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ObesityPhase 3NCT00474630

A Safety and Efficacy Study Comparing Naltrexone SR/Bupropion SR and Placebo in Obese Subjects With Type 2 Diabetes

A Phase 3 study testing Naltrexone SR 32 mg/bupropion SR 360 mg/ day and Ancillary therapy in people with Obesity and Overweight, run by Orexigen Therapeutics, Inc at 53 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is determine whether the combination of naltrexone SR and bupropion SR is safe and effective in treating obesity in subjects with type 2 diabetes. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Obesity, Overweight, Diabetes Mellitus, Type 2
What is being tested?
Naltrexone SR 32 mg/bupropion SR 360 mg/ day and Ancillary therapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
505 participants
Where
53 sitesUnited States
Study dates
May 2007to Jun 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Female or male subjects aged 18 to 70 years of age (inclusive)
  • Body mass index (BMI) ≥27 and ≤45 kg/m²
  • Diagnosed with type 2 diabetes mellitus and on no injectable antidiabetes medication or inhaled insulin for more than 3 months prior to randomization
  • Took stable doses of oral single or combination hypoglycemic medications (biguanides, thiazolidinediones, meglitinides, α-glucosidase inhibitors, sulfonylureas, DPP4 inhibitors) for at least 3 months prior to randomization or did not take medications for the treatment of type 2 diabetes mellitus
  • Normotensive (systolic ≤145 mm Hg and diastolic ≤95 mm Hg). Antihypertensive medications were allowed with the exception of alpha-adrenergic blockers, and clonidine. Antihypertensive treatment was stable for at least 4 weeks prior to randomization.
  • Medications for the treatment of dyslipidemia were allowed with the exception of cholestyramine and cholestypol as long as the medical regimen had been stable for at least 4 weeks prior to randomization.
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  • Free of opioid medication for 7 days prior to randomization
  • HbA1c between 7% and 10%, fasting blood glucose <270 mg/dL, and fasting triglycerides <400 mg/dL
  • No clinically significant abnormality of serum albumin, blood urea nitrogen (BUN), bilirubin, calcium, and phosphorus
  • Creatinine levels were ≤1.4 mg/dL for female subjects and ≤1.5 mg/dL for male subjects
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were within 2.5 × upper limit of laboratory normal range (ULN)
  • No clinically significant abnormality of hematocrit, white blood cell (WBC) count, WBC differential, or platelets
  • No clinically significant abnormality on urinalysis
  • TSH within normal limits or normal T3, if TSH is below normal limits
  • Female subjects of childbearing potential had a negative serum pregnancy test
  • Negative urine drug screen
  • 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

Who cannot join

  • Type I diabetes mellitus
  • "Brittle-diabetes" or any hospitalization or emergency room visit due to poor diabetic control within 6 months prior to screening, history of diabetes-related dehydration leading to hospitalization, or history or evidence of ketoacidosis
  • Obesity of known endocrine origin other than diabetes mellitus (e.g., untreated hypothyroidism, Cushing's syndrome, established polycystic ovary syndrome)
  • Diabetes mellitus secondary to pancreatitis or pancreatectomy
  • Serious medical condition including but not limited to renal or hepatic insufficiency and Class III or IV congestive heart failure; history of myocardial infarction, angina pectoris, claudication, or acute limb ischemia within 6 months prior to screening; lifetime history of stroke
  • History of malignancy with exception of non-melanoma skin cancer or surgically cured cervical cancer within 5 years prior to screening
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  • Loss or gain of more than 5.0 kg within the 3 months prior to screening
  • Severe microvascular or macrovascular complications of diabetes, including but not limited to proliferative retinopathy, active limb ulcerations, amputation of metatarsals or above
  • Serious psychiatric illness, including lifetime history of bipolar disorder, schizophrenia or other psychosis, bulimia, and anorexia nervosa; current serious personality disorder (e.g., borderline or antisocial); current severe major depressive disorder; recent (6 months prior to screening) suicide attempt or 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 6 months prior to screening
  • History of drug or alcohol abuse or dependence within 1 year prior to screening
  • Baseline ECG with a QTc interval (Bazett's formula) >450 msec (men) and >470 msec (women) or the presence of any clinically significant cardiac abnormalities, including but not limited to patterns consistent with recent myocardial ischemia, electrolyte abnormalities, or atrial or ventricular dysrhythmia or significant conduction abnormalities
  • Received the following excluded concomitant medications: any psychotropic agents (including antipsychotic, antidepressant, anxiolytic, mood stabilizer, anticonvulsant agents, and 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 intervention for obesity (e.g., gastric banding)
  • 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)
  • Treatment with bupropion or naltrexone within 12 months prior to screening
  • History of hypersensitivity or intolerance to bupropion or naltrexone
  • Changes in smoking status or in tobacco or nicotine use within 3 months prior to screening or planned during study participation
  • Participated in a weight loss management program within one month prior to randomization
  • Females who were pregnant or breast-feeding or planned 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

Trial locations and contacts

53 sites in 1 country.

53 sites in 1 country

United States53 sites

  • Lovelace Scientific Resources

    Albuquerque, New Mexico, 87108

  • CSRA Partners in Health, Inc

    Augusta, Georgia, 30909

  • Health Trends Research, LLC

    Baltimore, Maryland, 21209

  • Pennington Biomedical Research Center

    Baton Rouge, Louisiana, 70808

  • Impact Clinical Trials

    Beverly Hills, California, 90211

  • Twin Cities Clinical Research

    Brooklyn Center, Minnesota, 55430

  • Northern California Research

    Carmichael, California, 98608

  • Metrolina Medical Research

    Charlotte, North Carolina, 28209

  • ClinSearch

    Chattanooga, Tennessee, 37404

  • Rapid Medical Research, Inc.

    Cleveland, Ohio, 44122

  • Central Ohio Nutrition Center, Inc.

    Columbus, Ohio, 43213

  • The Cooper Institute

    Dallas, Texas, 75230

  • Baylor Endocrine Center

    Dallas, Texas, 75246

  • Endocrinology & Diabetes Consultants

    Dover, New Hampshire, 03820

  • Deaconess Clinic

    Evansville, Indiana, 47713

  • SelfCenter, PC

    Fairhope, Alabama, 36532

  • Diabetes care and Information Center

    Flushing, New York, 11365

  • LCFP Inc.

    Fort Myers, Florida, 33907

  • Sierra Medical Research

    Fresno, California, 93710

  • Mountain View Clinical Research

    Greer, South Carolina, 29349

  • East-West Medical Research Institute

    Honolulu, Hawaii, 96814

  • HealthStar Research

    Hot Springs, Arkansas, 71913

  • The Center for Pharmaceutical Research

    Kansas City, Missouri, 64114

  • Wells Institute for Health Awareness

    Kettering, Ohio, 45429

  • Central Kentucky Research Associates, Inc.

    Lexington, Kentucky, 40509

  • L-Marc

    Louisville, Kentucky, 40213

  • Trover Center for Clinical Studies

    Madisonville, Kentucky, 42431

  • Central New York Clinical Research

    Manlius, New York, 13104

  • Your Diabetes Endocrine and Nutrition Group

    Mentor, Ohio, 44060

  • Miami Research Associates

    Miami, Florida, 33143

  • Diabetes Center of the Southwest

    Midland, Texas, 79705

  • Palmetto Medical Research

    Mt. Pleasant, South Carolina, 29464

  • Clinical Research Associates, Inc.

    Nashville, Tennessee, 37203

  • Advance Clinical Research Institute

    Orange, California, 92869

  • Suncoast Clinical Research

    Palm Harbor, Florida, 34684

  • University Clinical Research

    Pembroke Pines, Florida, 33024

  • Pivotal Research Centers

    Peoria, Arizona, 85381

  • HOPE Research Institute

    Phoenix, Arizona, 85050

  • Center for Nutrition and Metabolic Diseases, Univ. of Nevada

    Reno, Nevada, 89557

  • Rochester Clinical Research, Inc

    Rochester, New York, 14609

  • InVisions Consultants, LLC

    San Antonio, Texas, 78217

  • Diabetes & Glandular Disease Research Associates, Inc.

    San Antonio, Texas, 78229-4801

  • Affiliated Research Institute

    San Diego, California, 92108

  • VA San Diego Healthcare System

    San Diego, California, 92161

  • Apex Research Institue

    Santa Ana, California, 92705

  • Summit Research Network, Inc.

    Seattle, Washington, 98104

  • Medical Research Institute

    Slidell, Louisiana, 70458

  • Northside Internal Medicine

    Spokane, Washington, 99208

  • FutureCare Studies

    Springfield, Massachusetts, 01103

  • Mercy Health Research

    St Louis, Missouri, 63141

  • Radiant Research, Inc.

    St Louis, Missouri, 63141

  • Northwest Indiana Center for Clinical Research

    Valparaiso, Indiana, 46383

  • Chase Medical Research, LLC

    Waterbury, Connecticut, 06708

Other trials in United States

About this study

Official title: A Multicenter, Randomized, Double Blind, Placebo Controlled Study Comparing the Safety and Efficacy of Naltrexone 32 mg Sustained Release (SR)/Bupropion 360 mg Sustained Release (SR) and Placebo in Obese Subjects With Type 2 Diabetes Mellitus

The purpose of this study is determine whether the combination of naltrexone SR and bupropion SR is safe and effective in treating obesity in subjects with type 2 diabetes.

Read the detailed description

Optimal care of patients with diabetes mellitus includes vigorous and persistent efforts to achieve physiologic control of blood glucose as well as other often associated conditions including hypertension, dyslipidemia and excess weight. Pharmacologic interventions for the treatment of obesity in type 2 diabetes have shown significant reductions in HbA1c. 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 the combination of naltrexone SR and bupropion SR compared to placebo in obese subjects with type 2 diabetes mellitus.

Being tested
Naltrexone SR 32 mg/bupropion SR 360 mg/ day, Placebo, Ancillary therapy
Keywords
Obesity, Overweight, Diabetes Mellitus, Type 2
Medical subject headings
Obesity, Overweight, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Naltrexone SR 32 mg/bupropion SR 360 mg/ dayDrug

    Also called NB32

  • PlaceboDrug

  • Ancillary therapyBehavioural

    Ancillary therapy consisting of diet instruction, advice on behavior modification, and exercise counseling

Study groups in NCT00474630
Study groupRoleWhat they receive
NB32ExperimentalNaltrexone SR 32 mg/bupropion SR 360 mg/ day with ancillary therapy
Receives: Drug: Naltrexone SR 32 mg/bupropion SR 360 mg/ day; Behavioral: Ancillary therapy
PlaceboPlacebo comparatorPlacebo with ancillary therapy
Receives: Drug: Placebo; Behavioral: Ancillary therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Co-primary: Body Weight- Mean Percent Change

    Measured: Baseline, 56 weeks

  2. Co-primary: Body Weight- Proportion of Subjects With ≥5% Decrease

    Measured: Baseline, 56 weeks

Secondary outcomes (23)

  1. Change in HbA1c Levels

    Measured: Baseline, 56 weeks

  2. Change in Fasting Triglycerides Levels, Using Log-transformed Data

    Measured: Baseline, 56 weeks

  3. Change in Fasting HDL Cholesterol Levels

    Measured: Baseline, 56 weeks

  4. Change in Fasting Blood Glucose Levels

    Measured: Baseline, 56 weeks

  5. Change in Waist Circumference

    Measured: Baseline, 56 weeks

  6. Body Weight- Proportion of Subjects With ≥10% Decrease

    Measured: Baseline, 56 weeks

  7. HbA1c- Proportion of Subjects With HbA1c <7% at Endpoint

    Measured: Baseline, 56 weeks

  8. Percent of Subjects Requiring Rescue Medications for Diabetes

    Measured: Baseline, 56 weeks

  9. Percent of Subjects With Dose Reduction in Oral Antidiabetes Medications

    Measured: Baseline, 56 weeks

  10. Percent of Subjects With Dose Increase in Oral Antidiabetes Medications

    Measured: Baseline, 56 weeks

  11. Change in HOMA-IR Levels, Using Log-transformed Data

    HOMA-IR= Homeostasis Model Assessment-Insulin Resistance

    Measured: Baseline, 56 weeks

  12. Change in Fasting Insulin Levels, Using Log-transformed Data

    Measured: Baseline, 56 weeks

  13. HbA1c- Proportion of Subjects With HbA1c <6.5% at Endpoint

    Measured: Baseline, 56 weeks

  14. 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

    Measured: Baseline, 56 weeks

  15. Change in High-sensitivity C Reactive Protein (Hs-CRP) Levels, Using Log-transformed Data

    Measured: Baseline, 56 weeks

  16. Percent of Subjects Discontinuing Due to Poor Glycemic Control

    Due to pre-specified hypothesis testing design, no formal statistical inference testing was performed. Odds ratio not calculated as there were no subjects in the NB32 group that discontinued due to poor glycemic control.

    Measured: Baseline, 56 weeks

  17. 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

    Measured: Baseline, 56 weeks

  18. Change in Fasting LDL Cholesterol Levels

    Measured: Baseline, 56 weeks

  19. Change in Systolic Blood Pressure

    Measured: Baseline, 56 weeks

  20. Change in Diastolic Blood Pressure

    Measured: Baseline, 56 weeks

  21. 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.

    Measured: Baseline, 56 weeks

  22. 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).

    Measured: Baseline, 56 weeks

  23. 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).

    Measured: Baseline, 56 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionJun 2009
  4. Study completionJun 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
505 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00474630
Sponsor's protocol ID
NB-304
Other IDs
COR-Diabetes
Status last verified
Nov 2014
First submitted
15 May 2007
Last updated
21 Nov 2014
Data monitoring committee
Yes

Publications

  • Hollander P, Gupta AK, Plodkowski R, Greenway F, Bays H, Burns C, Klassen P, Fujioka K; COR-Diabetes Study Group. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013 Dec;36(12):4022-9. doi: 10.2337/dc13-0234. Epub 2013 Oct 21.

    PubMed 24144653

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Naltrexone SR 32 mg/bupropion SR 360 mg/ day and Ancillary therapy in people with Obesity and Overweight, run by Orexigen Therapeutics, Inc at 53 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Co-primary: Body Weight- Mean Percent Change (time frame: Baseline, 56 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00474630, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2014; AzTrials last refreshed its copy on 1 Nov 2026.

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