Obesity, Overweight
Conditions
Keywords
Obesity
Brief summary
The purpose of this study is to determine whether the combination of naltrexone SR and bupropion SR is safe and effective in the treatment of obesity.
Detailed description
Two Phase II clinical trials demonstrated that a combination of bupropion SR and naltrexone is associated with greater weight loss than naltrexone alone, bupropion SR alone or placebo in subjects with uncomplicated obesity. The current study investigated the safety and efficacy of the combination of naltrexone SR and bupropion SR compared to placebo in obese subjects with uncomplicated obesity and in those with overweight/obesity and hypertension and/or dyslipidemia.
Interventions
DRUGPlacebo
BEHAVIORALAncillary therapy
Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling
Sponsors
Orexigen Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Female or male subjects aged 18 to 65 years (inclusive) * Body mass index (weight \[kg\]/height \[m²\]) ≥30 and ≤45 kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45 kg/m² for subjects with obesity with controlled hypertension and/or dyslipidemia * Normotensive (systolic ≤140 mm Hg and diastolic ≤90 mm Hg). Anti-hypertensive medications were allowed with the exception of alpha-adrenergic blockers and clonidine. Medical regimen was to be stable for at least 6 weeks prior to randomization. * Medications for the treatment of dyslipidemia were allowed as long as the medical regimen had been stable for at least 6 weeks prior to randomization. * Free of opioid medication for 7 days prior to randomization * No clinically significant abnormality of serum albumin, blood urea nitrogen (BUN), creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 times upper limit of normal (ULN) * No clinically significant abnormality of hematocrit, white blood cell (WBC) count, WBC differential, or platelets * Fasting glucose \<126 mg/dL and not receiving hypoglycemic agents and fasting triglycerides level \<400 mg/dL * No clinically significant abnormality on urinalysis * Thyroid stimulating hormone (TSH) within normal limits or normal triiodothyronine (T3), if TSH was below normal limits * Female subjects of childbearing potential had a negative serum pregnancy test * Negative urine drug screen (UDS) * An IDS-SR score \<2 on individual items: 5 (sadness), 6 (irritability), 7 (anxiety/tension), and 18 (suicidality) and an IDS-SR total score \<30 * Female subjects of childbearing potential were non-lactating and agreed to continue to use effective contraception throughout the study and 30 days after discontinuation of study drug * Able to comply with all required study procedures and schedule * Able to speak and read English * Provided written informed consent
Exclusion criteria
* Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome) * Serious medical condition (including but not limited to renal or hepatic insufficiency; Class III or IV congestive heart failure, history of angina pectoris, myocardial infarction, claudication, or acute limb ischemia within the previous 6 months; lifetime history of stroke) * History of malignancy within the previous 5 years, with exception of non-melanoma skin cancer or surgically cured cervical cancer * Lifetime history of serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, or anorexia nervosa * Current serious psychiatric illness including severe personality disorder (e.g., borderline or antisocial), current severe major depressive disorder, recent (previous 6 months) suicide attempt, current active suicidal ideation or recent hospitalization due to psychiatric illness * Response to the bipolar disorder questions that indicated the presence of bipolar disorder * Required medications for the treatment of a psychiatric disorder (with the exception of short-term insomnia) within the previous 6 months prior to randomization * History of drug or alcohol abuse or dependence (with the exception of nicotine dependence) within 1 year prior to study initiation * Type I or Type II diabetes mellitus * Screening ECG with a corrected QT (QTc) interval (using Bazett's formula \>450 millisecond (msec) \[males\] and \>470 msec \[females\]) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities * Received excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer or anticonvulsant agents or agents for the treatment of attention deficit disorder) with the exception of low-dose benzodiazepine or hypnotic agents for the treatment of insomnia (up to 2 mg lorazepam/day or equivalent dose of a benzodiazepine or hypnotic agent); any anorectic or weight loss agents; any over the-counter dietary supplements or herbs with psychoactive, appetite or weight effects; alpha-adrenergic blockers; dopamine agonists; clonidine; coumadin; theophylline; cimetidine; oral corticosteroids; cholestyramine; cholestypol; Depo-Provera®; smoking cessation agents; use of opioid or opioid-like analgesics, including analgesics and antitussives * History of surgical or device (e.g., gastric banding) intervention for obesity * History of seizures of any etiology, or of predisposition to seizures (e.g., history of cerebrovascular accident, head trauma with ≥5 minutes loss of consciousness, concussion symptoms lasting ≥15 minutes, brain surgery, skull fracture, subdural hematoma, or febrile seizures) * History of treatment with bupropion or naltrexone within the preceding 12 months * History of hypersensitivity or intolerance to bupropion or naltrexone * Initiation or discontinuation of tobacco products including inhaled tobacco (e.g., cigarettes, cigars, pipes, etc), chewing tobacco or snuff within 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (e.g., nicotine gum, patch, etc) during study participation was not allowed * Used drugs, herbs, or dietary supplements believed to significantly affect body weight or participated in a weight loss management program within one month prior to randomization * Loss or gained \>4.0 kilograms within the previous 3 months prior to randomization * Females who were pregnant or breast-feeding or planning to become pregnant during the study period or within 30 days of discontinuing study drug * Planned surgical procedure that could impact the conduct of the study * Received any investigational drug or used an experimental device or procedure within the previous 30 days * Participated in any previous clinical trial conducted by Orexigen * Had any condition that in the opinion of the investigator made the subject unsuitable for inclusion into the study * Investigators, study personnel, sponsor representatives and their immediate families
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Co-primary: Body Weight- Mean Percent Change From Baseline to Week 28 | Baseline, 28 weeks |
| Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 28 | Baseline, 28 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Insulin Levels, Using Log-transformed Data | Baseline, 28 weeks | — |
| Change in Fasting Blood Glucose Levels | Baseline, 28 weeks | — |
| Change in HOMA-IR Levels, Using Log-transformed Data | Baseline, 28 weeks | HOMA-IR= Homeostasis Model Assessment-Insulin Resistance |
| Body Weight- Mean Percent Change From Baseline to Week 56 | Baseline, 56 weeks | Beginning at Week 28 through Week 44, NB32-treated subjects who failed to achieve or maintain at least 5% body weight loss from baseline were re-randomized (1:1 ratio) to continue NB32 or begin treatment with a higher dose of naltrexone SR - naltrexone SR 48 mg/bupropion SR 360 mg (referred to as NB48) (daily dose of bupropion SR was 360 mg for NB32 and NB48).The analysis of NB32 vs. placebo at Week 56 was completed using a weighted analysis. This analysis was referred to as the weighted LOCF analysis. Subjects treated with NB32 who were re-randomized to NB48 were not included. Subjects re-randomized to NB32 were double-weighted and subjects who were not re-randomized were single-weighted. Subjects in the placebo group were single-weighted. The double weighting analysis restored the influence of poor performers at Weeks 28 to 44 in the NB32 group without including any data from the higher dose group (NB48). |
| Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 56 | Baseline, 56 weeks | Beginning at Week 28 through Week 44, NB32-treated subjects who failed to achieve or maintain at least 5% body weight loss from baseline were re-randomized (1:1 ratio) to continue NB32 or begin treatment with a higher dose of naltrexone SR - naltrexone SR 48 mg/bupropion SR 360 mg (referred to as NB48) (daily dose of bupropion SR was 360 mg for NB32 and NB48).The analysis of NB32 vs. placebo at Week 56 was completed using a weighted analysis. This analysis was referred to as the weighted LOCF analysis. Subjects treated with NB32 who were re-randomized to NB48 were not included. Subjects re-randomized to NB32 were double-weighted and subjects who were not re-randomized were single-weighted. Subjects in the placebo group were single-weighted. The double weighting analysis restored the influence of poor performers at Weeks 28 to 44 in the NB32 group without including any data from the higher dose group (NB48). |
| Body Weight- Proportion of Subjects With ≥10% Decrease From Baseline to Week 28 | Baseline, 28 weeks | — |
| Change in Waist Circumference | Baseline, 28 weeks | — |
| Change in Fasting HDL Cholesterol Levels | Baseline, 28 weeks | — |
| Change in IWQOL-Lite Total Scores | Baseline, 28 weeks | 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 |
| Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire | Baseline, 28 weeks | Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult |
| Change in Fasting LDL Cholesterol Levels | Baseline, 28 weeks | — |
| Change in Systolic Blood Pressure | Baseline, 28 weeks | — |
| Change in Diastolic Blood Pressure | Baseline, 28 weeks | — |
| Change in IDS-SR Total Score | Baseline, 28 weeks | 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. |
| Change in Food Craving Inventory Sweets Subscale Score | Baseline, 28 weeks | 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). |
| Change in Food Craving Inventory Carbohydrates Subscale Score | Baseline, 28 weeks | 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). |
| Change in Fasting Triglycerides Levels, Using Log-transformed Data | Baseline, 28 weeks | — |
| Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data | Baseline, 28 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NB32 Naltrexone SR 32 mg/bupropion SR 360 mg/day | 1,001 |
| Placebo Placebo | 495 |
| Total | 1,496 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 241 | 68 |
| Overall Study | Drug noncompliance,moved,other | 25 | 15 |
| Overall Study | Lack of Efficacy | 19 | 33 |
| Overall Study | Lost to Follow-up | 77 | 48 |
| Overall Study | Pregnancy | 6 | 0 |
| Overall Study | Protocol Violation | 20 | 8 |
| Overall Study | Withdrawal by Subject | 75 | 56 |
Baseline characteristics
| Characteristic | NB32 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 44.27 years STANDARD_DEVIATION 11.16 | 44.41 years STANDARD_DEVIATION 11.38 | 44.32 years STANDARD_DEVIATION 11.23 |
| BMI | 36.22 kg/m^2 STANDARD_DEVIATION 4.45 | 36.09 kg/m^2 STANDARD_DEVIATION 4.27 | 36.17 kg/m^2 STANDARD_DEVIATION 4.39 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 10 participants | 2 participants | 12 participants |
| Race/Ethnicity, Customized Asian | 12 participants | 4 participants | 16 participants |
| Race/Ethnicity, Customized Black or African American | 133 participants | 72 participants | 205 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized Other | 8 participants | 2 participants | 10 participants |
| Race/Ethnicity, Customized White | 835 participants | 414 participants | 1249 participants |
| Sex: Female, Male Female | 847 Participants | 420 Participants | 1267 Participants |
| Sex: Female, Male Male | 154 Participants | 75 Participants | 229 Participants |
| Weight | 100.3 kg STANDARD_DEVIATION 16.55 | 99.21 kg STANDARD_DEVIATION 15.86 | 99.95 kg STANDARD_DEVIATION 16.33 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 671 / 992 | 244 / 492 |
| serious Total, serious adverse events | 21 / 992 | 7 / 492 |
Outcome results
Primary
Co-primary: Body Weight- Mean Percent Change From Baseline to Week 28
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Co-primary: Body Weight- Mean Percent Change From Baseline to Week 28 | -6.45 percentage of body weight | Standard Error 0.2 |
| Placebo | Co-primary: Body Weight- Mean Percent Change From Baseline to Week 28 | -1.89 percentage of body weight | Standard Error 0.26 |
p-value: <0.00195% CI: [-5.19, -3.93]ANCOVA
Primary
Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 28
Time frame: Baseline, 28 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NB32 | Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 28 | 55.64 percentage of participants |
| Placebo | Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 28 | 17.54 percentage of participants |
p-value: <0.00195% CI: [4.95, 8.84]Regression, Logistic
Secondary
Body Weight- Mean Percent Change From Baseline to Week 56
Beginning at Week 28 through Week 44, NB32-treated subjects who failed to achieve or maintain at least 5% body weight loss from baseline were re-randomized (1:1 ratio) to continue NB32 or begin treatment with a higher dose of naltrexone SR - naltrexone SR 48 mg/bupropion SR 360 mg (referred to as NB48) (daily dose of bupropion SR was 360 mg for NB32 and NB48).The analysis of NB32 vs. placebo at Week 56 was completed using a weighted analysis. This analysis was referred to as the weighted LOCF analysis. Subjects treated with NB32 who were re-randomized to NB48 were not included. Subjects re-randomized to NB32 were double-weighted and subjects who were not re-randomized were single-weighted. Subjects in the placebo group were single-weighted. The double weighting analysis restored the influence of poor performers at Weeks 28 to 44 in the NB32 group without including any data from the higher dose group (NB48).
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Body Weight- Mean Percent Change From Baseline to Week 56 | -6.40 percentage of body weight | Standard Error 0.25 |
| Placebo | Body Weight- Mean Percent Change From Baseline to Week 56 | -1.23 percentage of body weight | Standard Error 0.33 |
p-value: <0.00195% CI: [-5.95, -4.38]ANCOVA
Secondary
Body Weight- Proportion of Subjects With ≥10% Decrease From Baseline to Week 28
Time frame: Baseline, 28 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NB32 | Body Weight- Proportion of Subjects With ≥10% Decrease From Baseline to Week 28 | 27.27 percentage of participants |
| Placebo | Body Weight- Proportion of Subjects With ≥10% Decrease From Baseline to Week 28 | 7.02 percentage of participants |
p-value: <0.00195% CI: [3.6, 7.98]Regression, Logistic
Secondary
Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 56
Beginning at Week 28 through Week 44, NB32-treated subjects who failed to achieve or maintain at least 5% body weight loss from baseline were re-randomized (1:1 ratio) to continue NB32 or begin treatment with a higher dose of naltrexone SR - naltrexone SR 48 mg/bupropion SR 360 mg (referred to as NB48) (daily dose of bupropion SR was 360 mg for NB32 and NB48).The analysis of NB32 vs. placebo at Week 56 was completed using a weighted analysis. This analysis was referred to as the weighted LOCF analysis. Subjects treated with NB32 who were re-randomized to NB48 were not included. Subjects re-randomized to NB32 were double-weighted and subjects who were not re-randomized were single-weighted. Subjects in the placebo group were single-weighted. The double weighting analysis restored the influence of poor performers at Weeks 28 to 44 in the NB32 group without including any data from the higher dose group (NB48).
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NB32 | Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 56 | 50.48 percentage of participants |
| Placebo | Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 56 | 17.11 percentage of participants |
p-value: <0.00195% CI: [4.05, 7.47]Regression, Logistic
Secondary
Change in Diastolic Blood Pressure
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Diastolic Blood Pressure | 0.20 mm Hg | Standard Error 0.22 |
| Placebo | Change in Diastolic Blood Pressure | -0.67 mm Hg | Standard Error 0.3 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [0.16, 1.58]
Secondary
Change in Fasting Blood Glucose Levels
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Fasting Blood Glucose Levels | -2.11 mg/dL | Standard Error 0.38 |
| Placebo | Change in Fasting Blood Glucose Levels | -1.73 mg/dL | Standard Error 0.52 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-1.6, 0.85]
Secondary
Change in Fasting HDL Cholesterol Levels
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Fasting HDL Cholesterol Levels | 1.19 mg/dL | Standard Error 0.3 |
| Placebo | Change in Fasting HDL Cholesterol Levels | -1.40 mg/dL | Standard Error 0.42 |
p-value: <0.00195% CI: [1.61, 3.57]ANCOVA
Secondary
Change in Fasting Insulin Levels, Using Log-transformed Data
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| NB32 | Change in Fasting Insulin Levels, Using Log-transformed Data | -14.14 percent change |
| Placebo | Change in Fasting Insulin Levels, Using Log-transformed Data | -0.50 percent change |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.
Secondary
Change in Fasting LDL Cholesterol Levels
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Fasting LDL Cholesterol Levels | -4.36 mg/dL | Standard Error 0.9 |
| Placebo | Change in Fasting LDL Cholesterol Levels | 0.00 mg/dL | Standard Error 1.25 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-7.29, -1.44]
Secondary
Change in Fasting Triglycerides Levels, Using Log-transformed Data
Time frame: Baseline, 28 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| NB32 | Change in Fasting Triglycerides Levels, Using Log-transformed Data | -7.32 percent change |
| Placebo | Change in Fasting Triglycerides Levels, Using Log-transformed Data | -1.36 percent change |
p-value: 0.007ANCOVA
Secondary
Change in Food Craving Inventory Carbohydrates Subscale Score
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).
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Food Craving Inventory Carbohydrates Subscale Score | -2.68 units on a scale | Standard Error 0.16 |
| Placebo | Change in Food Craving Inventory Carbohydrates Subscale Score | -2.20 units on a scale | Standard Error 0.21 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.98, 0.02]
Secondary
Change in Food Craving Inventory Sweets Subscale Score
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).
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Food Craving Inventory Sweets Subscale Score | -3.20 units on a scale | Standard Error 0.17 |
| Placebo | Change in Food Craving Inventory Sweets Subscale Score | -3.18 units on a scale | Standard Error 0.22 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.56, 0.52]
Secondary
Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| NB32 | Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data | -9.38 percent change |
| Placebo | Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data | -1.14 percent change |
p-value: 0.091ANCOVA
Secondary
Change in HOMA-IR Levels, Using Log-transformed Data
HOMA-IR= Homeostasis Model Assessment-Insulin Resistance
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| NB32 | Change in HOMA-IR Levels, Using Log-transformed Data | -16.44 percent change |
| Placebo | Change in HOMA-IR Levels, Using Log-transformed Data | -4.15 percent change |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.
Secondary
Change in IDS-SR Total Score
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.
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in IDS-SR Total Score | -0.23 units on a scale | Standard Error 0.17 |
| Placebo | Change in IDS-SR Total Score | -0.28 units on a scale | Standard Error 0.23 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.49, 0.6]
Secondary
Change in IWQOL-Lite Total Scores
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
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in IWQOL-Lite Total Scores | 9.94 units on a scale | Standard Error 0.41 |
| Placebo | Change in IWQOL-Lite Total Scores | 6.17 units on a scale | Standard Error 0.56 |
p-value: <0.00195% CI: [2.46, 5.09]ANCOVA
Secondary
Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire
Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire | -18.32 units on a scale | Standard Error 0.85 |
| Placebo | Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire | -11.09 units on a scale | Standard Error 1.12 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-9.92, -4.54]
Secondary
Change in Systolic Blood Pressure
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Systolic Blood Pressure | -0.93 mm Hg | Standard Error 0.31 |
| Placebo | Change in Systolic Blood Pressure | -1.23 mm Hg | Standard Error 0.42 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.7, 1.3]
Secondary
Change in Waist Circumference
Time frame: Baseline, 28 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB32 | Change in Waist Circumference | -6.16 cm | Standard Error 0.28 |
| Placebo | Change in Waist Circumference | -2.74 cm | Standard Error 0.38 |
p-value: <0.00195% CI: [-4.33, -2.53]ANCOVA