Brief Summary
The purpose of this study is to determine the effects of NB relative to placebo on major adverse cardiovascular events (MACE) such as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke in overweight and obese subjects who are at a higher risk of having these events because they have diabetes and/or other cardiovascular risk factors.
Brief Title
Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors (The Light Study)
Categories
Completion Date
Completion Date Type
Actual
Conditions
Obesity
Overweight
Eligibility Criteria
Inclusion Criteria:
1. ≥50 years of age (women) or ≥45 years of age (men)
2. Body mass index (BMI) ≥27 kg/m2 and ≤50 kg/m2
3. Waist circumference ≥88 cm (women) or ≥102 cm (men)
4. At increased risk of adverse cardiovascular outcomes:
* Cardiovascular disease (confirmed diagnosis or at high likelihood of cardiovascular disease) with at least one of the following:
* History of documented myocardial infarction \>3 months prior to screening
* History of coronary revascularization
* History of carotid or peripheral revascularization
* Angina with ischemic changes (resting ECG), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study
* Ankle brachial index \<0.9 (by simple palpation) within prior 2 years
* ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years
AND/OR
* Type 2 diabetes mellitus with at least 2 of the following:
* Hypertension (controlled with or without pharmacotherapy at \<145/95 mm Hg)
* Dyslipidemia requiring pharmacotherapy
* Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within prior 12 months
* Current tobacco smoker
Exclusion Criteria:
1. Myocardial infarction within 3 months prior to screening
2. Angina pectoris Grade III or IV as per the Canadian Cardiovascular Society grading scheme
3. Clinical history of cerebrovascular disease (stroke)
4. History of tachyarrhythmia other than sinus tachycardia
5. Planned bariatric surgery, cardiac surgery, or coronary angioplasty
6. History of seizures (including febrile seizures), cranial trauma, or other conditions that predispose the subject to seizures
7. History of mania or current diagnosis of active psychosis, active bulimia or anorexia nervosa (binge eating disorder is not exclusionary)
8. Any condition with life expectancy anticipated to be less than 4 years (e.g., congestive heart failure NYHA Class 3 or 4)
1. ≥50 years of age (women) or ≥45 years of age (men)
2. Body mass index (BMI) ≥27 kg/m2 and ≤50 kg/m2
3. Waist circumference ≥88 cm (women) or ≥102 cm (men)
4. At increased risk of adverse cardiovascular outcomes:
* Cardiovascular disease (confirmed diagnosis or at high likelihood of cardiovascular disease) with at least one of the following:
* History of documented myocardial infarction \>3 months prior to screening
* History of coronary revascularization
* History of carotid or peripheral revascularization
* Angina with ischemic changes (resting ECG), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study
* Ankle brachial index \<0.9 (by simple palpation) within prior 2 years
* ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years
AND/OR
* Type 2 diabetes mellitus with at least 2 of the following:
* Hypertension (controlled with or without pharmacotherapy at \<145/95 mm Hg)
* Dyslipidemia requiring pharmacotherapy
* Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within prior 12 months
* Current tobacco smoker
Exclusion Criteria:
1. Myocardial infarction within 3 months prior to screening
2. Angina pectoris Grade III or IV as per the Canadian Cardiovascular Society grading scheme
3. Clinical history of cerebrovascular disease (stroke)
4. History of tachyarrhythmia other than sinus tachycardia
5. Planned bariatric surgery, cardiac surgery, or coronary angioplasty
6. History of seizures (including febrile seizures), cranial trauma, or other conditions that predispose the subject to seizures
7. History of mania or current diagnosis of active psychosis, active bulimia or anorexia nervosa (binge eating disorder is not exclusionary)
8. Any condition with life expectancy anticipated to be less than 4 years (e.g., congestive heart failure NYHA Class 3 or 4)
Inclusion Criteria
Inclusion Criteria:
1. ≥50 years of age (women) or ≥45 years of age (men)
2. Body mass index (BMI) ≥27 kg/m2 and ≤50 kg/m2
3. Waist circumference ≥88 cm (women) or ≥102 cm (men)
4. At increased risk of adverse cardiovascular outcomes:
* Cardiovascular disease (confirmed diagnosis or at high likelihood of cardiovascular disease) with at least one of the following:
* History of documented myocardial infarction \>3 months prior to screening
* History of coronary revascularization
* History of carotid or peripheral revascularization
* Angina with ischemic changes (resting ECG), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study
* Ankle brachial index \<0.9 (by simple palpation) within prior 2 years
* ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years
AND/OR
* Type 2 diabetes mellitus with at least 2 of the following:
* Hypertension (controlled with or without pharmacotherapy at \<145/95 mm Hg)
* Dyslipidemia requiring pharmacotherapy
* Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within prior 12 months
* Current tobacco smoker
1. ≥50 years of age (women) or ≥45 years of age (men)
2. Body mass index (BMI) ≥27 kg/m2 and ≤50 kg/m2
3. Waist circumference ≥88 cm (women) or ≥102 cm (men)
4. At increased risk of adverse cardiovascular outcomes:
* Cardiovascular disease (confirmed diagnosis or at high likelihood of cardiovascular disease) with at least one of the following:
* History of documented myocardial infarction \>3 months prior to screening
* History of coronary revascularization
* History of carotid or peripheral revascularization
* Angina with ischemic changes (resting ECG), ECG changes on a graded exercise test (GXT), or positive cardiac imaging study
* Ankle brachial index \<0.9 (by simple palpation) within prior 2 years
* ≥50% stenosis of a coronary, carotid, or lower extremity artery within prior 2 years
AND/OR
* Type 2 diabetes mellitus with at least 2 of the following:
* Hypertension (controlled with or without pharmacotherapy at \<145/95 mm Hg)
* Dyslipidemia requiring pharmacotherapy
* Documented low HDL cholesterol (\<50 mg/dL in women or \<40 mg/dL in men) within prior 12 months
* Current tobacco smoker
Gender
All
Gender Based
false
Keywords
Body Weight
Bupropion
Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Heart Diseases
Metabolic Diseases
Narcotic Antagonists
Naltrexone
Nutrition Disorders
Obesity
Overnutrition
Overweight
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
45 Years
NCT Id
NCT01601704
Org Class
Industry
Org Full Name
Orexigen Therapeutics, Inc
Org Study Id
NB-CVOT
Overall Status
Terminated
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Assessing the Occurrence of Major Adverse Cardiovascular Events (MACE) in Overweight and Obese Subjects With Cardiovascular Risk Factors Receiving Naltrexone SR/Bupropion SR
Primary Outcomes
Outcome Description
The primary endpoint is the time from randomization to the first confirmed occurrence of any event within the primary MACE composite (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). Due to early termination of the study, pre-planned 50% interim analysis is considered the primary analysis for outcome measures. The pre-planned 50% interim analysis was conducted when 50% of the total planned MACE were observed.
Outcome Measure
Percentage of Participants With a Confirmed Occurrence of Major Adverse Cardiovascular Event (MACE)
Outcome Time Frame
Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Secondary Ids
Secondary Id
The Light Study
Secondary Id
U1111-1162-4981
Secondary Outcomes
Outcome Description
Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Outcome Time Frame
Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Outcome Measure
Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death, Nonfatal Myocardial Infarction, Nonfatal Stroke, or Nonfatal Unstable Angina Requiring Hospitalization
Outcome Description
Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Outcome Time Frame
Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Outcome Measure
Percentage of Participants With a Confirmed Occurrence of Cardiovascular Death (Including Fatal Myocardial Infarction, Fatal Stroke)
Outcome Description
Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Outcome Time Frame
Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Outcome Measure
Percentage of Participants With a Confirmed Occurrence of Myocardial Infarction (Nonfatal or Fatal)
Outcome Description
Due to early termination of the study, the pre-planned 50% interim analysis is considered the primary analysis for outcome measures.
Outcome Time Frame
Confirmed occurrence of event between Day 1 (randomization) and up to a maximum of 4 years of follow-up
Outcome Measure
Percentage of Participants With a Confirmed Occurrence of Stroke (Nonfatal or Fatal)
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
45
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ruth Freeman
Investigator Email
rfreeman@montefiore.org
Investigator Phone