1 mg/dL Standard Error 3.35	-3.7 mg/dL Standard Error 3.82	-2.1 mg/dL Standard Error 3.54	-2.5 mg/dL Standard Error 3.60	-0.6 mg/dL Standard Error 3.60	-4.0 mg/dL Standard Error 3.61	-1.3 mg/dL Standard Error 3.88	4.3 mg/dL Standard Error 3.57
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 LDL Cholesterol	-3.5 mg/dL Standard Error 2.65	-2.3 mg/dL Standard Error 3.02	-3.7 mg/dL Standard Error 2.80	-0.0 mg/dL Standard Error 2.85	-2.7 mg/dL Standard Error 2.85	-3.7 mg/dL Standard Error 2.86	-1.2 mg/dL Standard Error 3.08	4.3 mg/dL Standard Error 2.82
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 HDL Cholesterol	0.6 mg/dL Standard Error 0.90	2.6 mg/dL Standard Error 1.03	0.7 mg/dL Standard Error 0.95	1.0 mg/dL Standard Error 0.96	2.9 mg/dL Standard Error 0.97	0.97 mg/dL Standard Error 0.97	1.05 mg/dL Standard Error 1.05	1.5 mg/dL Standard Error 0.96

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding.

Baseline refers to Visit 5 (Day 1). If Day 1 value is missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 is used. Fasting samples were obtained at baseline, Weeks 4, 12, and 28. Parameter was measured micro international units per milliliter. (µIU/mL).

Outcome measures

Measure	Pramlintide 360 mcg n=49 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=40 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=43 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=43 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=36 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=42 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Absolute Change From Baseline to Week 28 for Insulin - Evaluable Population	-0.4 µIU/mL Standard Error 0.94	-1.6 µIU/mL Standard Error 1.0	-1.0 µIU/mL Standard Error 1.00	-2.5 µIU/mL Standard Error 0.99	-1.4 µIU/mL Standard Error 1.00	-0.8 µIU/mL Standard Error 1.01	-0.5 µIU/mL Standard Error 1.08	1.1 µIU/mL Standard Error 1.01

SECONDARY outcome

Timeframe: Screening to Week 24

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Missing item responses may be imputed for each subject as appropriate before summarization.

Subjective effects of weight loss were measured using the IWQOL-Lite questionnaire, a 31-item patient reported outcome (PRO) instrument used to assess the effect of weight on physical function, self-esteem, sexual life, public distress, and work. Individual items have a range of 1 to 5 with 5=always true and 1= never true. The total score for the IWQOL-Lite instrument is measured on a scale from 0 (worst) to 100 (best). Higher scores indicate improvement. Values were obtained for this questionnaire on Visit 3 in the screening period.

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=35 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
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	10.31 units on a scale Standard Deviation 11.629	11.09 units on a scale Standard Deviation 13.503	10.14 units on a scale Standard Deviation 10.957	16.15 units on a scale Standard Deviation 15.193	13.84 units on a scale Standard Deviation 11.535	13.44 units on a scale Standard Deviation 11.175	11.68 units on a scale Standard Deviation 10.271	10.52 units on a scale Standard Deviation 12.480

SECONDARY outcome

Timeframe: Screening to Week 24

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Missing item responses may be imputed for each subject as appropriate before summarization.

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. 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.

Outcome measures

Measure	Pramlintide 360 mcg n=49 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=43 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=36 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Absolute Change From Screening to Week 24 in Binge Eating Scale (BES) Total Score - Evaluable Population	-3.4 units on a scale Standard Deviation 6.96	-4.0 units on a scale Standard Deviation 6.21	-4.4 units on a scale Standard Deviation 6.45	-6.6 units on a scale Standard Deviation 8.28	-3.5 units on a scale Standard Deviation 5.87	-5.9 units on a scale Standard Deviation 7.44	-5.2 units on a scale Standard Deviation 6.17	-3.0 units on a scale Standard Deviation 6.31

SECONDARY outcome

Timeframe: Screening to Week 24

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Missing item responses may be imputed for each subject as appropriate before summarization.

The eating questionnaire is an exploratory measure of appetite, satiety, and perceived control over portion size using 10 VAS items with each response measured on a 100 mm visual analogue scale (ranges vary from Never to Very Often; Not at All Difficult to Extremely Difficult; Not at all Strong to Very Strong). Lower scores indicate 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.

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=36 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population How Pleasant Meals	-2.3 units on a scale Standard Deviation 24.55	-2.1 units on a scale Standard Deviation 21.00	1.2 units on a scale Standard Deviation 27.11	-1.2 units on a scale Standard Deviation 25.96	3.7 units on a scale Standard Deviation 24.87	5.3 units on a scale Standard Deviation 22.41	-2.1 units on a scale Standard Deviation 28.08	-6.1 units on a scale Standard Deviation 19.72
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population Frequency of Food Cravings	-6.6 units on a scale Standard Deviation 27.17	-4.0 units on a scale Standard Deviation 24.28	-14.1 units on a scale Standard Deviation 24.55	-19.8 units on a scale Standard Deviation 31.06	-15.7 units on a scale Standard Deviation 21.76	-18.5 units on a scale Standard Deviation 27.69	-13.5 units on a scale Standard Deviation 29.56	-9.0 units on a scale Standard Deviation 25.85
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population Strength of Food Cravings	-6.1 units on a scale Standard Deviation 26.86	-1.1 units on a scale Standard Deviation 24.97	-13.9 units on a scale Standard Deviation 25.45	-13.8 units on a scale Standard Deviation 28.02	-12.9 units on a scale Standard Deviation 19.19	-19.6 units on a scale Standard Deviation 25.66	-15.2 units on a scale Standard Deviation 32.56	-5.1 units on a scale Standard Deviation 27.60
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population Difficult to Control Eating	-15.2 units on a scale Standard Deviation 26.37	-9.5 units on a scale Standard Deviation 27.44	-19.7 units on a scale Standard Deviation 23.00	-27.3 units on a scale Standard Deviation 27.02	-18.3 units on a scale Standard Deviation 19.46	-26.3 units on a scale Standard Deviation 28.89	-18.0 units on a scale Standard Deviation 35.40	-8.1 units on a scale Standard Deviation 27.45
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population Difficult to Resist Food Cravings	-11.1 units on a scale Standard Deviation 24.52	9.6 units on a scale Standard Deviation 25.02	-19.5 units on a scale Standard Deviation 26.28	-21.8 units on a scale Standard Deviation 28.65	-19.0 units on a scale Standard Deviation 26.49	-28.0 units on a scale Standard Deviation 29.90	-18.2 units on a scale Standard Deviation 29.80	-11.4 units on a scale Standard Deviation 30.32
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population Eating in Response to Food Cravings	-12.2 units on a scale Standard Deviation 25.14	-12.6 units on a scale Standard Deviation 27.34	-15.4 units on a scale Standard Deviation 22.17	-22.2 units on a scale Standard Deviation 32.94	-18.5 units on a scale Standard Deviation 24.95	-22.9 units on a scale Standard Deviation 27.85	-15.9 units on a scale Standard Deviation 27.04	-11.1 units on a scale Standard Deviation 28.41
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population Difficult to Control Portion Sizes	-16.9 units on a scale Standard Deviation 29.58	-27.6 units on a scale Standard Deviation 30.70	-19.6 units on a scale Standard Deviation 21.19	-25.2 units on a scale Standard Deviation 28.00	-20.8 units on a scale Standard Deviation 21.18	-24.0 units on a scale Standard Deviation 26.91	-27.6 units on a scale Standard Deviation 34.18	-10.8 units on a scale Standard Deviation 23.37
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population How Hungry	-9.7 units on a scale Standard Deviation 22.92	-17.5 units on a scale Standard Deviation 23.18	-16.4 units on a scale Standard Deviation 24.00	-17.0 units on a scale Standard Deviation 24.09	-17.5 units on a scale Standard Deviation 22.53	-19.2 units on a scale Standard Deviation 24.64	-19.9 units on a scale Standard Deviation 31.32	-0.1 units on a scale Standard Deviation 20.59
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population How Full After Meals	0.5 units on a scale Standard Deviation 25.05	-7.6 units on a scale Standard Deviation 19.94	-3.8 units on a scale Standard Deviation 26.19	-8.8 units on a scale Standard Deviation 31.83	-6.5 units on a scale Standard Deviation 26.46	-4.2 units on a scale Standard Deviation 27.71	1.1 units on a scale Standard Deviation 23.42	-5.8 units on a scale Standard Deviation 25.37
Mean Absolute Change From Screening to Week 24 in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Evaluable Population Thoughts of Food	-10.7 units on a scale Standard Deviation 25.84	-10.6 units on a scale Standard Deviation 30.04	-9.4 units on a scale Standard Deviation 22.33	-16.7 units on a scale Standard Deviation 27.75	-12.0 units on a scale Standard Deviation 20.98	-20.0 units on a scale Standard Deviation 27.90	-5.6 units on a scale Standard Deviation 30.73	-2.7 units on a scale Standard Deviation 21.70

SECONDARY outcome

Timeframe: Screening to Week 24

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Missing item responses may be imputed for each subject as appropriate before summarization.

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. The higher the score, the worse the outcome. Values were obtained for this questionnaire on Visit 3 in the screening period

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=36 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Absolute Change From Screening to Week 24 in Hospital Anxiety and Depression Scale (HADS) Total Scores - Evaluable Population Anxiety Total Scores	0.08 units on a scale Standard Error 0.274	-0.56 units on a scale Standard Error 0.342	-0.11 units on a scale Standard Error 0.431	-0.43 units on a scale Standard Error 0.373	-0.59 units on a scale Standard Error 0.370	-0.58 units on a scale Standard Error 0.429	0.06 units on a scale Standard Error 0.465	0.02 units on a scale Standard Error 0.475
Mean Absolute Change From Screening to Week 24 in Hospital Anxiety and Depression Scale (HADS) Total Scores - Evaluable Population Depression Total Scores	-0.76 units on a scale Standard Error 0.357	-0.98 units on a scale Standard Error 0.394	-0.66 units on a scale Standard Error 0.332	-1.37 units on a scale Standard Error 0.387	-1.23 units on a scale Standard Error 0.416	-1.02 units on a scale Standard Error 0.294	0.00 units on a scale Standard Error 0.481	-0.85 units on a scale Standard Error 0.435

SECONDARY outcome

Timeframe: Screening to Week 24

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Missing item responses may be imputed for each subject as appropriate before summarization.

The POMS is a mood scale consisting of 65 mood adjectives that assess participants' mood over the past seven days. The POMS-B is an authorized, 30-item brief version of the POMS consisting of five items for each of the six POMS factors. The mood adjectives load onto 6 mood factors, which are as follows: Tension-Anxiety, Depression-Dejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment. Scores range from 0= Not at All to 4=Extremely. The factor scores are added to obtain the total mood disturbance score. A lower total mood disturbance score indicates improvement. Values were obtained for this questionnaire on Visit 3 in the screening period.

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=43 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=35 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population Tension - Anxiety	0.39 units on a scale Standard Error 0.308	-0.17 units on a scale Standard Error 0.389	0.87 units on a scale Standard Error 0.518	-0.30 units on a scale Standard Error 0.408	-0.21 units on a scale Standard Error 0.358	0.00 units on a scale Standard Error 0.423	0.66 units on a scale Standard Error 0.583	0.35 units on a scale Standard Error 0.518
Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population Vigor - Activity	0.27 units on a scale Standard Error 0.681	0.78 units on a scale Standard Error 0.670	1.04 units on a scale Standard Error 0.603	1.20 units on a scale Standard Error 0.632	0.95 units on a scale Standard Error 0.773	1.13 units on a scale Standard Error 0.641	1.29 units on a scale Standard Error 0.787	1.11 units on a scale Standard Error 0.534
Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population Fatigue - Inertia	-0.53 units on a scale Standard Error 0.709	-1.10 units on a scale Standard Error 0.688	0.02 units on a scale Standard Error 0.660	-0.30 units on a scale Standard Error 0.676	-1.49 units on a scale Standard Error 0.626	-0.82 units on a scale Standard Error 0.667	0.09 units on a scale Standard Error 0.779	-1.22 units on a scale Standard Error 0.852
Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population Confusion - Bewilderment	0.51 units on a scale Standard Error 0.334	0.17 units on a scale Standard Error 0.296	0.40 units on a scale Standard Error 0.387	0.20 units on a scale Standard Error 0.400	0.05 units on a scale Standard Error 0.286	0.02 units on a scale Standard Error 0.280	0.00 units on a scale Standard Error 0.393	0.43 units on a scale Standard Error 0.471
Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population Depression - Dejection	0.27 units on a scale Standard Error 0.489	0.44 units on a scale Standard Error 0.466	0.64 units on a scale Standard Error 0.410	0.26 units on a scale Standard Error 0.464	0.37 units on a scale Standard Error 0.381	-0.29 units on a scale Standard Error 0.348	0.23 units on a scale Standard Error 0.666	0.41 units on a scale Standard Error 0.628
Mean Absolute Change From Screening to Week 24 in Summary Scores for Profile of Mood States - Brief (POMS-B) - Evaluable Population Anger - Hostility	0.16 units on a scale Standard Error 0.418	-0.22 units on a scale Standard Error 0.468	0.53 units on a scale Standard Error 0.489	-0.30 units on a scale Standard Error 0.409	-0.05 units on a scale Standard Error 0.410	-0.18 units on a scale Standard Error 0.476	0.71 units on a scale Standard Error 0.515	0.04 units on a scale Standard Error 0.577

SECONDARY outcome

Timeframe: Screening to Week 24

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Missing item responses may be imputed for each subject as appropriate before summarization.

The Pittsburgh Sleep Quality Index (PSQI) is a questionnaire which assesses sleep quality and sleep disturbances over a period of 1 month. The PSQI provides ratings on seven domains of sleep (subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction). The sum of the individual domains yields a global sleep quality score with a range of 0-21. A PSQI score >5 is indicative of poor sleep, which is characterized by severe difficulties in at least two domains, or moderate difficulties in three or more domains. Values were obtained for this questionnaire on Visit 3 in the screening period.

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=38 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
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 Minutes to Fall Asleep	1.3 units on a scale Standard Deviation 17.83	-2.1 units on a scale Standard Deviation 14.81	-4.3 units on a scale Standard Deviation 15.09	-4.6 units on a scale Standard Deviation 12.00	-4.3 units on a scale Standard Deviation 19.50	-1.0 units on a scale Standard Deviation 14.74	2.7 units on a scale Standard Deviation 16.04	-0.5 units on a scale Standard Deviation 11.17
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 Hours Asleep	0.1 units on a scale Standard Deviation 0.91	-0.1 units on a scale Standard Deviation 0.76	0.2 units on a scale Standard Deviation 1.09	0.1 units on a scale Standard Deviation 1.15	0.2 units on a scale Standard Deviation 1.01	0.2 units on a scale Standard Deviation 1.18	-0.4 units on a scale Standard Deviation 1.06	0.1 units on a scale Standard Deviation 0.80
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 PSQI Global Score	-0.3 units on a scale Standard Deviation 2.46	-0.3 units on a scale Standard Deviation 2.81	-0.8 units on a scale Standard Deviation 2.43	-0.9 units on a scale Standard Deviation 2.92	-1.0 units on a scale Standard Deviation 2.57	-1.0 units on a scale Standard Deviation 2.44	-0.1 units on a scale Standard Deviation 2.64	-0.9 units on a scale Standard Deviation 2.18

SECONDARY outcome

Timeframe: Screening to Week 24

Population: Evaluable population includes participants received at least one dose of randomized treatment, had adequate exposure to treatment, and complied with the protocol as assessed prior to database lock and unblinding. Missing item responses may be imputed for each subject as appropriate before summarization.

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 indicate improvement. Values were obtained for this questionnaire on Visit 3 in the screening period

Outcome measures

Measure	Pramlintide 360 mcg n=51 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=46 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=45 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=36 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=45 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Absolute Change From Screening to Week 24 in the Epworth Sleepiness Scale (ESS) Total Score - Evaluable Population	-0.63 units on a scale Standard Error 0.450	0.12 units on a scale Standard Error 0.621	-1.32 units on a scale Standard Error 0.319	-1.80 units on a scale Standard Error 0.426	-1.05 units on a scale Standard Error 0.662	-1.80 units on a scale Standard Error 0.448	-0.42 units on a scale Standard Error 0.522	-0.69 units on a scale Standard Error 0.552

SECONDARY outcome

Timeframe: Screening to Week 28

Population: Intent to treat population included all randomized participants who received at least one injection of study medication.

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. Values obtained at Screening, Day -7, Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28. Numbers of values are cumulative across the study.

Outcome measures

Measure	Pramlintide 360 mcg n=77 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=72 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=75 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Platelet Count	0 Number of Laboratory Values	1 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	10 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values
Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population White Blood Cell Count	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values
Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Urine Ketones	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values
Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Hematocrit	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	4 Number of Laboratory Values	3 Number of Laboratory Values	4 Number of Laboratory Values
Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Hemoglobin	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	5 Number of Laboratory Values	7 Number of Laboratory Values	4 Number of Laboratory Values	7 Number of Laboratory Values
Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Urine Glucose	1 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values
Number of Hematology and Urinalysis Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Urine protein	2 Number of Laboratory Values	0 Number of Laboratory Values	2 Number of Laboratory Values	3 Number of Laboratory Values	4 Number of Laboratory Values	2 Number of Laboratory Values	1 Number of Laboratory Values	1 Number of Laboratory Values

SECONDARY outcome

Timeframe: Screening to Week 28

Population: Intent to treat population included all randomized participants who received at least one injection of study medication.

Obtained at: Screening, Days -7, 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28. Numbers of laboratory values are cumulative across the study. Criteria for values of potential clinical importance for obese and overweight (BMI>=25 kg/m^2) participants: Total bilirubin High (H) > 2 mg/dL; Plasma/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.

Outcome measures

Measure	Pramlintide 360 mcg n=77 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=72 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=75 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Total Bilirubin	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	1 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Uric Acid	10 Number of Laboratory Values	5 Number of Laboratory Values	11 Number of Laboratory Values	19 Number of Laboratory Values	21 Number of Laboratory Values	9 Number of Laboratory Values	25 Number of Laboratory Values	4 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population alanine aminotransferase	8 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	3 Number of Laboratory Values	0 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population aspartate aminotransferase	2 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	2 Number of Laboratory Values	0 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Bicarbonate	5 Number of Laboratory Values	1 Number of Laboratory Values	5 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Gamma-glutamyltransferase	3 Number of Laboratory Values	5 Number of Laboratory Values	1 Number of Laboratory Values	13 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	6 Number of Laboratory Values	17 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Creatine kinase	4 Number of Laboratory Values	4 Number of Laboratory Values	9 Number of Laboratory Values	8 Number of Laboratory Values	4 Number of Laboratory Values	2 Number of Laboratory Values	2 Number of Laboratory Values	18 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Calcium	2 Number of Laboratory Values	2 Number of Laboratory Values	7 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values	13 Number of Laboratory Values	0 Number of Laboratory Values	2 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Potassium	1 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	2 Number of Laboratory Values	1 Number of Laboratory Values	2 Number of Laboratory Values	6 Number of Laboratory Values	0 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Sodium	4 Number of Laboratory Values	2 Number of Laboratory Values	4 Number of Laboratory Values	2 Number of Laboratory Values	0 Number of Laboratory Values	3 Number of Laboratory Values	0 Number of Laboratory Values	2 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Creatinine	0 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	2 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	3 Number of Laboratory Values	0 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Alkaline Phosphatase	0 Number of Laboratory Values	0 Number of Laboratory Values	1 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From Screening to Week 28 - Intent to Treat Population Blood urea nitrogen	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	0 Number of Laboratory Values	2 Number of Laboratory Values	0 Number of Laboratory Values

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Intent to treat population included all randomized participants who received at least one injection of study medication.

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. Blood pressure was taken while the participant was sitting and was measured in millimeters of mercury (mm Hg). Values obtained at Screening, Day -7, Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28

Outcome measures

Measure	Pramlintide 360 mcg n=77 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=72 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=75 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 28 - Intent to Treat Population Systolic Blood Pressure	-0.9 mm Hg Standard Deviation 11.9	-3.4 mm Hg Standard Deviation 12.54	-3.2 mm Hg Standard Deviation 10.84	0.4 mm Hg Standard Deviation 11.84	-2.0 mm Hg Standard Deviation 12.47	-1.2 mm Hg Standard Deviation 10.78	-1.5 mm Hg Standard Deviation 12.54	2.4 mm Hg Standard Deviation 10.65
Mean Change in Systolic and Diastolic Blood Pressure From Baseline to Week 28 - Intent to Treat Population Diastolic Blood Pressure	-1.7 mm Hg Standard Deviation 6.83	-2.6 mm Hg Standard Deviation 7.21	-0.4 mm Hg Standard Deviation 8.07	-1.0 mm Hg Standard Deviation 6.99	-1.3 mm Hg Standard Deviation 7.96	-1.8 mm Hg Standard Deviation 6.77	-0.1 mm Hg Standard Deviation 9.93	1.2 mm Hg Standard Deviation 7.31

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Intent to treat population included all randomized participants who received at least one injection of study medication.

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. Heart rate was measured while the participant was sitting and was measured in beats per minute (bpm). Values obtained at Screening, Day -7, Day 1, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28.

Outcome measures

Measure	Pramlintide 360 mcg n=77 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=72 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=78 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=75 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=74 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Change in Heart Rate From Baseline to Week 28 - Intent to Treat Population	-1.3 bpm Standard Deviation 7.70	-2.6 bpm Standard Deviation 6.66	-1.4 bpm Standard Deviation 8.40	-2.1 bpm Standard Deviation 7.38	-0.5 bpm Standard Deviation 9.34	-2.4 bpm Standard Deviation 7.54	-0.1 bpm Standard Deviation 10.80	1.6 bpm Standard Deviation 9.29

SECONDARY outcome

Timeframe: Baseline to Week 28

Population: Intent to treat population included all randomized participants who received at least one injection of study medication.

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. 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.

Outcome measures

Measure	Pramlintide 360 mcg n=49 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=50 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=50 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=43 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=45 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Number of Participants With Treatment-emergent Positive Anti-leptin Antibody Titers at Week 28 - Intent to Treat Population	49 participants	48 participants	42 participants	50 participants	42 participants	—	—	43 participants

SECONDARY outcome

Timeframe: Screening to Week 28 (or study termination)

Population: Intent to treat population included all randomized participants who received at least one injection of study medication.

A 12-Lead electrocardiogram (ECG) was obtained at Screening, Day 1, Weeks 1, 12, 28 (study termination). The PR interval, which is 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 (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).

Outcome measures

Measure	Pramlintide 360 mcg n=54 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=49 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=39 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Change From Screening to Week 28 in Electrocardiogram Parameters - Intent to Treat Population PR Interval	-0.1 msec Standard Deviation 12.23	0.3 msec Standard Deviation 10.37	0.1 msec Standard Deviation 13.74	16.8 msec Standard Deviation 97.51	4.4 msec Standard Deviation 17.89	0.4 msec Standard Deviation 11.86	-1.6 msec Standard Deviation 14.27	1.1 msec Standard Deviation 12.73
Mean Change From Screening to Week 28 in Electrocardiogram Parameters - Intent to Treat Population QRS Interval	-1.4 msec Standard Deviation 8.76	1.0 msec Standard Deviation 4.66	-0.5 msec Standard Deviation 6.26	-1.8 msec Standard Deviation 5.62	-0.2 msec Standard Deviation 4.12	0.3 msec Standard Deviation 4.78	-0.4 msec Standard Deviation 5.33	-0.3 msec Standard Deviation 5.20
Mean Change From Screening to Week 28 in Electrocardiogram Parameters - Intent to Treat Population QT Interval	9.9 msec Standard Deviation 21.80	16.2 msec Standard Deviation 28.64	7.0 msec Standard Deviation 19.33	8.9 msec Standard Deviation 20.53	4.4 msec Standard Deviation 24.97	15.0 msec Standard Deviation 21.56	6.3 msec Standard Deviation 28.03	0.4 msec Standard Deviation 28.72
Mean Change From Screening to Week 28 in Electrocardiogram Parameters - Intent to Treat Population QTcF	4.0 msec Standard Deviation 15.58	8.2 msec Standard Deviation 21.39	-1.2 msec Standard Deviation 16.02	-0.8 msec Standard Deviation 15.13	0.3 msec Standard Deviation 15.40	1.3 msec Standard Deviation 12.34	-2.3 msec Standard Deviation 22.00	-0.3 msec Standard Deviation 21.75

SECONDARY outcome

Timeframe: Screening to Week 28 (or early termination)

Population: Intent to treat population included all randomized participants who received at least one injection of study medication.

A 12-Lead electrocardiogram (ECG) was obtained at Screening (visit 2), Day 1, Weeks 1, 12, 28 (study termination). Heart Rate was measured in beats per min (bpm).

Outcome measures

Measure	Pramlintide 360 mcg n=54 Participants Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=41 Participants Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=49 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg	Pramlintide 360 mcg + Metreleptin 1.25 mg n=44 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=47 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=39 Participants Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Placebo n=46 Participants Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).
Mean Change From Screening to Week 28 in the Electrocardiogram Parameter of Heart Rate - Intent to Treat Population	-2.8 bpm Standard Deviation 8.45	-4.1 bpm Standard Deviation 8.18	-4.7 bpm Standard Deviation 10.12	-4.9 bpm Standard Deviation 9.42	-1.9 bpm Standard Deviation 9.73	-6.6 bpm Standard Deviation 8.41	-3.4 bpm Standard Deviation 9.69	0.3 bpm Standard Deviation 13.96

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 60 other events

Deaths: 0 deaths

Pramlintide 360 mcg

Serious events: 1 serious events

Other events: 66 other events

Deaths: 0 deaths

Metreleptin 5.0 mg

Serious events: 0 serious events

Other events: 63 other events

Deaths: 0 deaths

Pramlintide 180 mcg + Metreleptin 2.5 mg

Serious events: 2 serious events

Other events: 67 other events

Deaths: 0 deaths

Pramlintide 180 mcg + Metreleptin 5.0 mg

Serious events: 0 serious events

Other events: 71 other events

Deaths: 0 deaths

Pramlintide 360 mcg + Metreleptin 1.25 mg

Serious events: 0 serious events

Other events: 68 other events

Deaths: 0 deaths

Pramlintide 360 mcg + Metreleptin 2.5 mg

Serious events: 0 serious events

Other events: 72 other events

Deaths: 0 deaths

Pramlintide 360 mcg + Metreleptin 5.0 mg

Serious events: 2 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=75 participants at risk Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).	Pramlintide 360 mcg n=77 participants at risk Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=72 participants at risk Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=75 participants at risk Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=78 participants at risk Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg.	Pramlintide 360 mcg + Metreleptin 1.25 mg n=78 participants at risk Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=78 participants at risk Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=75 participants at risk Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).
Immune system disorders Food Allergy	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Vascular disorders Hypertension	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Nervous system disorders Cervicobrachial syndrome	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders Non-cardiac chest pain	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Vascular disorders Deep Vein Thrombosis	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/77 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Nervous system disorders Convulsion	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Nervous system disorders Syncope vasovagal	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Cardiac disorders Cardiac arrest	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid Tumor benign	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Endocrine disorders Goiter	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Blood and lymphatic system disorders lymphadenopathy	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).

Other adverse events

Measure	Placebo n=75 participants at risk Self administered BID for 28 weeks, SC placebo matched to pramlintide (Placebo-P) plus SC placebo matched to metreleptin (Placebo-M).	Pramlintide 360 mcg n=77 participants at risk Self administered BID for 28 weeks, SC 360 mcg pramlintide acetate plus SC Placebo matched to Metreleptin (Placebo-M). The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Metreleptin 5.0 mg n=72 participants at risk Self administered BID for 28 weeks, SC metreleptin 5.0 mg plus SC Placebo matched to pramlintide (Placebo-P).	Pramlintide 180 mcg + Metreleptin 2.5 mg n=75 participants at risk Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 2.5 mg.	Pramlintide 180 mcg + Metreleptin 5.0 mg n=78 participants at risk Self administered BID for 28 weeks, SC Pramlintide 180 mcg plus SC Metreleptin 5.0 mg.	Pramlintide 360 mcg + Metreleptin 1.25 mg n=78 participants at risk Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 1.25 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 2.5 mg n=78 participants at risk Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 2.5 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).	Pramlintide 360 mcg + Metreleptin 5.0 mg n=75 participants at risk Self administered BID for 28 weeks, SC Pramlintide 360 mcg plus SC Metreleptin 5.0 mg. The first week of the 28 weeks started with a lower pramlintide dose (180 mcg) in a blinded fashion (using 2 different concentrations of pramlintide so the dose change was not apparent to the participant).
Gastrointestinal disorders nausea	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	40.3% 31/77 • Number of events 37 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.6% 4/72 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	36.0% 27/75 • Number of events 30 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	26.9% 21/78 • Number of events 22 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	33.3% 26/78 • Number of events 27 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	37.2% 29/78 • Number of events 32 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	25.3% 19/75 • Number of events 20 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site erythema	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	9.1% 7/77 • Number of events 8 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	20.8% 15/72 • Number of events 25 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	20.0% 15/75 • Number of events 17 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	21.8% 17/78 • Number of events 21 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	10.3% 8/78 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	30.8% 24/78 • Number of events 25 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	28.0% 21/75 • Number of events 24 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site pruritus	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.2% 4/77 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	18.1% 13/72 • Number of events 19 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	25.3% 19/75 • Number of events 20 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	26.9% 21/78 • Number of events 23 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	14.1% 11/78 • Number of events 11 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	23.1% 18/78 • Number of events 20 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	29.3% 22/75 • Number of events 23 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site bruising	14.7% 11/75 • Number of events 14 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	14.3% 11/77 • Number of events 13 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	12.5% 9/72 • Number of events 13 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	12.0% 9/75 • Number of events 16 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	11.5% 9/78 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	14.1% 11/78 • Number of events 13 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	10.3% 8/78 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	21.3% 16/75 • Number of events 23 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site hemorrhage	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	13.0% 10/77 • Number of events 11 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	18.1% 13/72 • Number of events 17 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	18.7% 14/75 • Number of events 17 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	12.8% 10/78 • Number of events 10 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	9.0% 7/78 • Number of events 7 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	12.8% 10/78 • Number of events 11 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	14.7% 11/75 • Number of events 12 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site urticaria	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/77 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	16.7% 12/72 • Number of events 12 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	17.3% 13/75 • Number of events 13 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	15.4% 12/78 • Number of events 12 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.4% 5/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	14.1% 11/78 • Number of events 14 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	14.7% 11/75 • Number of events 11 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Infections and infestations Upper respiratory tract infection	10.7% 8/75 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	10.4% 8/77 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.8% 2/72 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	9.3% 7/75 • Number of events 7 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	12.8% 10/78 • Number of events 10 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	14.1% 11/78 • Number of events 11 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	11.5% 9/78 • Number of events 13 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.7% 5/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site rash	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/77 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	18.1% 13/72 • Number of events 15 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	10.3% 8/78 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	11.5% 9/78 • Number of events 12 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	15.4% 12/78 • Number of events 12 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	9.3% 7/75 • Number of events 10 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Infections and infestations nasopharyngitis	5.3% 4/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	10.4% 8/77 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	11.1% 8/72 • Number of events 11 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.1% 4/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	7.7% 6/78 • Number of events 9 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	7.7% 6/78 • Number of events 7 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.3% 4/75 • Number of events 7 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site nodule	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/77 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	11.1% 8/72 • Number of events 11 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	12.8% 10/78 • Number of events 10 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	7.7% 6/78 • Number of events 6 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	10.7% 8/75 • Number of events 10 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Nervous system disorders headache	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.5% 5/77 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.6% 4/72 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	9.0% 7/78 • Number of events 13 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Gastrointestinal disorders diarrhea	6.7% 5/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.5% 5/77 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.2% 3/72 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.7% 5/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.1% 4/78 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.1% 4/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	9.0% 7/78 • Number of events 7 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Infections and infestations urinary tract infection	6.7% 5/75 • Number of events 6 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	9.1% 7/77 • Number of events 13 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.2% 3/72 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Investigations blood creatine phosphokinase increased	8.0% 6/75 • Number of events 6 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/77 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.4% 1/72 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.4% 5/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site induration	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/77 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.8% 2/72 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	7.7% 6/78 • Number of events 7 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.7% 5/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders injection site inflammation	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/77 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.4% 1/72 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.1% 4/78 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/77 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.2% 3/72 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
General disorders fatigue	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.9% 3/77 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.2% 3/72 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.7% 5/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.1% 4/78 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Infections and infestations gastroenteritis viral	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.2% 4/77 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.8% 2/72 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.0% 3/75 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Gastrointestinal disorders constipation	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.9% 3/77 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.8% 2/72 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.7% 5/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Gastrointestinal disorders vomiting	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	7.8% 6/77 • Number of events 6 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	4.2% 3/72 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.4% 5/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Nervous system disorders dizziness	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.9% 3/77 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.4% 1/72 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Respiratory, thoracic and mediastinal disorders pharyngolaryngeal pain	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.9% 3/77 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.4% 1/72 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Infections and infestations bronchitis	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/77 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.4% 1/72 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.1% 4/78 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	3.8% 3/78 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/75 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Respiratory, thoracic and mediastinal disorders sinus congestion	5.3% 4/75 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/77 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/72 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/78 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.6% 2/78 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	0.00% 0/78 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/75 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).
Respiratory, thoracic and mediastinal disorders sinusitis	4.0% 3/75 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	1.3% 1/77 • Number of events 1 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.8% 2/72 • Number of events 3 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	5.1% 4/78 • Number of events 4 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.4% 5/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	6.4% 5/78 • Number of events 5 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).	2.7% 2/75 • Number of events 2 • From enrollment to Study Termination (Week 28). Clinically significant events that continued beyond termination were followed until diagnosis/resolution occurred. Serious adverse events were followed 30 days post last dose of study medication. All participants enrolled were treated with Placebo for 1 week and then randomized into a treatment group. Enrolled = 636 (commenced placebo for 1 week); Enrolled but not randomized = 28; Randomized = 608; Intent to treat = Randomized and received at least 1 dose. Events presented below from Randomized population, treatment-emergent (ITT).

Additional Information

Peter Ohman, Medical Science Director

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER