Naltrexone + Bupropion for Obesity

(INFORMUS Trial)

Recruiting at 127 trial locations

Overseen By Hany Salama, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Currax Pharmaceuticals

Must not be taking: Bupropion, Opioids, MAOIs, others

Disqualifiers: Recent MI, Stroke, Hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

8600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medicines, naltrexone and bupropion, to assess their effects on heart health in individuals who are overweight or obese. Researchers aim to determine if this treatment safely improves outcomes for those at risk of heart issues. Participants will receive either the actual medicine or a placebo (a pill with no active ingredients) to compare results. Ideal participants are those who are overweight, have conditions like diabetes or high blood pressure, and are at risk for heart problems. As a Phase 4 trial, this research seeks to understand how the already FDA-approved treatment benefits a broader patient population.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of 2 weeks or 5 half-lives, whichever is longer, for prohibited medications. You may need to stop some medications, especially if they are not allowed during the trial.

What is the safety track record for the Naltrexone-Bupropion (NB) combination?

Research shows that using naltrexone and bupropion together aids in weight loss and is generally safe. Studies have found that this combination can promote weight loss, though it may also increase side effects. Some research tracked patients for several years and found no major heart-related safety issues when the treatment was used for up to 12 months. While this combination is approved for weight management, trial participants should be aware of the possible side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the Naltrexone-Bupropion (NB) combination for obesity because it offers a dual-action approach that is different from many existing treatments. While standard options often focus on appetite suppression or fat absorption, NB targets both the brain's reward system and appetite regulation, thanks to its unique combination of naltrexone and bupropion. Naltrexone works to modulate the brain's response to food cravings, while bupropion aids in reducing appetite, potentially leading to more effective and sustained weight loss. This combination could offer a more comprehensive solution for managing obesity compared to treatments that rely on a single mechanism.

What is the effectiveness track record for Naltrexone-Bupropion in treating obesity?

In this trial, participants will be randomly assigned to receive either the Naltrexone-Bupropion (NB) combination or a placebo. Research has shown that using naltrexone and bupropion together can aid in weight loss. One study found that participants taking this combination lost an average of 9.5% of their body weight over 56 weeks, while those on a placebo lost only 2.7%. Another study found that after 12 weeks, patients could expect to lose at least 5% of their weight. This treatment is approved for obesity and has demonstrated significantly greater weight reduction than a placebo. While effective, it may also increase the risk of some side effects. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with obesity or overweight with conditions like hypertension, type 2 diabetes, or dyslipidemia. Participants must have a history of heart issues but stable for at least 90 days and not currently on other weight loss medications. They should understand the study and consent to participate.

Inclusion Criteria

Do you struggle with diabetes?

Do you have a doctor that you see, and would be able to obtain your past medical history records if needed?

Do you have a past history of any heart disease (i.e heart attack, cardiac stents, abnormal ekg )?

Exclusion Criteria

Have you experienced a heart attack or stroke within the last 90 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Naltrexone/Bupropion or placebo, with counseling for weight loss via a reduced-calorie diet and increased physical activity

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on cardiovascular outcomes

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Naltrexone-Bupropion (NB) Combination

Trial Overview The study tests if a combination drug (Naltrexone-Bupropion) affects major cardiovascular events compared to a placebo. It's randomized and double-blinded, meaning participants are put into groups by chance without knowing which treatment they receive.

How Is the Trial Designed?

Group I: Naltrexone/Bupropion (NB) Active Control 1 Intervention

Patients will be randomly assigned to NB (naltrexone 8 mg and bupropion 90 mg) extended-release oral tablet.

Group II: Placebo Placebo Group 1 Intervention

Patients will be randomly assigned to placebo.

Naltrexone-Bupropion (NB) Combination is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Contrave for:

• Chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m^2 or greater (obese) or 27 kg/m^2 or greater (overweight) in the presence of at least one weight-related comorbidity

Approved in European Union as Mysimba for:

• Management of weight in adults with an initial body mass index (BMI) of 30 kg/m^2 or greater (obese) or 27 kg/m^2 to < 30 kg/m^2 (overweight) in the presence of one or more weight-related comorbidities

Approved in Canada as Contrave for:

• Chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m^2 or greater (obese) or 27 kg/m^2 or greater (overweight) in the presence of at least one weight-related comorbidity

Who Is Running the Clinical Trial?

Currax Pharmaceuticals

Lead Sponsor

Trials

7

Recruited

77,000+

Published Research Related to This Trial

Naltrexone/bupropion ER, marketed as Contrave, is a newly approved medication specifically designed for chronic weight management in obese adults.

This combination therapy targets both appetite suppression and energy expenditure, offering a new option for individuals struggling with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults. Sherman, MM., Ungureanu, S., Rey, JA.[2020]

Naltrexone/bupropion, an investigational weight loss medication, resulted in a significant mean weight loss of 4.7% after one year in obese patients, with 26-33% of participants achieving at least 5% weight loss compared to placebo.

In addition to weight loss, naltrexone/bupropion improved various health markers, including waist circumference and triglyceride levels, and reduced hemoglobin A1c by approximately 0.5% in patients with diabetes, although it had some common side effects like nausea and dizziness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion: an investigational combination for weight loss and maintenance. Makowski, CT., Gwinn, KM., Hurren, KM.[2022]

In a 78-week study involving adults with obesity, the combination of 32 mg naltrexone sustained release and 360 mg bupropion sustained release (NB) with a comprehensive lifestyle intervention (CLI) led to significantly greater weight loss compared to usual care, with an 8.52% difference at week 26.

The weight loss achieved with NB and CLI was maintained over the entire study period, and the treatment was generally safe and well tolerated, although 20.7% of participants discontinued due to adverse events, primarily nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Method-of-use study of naltrexone sustained release (SR)/bupropion SR on body weight in individuals with obesity. Halseth, A., Shan, K., Walsh, B., et al.[2018]

In a 56-week study involving 505 overweight or obese individuals with type 2 diabetes, the combination of naltrexone and bupropion (NB) led to significantly greater weight loss (-5.0% vs. -1.8%) and a higher percentage of participants achieving at least 5% weight loss compared to placebo (44.5% vs. 18.9%).

NB therapy also improved glycemic control, with a greater reduction in HbA1c levels (-0.6% vs. -0.1%) and a higher proportion of patients reaching HbA1c <7% (44.1% vs. 26.3%), although it was associated with increased gastrointestinal side effects like nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Hollander, P., Gupta, AK., Plodkowski, R., et al.[2022]

Naltrexone sustained release (SR) combined with bupropion SR (Contrave) has been submitted for FDA approval as a treatment for obesity, showing promise in clinical trials.

The drug has been tested in four phase III randomized, double-blind, placebo-controlled trials, successfully meeting co-primary endpoints in each trial, indicating its potential efficacy for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion: Contrave(R); naltrexone SR/bupropion SR. [2021]

Naltrexone/bupropion (Mysimba) is an effective treatment for adults who are obese or overweight with at least one weight-related health issue, and it is intended to be used alongside diet and lifestyle changes.

The combination product was licensed by the European Medicines Agency in 2015 and has recently been introduced in the UK, indicating its recognized safety and efficacy in managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion for obesity. [2018]

In 56-week phase III trials, naltrexone extended-release/bupropion extended-release (Contrave) significantly reduced body weight compared to placebo, with many patients achieving weight loss of 5% or more.

The treatment also led to notable improvements in cardiometabolic risk factors and glycated hemoglobin levels in overweight or obese adults with type 2 diabetes, and was generally well tolerated, with nausea being the most common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone ER/Bupropion ER: A Review in Obesity Management. Greig, SL., Keating, GM.[2018]

The combination of 32 mg naltrexone and 360 mg bupropion (NB32) led to significant weight loss of 5.0-9.3% over 56 weeks, with 45-66% of patients achieving at least 5% weight loss, indicating its efficacy as a weight management treatment.

NB32 also improved metabolic health by decreasing waist circumference, serum triglycerides, and insulin resistance, while increasing HDL cholesterol, although it was associated with mild side effects like nausea and a small increase in heart rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of the naltrexone/bupropion combination for the treatment of obesity: an update. Christou, GA., Kiortsis, DN.[2019]

Contrave, a combination of naltrexone and bupropion, was shown to be effective for weight loss in a large study involving 4536 adults over 56 weeks, with participants losing an average of 11-22 lbs (5-9 kg) compared to placebo.

In addition to weight loss, Contrave also led to significant improvements in cardiometabolic markers, highlighting its potential benefits beyond just weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion for the treatment of obesity and obesity with Type 2 diabetes. Apovian, CM.[2016]

Citations

1. curraxpharma.com curraxpharma.com/press-releases/currax-announces-obesityweek-data-showing-that-contrave-helps-curb-cravings-and-offers-marked-effectiveness-in-certain-populations-with-obesity/

Currax Announces ObesityWeek® Data Showing that ... The study further showed that patients taking CONTRAVE had an average weight loss of 9.5% at 56 weeks compared to 2.7% for placebo (p <0.0001).

2. prnewswire.com prnewswire.com/news-releases/currax-announces-obesityweek-data-showing-that-contrave-helps-curb-cravings-and-offers-marked-effectiveness-in-certain-populations-with-obesity-302604348.html

Currax Announces ObesityWeek® Data Showing that ... The study further showed that patients taking CONTRAVE had an average weight loss of 9.5% at 56 weeks compared to 2.7% for placebo (p <0.0001).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7098870/

Naltrexone–bupropion (Mysimba) in management of obesity Naltrexone–bupropion significantly reduces body weight by a small amount but significantly increases the risk of adverse events.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4771085/

Naltrexone/Bupropion ER (Contrave) - PubMed Central - NIH After 12 weeks of treatment with naltrexone/bupropion, a patient should have achieved at least a 5% weight loss since initiation of therapy. If this result is ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2667368125000142

Appropriate use of the fixed-dose, extended-release ... NB-ER is approved for the treatment of patients with obesity, with studies showing that patients can achieve significant weight reduction compared with placebo.

6. ema.europa.eu ema.europa.eu/en/news/ema-concludes-review-weight-management-medicine-mysimba

EMA concludes review of weight management medicine ... To date, studies have shown that there is no cardiovascular safety concern when Mysimba is used for up to 12 months. However, the data available ...

7. curraxpharma.com curraxpharma.com/press-releases/currax-pharmaceuticals-peer-reviewed-study-in-obesity-pillars-further-substantiates-cardiovascular-safety-profile-of-contrave-mysimba/

Currax Pharmaceuticals: Peer-Reviewed Study in Obesity ... This peer-reviewed study, based on electronic health record data from more than 24,600 patients followed for over 4.7 years, found no evidence ...