Trial Outcomes & Findings for A Study Using Functional Magnetic Resonance Imaging (fMRI) to Assess the Effects of Naltrexone SR/ Bupropion SR Therapy in Overweight or Obese Subjects (NCT NCT00711477)

NCT ID: NCT00711477

Last Updated: 2015-01-06

Results Overview

Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Baseline, 4 weeks
• Results posted on: 2015-01-06

Participant Flow

Participant milestones

Measure	NB32 Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	Placebo Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Overall Study STARTED	23	23
Overall Study COMPLETED	20	20
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Measure	NB32 Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	Placebo Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Overall Study Adverse Event	3	1
Overall Study Lost to Follow-up	0	1
Overall Study Noncompliance	0	1

Baseline Characteristics

A Study Using Functional Magnetic Resonance Imaging (fMRI) to Assess the Effects of Naltrexone SR/ Bupropion SR Therapy in Overweight or Obese Subjects

Baseline characteristics by cohort

Measure	NB32 n=23 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	Placebo n=23 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	Total n=46 Participants Total of all reporting groups
Age, Continuous	30.96 years STANDARD_DEVIATION 7.68 • n=5 Participants	30.39 years STANDARD_DEVIATION 8.46 • n=7 Participants	30.67 years STANDARD_DEVIATION 7.99 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	12 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants
Race/Ethnicity, Customized White	3 participants n=5 Participants	8 participants n=7 Participants	11 participants n=5 Participants
Race/Ethnicity, Customized Other	7 participants n=5 Participants	5 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Weight	87.70 kg STANDARD_DEVIATION 15.83 • n=5 Participants	89.59 kg STANDARD_DEVIATION 13.34 • n=7 Participants	88.64 kg STANDARD_DEVIATION 14.50 • n=5 Participants
BMI	32.96 kg/m^2 STANDARD_DEVIATION 4.30 • n=5 Participants	31.80 kg/m^2 STANDARD_DEVIATION 3.10 • n=7 Participants	32.38 kg/m^2 STANDARD_DEVIATION 3.75 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Superior Frontal	-0.35 percent activation Interval -0.48 to -0.22	0.34 percent activation Interval 0.21 to 0.47

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Anterior Cingulate	-0.42 percent activation Interval -0.52 to -0.32	0.16 percent activation Interval 0.04 to 0.28

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Hippocampal Region 1	-0.16 percent activation Interval -0.32 to 0.0	0.60 percent activation Interval 0.4 to 0.8

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Hippocampal Region 2	-0.79 percent activation Interval -0.99 to -0.59	0.21 percent activation Interval 0.01 to 0.41

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Superior Parietal	-0.56 percent activation Interval -0.87 to -0.25	0.74 percent activation Interval 0.34 to 1.04

PRIMARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

Assessment of differences in brain activation in response to food cues before and after 4 weeks of treatment in subjects receiving NB or placebo.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Response to Food Related Cues Using Functional Magnetic Resonance Imaging - Posterior Insula	-0.16 percent activation Interval -0.25 to -0.07	0.30 percent activation Interval 0.2 to 0.4

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Percent Change in Body Weight	-0.99 percentage of body weight Standard Error 0.44	-0.43 percentage of body weight Standard Error 0.44

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale, where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The Restrained Eating subscale consisted of 10 items and the scores ranged from 10 (worse outcome) to 50 (better outcome).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Dutch Eating Behavior Questionnaire - Change in Restrained Eating Subscale Score	1.47 units on a scale Standard Error 0.86	1.87 units on a scale Standard Error 0.86

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale, where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The Emotional Eating A subscale (clearly labeled emotions) consisted of 9 items and the scores ranged from 9 (better outcome) to 45 (worse outcome).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Dutch Eating Behavior Questionnaire - Change in Emotional Eating A Subscale Score	-1.16 units on a scale Standard Error 0.77	0.48 units on a scale Standard Error 0.77

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale, where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The Emotional Eating B subscale (diffuse emotions) consisted of 4 items and the scores ranged from 4 (better outcome) to 20 (worse outcome).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Dutch Eating Behavior Questionnaire - Change in Emotional Eating B Subscale Score	-0.90 units on a scale Standard Error 0.55	0.45 units on a scale Standard Error 0.55

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

The Dutch Eating Behavior Questionnaire is a 33-item self-report measure designed to assess the type of eating behavior and is organized into 3 subscales (emotional eating, externally-induced eating, and restrained eating). Subjects rated the frequency of their eating behaviors using a 5-point scale where 1=never, 2=seldom, 3=sometimes, 4=often, and 5=very often. The External Eating subscale consisted of 10 items and the scores ranged from 10 (better outcome) to 50 (worse outcome).

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Dutch Eating Behavior Questionnaire - Change in External Eating Subscale Score	-2.64 units on a scale Standard Error 1.03	-0.16 units on a scale Standard Error 1.03

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: ITT (Intent-to-Treat): Included all subjects who were randomized, had a baseline measurement, and had at least one post-baseline fMRI measurement during the defined treatment phase.

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

Outcome measures

Measure	Placebo n=20 Participants Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	NB32 n=20 Participants Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire	-13.55 units on a scale Standard Error 4.67	-4.14 units on a scale Standard Error 4.41

Adverse Events

NB32

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	NB32 n=23 participants at risk Naltrexone SR 32 mg/day plus bupropion SR 360 mg/day fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain	Placebo n=22 participants at risk Placebo tablets fMRI scan: fMRI to assess the effects of the drug/placebo on areas of the brain
Gastrointestinal disorders Nausea	21.7% 5/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Gastrointestinal disorders Vomiting	21.7% 5/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Gastrointestinal disorders Constipation	4.3% 1/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Nervous system disorders Headache	13.0% 3/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	4.5% 1/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Nervous system disorders Dizziness	4.3% 1/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Nervous system disorders Migraine	0.00% 0/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	4.5% 1/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Psychiatric disorders Anxiety	8.7% 2/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Psychiatric disorders Depression	4.3% 1/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Cardiac disorders Palpitations	4.3% 1/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
General disorders Feeling abnormal	4.3% 1/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)
Investigations Blood thyroid stimulating hormone increased	4.3% 1/23 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)	0.00% 0/22 • baseline to week 4 The safety analysis set (i.e., all randomized subjects with at least one tablet of study treatment administered and with at least one investigator contact/assessment at any time after the start of study treatment, regardless of whether they completed the study) included 45 subjects (placebo, N=22; NB32, N=23)

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 Upon completion or termination of the CRADA, a final report including a list of inventions must be prepared and delivered to the Dept. of Energy Office of Scientific and Technical Information. Each party must provide the other with up to 45 days to review any proposed publication associated with the CRADA results. Approval of the planned publication will not be unreasonably withheld.
• Publication restrictions are in place

Restriction type: OTHER