Naltrexone + Bupropion for Obesity

(INFORMUS Trial)

Recruiting at 124 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

Trial Summary

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 data supports the effectiveness of the drug Naltrexone-Bupropion for obesity?

Research shows that the drug Naltrexone-Bupropion, when combined with a reduced-calorie diet and increased physical activity, helps people with obesity lose weight more effectively than a placebo. In studies, more patients taking this drug lost at least 5% to 10% of their body weight compared to those not taking it, and it also improved other health factors like blood sugar levels in people with type 2 diabetes. ^{1 2 3 4 5}

Is the Naltrexone + Bupropion combination safe for humans?

The Naltrexone + Bupropion combination, used for weight management, is generally well tolerated in humans, with nausea being the most common side effect. ^{1 2 5 6 7}

What makes the drug Naltrexone-Bupropion unique for obesity treatment?

Naltrexone-Bupropion is unique because it combines two medications, naltrexone and bupropion, to help with weight loss when used alongside a reduced-calorie diet and increased physical activity. This combination has been shown to be more effective than a placebo in reducing body weight and improving related health factors like blood sugar levels in people with obesity or overweight individuals with conditions like diabetes or high blood pressure. ^{1 2 6 8 9}

What is the purpose of this trial?

This trial studies the effects of a medication combination (naltrexone and bupropion) on heart health. It targets patients to see if this treatment increases the risk of major heart problems. The study also includes advice on diet and exercise. Naltrexone and bupropion have been used in combination for weight loss, but they have been associated with various adverse effects, including neuropsychiatric disorders and cardiovascular risks.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Naltrexone ER/Bupropion ER: A Review in Obesity Management. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Method-of-use study of naltrexone sustained release (SR)/bupropion SR on body weight in individuals with obesity. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults. [2020]

4. United States 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. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion for obesity. [2018]

7. England pubmed.ncbi.nlm.nih.gov

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Naltrexone/bupropion: an investigational combination for weight loss and maintenance. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

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