NCT00567255已完成3 期
A Multicenter, Randomized, Double Blind, Placebo Controlled Study Comparing the Safety and Efficacy of Naltrexone Sustained Release (SR)/Bupropion Sustained Release (SR) and Placebo in Obese Subjects
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,496
- 试验地点
- 34
- 主要终点
- Co-primary: Body Weight- Mean Percent Change From Baseline to Week 28
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
NB32
Experimental
Naltrexone SR 32 mg/bupropion SR 360 mg/day with ancillary therapy
干预措施: Naltrexone SR 32 mg/bupropion SR 360 mg/day (Drug)
NB32
Experimental
Naltrexone SR 32 mg/bupropion SR 360 mg/day with ancillary therapy
干预措施: Ancillary therapy (Behavioral)
Placebo
Placebo Comparator
Placebo with ancillary therapy
干预措施: Placebo (Drug)
Placebo
Placebo Comparator
Placebo with ancillary therapy
干预措施: Ancillary therapy (Behavioral)
结局指标
主要结局
Co-primary: Body Weight- Mean Percent Change From Baseline to Week 28
时间窗: Baseline, 28 weeks
Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 28
时间窗: Baseline, 28 weeks
次要结局
- Body Weight- Mean Percent Change From Baseline to Week 56(Baseline, 56 weeks)
- Body Weight- Proportion of Subjects With ≥5% Decrease From Baseline to Week 56(Baseline, 56 weeks)
- 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 Fasting Triglycerides Levels, Using Log-transformed Data(Baseline, 28 weeks)
- Change in IWQOL-Lite Total Scores(Baseline, 28 weeks)
- Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data(Baseline, 28 weeks)
- 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)
- Change in Question 19 From 21-Item COE (Control of Eating) Questionnaire(Baseline, 28 weeks)
- 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)
- Change in Food Craving Inventory Sweets Subscale Score(Baseline, 28 weeks)
- Change in Food Craving Inventory Carbohydrates Subscale Score(Baseline, 28 weeks)
研究者
研究点 (34)
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