Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults.
Ontology highlight
ABSTRACT:
SUBMITTER: Sherman MM
PROVIDER: S-EPMC4771085 | biostudies-other | 2016 Mar
REPOSITORIES: biostudies-other
Publications
Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults.
Sherman Matthew M MM Ungureanu Sinziana S Rey Jose A JA
P & T : a peer-reviewed journal for formulary management 20160301 3
Naltrexone/bupropion ER (Contrave): newly approved treatment option for chronic weight management in obese adults. ...[more]
Similar Datasets
Project description:In March 2010, Orexigen(R) Therapeutics submitted a new drug application (NDA) for approval of naltrexone sustained release (SR)/bupropion SR (Contrave(R)) for the treatment of obesity in the US. The tablet contains naltrexone SR 32 mg and bupropion SR 360 mg. The drug has been tested in four randomized, double-blind, placebo-controlled, phase III trials and the co-primary endpoints were met in each case. This review discusses the key development milestones and clinical trial program to date.
| S-EPMC3586099 | biostudies-literature
Project description:Objective. The pharmacology, pharmacokinetics, efficacy, and safety of bupropion plus naltrexone for weight loss were reviewed. Data Sources. A MEDLINE search (1970 to November 2015) was conducted for English-language articles using specific MESH terms. Study Selection and Data Extraction. Published Phase 3 clinical trials with primary endpoints related to weight loss were included and critiqued in this review. Study Selection and Data Extraction. Five trials were retrieved and reviewed regarding the efficacy and safety of bupropion plus naltrexone among obese and overweight patients. Data Synthesis. Bupropion is a dopamine/norepinephrine reuptake inhibitor, and naltrexone is an opioid receptor antagonist. The combination of these agents has led to increased weight loss, compared to placebo, among overweight and obese patients with a body mass index (BMI) at or above 30 or BMI at or above 27 with a comorbid condition. The combination of bupropion and naltrexone can produce an average placebo-subtracted weight loss of 4.25% over 56 weeks. Gastrointestinal (ie, nausea, vomiting, constipation) and central nervous system adverse events (ie, headache, dizziness) were commonly reported, and there was a high dropout rate among participants. Conclusions. Bupropion plus naltrexone has demonstrated effective weight loss, in conjunction with lifestyle modifications, among overweight and obese patients with and without comorbidities. Bupropion plus naltrexone has not been studied among special patient populations, such as those with sleep apnea, osteoarthritis, or extreme BMIs. Additional clinical trials and postmarketing data will provide a better understanding of this medication for weight loss.
| S-EPMC5998459 | biostudies-other
Project description:Objective: The rates of obesity and cigarette smoking are much higher in patients with schizophrenia compared to the general population. This study was to examine whether naltrexone and bupropion combination treatment can help weight loss and smoking cessation in patients with schizophrenia. Methods: Obese male schizophrenia patients with current cigarette smoking were randomized to receive adjunctive naltrexone (25 mg/day) and bupropion (300 mg/day) combination or placebo for 24 weeks. Twenty-two patients were enrolled in the study, and 21 patients completed the study (11 in the treatment group, and 10 in the placebo group). Body weight, body mass index (BMI), fasting lipids, smoking urge, expired carbon monoxide (CO) level and cigarettes smoked per week were measured at baseline and week 24. Results: There was no significant difference between two groups in changes in weight, BMI, fasting lipids, or cigarette smoking measures (p's > 0.05) Conclusion: Naltrexone and bupropion combination treatment didn't show weight loss or smoking cessation effect in patients with schizophrenia in this pilot study.Implications for future studies were discussed. ClinicalTrials.gov identifier: NCT02736474.
| S-EPMC5850123 | biostudies-literature
Project description:To assess the efficacy and safety of 32 mg naltrexone sustained-release (SR)/360 mg bupropion SR (NB) in overweight/obese individuals with type 2 diabetes with or without background oral antidiabetes drugs.This was a 56-week, double-blind, placebo-controlled study in which 505 patients received standardized lifestyle intervention and were randomized 2:1 to NB or placebo. Coprimary end points were percent weight change and achievement of ?5% weight loss. Secondary end points included achievement of HbA1c <7% (53 mmol/mol), achievement of weight loss ?10%, and change in HbA1c, waist circumference, fasting blood glucose, and lipids.In the modified intent-to-treat population (54% female, 80% Caucasian, and mean age 54 years, weight 106 kg, BMI 37 kg/m(2), and HbA1c 8.0% [64 mmol/mol]), NB resulted in significantly greater weight reduction (-5.0 vs. -1.8%; P < 0.001) and proportion of patients achieving ?5% weight loss (44.5 vs. 18.9%, P < 0.001) compared with placebo. NB also resulted in significantly greater HbA1c reduction (-0.6 vs. -0.1% [6.6 vs. 1.1 mmol/mol]; P < 0.001), percent of patients achieving HbA1c <7% (53 mmol/mol) (44.1 vs. 26.3%; P < 0.001), and improvement in triglycerides and HDL cholesterol compared with placebo. NB was associated with higher incidence of nausea (42.3 vs. 7.1%), constipation (17.7 vs. 7.1%), and vomiting (18.3 vs. 3.6%). No difference was observed between groups in the incidence of depression, suicidal ideation, or hypoglycemia.NB therapy in overweight/obese patients with type 2 diabetes induced weight loss, which was associated with improvements in glycemic control and select cardiovascular risk factors and was generally well tolerated with a safety profile similar to that in patients without diabetes.
| S-EPMC3836105 | biostudies-literature
Project description:Introduction:The objective of this pilot randomized controlled trial was to investigate the combined effect of a Mediterranean diet and naltrexone/bupropion treatment on body weight, metabolic parameters, and quality of life in overweight or obese breast cancer survivors. Methods:Forty-four breast cancer survivors were randomly assigned to receive the Mediterranean diet plus naltrexone/bupropion medication (breast cancer survivor MeDiet+NB group) or the Mediterranean diet alone (breast cancer survivor MeDiet-only group). Twenty-eight age-matched non-cancer patients were instructed to consume the Mediterranean diet plus naltrexone/bupropion medication (non-cancer MeDiet+NB group). After the 8-week intervention, changes in body weight, metabolic parameters, nutrient intake, and quality of life of the three groups were assessed. Results:Significant weight loss of 2.8 kg was noted for the breast cancer survivor MeDiet+NB group, 1.8 kg for the breast cancer survivor MeDiet-only group, and 2.5 kg for the non-cancer MeDiet+NB group after 8 weeks (P < 0.05 versus baseline by Wilcoxon's signed-rank test). All three groups also exhibited significantly lower fasting glucose, insulin, and homeostasis model assessment of insulin resistance levels (P < 0.05). Quality of life as assessed by self-reported questionnaires showed improvement in all participants (P < 0.05). However, there were no significant differences of changes in body weights, metabolic parameters, and quality of life among the three groups or between the MeDiet+NB and MeDiet-only groups. Conclusion:We found that the Mediterranean diet, with or without naltrexone/bupropion treatment, facilitates weight loss, improves metabolic parameters, and increases quality of life. The combination of the Mediterranean diet with naltrexone/bupropion treatment did not produce superior changes when compared to the Mediterranean diet alone. Trial Registration:This trial was retrospectively registered on 10 July 2018 as NCT03581630 at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03581630).
| S-EPMC7532917 | biostudies-literature
Project description:BackgroundThe use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.MethodsWe conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.ResultsA total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial.ConclusionsAmong adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).
| S-EPMC8111570 | biostudies-literature
Project description:To evaluate the effect of 32-mg/d naltrexone sustained release and 360-mg/d bupropion sustained release (NB32) in overweight and obese patients with major depressive disorder (MDD).Twenty-five female patients with a DSM-IV diagnosis of MDD, an Inventory of Depressive Symptomatology-Self-Report score > 26, and a body mass index ? 27 and ? 43 kg/m(2) received up to 24 weeks of open-label treatment with NB32 with dietary and behavioral counseling (data collection: March 2008-July 2009). The primary endpoint was change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 12 weeks; secondary endpoints included MADRS total score at week 24, change in weight, and Clinical Global Impressions-Improvement scale responder status (CGI-I score ? 2) at weeks 12 and 24 (modified intent-to-treat [mITT]: patients with ? 1 postbaseline MADRS total score on study drug; N = 23).MADRS scores showed significant reductions at weeks 12 and 24 (mITT-last observation carried forward [LOCF]: -13.1 ± 7.1 and -15.3 ± 8.1, respectively, P < .001 vs baseline for all). Mean ± SD weight loss was -4.0% ± 4.6% (mITT-LOCF) and -6.1% ± 4.7% (observed cases) at week 12 and -5.3% ± 6.5% (mITT-LOCF) and -9.2% ± 6.2% (observed cases) at week 24 (P < .001 vs baseline for all). By week 24, 95% of patients (mITT-LOCF) were responders (CGI-I score ? 2) and 70% were in remission (CGI-I score = 1). The safety/tolerability profile of NB32 was consistent with its individual components; the most common adverse events were nausea, constipation, headache, and insomnia, with no serious adverse events attributed to NB32.Twenty-four weeks of open-label NB32 therapy with dietary and behavioral counseling was associated with improvement in depressive symptoms and reduced body weight in overweight/obese women with MDD.ClinicalTrials.gov Identifier: NCT00624858.
| S-EPMC3795584 | biostudies-literature
Project description:This study assessed the effects of 32 mg naltrexone sustained release (SR)/360 mg bupropion SR (NB) on body weight in adults with obesity, with comprehensive lifestyle intervention (CLI), for 78 weeks.In this phase 3b, randomized, open-label, controlled study, subjects received NB?+?CLI or usual care (standard diet/exercise advice) for 26 weeks. NB subjects not achieving 5% weight loss at week 16 were discontinued, as indicated by product labeling. After week 26, usual care subjects began NB?+?CLI. Assessments continued through week 78. The primary end point was percent change in weight from baseline to week 26 in the per protocol population. Other end points included percentage of subjects achieving ?5%, ?10%, and ?15% weight loss, percent change in weight at week 78, and adverse events (AEs) necessitating study medication discontinuation.NB?+?CLI subjects lost significantly more weight than usual care subjects at week 26 (8.52% difference; P < 0.0001). Weight loss persisted through 78 weeks. In total, 20.7% of subjects discontinued medication for AEs, including 7.0% for nausea.Treatment with NB, used as indicated by prescribing information and with CLI, significantly improved weight loss over usual care alone. NB-facilitated weight loss was sustained for 78 weeks and was deemed safe and well tolerated.
| S-EPMC5299461 | biostudies-literature
Project description:Obesity is an emerging disease worldwide. Changes in living habits, especially with increased consumption of high-calorie foods and decreased levels of physical activity, lead to an energy imbalance that brings weight gain. Overweight and obesity are major risk factors for several chronic diseases (including cardiovascular diseases, diabetes, and cancer), reduce quality of life, and are associated with higher mortality. For all these reasons, it is of the utmost importance that the trend be reversed and obese people enabled to lose weight. It is known that eating a healthy diet and exercising regularly can help prevent obesity, but data show that in many cases these steps are not enough. This is the reason why, over the last few decades, several antiobesity drugs have been developed. However, the disappointing results demonstrated for the vast majority of them have not discouraged the pharmaceutical industry from continuing to look for an effective drug or combination of drugs. The systematic review presented here focuses on naltrexone sustained-release/bupropion sustained-release combination (Contrave(®)). We conclude from the current published reports that its effectiveness in the treatment of obesity can be estimated as a placebo-subtracted weight loss of around 4.5%. This weight reduction is moderate but similar to other antiobesity drugs. The safety profile of this combination is acceptable, despite additional data regarding cardiovascular disease being needed.
| S-EPMC4174046 | biostudies-other
Project description:ObjectiveTo examine the effects of naltrexone/bupropion (NB) combination therapy on weight and weight-related risk factors in overweight and obese participants.Design and methodsCONTRAVE Obesity Research-II (COR-II) was a double-blind, placebo-controlled study of 1,496 obese (BMI 30-45 kg/m(2) ) or overweight (27-45 kg/m(2) with dyslipidemia and/or hypertension) participants randomized 2:1 to combined naltrexone sustained-release (SR) (32 mg/day) plus bupropion SR (360 mg/day) (NB32) or placebo for up to 56 weeks. The co-primary endpoints were percent weight change and proportion achieving ≥ 5% weight loss at week 28.ResultsSignificantly (P < 0.001) greater weight loss was observed with NB32 versus placebo at week 28 (-6.5% vs. -1.9%) and week 56 (-6.4% vs. -1.2%). More NB32-treated participants (P < 0.001) experienced ≥ 5% weight loss versus placebo at week 28 (55.6% vs. 17.5%) and week 56 (50.5% vs. 17.1%). NB32 produced greater improvements in various cardiometabolic risk markers, participant-reported weight-related quality of life, and control of eating. The most common adverse event with NB was nausea, which was generally mild to moderate and transient. NB was not associated with increased events of depression or suicidality versus placebo.ConclusionNB represents a novel pharmacological approach to the treatment of obesity, and may become a valuable new therapeutic option.
| S-EPMC3739931 | biostudies-literature