Trial Outcomes & Findings for Extension Study of Protocol DFA102 to Examine the Long-Term Safety, Tolerability, and Effect on Body Weight of Pramlintide Administered in Combination With Metreleptin (NCT NCT00819234)

NCT ID: NCT00819234

Last Updated: 2015-04-15

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 274 participants
• Primary outcome timeframe: Original Study Baseline to Week 52
• Results posted on: 2015-04-15

Participant Flow

Participants (overweight and obese) must have been randomized and treated in original DFA102 Study (NCT00673387) in order to be enrolled into this extension study DFA102E and followed for a total of up to 52 weeks, inclusive of DFA102 (ie, DFA102 and DFA102E studies together have a total length of 52 weeks).

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

Participant milestones

Measure	Placebo - Stable Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E.	360 mcg Pramlintide + 1.25mg Metreleptin - Stable Participants who received 360 mcg pramlintide plus 1.25 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 2.5 Metreleptin - Stable Participants who received 360 mcg pramlintide plus 2.5 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 5.0 Metreleptin - Stable Participants who received 360 mcg pramlintide plus 5.0 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Overall Study STARTED	31	35	36	28	13	14	13	29	37	37
Overall Study COMPLETED	21	20	28	22	12	7	8	20	31	30
Overall Study NOT COMPLETED	10	15	8	6	1	7	5	9	6	7

Reasons for withdrawal

Measure	Placebo - Stable Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E.	360 mcg Pramlintide + 1.25mg Metreleptin - Stable Participants who received 360 mcg pramlintide plus 1.25 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 2.5 Metreleptin - Stable Participants who received 360 mcg pramlintide plus 2.5 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 5.0 Metreleptin - Stable Participants who received 360 mcg pramlintide plus 5.0 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Monotherapy Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Overall Study Withdrawal by Subject	8	13	6	3	0	4	4	8	5	3
Overall Study Adverse Event	0	0	1	0	0	2	0	0	0	0
Overall Study Physician Decision	0	0	0	1	0	0	0	0	0	2
Overall Study Protocol Violation	0	0	1	0	0	0	0	0	0	0
Overall Study Lost to Follow-up	2	2	0	2	1	1	1	1	1	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	All Participants n=273 Participants All participants who completed the original study and chose to enter the extension study.
Age, Continuous	47.3 years STANDARD_DEVIATION 10.27 • n=5 Participants
Sex: Female, Male Female	191 Participants n=5 Participants
Sex: Female, Male Male	82 Participants n=5 Participants
Region of Enrollment United States	273 participants n=5 Participants
Body Weight at Baseline	95.83 kilograms STANDARD_DEVIATION 17.007 • n=5 Participants
Body Mass Index (BMI) at Baseline	34.16 kg/m^2 STANDARD_DEVIATION 4.988 • n=5 Participants

PRIMARY outcome

Timeframe: Original Study Baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
LS Mean Percent Change in Body Weight From Original Study DFA102 (NCT00673387) Baseline (Day 1) at Week 52 in Extension Study DFA102E - Evaluable Treatment Stable Population	—	—	-2.68 percentage of change in weight 95% Confidence Interval 2.170 • Interval -7.0 to 1.64	-9.92 percentage of change in weight 95% Confidence Interval 2.203 • Interval -14.3 to -5.53	-9.24 percentage of change in weight 95% Confidence Interval 1.944 • Interval -13.1 to -5.37	-8.20 percentage of change in weight 95% Confidence Interval 2.201 • Interval -12.58 to -3.82	—	—	—	—

SECONDARY outcome

Timeframe: Original baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=31 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=35 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=36 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=28 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
LS Mean Absolute Change in Body Weight From Original Study Baseline (Day 1) at Weeks 12, 28, 36, 44, and 52 - Evaluable Treatment Stable Population Week 12 (original study)	—	—	-4.59 kg Interval -6.55 to -2.62	-6.72 kg Interval -8.71 to -4.73	-7.31 kg Interval -9.07 to -5.55	-7.06 kg Interval -9.05 to -5.07	—	—	—	—
LS Mean Absolute Change in Body Weight From Original Study Baseline (Day 1) at Weeks 12, 28, 36, 44, and 52 - Evaluable Treatment Stable Population Week 28 (Baseline for Extension)	—	—	-3.70 kg Interval -6.74 to -0.66	-8.63 kg Interval -11.72 to -5.55	-9.91 kg Interval -12.64 to -7.19	-9.46 kg Interval -12.55 to -6.38	—	—	—	—
LS Mean Absolute Change in Body Weight From Original Study Baseline (Day 1) at Weeks 12, 28, 36, 44, and 52 - Evaluable Treatment Stable Population Week 36 in Extension Study	—	—	-3.53 kg Interval -6.95 to -0.12	-9.74 kg Interval -13.21 to -6.27	-10.69 kg Interval -13.75 to -7.63	-9.21 kg Interval -12.68 to -5.75	—	—	—	—
LS Mean Absolute Change in Body Weight From Original Study Baseline (Day 1) at Weeks 12, 28, 36, 44, and 52 - Evaluable Treatment Stable Population Week 44 in Extension Study	—	—	-3.10 kg Interval -6.82 to 0.63	-9.38 kg Interval -13.16 to -5.6	-10.00 kg Interval -13.33 to -6.66	-8.60 kg Interval -12.38 to -4.82	—	—	—	—
LS Mean Absolute Change in Body Weight From Original Study Baseline (Day 1) at Weeks 12, 28, 36, 44, and 52 - Evaluable Treatment Stable Population Week 52 in Extension Study	—	—	-2.85 kg Interval -6.98 to 1.28	-9.26 kg Interval -13.45 to -5.07	-9.65 kg Interval -13.35 to -5.96	-7.98 kg Interval -12.16 to -3.79	—	—	—	—

SECONDARY outcome

Timeframe: Original Study Baseline to Extension Week 52 and follow up

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=20 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Fasting Total Leptin Concentration by Visit and Pooled Metreleptin Stable Treatment by Metreleptin Dose - Week 52 Stable Evaluable Population DFA102 Baseline	—	—	32.50 ng/mL Standard Error 4.990	34.48 ng/mL Standard Error 3.089	29.50 ng/mL Standard Error 2.251	—	—	—	—	—
Fasting Total Leptin Concentration by Visit and Pooled Metreleptin Stable Treatment by Metreleptin Dose - Week 52 Stable Evaluable Population DFA102E Baseline (Week 28)	—	—	102.02 ng/mL Standard Error 17.466	232.48 ng/mL Standard Error 29.371	420.24 ng/mL Standard Error 48.012	—	—	—	—	—
Fasting Total Leptin Concentration by Visit and Pooled Metreleptin Stable Treatment by Metreleptin Dose - Week 52 Stable Evaluable Population Week 40	—	—	96.23 ng/mL Standard Error 19.418	236.02 ng/mL Standard Error 29.856	416.52 ng/mL Standard Error 58.352	—	—	—	—	—
Fasting Total Leptin Concentration by Visit and Pooled Metreleptin Stable Treatment by Metreleptin Dose - Week 52 Stable Evaluable Population Week 52	—	—	88.47 ng/mL Standard Error 17.576	177.32 ng/mL Standard Error 25.765	259.85 ng/mL Standard Error 40.650	—	—	—	—	—
Fasting Total Leptin Concentration by Visit and Pooled Metreleptin Stable Treatment by Metreleptin Dose - Week 52 Stable Evaluable Population Follow up post treatment	—	—	52.90 ng/mL Standard Error 9.584	89.21 ng/mL Standard Error 11.180	89.49 ng/mL Standard Error 11.712	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
LS Mean Absolute Change in Waist Circumference From Baseline in the Original Study to Week 52 in the Extension Study - Week 52 Evaluable Stable Population Week 12 (original study)	—	—	-4.62 cm Interval -7.15 to -2.08	-4.03 cm Interval -6.57 to -1.49	-5.77 cm Interval -8.03 to -3.51	-5.70 cm Interval -8.25 to -3.15	—	—	—	—
LS Mean Absolute Change in Waist Circumference From Baseline in the Original Study to Week 52 in the Extension Study - Week 52 Evaluable Stable Population Week 28 (baseline in Extension study)	—	—	-3.37 cm Interval -6.63 to -0.1	-6.48 cm Interval -9.75 to -3.2	-7.95 cm Interval -10.92 to -4.97	-8.36 cm Interval -11.65 to -5.07	—	—	—	—
LS Mean Absolute Change in Waist Circumference From Baseline in the Original Study to Week 52 in the Extension Study - Week 52 Evaluable Stable Population Week 36 Extension study	—	—	-3.24 cm Interval -6.77 to 0.29	-8.79 cm Interval -12.33 to -5.25	-9.19 cm Interval -12.34 to -6.04	-8.16 cm Interval -11.71 to -4.6	—	—	—	—
LS Mean Absolute Change in Waist Circumference From Baseline in the Original Study to Week 52 in the Extension Study - Week 52 Evaluable Stable Population Week 44 Extension study	—	—	-3.46 cm Interval -7.2 to 0.28	-9.09 cm Interval -12.74 to -5.44	-9.03 cm Interval -12.27 to -5.78	-8.76 cm Interval -12.42 to -5.1	—	—	—	—
LS Mean Absolute Change in Waist Circumference From Baseline in the Original Study to Week 52 in the Extension Study - Week 52 Evaluable Stable Population Week 52 Extension study	—	—	-3.69 cm Interval -7.43 to 0.05	-9.08 cm Interval -12.95 to -5.21	-9.18 cm Interval -12.52 to -5.84	-7.41 cm Interval -11.18 to -3.65	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
LS Mean Percent Change in Body Weight From Baseline of Original Study DFA102 at Week 12, and at Weeks 28, 36, 44, and 52 in the Extension Study DFA102E - Week 52 Evaluable Treatment Stable Population Week 36 Extension study	—	—	-3.43 Percentage of change in weight Interval -6.91 to 0.05	-10.27 Percentage of change in weight Interval -13.8 to -6.74	-10.43 Percentage of change in weight Interval -13.55 to -7.32	-9.51 Percentage of change in weight Interval -13.04 to -5.98	—	—	—	—
LS Mean Percent Change in Body Weight From Baseline of Original Study DFA102 at Week 12, and at Weeks 28, 36, 44, and 52 in the Extension Study DFA102E - Week 52 Evaluable Treatment Stable Population Week 44 Extension study	—	—	-3.01 Percentage of change in weight Interval -6.86 to 0.84	-9.95 Percentage of change in weight Interval -13.86 to -6.04	-9.65 Percentage of change in weight Interval -13.09 to -6.2	-8.84 Percentage of change in weight Interval -12.75 to -4.94	—	—	—	—
LS Mean Percent Change in Body Weight From Baseline of Original Study DFA102 at Week 12, and at Weeks 28, 36, 44, and 52 in the Extension Study DFA102E - Week 52 Evaluable Treatment Stable Population Week 52 Extension study	—	—	-2.68 Percentage of change in weight Interval -7.0 to 1.64	-9.92 Percentage of change in weight Interval -14.3 to -5.53	-9.24 Percentage of change in weight Interval -13.1 to -5.37	-8.20 Percentage of change in weight Interval -12.58 to -3.82	—	—	—	—
LS Mean Percent Change in Body Weight From Baseline of Original Study DFA102 at Week 12, and at Weeks 28, 36, 44, and 52 in the Extension Study DFA102E - Week 52 Evaluable Treatment Stable Population Week 12 of original study	—	—	-4.56 Percentage of change in weight Interval -6.48 to -2.65	-6.93 Percentage of change in weight Interval -8.87 to -4.99	-7.23 Percentage of change in weight Interval -8.95 to -5.52	-7.17 Percentage of change in weight Interval -9.11 to -5.23	—	—	—	—
LS Mean Percent Change in Body Weight From Baseline of Original Study DFA102 at Week 12, and at Weeks 28, 36, 44, and 52 in the Extension Study DFA102E - Week 52 Evaluable Treatment Stable Population Week 28 Extension study	—	—	-3.78 Percentage of change in weight Interval -6.83 to -0.74	-9.14 Percentage of change in weight Interval -12.22 to -6.05	-9.72 Percentage of change in weight Interval -12.44 to -6.99	-9.83 Percentage of change in weight Interval -12.91 to -6.74	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E for Glucose and Lipids - Week 52 Evaluable Treatment Stable Population glucose	—	—	-1.88 mg/dL Interval -5.62 to 1.85	-0.60 mg/dL Interval -4.36 to 3.17	0.03 mg/dL Interval -3.38 to 3.43	-6.29 mg/dL Interval -10.07 to -2.5	—	—	—	—
LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E for Glucose and Lipids - Week 52 Evaluable Treatment Stable Population total cholesterol	—	—	4.19 mg/dL Interval -8.25 to 16.63	-2.21 mg/dL Interval -15.1 to 10.68	-3.24 mg/dL Interval -14.84 to 8.35	-3.84 mg/dL Interval -17.12 to 9.43	—	—	—	—
LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E for Glucose and Lipids - Week 52 Evaluable Treatment Stable Population triglycerides	—	—	-10.05 mg/dL Interval -26.77 to 6.67	-5.41 mg/dL Interval -22.58 to 11.76	-5.86 mg/dL Interval -21.16 to 9.43	-12.74 mg/dL Interval -30.12 to 4.64	—	—	—	—
LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E for Glucose and Lipids - Week 52 Evaluable Treatment Stable Population low density lipoprotein (LDL)	—	—	13.43 mg/dL Interval 1.96 to 24.9	4.43 mg/dL Interval -7.49 to 16.35	6.03 mg/dL Interval -4.64 to 16.7	4.43 mg/dL Interval -7.97 to 16.82	—	—	—	—
LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E for Glucose and Lipids - Week 52 Evaluable Treatment Stable Population high density lipoprotein (HDL)	—	—	2.92 mg/dL Interval -0.36 to 6.21	7.96 mg/dL Interval 4.57 to 11.36	5.04 mg/dL Interval 2.01 to 8.08	7.61 mg/dL Interval 4.1 to 11.12	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=25 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=18 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
LS Mean Absolute Change From Baseline in Original Study DFA102 to Week 52 in Extension Study DFA102E in Total Insulin - Week 52 Evaluable Treatment Stable Population	—	—	-0.54 µIU/mL Interval -2.97 to 1.89	-2.16 µIU/mL Interval -4.71 to 0.39	-0.62 µIU/mL Interval -2.94 to 1.7	-1.61 µIU/mL Interval -4.2 to 0.97	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=6 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=29 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Number of Participants Achieving at Least 5%, 10%, and 15% of Body Weight Loss From Original Study DFA102 Baseline to Week 52 in Extension Study DFA102E - Week 52 Evaluable Population Weight Loss >=10% and <15%	1 participants	4 participants	3 participants	2 participants	5 participants	4 participants	0 participants	1 participants	6 participants	5 participants
Number of Participants Achieving at Least 5%, 10%, and 15% of Body Weight Loss From Original Study DFA102 Baseline to Week 52 in Extension Study DFA102E - Week 52 Evaluable Population Weight Loss >=5% and <10%	1 participants	6 participants	3 participants	4 participants	10 participants	6 participants	6 participants	1 participants	7 participants	7 participants
Number of Participants Achieving at Least 5%, 10%, and 15% of Body Weight Loss From Original Study DFA102 Baseline to Week 52 in Extension Study DFA102E - Week 52 Evaluable Population Weight Loss >=5%	4 participants	15 participants	8 participants	12 participants	21 participants	12 participants	7 participants	3 participants	18 participants	18 participants
Number of Participants Achieving at Least 5%, 10%, and 15% of Body Weight Loss From Original Study DFA102 Baseline to Week 52 in Extension Study DFA102E - Week 52 Evaluable Population Weight Loss >=10%	3 participants	9 participants	5 participants	8 participants	11 participants	6 participants	1 participants	2 participants	11 participants	11 participants
Number of Participants Achieving at Least 5%, 10%, and 15% of Body Weight Loss From Original Study DFA102 Baseline to Week 52 in Extension Study DFA102E - Week 52 Evaluable Population Weight Loss >=15%	2 participants	5 participants	2 participants	6 participants	6 participants	2 participants	1 participants	1 participants	5 participants	6 participants

SECONDARY outcome

Timeframe: Baseline (Week 28) to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=6 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=29 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Number of Participants Achieving at Least 5%, 10% and 15% Body Weight Loss From Extension Study DFA102E Baseline (Week 28) to Week 52 - Week 52 Evaluable Population Weight Loss >=10%	2 participants	1 participants	0 participants	2 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants
Number of Participants Achieving at Least 5%, 10% and 15% Body Weight Loss From Extension Study DFA102E Baseline (Week 28) to Week 52 - Week 52 Evaluable Population Weight Loss >=5% and <10%	0 participants	7 participants	2 participants	1 participants	4 participants	1 participants	0 participants	0 participants	3 participants	3 participants
Number of Participants Achieving at Least 5%, 10% and 15% Body Weight Loss From Extension Study DFA102E Baseline (Week 28) to Week 52 - Week 52 Evaluable Population Weight Loss >=10% and <15%	2 participants	1 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	2 participants
Number of Participants Achieving at Least 5%, 10% and 15% Body Weight Loss From Extension Study DFA102E Baseline (Week 28) to Week 52 - Week 52 Evaluable Population Weight Loss >=5%	2 participants	8 participants	2 participants	3 participants	4 participants	1 participants	0 participants	0 participants	3 participants	5 participants
Number of Participants Achieving at Least 5%, 10% and 15% Body Weight Loss From Extension Study DFA102E Baseline (Week 28) to Week 52 - Week 52 Evaluable Population Weight Loss >=15%	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Screening to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=6 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=29 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population How Hungry	-5.0 units on a scale Standard Deviation 20.61	-20.8 units on a scale Standard Deviation 26.63	-1.2 units on a scale Standard Deviation 20.40	-12.8 units on a scale Standard Deviation 19.31	-20.3 units on a scale Standard Deviation 23.23	-12.9 units on a scale Standard Deviation 29.00	0.1 units on a scale Standard Deviation 25.54	-17.9 units on a scale Standard Deviation 12.13	-8.2 units on a scale Standard Deviation 25.80	-16.2 units on a scale Standard Deviation 28.58
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population Frequency of Food Cravings	-13.7 units on a scale Standard Deviation 41.94	-18.9 units on a scale Standard Deviation 21.06	-14.1 units on a scale Standard Deviation 16.91	-14.4 units on a scale Standard Deviation 18.61	-15.0 units on a scale Standard Deviation 23.59	-21.4 units on a scale Standard Deviation 33.81	-3.1 units on a scale Standard Deviation 19.21	-22.6 units on a scale Standard Deviation 33.53	-12.8 units on a scale Standard Deviation 21.82	-21.4 units on a scale Standard Deviation 25.56
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population Strength of Food Cravings	-9.5 units on a scale Standard Deviation 32.57	-13.0 units on a scale Standard Deviation 28.56	-14.3 units on a scale Standard Deviation 15.48	-13.3 units on a scale Standard Deviation 22.96	-14.2 units on a scale Standard Deviation 22.26	-17.9 units on a scale Standard Deviation 28.54	5.3 units on a scale Standard Deviation 19.35	-30.3 units on a scale Standard Deviation 30.57	-8.8 units on a scale Standard Deviation 25.08	-14.6 units on a scale Standard Deviation 22.39
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population Difficult to Control Eating	-17.7 units on a scale Standard Deviation 27.47	-22.1 units on a scale Standard Deviation 22.64	-18.3 units on a scale Standard Deviation 25.17	-19.7 units on a scale Standard Deviation 20.36	-23.3 units on a scale Standard Deviation 27.38	-17.6 units on a scale Standard Deviation 28.98	-8.8 units on a scale Standard Deviation 19.64	-31.6 units on a scale Standard Deviation 29.38	-16.6 units on a scale Standard Deviation 24.54	-28.7 units on a scale Standard Deviation 23.15
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population Difficult to Resist Food Cravings	-15.7 units on a scale Standard Deviation 36.47	-25.6 units on a scale Standard Deviation 22.32	-17.6 units on a scale Standard Deviation 25.36	-20.0 units on a scale Standard Deviation 23.08	-24.2 units on a scale Standard Deviation 25.77	-16.9 units on a scale Standard Deviation 30.90	-3.0 units on a scale Standard Deviation 20.43	-30.9 units on a scale Standard Deviation 31.20	-18.5 units on a scale Standard Deviation 23.65	-25.8 units on a scale Standard Deviation 26.29
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population Eating in Response to Food Cravings	-7.3 units on a scale Standard Deviation 30.61	-27.4 units on a scale Standard Deviation 17.41	-18.4 units on a scale Standard Deviation 31.97	-18.7 units on a scale Standard Deviation 26.60	-20.4 units on a scale Standard Deviation 22.96	-21.3 units on a scale Standard Deviation 30.83	-1.8 units on a scale Standard Deviation 20.91	-26.6 units on a scale Standard Deviation 32.46	-13.4 units on a scale Standard Deviation 22.50	-29.2 units on a scale Standard Deviation 26.61
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population Difficult to Control Portion Sizes	-11.5 units on a scale Standard Deviation 23.42	-33.1 units on a scale Standard Deviation 20.46	-24.6 units on a scale Standard Deviation 25.85	-19.9 units on a scale Standard Deviation 21.13	-25.0 units on a scale Standard Deviation 25.80	-31.7 units on a scale Standard Deviation 30.85	-6.6 units on a scale Standard Deviation 25.50	-24.4 units on a scale Standard Deviation 26.68	-24.4 units on a scale Standard Deviation 21.62	-27.4 units on a scale Standard Deviation 24.34
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population How Full After Meals	11.8 units on a scale Standard Deviation 21.18	-6.2 units on a scale Standard Deviation 23.42	-6.5 units on a scale Standard Deviation 33.57	-10.1 units on a scale Standard Deviation 22.03	-1.9 units on a scale Standard Deviation 24.74	3.5 units on a scale Standard Deviation 29.96	0.8 units on a scale Standard Deviation 24.77	-4.3 units on a scale Standard Deviation 44.84	-1.3 units on a scale Standard Deviation 20.86	-10.2 units on a scale Standard Deviation 27.99
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population Thoughts of Food	-14.5 units on a scale Standard Deviation 44.56	-16.3 units on a scale Standard Deviation 22.70	-8.5 units on a scale Standard Deviation 17.01	-12.3 units on a scale Standard Deviation 16.06	-17.9 units on a scale Standard Deviation 22.54	-17.4 units on a scale Standard Deviation 32.05	-1.5 units on a scale Standard Deviation 29.05	-26.3 units on a scale Standard Deviation 22.97	-6.0 units on a scale Standard Deviation 22.34	-18.4 units on a scale Standard Deviation 24.90
Mean Absolute Change From Original Study DFA102 Screening at Week 52 in Extension Study DFA102E in Susceptibility to Eating Questionnaire (SEQ) Item Scores - Week 52 Evaluable Population How Pleasant Meals	7.7 units on a scale Standard Deviation 13.09	7.1 units on a scale Standard Deviation 17.29	-1.0 units on a scale Standard Deviation 17.16	-2.8 units on a scale Standard Deviation 22.85	8.4 units on a scale Standard Deviation 24.09	15.5 units on a scale Standard Deviation 30.30	8.8 units on a scale Standard Deviation 21.84	8.4 units on a scale Standard Deviation 16.00	1.3 units on a scale Standard Deviation 20.91	-5.2 units on a scale Standard Deviation 24.10

SECONDARY outcome

Timeframe: Screening to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=6 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=29 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Mean Absolute Change From Original Study DFA102 Screening to Week 52 in Extension Study DFA102E in Binge Eating Scale (BES) Total Score - Week 52 Evaluable Population	-8.6 units on a scale Standard Deviation 2.41	-8.1 units on a scale Standard Deviation 4.92	-5.8 units on a scale Standard Deviation 7.09	-5.7 units on a scale Standard Deviation 4.60	-7.1 units on a scale Standard Deviation 7.31	-7.4 units on a scale Standard Deviation 7.90	-0.3 units on a scale Standard Deviation 7.98	-10.4 units on a scale Standard Deviation 7.98	-5.3 units on a scale Standard Deviation 7.97	-8.1 units on a scale Standard Deviation 8.22

SECONDARY outcome

Timeframe: Screening to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=13 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=29 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=31 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=35 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=36 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=28 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=13 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=14 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=37 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=37 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Mean Absolute Change From Original Study DFA102 Screening to Week 52 in Extension Study DFA102E in Hospital Anxiety and Depression Scale (HADS) Total Scores - Week 52 Evaluable Population Change in Total Scores for Anxiety	0.4 units on a scale Standard Deviation 1.43	-0.7 units on a scale Standard Deviation 2.69	-0.4 units on a scale Standard Deviation 2.94	-1.2 units on a scale Standard Deviation 2.33	-0.5 units on a scale Standard Deviation 2.84	-0.2 units on a scale Standard Deviation 3.42	-0.8 units on a scale Standard Deviation 3.31	0.1 units on a scale Standard Deviation 2.11	-1.2 units on a scale Standard Deviation 3.45	-0.8 units on a scale Standard Deviation 3.00
Mean Absolute Change From Original Study DFA102 Screening to Week 52 in Extension Study DFA102E in Hospital Anxiety and Depression Scale (HADS) Total Scores - Week 52 Evaluable Population Change in Total Scores for Depression	-0.8 units on a scale Standard Deviation 2.44	-1.3 units on a scale Standard Deviation 2.59	-1.0 units on a scale Standard Deviation 3.46	-2.1 units on a scale Standard Deviation 2.60	-0.9 units on a scale Standard Deviation 1.70	-0.3 units on a scale Standard Deviation 2.85	0.3 units on a scale Standard Deviation 2.66	-1.0 units on a scale Standard Deviation 2.80	-0.9 units on a scale Standard Deviation 2.26	-1.7 units on a scale Standard Deviation 2.57

SECONDARY outcome

Timeframe: Screening to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=6 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=19 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=29 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Mean Absolute Change From Original Study DFA102 Screening to Week 52 in Extension Study DFA102E in the Epworth Sleepiness Scale (ESS) Total Score - Week 52 Evaluable Population	0.0 units on a scale Standard Deviation 1.67	-1.3 units on a scale Standard Deviation 3.34	-2.0 units on a scale Standard Deviation 4.52	-2.5 units on a scale Standard Deviation 3.17	-2.5 units on a scale Standard Deviation 3.13	-1.3 units on a scale Standard Deviation 3.28	0.2 units on a scale Standard Deviation 4.41	-3.9 units on a scale Standard Deviation 3.18	-1.2 units on a scale Standard Deviation 2.42	-1.1 units on a scale Standard Deviation 4.15

SECONDARY outcome

Timeframe: Baseline to end of treatment follow up

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=20 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=56 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=68 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Total Trough Concentration of Plasma Leptin at Baseline and at Weeks 40, 52, and End of Treatment Follow up - Week 52 Stable Evaluable Population Baseline in DFA102 (Day 1)	—	—	32.50 ng/mL Standard Error 4.990	34.48 ng/mL Standard Error 3.089	29.50 ng/mL Standard Error 2.251	—	—	—	—	—
Total Trough Concentration of Plasma Leptin at Baseline and at Weeks 40, 52, and End of Treatment Follow up - Week 52 Stable Evaluable Population Baseline in DFA102E (Week 28)	—	—	102.02 ng/mL Standard Error 17.466	232.48 ng/mL Standard Error 29.371	420.24 ng/mL Standard Error 48.012	—	—	—	—	—
Total Trough Concentration of Plasma Leptin at Baseline and at Weeks 40, 52, and End of Treatment Follow up - Week 52 Stable Evaluable Population Week 40	—	—	96.23 ng/mL Standard Error 19.418	236.02 ng/mL Standard Error 29.856	416.52 ng/mL Standard Error 58.352	—	—	—	—	—
Total Trough Concentration of Plasma Leptin at Baseline and at Weeks 40, 52, and End of Treatment Follow up - Week 52 Stable Evaluable Population Week 52	—	—	88.47 ng/mL Standard Error 17.576	177.32 ng/mL Standard Error 25.765	259.85 ng/mL Standard Error 40.650	—	—	—	—	—
Total Trough Concentration of Plasma Leptin at Baseline and at Weeks 40, 52, and End of Treatment Follow up - Week 52 Stable Evaluable Population Follow up after end of treatment	—	—	52.90 ng/mL Standard Error 9.584	89.21 ng/mL Standard Error 11.180	89.49 ng/mL Standard Error 11.712	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1) to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=8 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=28 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=22 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=31 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Mean Change in Systolic and Diastolic Blood Pressure From Baseline of DFA102 at Week 52 of DFA102E - Intent to Treat Population Systolic Blood Pressure	-6.4 mm Hg Standard Deviation 6.21	-2.9 mm Hg Standard Deviation 9.75	-1.0 mm Hg Standard Deviation 9.91	1.8 mm Hg Standard Deviation 12.74	-4.6 mm Hg Standard Deviation 14.54	-4.9 mm Hg Standard Deviation 10.88	0.7 mm Hg Standard Deviation 14.57	3.7 mm Hg Standard Deviation 14.35	-7.0 mm Hg Standard Deviation 9.63	-4.8 mm Hg Standard Deviation 10.94
Mean Change in Systolic and Diastolic Blood Pressure From Baseline of DFA102 at Week 52 of DFA102E - Intent to Treat Population Diastolic Blood Pressure	-5.3 mm Hg Standard Deviation 8.94	-5.8 mm Hg Standard Deviation 8.17	-0.6 mm Hg Standard Deviation 5.40	-0.6 mm Hg Standard Deviation 9.17	-2.7 mm Hg Standard Deviation 7.29	-1.5 mm Hg Standard Deviation 9.98	-1.7 mm Hg Standard Deviation 8.56	-0.3 mm Hg Standard Deviation 7.74	-2.5 mm Hg Standard Deviation 9.77	-4.0 mm Hg Standard Deviation 5.99

SECONDARY outcome

Timeframe: Baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=8 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=28 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=22 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=31 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Mean Change in Heart Rate From Baseline of DFA102 at Week 52 of DFA102E - Intent to Treat Population	-0.9 bpm Standard Deviation 11.75	-2.6 bpm Standard Deviation 8.39	-3.1 bpm Standard Deviation 9.22	-1.8 bpm Standard Deviation 9.39	-3.1 bpm Standard Deviation 6.49	-1.4 bpm Standard Deviation 7.73	-1.6 bpm Standard Deviation 5.81	0.9 bpm Standard Deviation 9.25	-4.0 bpm Standard Deviation 7.12	-2.8 bpm Standard Deviation 6.58

SECONDARY outcome

Timeframe: Screening to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=8 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=19 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=28 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=21 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=31 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Mean Change From DFA102 Screening at Week 52 in Study DFA102E for Electrocardiogram Parameters - Intent to Treat Population PR Interval	2.5 msec Standard Deviation 9.50	-2.3 msec Standard Deviation 10.83	1.2 msec Standard Deviation 10.29	1.2 msec Standard Deviation 22.15	3.6 msec Standard Deviation 14.11	0.6 msec Standard Deviation 13.14	15.8 msec Standard Deviation 52.77	6.0 msec Standard Deviation 8.49	1.8 msec Standard Deviation 13.80	0.9 msec Standard Deviation 10.82
Mean Change From DFA102 Screening at Week 52 in Study DFA102E for Electrocardiogram Parameters - Intent to Treat Population QRS	0.0 msec Standard Deviation 9.56	1.7 msec Standard Deviation 5.50	-0.2 msec Standard Deviation 5.19	3.4 msec Standard Deviation 11.05	1.8 msec Standard Deviation 6.81	1.0 msec Standard Deviation 5.76	-2.4 msec Standard Deviation 14.09	1.6 msec Standard Deviation 4.24	0.5 msec Standard Deviation 6.15	-0.9 msec Standard Deviation 4.35
Mean Change From DFA102 Screening at Week 52 in Study DFA102E for Electrocardiogram Parameters - Intent to Treat Population QT Interval	2.5 msec Standard Deviation 23.10	14.4 msec Standard Deviation 31.39	15.3 msec Standard Deviation 28.67	8.1 msec Standard Deviation 32.50	15.6 msec Standard Deviation 22.54	8.2 msec Standard Deviation 26.37	19.4 msec Standard Deviation 18.57	13.3 msec Standard Deviation 25.00	5.5 msec Standard Deviation 20.21	16.7 msec Standard Deviation 16.94
Mean Change From DFA102 Screening at Week 52 in Study DFA102E for Electrocardiogram Parameters - Intent to Treat Population QTcF	6.5 msec Standard Deviation 15.19	3.2 msec Standard Deviation 24.49	1.3 msec Standard Deviation 22.08	0.3 msec Standard Deviation 16.64	1.4 msec Standard Deviation 16.69	-2.2 msec Standard Deviation 18.96	7.1 msec Standard Deviation 11.66	5.1 msec Standard Deviation 24.22	-1.7 msec Standard Deviation 16.34	0.8 msec Standard Deviation 16.23

SECONDARY outcome

Timeframe: Baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=8 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=20 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=27 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=22 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=31 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Number of Hematology or Urinalysis Laboratory Values of Potential Clinical Importance Observed From Baseline of DFA102E to Week 52 - 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	4 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 or Urinalysis Laboratory Values of Potential Clinical Importance Observed From Baseline of DFA102E to Week 52 - Intent to Treat Population Hemoglobin	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	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 or Urinalysis Laboratory Values of Potential Clinical Importance Observed From Baseline of DFA102E to Week 52 - Intent to Treat Population Platelet Count	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	0 number of laboratory values	0 number of laboratory values	0 number of laboratory values	0 number of laboratory values
Number of Hematology or Urinalysis Laboratory Values of Potential Clinical Importance Observed From Baseline of DFA102E to Week 52 - Intent to Treat Population WBC	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	0 number of laboratory values	0 number of laboratory values
Number of Hematology or Urinalysis Laboratory Values of Potential Clinical Importance Observed From Baseline of DFA102E to Week 52 - Intent to Treat Population Urinalysis	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	0 number of laboratory values	0 number of laboratory values

SECONDARY outcome

Timeframe: Baseline to Week 52

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=8 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=20 Participants Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=21 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=20 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=28 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=22 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=12 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=31 Participants Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=30 Participants Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From DFA102E Baseline to Week 52 - Intent to Treat Population Potassium	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	2 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 DFA102E Baseline to Week 52 - Intent to Treat Population alanine aminotransferase (ALT)	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	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
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From DFA102E Baseline to Week 52 - Intent to Treat Population Bicarbonate	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	1 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 DFA102E Baseline to Week 52 - Intent to Treat Population Creatine kinase	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	2 Number of Laboratory values	0 Number of Laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From DFA102E Baseline to Week 52 - Intent to Treat Population Calcium	1 Number of Laboratory values	0 Number of Laboratory values	0 Number of Laboratory values	0 Number of Laboratory values	1 Number of Laboratory values	0 Number of Laboratory values	1 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 DFA102E Baseline to Week 52 - Intent to Treat Population Creatinine	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	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 DFA102E Baseline to Week 52 - Intent to Treat Population Gamma-glutamyltransferase	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	3 Number of Laboratory values	0 Number of Laboratory values	0 Number of Laboratory values	0 Number of Laboratory values	1 Number of Laboratory values
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From DFA102E Baseline to Week 52 - Intent to Treat Population Sodium	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	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
Number of Chemistry Laboratory Values of Potential Clinical Importance Observed From DFA102E Baseline to Week 52 - Intent to Treat Population Uric Acid	0 Number of Laboratory values	1 Number of Laboratory values	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	2 Number of Laboratory values

SECONDARY outcome

Timeframe: Baseline to end of treatment follow up

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

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

Outcome measures

Measure	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	Placebo - Stable n=20 Participants Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	Pramlintide 360 Mcg + Metreleptin 1.25 mg - Stable n=58 Participants Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 2.5 mg - Stable n=71 Participants Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID self administered SC. All participants entered treatment for 52 Weeks, inclusive of DFA102.	Pramlintide 360 Mcg + Metreleptin 5.0 mg - Stable n=12 Participants Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID self administered SC for 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=7 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=8 Participants Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Number of Participants With Treatment Emergent Positive Anti-leptin Antibody Titers at Week 52 and at Follow up by Metreleptin Dose - Intent to Treat Population Week 52	—	—	20 participants	58 participants	71 participants	8 participants	7 participants	7 participants	—	—
Number of Participants With Treatment Emergent Positive Anti-leptin Antibody Titers at Week 52 and at Follow up by Metreleptin Dose - Intent to Treat Population Follow up after end of treatment	—	—	17 participants	57 participants	68 participants	8 participants	7 participants	7 participants	—	—

Adverse Events

Placebo - Stable

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

360 mcg Pramlintide + 1.25mg Metreleptin - Stable

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

360 mcg Pramlintide + 2.5 Metreleptin - Stable

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

360 mcg Pramlintide + 5.0 Metreleptin - Stable

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo - Stable n=31 participants at risk Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E.	360 mcg Pramlintide + 1.25mg Metreleptin - Stable n=35 participants at risk Participants who received 360 mcg pramlintide plus 1.25 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 2.5 Metreleptin - Stable n=36 participants at risk Participants who received 360 mcg pramlintide plus 2.5 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 5.0 Metreleptin - Stable n=28 participants at risk Participants who received 360 mcg pramlintide plus 5.0 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=13 participants at risk Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=14 participants at risk Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=13 participants at risk Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=29 participants at risk Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=37 participants at risk Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=37 participants at risk Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Infections and infestations Staphylococcal infection	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Investigations Cardiac enzymes increased	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.

Other adverse events

Measure	Placebo - Stable n=31 participants at risk Placebo matched to pramlintide BID plus placebo matched to metreleptin BID self administered subcutaneously (SC) for 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E.	360 mcg Pramlintide + 1.25mg Metreleptin - Stable n=35 participants at risk Participants who received 360 mcg pramlintide plus 1.25 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 2.5 Metreleptin - Stable n=36 participants at risk Participants who received 360 mcg pramlintide plus 2.5 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 5.0 Metreleptin - Stable n=28 participants at risk Participants who received 360 mcg pramlintide plus 5.0 mg metreleptin self administered SC for up to 52 Weeks, inclusive of DFA102. Stable: same treatment regimen in both DFA102 and DFA102E	360 mcg Pramlintide + 1.25 mg Metreleptin - Prior Mono+1.25 n=13 participants at risk Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 1.25 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Mono+2.5 n=14 participants at risk Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 2.5 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Mono+5.0 n=13 participants at risk Participants who received 360 mcg pramlintide plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Metre Mono n=29 participants at risk Participants who received 5.0 mg metreleptin plus placebo (monotherapy) self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg Pramlintide plus 5.0 metreleptin in this group of the extension study, for up to 52 Weeks, inclusive of DFA102.A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who had not received 360 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 2.5 mg Metreleptin - Prior Lower Pram n=37 participants at risk Participants who received 180 mcg pramlintide plus 2.5 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 2.5 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.	360 mcg Pramlintide + 5.0 mg Metreleptin - Prior Lower Pram n=37 participants at risk Participants who received 180 mcg pramlintide plus 5.0 mg metreleptin self administered SC in the original study DFA102, and who consented to enter the extension study DFA102E, were treated with 360 mcg pramlintide plus 5.0 mg metreleptin in the extension study for up to 52 Weeks, inclusive of DFA102. A blinded pramlintide dose escalation/titration in the first week of treatment was performed for participants who received 180 mcg pramlintide in DFA102, to minimize nausea and/or vomiting.
Immune system disorders hypersensitivity	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders nausea	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.6% 3/35 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	17.9% 5/28 • Number of events 5 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	15.4% 2/13 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	37.9% 11/29 • Number of events 13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	18.9% 7/37 • Number of events 9 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	21.6% 8/37 • Number of events 12 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations Upper respiratory tract infection	9.7% 3/31 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.6% 3/35 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	13.9% 5/36 • Number of events 8 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	25.0% 7/28 • Number of events 7 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	23.1% 3/13 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.8% 4/37 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	58.3% 7/12 • Number of events 8 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations sinusitis	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	19.4% 7/36 • Number of events 7 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 2/28 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	14.3% 2/14 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	16.2% 6/37 • Number of events 6 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.8% 4/37 • Number of events 5 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations nasopharyngitis	12.9% 4/31 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.7% 2/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	14.3% 2/14 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	17.2% 5/29 • Number of events 6 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.1% 3/37 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site hemorrhage	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	15.4% 2/13 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	6.9% 2/29 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.1% 3/37 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.8% 4/37 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site bruising	6.5% 2/31 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 2/28 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	14.3% 2/14 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.3% 3/29 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders diarrhea	3.2% 1/31 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	15.4% 2/13 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Nervous system disorders headache	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 2/28 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	15.4% 2/13 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	6.9% 2/29 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.1% 3/37 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site pruritus	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	15.4% 2/13 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	21.4% 3/14 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.3% 3/29 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site nodule	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.1% 3/37 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations gastroenteritis	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	15.4% 2/13 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.3% 3/29 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site erythema	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	30.8% 4/13 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations urinary tract infection	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.3% 3/36 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations bronchitis	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	14.3% 2/14 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations influenza	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.7% 3/28 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Musculoskeletal and connective tissue disorders back pain	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site urticaria	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	15.4% 2/13 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	21.4% 3/14 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders vomiting	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	10.8% 4/37 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Psychiatric disorders anxiety	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations gastroenteritis viral	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	6.9% 2/29 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Musculoskeletal and connective tissue disorders muscle strain	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.7% 2/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Respiratory, thoracic and mediastinal disorders sinus congestion	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders abdominal pain	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders abdominal pain upper	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 2/28 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Musculoskeletal and connective tissue disorders arthralgia	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	6.9% 2/29 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders constipation	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Nervous system disorders dizziness	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	8.1% 3/37 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations ear infection	6.5% 2/31 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site induration	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Injury, poisoning and procedural complications back injury	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site pain	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	6.9% 2/29 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Respiratory, thoracic and mediastinal disorders nasal congestion	6.5% 2/31 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Respiratory, thoracic and mediastinal disorders pharyngolaryngeal pain	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders abdominal distension	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders acne	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations bacteriuria	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Vascular disorders flushing	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Renal and urinary disorders hematuria	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Metabolism and nutrition disorders increased appetite	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders injection site irritation	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Musculoskeletal and connective tissue disorders joint swelling	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Musculoskeletal and connective tissue disorders muscle spasms	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.7% 2/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders edema peripheral	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 4 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders pyrexia	3.2% 1/31 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.6% 1/28 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders toothache	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 3 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders alopecia	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.6% 2/36 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Gastrointestinal disorders aphthous stomatitis	6.5% 2/31 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
General disorders chest pain	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.4% 2/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations enteritis	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.8% 1/36 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Nervous system disorders hypoesthesia	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Investigations eosinophil count increased	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Psychiatric disorders insomnia	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Musculoskeletal and connective tissue disorders intervertebral disc protusion	6.5% 2/31 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Nervous system disorders nerve compression	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.9% 1/35 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations pharyngitis streptococcal	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Nervous system disorders presyncope	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Nervous system disorders sinus headache	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	2.7% 1/37 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Injury, poisoning and procedural complications thermal burn	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	3.4% 1/29 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations tooth abscess	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	5.7% 2/35 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Investigations urine analysis abnormal	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 2/28 • Number of events 2 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Investigations blood chloride decreased	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Investigations blood sodium increased	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations cellulitis	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Eye disorders conjunctival edema	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders dermal cyst	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Investigations electrocardiogram QT prolonged	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders erythema	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Eye disorders eye pruritus	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Metabolism and nutrition disorders hypercalcemia	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) malignant melanoma	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Renal and urinary disorders nephrolithiasis	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders palmar erythema	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Infections and infestations pharyngitis	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders pruritus	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders psoriasis	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Renal and urinary disorders pyuria	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Nervous system disorders somnolence	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/14 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.7% 1/13 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.
Skin and subcutaneous tissue disorders urticaria	0.00% 0/31 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/35 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/36 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/28 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	7.1% 1/14 • Number of events 1 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/13 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/29 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.	0.00% 0/37 • 52 Weeks, intent to treat population. Enrolled and treated with at least one injection during the extension study DFA102E.

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