Obesity, Overweight
Conditions
Keywords
Obesity, Antiobesity agents, Antiobesity drugs, Overweight drug therapy, Obese drug therapy, Weight loss drug effects, Bupropion administration and dosage, Naltrexone administration and dosage, Double blind method, Combination drug therapy, Delayed action preparations
Brief summary
The purpose of this study is to determine whether 2 doses of the combination of naltrexone SR and bupropion SR are 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 bupropion SR alone, naltrexone alone, or placebo in subjects with uncomplicated obesity. The current study investigated the safety and efficacy of 2 doses 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
DRUGNaltrexone SR 16 mg/Bupropion SR 360 mg /day
DRUGNaltrexone SR 32 mg/Bupropion SR 360 mg /day
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 and male subjects, 18 to 65 years of age; * Have BMI ≥30 and ≤45kg/m² for subjects with uncomplicated obesity, and BMI of ≥27 and ≤45kg/m² for subjects with obesity and controlled hypertension and/or dyslipidemia; * Normotensive (systolic ≤140 mm Hg; diastolic ≤90 mm Hg). Anti-hypertensive medications are allowed with the exception of alpha-adrenergic blockers and clonidine; medical regimen must be stable for at least 6 weeks prior to randomization; * Medications for treatment of dyslipidemia are allowed as long as medical regimen has 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, creatinine, bilirubin, sodium, potassium, chloride, calcium or phosphorus; * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within 2.5 x upper limit of normal range (ULN); * No clinically significant abnormality of hematocrit, white blood cell (WBC) count, white cell differential, or platelets; * Fasting glucose \< 126 mg/dL on no hypoglycemic agents, fasting triglycerides \<400 mg/dL; * No clinically significant abnormality on urinalysis; * TSH within normal limits or normal T3, if TSH is below normal limits; * Negative serum pregnancy test in women of child-bearing potential; * Negative urine drug screen; * IDS-SR scores \< 2 on items 5 (sadness), 6 (irritability), 7 (anxiety/tension) and 18 (suicidality), and IDS-SR total score \< 30; * Women of child bearing potential had to be non-lactating and agree to use effective contraception throughout the study period and 30 days after discontinuation of study drug; * Able to comply with all required study procedures and schedule; * Able to speak and read English; * Willing and able to give written informed consent.
Exclusion criteria
* Obesity of known endocrine origin (e.g., untreated hypothyroidism, Cushing's syndrome, established Polycystic Ovary Syndrome); * Serious medical conditions (including but not limited to ongoing renal or hepatic insufficiency, Class III or IV congestive heart failure; myocardial infarction, history of angina pectoris, 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; * A 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; * A response to bipolar disorder questions indicating the presence of bipolar disorder; * In need of 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 1 or Type 2 diabetes mellitus; * Screening ECG with a corrected QT interval by the method of Bazett (QTcB) \>450 msec (men) and \> 470 millisecond (msec) (women) 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; * Excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, 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 medications, 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 (such as cigarettes, cigars, pipes, etc), chewing tobacco or snuff in the 3 months prior to randomization or planned during study participation. Use of nicotine replacement products (nicotine gum, patch) during study participation was not allowed; * Use of drugs, herbs, or dietary supplements believed to significantly affect body weight or participation in a weight loss management program within one month prior to randomization; * Loss or gain of more than 4.0 kilograms within 3 months prior to randomization; * Pregnant or breast-feeding women or planning to become pregnant during the study period or within 30 days of discontinuing study drug; * Planned surgical procedure that can impact the conduct of the study; * Use of investigational drug, device or procedure within the previous 30 days; * Participation in any previous clinical trial sponsored by Orexigen Therapeutics; * Any condition which in the opinion of the investigator makes the subject unsuitable for inclusion in the study; * Investigators, study personnel, sponsor representatives and their immediate families.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Co-primary: Body Weight- Mean Percent Change | Baseline, 56 weeks |
| Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease | Baseline, 56 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Waist Circumference | Baseline, 56 weeks | — |
| Change in Fasting HDL Cholesterol Levels | Baseline, 56 weeks | — |
| Change in IWQOL-Lite Total Scores | Baseline, 56 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 High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data | Baseline, 56 weeks | — |
| Change in Fasting Insulin Levels, Using Log-transformed Data | Baseline, 56 weeks | — |
| Change in Fasting Blood Glucose Levels | Baseline, 56 weeks | — |
| Change in HOMA-IR Levels, Using Log-transformed Data | Baseline, 56 weeks | HOMA-IR= Homeostasis Model Assessment-Insulin Resistance |
| Change in Fasting Triglycerides Levels, Using Log-transformed Data | Baseline, 56 weeks | — |
| Change in Fasting LDL Cholesterol Levels | Baseline, 56 weeks | — |
| Change in Systolic Blood Pressure | Baseline, 56 weeks | — |
| Change in Diastolic Blood Pressure | Baseline, 56 weeks | — |
| Change in IDS-SR Total Scores | Baseline, 56 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, 56 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, 56 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 Question 19 From 21-Item COE (Control of Eating) Questionnaire | Baseline, 56 weeks | Question 19: Generally, how difficult has it been to control your eating? Scoring: 0=not at all difficult; 100=extremely difficult |
| Body Weight- Proportion of Subjects With ≥10% Decrease | Baseline, 56 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NB16 Naltrexone SR 16 mg/Bupropion SR 360 mg /day | 578 |
| NB32 Naltrexone SR 32 mg/Bupropion SR 360 mg /day | 583 |
| Placebo Placebo | 581 |
| Total | 1,742 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 122 | 112 | 56 |
| Overall Study | Death | 0 | 1 | 0 |
| Overall Study | Drug noncompliance, moved, other | 14 | 23 | 29 |
| Overall Study | Lack of Efficacy | 12 | 12 | 40 |
| Overall Study | Lost to Follow-up | 76 | 65 | 66 |
| Overall Study | Pregnancy | 2 | 5 | 3 |
| Overall Study | Protocol Violation | 5 | 9 | 7 |
| Overall Study | Withdrawal by Subject | 63 | 60 | 90 |
Baseline characteristics
| Characteristic | NB16 | Total | Placebo | NB32 |
|---|---|---|---|---|
| Age, Continuous | 44.35 years STANDARD_DEVIATION 11.25 | 44.14 years STANDARD_DEVIATION 11.17 | 43.66 years STANDARD_DEVIATION 11.14 | 44.41 years STANDARD_DEVIATION 11.14 |
| BMI | 36.22 kg/m^2 STANDARD_DEVIATION 4.28 | 36.17 kg/m^2 STANDARD_DEVIATION 4.21 | 36.18 kg/m^2 STANDARD_DEVIATION 4 | 36.10 kg/m^2 STANDARD_DEVIATION 4.35 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 13 participants | 48 participants | 17 participants | 18 participants |
| Race/Ethnicity, Customized Asian | 4 participants | 14 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Black or African American | 122 participants | 338 participants | 110 participants | 106 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 6 participants | 15 participants | 4 participants | 5 participants |
| Race/Ethnicity, Customized Other | 6 participants | 20 participants | 6 participants | 8 participants |
| Race/Ethnicity, Customized White | 427 participants | 1307 participants | 440 participants | 440 participants |
| Sex: Female, Male Female | 490 Participants | 1482 Participants | 496 Participants | 496 Participants |
| Sex: Female, Male Male | 88 Participants | 260 Participants | 85 Participants | 87 Participants |
| Weight | 99.49 kg STANDARD_DEVIATION 14.76 | 99.55 kg STANDARD_DEVIATION 14.99 | 99.45 kg STANDARD_DEVIATION 14.31 | 99.70 kg STANDARD_DEVIATION 15.88 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 345 / 569 | 365 / 573 | 230 / 569 |
| serious Total, serious adverse events | 9 / 569 | 9 / 573 | 8 / 569 |
Outcome results
Primary
Co-primary: Body Weight- Mean Percent Change
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| NB16 | Co-primary: Body Weight- Mean Percent Change | -5.00 percentage of body weight | Standard Error 0.31 |
| NB32 | Co-primary: Body Weight- Mean Percent Change | -6.14 percentage of body weight | Standard Error 0.31 |
| Placebo | Co-primary: Body Weight- Mean Percent Change | -1.33 percentage of body weight | Standard Error 0.3 |
p-value: <0.00195% CI: [-4.5, -2.85]ANCOVA
p-value: <0.00195% CI: [-5.63, -3.99]ANCOVA
Primary
Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease
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) |
|---|---|---|
| NB16 | Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease | 39.49 percentage of participants |
| NB32 | Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease | 47.98 percentage of participants |
| Placebo | Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease | 16.44 percentage of participants |
p-value: <0.00195% CI: [2.52, 4.63]Regression, Logistic
p-value: <0.00195% CI: [3.6, 6.57]Regression, Logistic
Secondary
Body Weight- Proportion of Subjects With ≥10% Decrease
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) |
|---|---|---|
| NB16 | Body Weight- Proportion of Subjects With ≥10% Decrease | 20.17 Percentage of participants |
| NB32 | Body Weight- Proportion of Subjects With ≥10% Decrease | 24.63 Percentage of participants |
| Placebo | Body Weight- Proportion of Subjects With ≥10% Decrease | 7.44 Percentage of participants |
p-value: <0.00195% CI: [2.14, 4.81]Regression, Logistic
p-value: <0.00195% CI: [2.82, 6.23]Regression, Logistic
Secondary
Change in Diastolic Blood Pressure
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 |
|---|---|---|---|
| NB16 | Change in Diastolic Blood Pressure | 0.09 mm Hg | Standard Error 0.29 |
| NB32 | Change in Diastolic Blood Pressure | 0.04 mm Hg | Standard Error 0.29 |
| Placebo | Change in Diastolic Blood Pressure | -0.86 mm Hg | Standard Error 0.28 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [0.19, 1.73]
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [0.13, 1.67]
Secondary
Change in Fasting Blood Glucose Levels
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 |
|---|---|---|---|
| NB16 | Change in Fasting Blood Glucose Levels | -2.39 mg/dL | Standard Error 0.57 |
| NB32 | Change in Fasting Blood Glucose Levels | -3.24 mg/dL | Standard Error 0.55 |
| Placebo | Change in Fasting Blood Glucose Levels | -1.30 mg/dL | Standard Error 0.56 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-2.6, 0.42]
p-value: =0.0195% CI: [-3.42, -0.46]ANCOVA
Secondary
Change in Fasting HDL Cholesterol Levels
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 |
|---|---|---|---|
| NB16 | Change in Fasting HDL Cholesterol Levels | 3.36 mg/dL | Standard Error 0.47 |
| NB32 | Change in Fasting HDL Cholesterol Levels | 3.42 mg/dL | Standard Error 0.45 |
| Placebo | Change in Fasting HDL Cholesterol Levels | -0.06 mg/dL | Standard Error 0.47 |
p-value: <0.00195% CI: [2.17, 4.66]ANCOVA
p-value: <0.00195% CI: [2.26, 4.7]ANCOVA
Secondary
Change in Fasting Insulin Levels, Using Log-transformed Data
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) |
|---|---|---|
| NB16 | Change in Fasting Insulin Levels, Using Log-transformed Data | -11.84 percent change |
| NB32 | Change in Fasting Insulin Levels, Using Log-transformed Data | -17.14 percent change |
| Placebo | Change in Fasting Insulin Levels, Using Log-transformed Data | -4.57 percent change |
p-value: =0.063ANCOVA
p-value: <0.001ANCOVA
Secondary
Change in Fasting LDL Cholesterol Levels
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 |
|---|---|---|---|
| NB16 | Change in Fasting LDL Cholesterol Levels | -3.67 mg/dL | Standard Error 1.21 |
| NB32 | Change in Fasting LDL Cholesterol Levels | -4.41 mg/dL | Standard Error 1.17 |
| Placebo | Change in Fasting LDL Cholesterol Levels | -3.28 mg/dL | Standard Error 1.2 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-3.62, 2.84]
p-value: 0.48495% CI: [-4.29, 2.04]ANCOVA
Secondary
Change in Fasting Triglycerides Levels, Using Log-transformed Data
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) |
|---|---|---|
| NB16 | Change in Fasting Triglycerides Levels, Using Log-transformed Data | -7.96 percent change |
| NB32 | Change in Fasting Triglycerides Levels, Using Log-transformed Data | -12.69 percent change |
| Placebo | Change in Fasting Triglycerides Levels, Using Log-transformed Data | -3.08 percent change |
p-value: =0.046ANCOVA
p-value: <0.001ANCOVA
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, 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 |
|---|---|---|---|
| NB16 | Change in Food Craving Inventory Carbohydrates Subscale Score | -1.85 units on a scale | Standard Error 0.2 |
| NB32 | Change in Food Craving Inventory Carbohydrates Subscale Score | -2.11 units on a scale | Standard Error 0.2 |
| Placebo | Change in Food Craving Inventory Carbohydrates Subscale Score | -1.84 units on a scale | Standard Error 0.19 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.53, 0.53]
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.8, 0.27]
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, 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 |
|---|---|---|---|
| NB16 | Change in Food Craving Inventory Sweets Subscale Score | -2.08 units on a scale | Standard Error 0.21 |
| NB32 | Change in Food Craving Inventory Sweets Subscale Score | -2.62 units on a scale | Standard Error 0.21 |
| Placebo | Change in Food Craving Inventory Sweets Subscale Score | -2.77 units on a scale | Standard Error 0.2 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [0.14, 1.23]
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.4, 0.69]
Secondary
Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data
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) |
|---|---|---|
| NB16 | Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data | -28.02 percent change |
| NB32 | Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data | -28.98 percent change |
| Placebo | Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data | -16.66 percent change |
p-value: =0.016ANCOVA
p-value: =0.008ANCOVA
Secondary
Change in HOMA-IR Levels, Using Log-transformed Data
HOMA-IR= Homeostasis Model Assessment-Insulin Resistance
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) |
|---|---|---|
| NB16 | Change in HOMA-IR Levels, Using Log-transformed Data | -14.33 percent change |
| NB32 | Change in HOMA-IR Levels, Using Log-transformed Data | -20.19 percent change |
| Placebo | Change in HOMA-IR Levels, Using Log-transformed Data | -5.90 percent change |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.
p-value: <0.001ANCOVA
Secondary
Change in IDS-SR Total Scores
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, 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 |
|---|---|---|---|
| NB16 | Change in IDS-SR Total Scores | 0.02 units on a scale | Standard Error 0.21 |
| NB32 | Change in IDS-SR Total Scores | -0.27 units on a scale | Standard Error 0.21 |
| Placebo | Change in IDS-SR Total Scores | -0.72 units on a scale | Standard Error 0.2 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [0.19, 1.28]
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-0.09, 1]
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, 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 |
|---|---|---|---|
| NB16 | Change in IWQOL-Lite Total Scores | 11.68 units on a scale | Standard Error 0.54 |
| NB32 | Change in IWQOL-Lite Total Scores | 12.69 units on a scale | Standard Error 0.54 |
| Placebo | Change in IWQOL-Lite Total Scores | 8.55 units on a scale | Standard Error 0.51 |
p-value: <0.00195% CI: [1.72, 4.54]ANCOVA
p-value: <0.00195% CI: [2.73, 5.56]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, 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 |
|---|---|---|---|
| NB16 | Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire | -12.49 units on a scale | Standard Error 1.1 |
| NB32 | Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire | -14.52 units on a scale | Standard Error 1.09 |
| Placebo | Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire | -8.68 units on a scale | Standard Error 1.04 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [-6.68, -0.94]
p-value: <0.00195% CI: [-8.71, -2.98]ANCOVA
Secondary
Change in Systolic Blood Pressure
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 |
|---|---|---|---|
| NB16 | Change in Systolic Blood Pressure | 0.29 mm Hg | Standard Error 0.4 |
| NB32 | Change in Systolic Blood Pressure | -0.11 mm Hg | Standard Error 0.41 |
| Placebo | Change in Systolic Blood Pressure | -1.94 mm Hg | Standard Error 0.39 |
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [1.16, 3.3]
Comparison: Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed.95% CI: [0.76, 2.9]
Secondary
Change in Waist Circumference
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 |
|---|---|---|---|
| NB16 | Change in Waist Circumference | -5.04 cm | Standard Error 0.43 |
| NB32 | Change in Waist Circumference | -6.24 cm | Standard Error 0.42 |
| Placebo | Change in Waist Circumference | -2.46 cm | Standard Error 0.43 |
p-value: <0.00195% CI: [-3.74, -1.43]ANCOVA
p-value: <0.00195% CI: [-4.93, -2.64]ANCOVA