Trial Outcomes & Findings for A Safety and Efficacy Study Comparing Naltrexone SR/Bupropion SR and Placebo in Obese Subjects With Type 2 Diabetes (NCT NCT00474630)

NCT ID: NCT00474630

Last Updated: 2014-11-21

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 505 participants
• Primary outcome timeframe: Baseline, 56 weeks
• Results posted on: 2014-11-21

Participant Flow

Participant milestones

Measure	NB32 Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo Placebo
Overall Study STARTED	335	170
Overall Study COMPLETED	175	100
Overall Study NOT COMPLETED	160	70

Reasons for withdrawal

Measure	NB32 Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo Placebo
Overall Study Adverse Event	98	26
Overall Study Lost to Follow-up	22	15
Overall Study Withdrawal by Subject	21	15
Overall Study Protocol Violation	3	4
Overall Study Lack of Efficacy	5	6
Overall Study Drug noncompliance, other	11	4

Baseline Characteristics

A Safety and Efficacy Study Comparing Naltrexone SR/Bupropion SR and Placebo in Obese Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Measure	NB32 n=335 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=170 Participants Placebo	Total n=505 Participants Total of all reporting groups
Age, Continuous	54.02 years STANDARD_DEVIATION 9.05 • n=93 Participants	53.46 years STANDARD_DEVIATION 9.83 • n=4 Participants	53.83 years STANDARD_DEVIATION 9.32 • n=27 Participants
Sex: Female, Male Female	195 Participants n=93 Participants	90 Participants n=4 Participants	285 Participants n=27 Participants
Sex: Female, Male Male	140 Participants n=93 Participants	80 Participants n=4 Participants	220 Participants n=27 Participants
Race/Ethnicity, Customized White	261 participants n=93 Participants	140 participants n=4 Participants	401 participants n=27 Participants
Race/Ethnicity, Customized Black or African American	63 participants n=93 Participants	18 participants n=4 Participants	81 participants n=27 Participants
Race/Ethnicity, Customized Asian	7 participants n=93 Participants	5 participants n=4 Participants	12 participants n=27 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=93 Participants	0 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 participants n=93 Participants	2 participants n=4 Participants	4 participants n=27 Participants
Race/Ethnicity, Customized Other	1 participants n=93 Participants	5 participants n=4 Participants	6 participants n=27 Participants
Weight	104.22 kg STANDARD_DEVIATION 18.93 • n=93 Participants	105.08 kg STANDARD_DEVIATION 16.99 • n=4 Participants	104.51 kg STANDARD_DEVIATION 18.28 • n=27 Participants
BMI	36.40 kg/m^2 STANDARD_DEVIATION 4.75 • n=93 Participants	36.40 kg/m^2 STANDARD_DEVIATION 4.50 • n=4 Participants	36.40 kg/m^2 STANDARD_DEVIATION 4.66 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT (Full Analysis Set): Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Co-primary: Body Weight- Mean Percent Change	-5.03 percentage of body weight Standard Error 0.34	-1.75 percentage of body weight Standard Error 0.43

PRIMARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease	44.53 percentage of participants Interval 38.54 to 50.51	18.87 percentage of participants Interval 12.79 to 24.95

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=222 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=137 Participants Placebo
Change in HbA1c Levels	-0.63 percent Standard Error 0.07	-0.14 percent Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=222 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=135 Participants Placebo
Change in Fasting Triglycerides Levels, Using Log-transformed Data	-11.20 percent change Interval -15.59 to -6.58	-0.80 percent change Interval -6.95 to 5.76

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=222 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=135 Participants Placebo
Change in Fasting HDL Cholesterol Levels	3.03 mg/dL Standard Error 0.49	-0.29 mg/dL Standard Error 0.61

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=264 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=158 Participants Placebo
Change in Fasting Blood Glucose Levels	-11.87 mg/dL Standard Error 2.70	-4.02 mg/dL Standard Error 3.39

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=208 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=124 Participants Placebo
Change in Waist Circumference	-4.97 cm Standard Error 0.47	-2.89 cm Standard Error 0.61

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Body Weight- Proportion of Subjects With ≥10% Decrease	18.49 percentage of participants Interval 13.82 to 23.16	5.66 percentage of participants Interval 2.07 to 9.25

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=222 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=137 Participants Placebo
HbA1c- Proportion of Subjects With HbA1c <7% at Endpoint	44.14 percentage of participants Interval 37.61 to 50.68	26.28 percentage of participants Interval 18.91 to 33.65

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Percent of Subjects Requiring Rescue Medications for Diabetes	22.26 percentage of participants Interval 19.05 to 29.91	35.22 percentage of participants Interval 29.81 to 45.36

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Percent of Subjects With Dose Reduction in Oral Antidiabetes Medications	1.89 percentage of participants Interval 0.28 to 3.87	1.26 percentage of participants Interval 0.0 to 3.19

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Percent of Subjects With Dose Increase in Oral Antidiabetes Medications	3.02 percentage of participants Interval 1.06 to 5.58	1.26 percentage of participants Interval 0.0 to 3.19

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

HOMA-IR= Homeostasis Model Assessment-Insulin Resistance

Outcome measures

Measure	NB32 n=199 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=112 Participants Placebo
Change in HOMA-IR Levels, Using Log-transformed Data	-20.56 percent change Interval -27.77 to -12.62	-14.67 percent change Interval -24.69 to -3.31

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=201 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=113 Participants Placebo
Change in Fasting Insulin Levels, Using Log-transformed Data	-13.48 percent change Interval -19.7 to -6.78	-10.35 percent change Interval -18.75 to -1.09

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=222 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=137 Participants Placebo
HbA1c- Proportion of Subjects With HbA1c <6.5% at Endpoint	20.72 percentage of participants Interval 15.39 to 26.05	10.22 percentage of participants Interval 5.15 to 15.29

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

IWQOL-Lite= Impact of Weight on Quality of Life-Lite Questionnaire Total score is based on a scale from 0 to 100, with 0 representing the poorest and 100 the best quality of life and where a score of 71-79 indicates moderate impairment

Outcome measures

Measure	NB32 n=241 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=153 Participants Placebo
Change in IWQOL-Lite Total Scores	9.27 units on a scale Standard Error 0.70	7.90 units on a scale Standard Error 0.86

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=202 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=119 Participants Placebo
Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data	-20.91 percent change Interval -29.29 to -11.54	-13.29 percent change Interval -24.94 to 0.17

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed. Odds ratio not calculated as there were no subjects in the NB32 group that discontinued due to poor glycemic control.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Percent of Subjects Discontinuing Due to Poor Glycemic Control	0 percentage of participants There were no subjects in the NB32 group that discontinued due to poor glycemic control.	1.89 percentage of participants Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult

Outcome measures

Measure	NB32 n=225 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=146 Participants Placebo
Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire	-11.89 units on a scale Standard Error 1.39	-6.91 units on a scale Standard Error 1.69

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=220 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=134 Participants Placebo
Change in Fasting LDL Cholesterol Levels	-1.44 mg/dL Standard Error 1.94	-0.01 mg/dL Standard Error 2.44

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Change in Systolic Blood Pressure	0.03 mm Hg Standard Error 0.70	-1.12 mm Hg Standard Error 0.88

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Change in Diastolic Blood Pressure	-1.06 mm Hg Standard Error 0.47	-1.47 mm Hg Standard Error 0.59

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

IDS-SR= Inventory of Depressive Symptoms-Subject Rated IDS-SR total score is based on 30 items. The total score can range from 0-84, with 0 being no depressive symptoms and 84 being very severe depressive symptoms. A total score ≤ 13 indicates no depression.

Outcome measures

Measure	NB32 n=265 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=159 Participants Placebo
Change in IDS-SR Total Scores	0.01 units on a scale Standard Error 0.33	-1.60 units on a scale Standard Error 0.42

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The sweets subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).

Outcome measures

Measure	NB32 n=241 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=155 Participants Placebo
Change in Food Craving Inventory Sweets Subscale Score	-1.97 units on a scale Standard Error 0.28	-2.40 units on a scale Standard Error 0.34

SECONDARY outcome

Timeframe: Baseline, 56 weeks

Population: Modified ITT: Included all subjects who were randomized, had a baseline weight measurement, and had at least one post-baseline weight measurement while on study drug. Missing data were imputed with the LOCF method.

The Food Craving Inventory is a 33-item self-report measure designed to assess specific food cravings and is organized into 4 subscales (high fats, sweets, carbohydrates/starches, and fast-food fats). A craving was defined as an intense desire to consume a particular food (or food type) that was difficult to resist over the past month. Subjects rated their frequency of cravings for each of the 33 items using a 5-point scale, where 1=never, 2=rarely, 3=sometimes, 4=often, and 5=always. The carbohydrates subscale consisted of 8 items and the score ranges from 8 (better outcome) to 40 (worse outcome).

Outcome measures

Measure	NB32 n=241 Participants Naltrexone SR 32 mg/Bupropion SR 360 mg/day	Placebo n=155 Participants Placebo
Change in Food Craving Inventory Carbohydrates Subscale Score	-1.48 units on a scale Standard Error 0.26	-1.52 units on a scale Standard Error 0.32

Adverse Events

NB32

Serious events: 13 serious events

Other events: 275 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 109 other events

Deaths: 0 deaths

Serious adverse events

Measure	NB32 n=333 participants at risk Naltrexone SR 32 mg/Bupropion SR 360 mg daily	Placebo n=169 participants at risk Placebo
Cardiac disorders Angina pectoris	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	1.2% 2/169 • Number of events 2 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Cardiac disorders Arrhythmia	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Cardiac disorders Atrial fibrillation	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	1.2% 2/169 • Number of events 2 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Cardiac disorders Coronary artery occlusion	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Cardiac disorders Myocardial infarction	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Ear and labyrinth disorders Vertigo	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Gastrointestinal disorders Inguinal hernia, obstructive	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Hepatobiliary disorders Cholecystitis	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Immune system disorders Anaphylactic reaction	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Cellulitis	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Diverticulitis	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Gastroenteritis	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Lobar pneumonia	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Staphylococcal infection	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Investigations Troponin increased	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Nervous system disorders Cerebrovascular accident	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Nervous system disorders Grand mal convulsion	0.30% 1/333 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Nervous system disorders Syncope vasovagal	0.60% 2/333 • Number of events 2 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.00% 0/169 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Renal and urinary disorders Calculus ureteric	0.00% 0/333 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	0.59% 1/169 • Number of events 1 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.

Other adverse events

Measure	NB32 n=333 participants at risk Naltrexone SR 32 mg/Bupropion SR 360 mg daily	Placebo n=169 participants at risk Placebo
Gastrointestinal disorders Abdominal pain upper	5.1% 17/333 • Number of events 18 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	1.8% 3/169 • Number of events 4 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Gastrointestinal disorders Constipation	17.7% 59/333 • Number of events 69 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	7.1% 12/169 • Number of events 13 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Gastrointestinal disorders Diarrhoea	15.6% 52/333 • Number of events 60 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	9.5% 16/169 • Number of events 21 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Gastrointestinal disorders Dry mouth	6.3% 21/333 • Number of events 22 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	3.0% 5/169 • Number of events 5 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Gastrointestinal disorders Nausea	42.3% 141/333 • Number of events 196 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	7.1% 12/169 • Number of events 13 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Gastrointestinal disorders Vomiting	18.3% 61/333 • Number of events 80 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	3.6% 6/169 • Number of events 7 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
General disorders Oedema peripheral	0.60% 2/333 • Number of events 3 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	5.9% 10/169 • Number of events 15 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Influenza	2.7% 9/333 • Number of events 9 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	5.3% 9/169 • Number of events 9 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Nasopharyngitis	8.4% 28/333 • Number of events 32 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	13.6% 23/169 • Number of events 25 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Sinusitis	4.8% 16/333 • Number of events 19 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	8.3% 14/169 • Number of events 19 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Infections and infestations Upper respiratory tract infection	7.8% 26/333 • Number of events 30 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	9.5% 16/169 • Number of events 22 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Metabolism and nutrition disorders Diabetes mellitus	4.5% 15/333 • Number of events 16 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	8.9% 15/169 • Number of events 15 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Metabolism and nutrition disorders Hypoglycaemia	7.5% 25/333 • Number of events 65 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	7.1% 12/169 • Number of events 18 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Musculoskeletal and connective tissue disorders Back pain	2.7% 9/333 • Number of events 11 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	5.3% 9/169 • Number of events 9 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Musculoskeletal and connective tissue disorders Pain in extremity	3.9% 13/333 • Number of events 15 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	7.1% 12/169 • Number of events 13 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Nervous system disorders Dizziness	11.7% 39/333 • Number of events 52 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	5.3% 9/169 • Number of events 11 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Nervous system disorders Headache	13.8% 46/333 • Number of events 53 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	8.9% 15/169 • Number of events 18 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Nervous system disorders Tremor	6.6% 22/333 • Number of events 26 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	2.4% 4/169 • Number of events 4 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Psychiatric disorders Anxiety	5.4% 18/333 • Number of events 20 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	1.2% 2/169 • Number of events 2 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Psychiatric disorders Insomnia	11.1% 37/333 • Number of events 42 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	5.3% 9/169 • Number of events 10 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.
Vascular disorders Hypertension	9.9% 33/333 • Number of events 33 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.	4.1% 7/169 • Number of events 8 • Baseline, 56 weeks The safety analysis set includes all randomized subjects who took study drug and were assessed by investigator after their first dose, whether or not they discontinue the study. Treatment-emergent adverse events were defined as events that started or worsened in the double-blind treatment phase after the first dose and before 7 days post last dose.

Additional Information

Senior Vice President, Head of Global Development

Orexigen Therapeutics, Inc.

Phone: (858) 875-8600

Email: MedInfo@Orexigen.com

Results disclosure agreements

• Principal investigator is a sponsor employee If not already published by Sponsor as part of a multi-center publication, 18 months after conclusion of the study at all study centers, PI may publish the results for PI's study center individually. Prior to such publication, PI must provide Sponsor with at least 60 days to review and comment on the proposed publication. The review period may be extended by an additional 30 days upon request. Sponsor may delay publication for up to an additional 6 month period to file for patent protection.
• Publication restrictions are in place

Restriction type: OTHER