Phentermine-Topiramate for Obesity

Overseen By Claudia Fox, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Must not be taking: Stimulants, MAO inhibitors

Disqualifiers: Diabetes, Bariatric surgery, Glaucoma, 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: 1

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, phentermine and topiramate, to help adolescents with severe obesity maintain weight loss. The goal is to prevent weight regain after initial weight loss achieved through a special meal plan. Researchers aim to determine if these medications can reduce appetite and increase energy use, making it easier to maintain weight loss. Adolescents with severe obesity who have successfully lost weight through meal replacements might be suitable candidates for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as anti-obesity drugs and stimulant medications, before joining. If you are currently using any of these, you will need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of phentermine and topiramate is generally well-tolerated by people with obesity. Studies have found that this treatment can lead to significant weight loss, with some individuals losing up to 13% of their body weight.

The treatment is considered safe for most people, with mild side effects such as dry mouth, tingling in the fingers and toes, dizziness, and changes in taste. More serious side effects are rare but can include a faster heart rate and mood changes.

The FDA has approved the combination of phentermine and topiramate for weight loss in adults, indicating its safety for this group. Although researchers are studying its use in teenagers, early data suggest it is also safe for younger people.

Overall, this treatment has been shown to aid in weight loss and is fairly safe for most individuals. However, careful monitoring is important, especially for heart health and mood. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Phentermine-Topiramate is unique because it combines two active ingredients that work together to promote weight loss. Phentermine acts as an appetite suppressant, while Topiramate is believed to alter taste perception and increase feelings of fullness. This dual-action approach sets it apart from standard treatments like orlistat, which focuses primarily on reducing fat absorption. Researchers are particularly excited about Phentermine-Topiramate as it has shown promising results in achieving significant weight loss, potentially offering a more effective and comprehensive solution for obesity management compared to existing therapies.

What evidence suggests that phentermine-topiramate might be an effective treatment for obesity?

Research shows that the combination of phentermine and topiramate, which participants in this trial may receive, can aid in weight loss. In earlier studies, people taking this medication lost up to 13% of their body weight, while those on a placebo lost significantly less. This treatment reduces appetite and enhances feelings of fullness, supporting long-term weight loss. It may also boost energy use, making it easier to maintain weight loss. Overall, this combination is considered safe and effective for adult weight management and might also benefit teenagers. ^{2 3 6 7 8}

Who Is on the Research Team?

Aaron Kelly, PhD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

Adolescents aged 12-17 with severe obesity (BMI ≥120% of the 95th percentile or BMI ≥35 kg/m2) can join this trial. They must not be using stimulants, have diabetes, major psychiatric disorders, uncontrolled hypertension, or a history of certain medical conditions like kidney stones. Sexually active females must use two forms of contraception.

Inclusion Criteria

I am between 12 and 17 years old, in puberty stage 2 or higher, and agree to use two forms of birth control if sexually active.

I am severely obese according to BMI standards.

Exclusion Criteria

I have a history of glaucoma.

ALT or AST >/= 3 times the upper limit of normal

You currently smoke or use tobacco products.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Meal Replacement Therapy

Participants undergo a short-term meal replacement induction period to achieve at least 5% BMI reduction

6 weeks

Weekly visits for monitoring

Treatment

Participants receive phentermine/topiramate or placebo to maintain weight loss

52 weeks

Visits at Baseline, 1 day of Randomization, Week 26, and Week 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phentermine-Topiramate

Trial Overview The trial is testing if phentermine-topiramate can help maintain weight loss after meal replacement therapy in adolescents with severe obesity. It compares this drug combination to a placebo and measures its effects on appetite control and energy expenditure.

How Is the Trial Designed?

Group I: Meal Replacement Therapy Experimental Treatment 1 Intervention

Participants who are enrolled in the study will be administered a short-term (six weeks) meal replacement induction period. Because the trial is deigned to evaluate weight loss maintenance, participants must achieve at least 5% BMI reduction at week six of the meal replacement period in order to be randomized. Subjects will be asked to strictly follow the eating regimen, which will include a total of approximately 1,000 kcals per day of commercially-available liquid shakes (breakfast and lunch), pre-packaged frozen entrée meals for dinner, two servings of fruit, and three servings of vegetables. Shakes/meals will be provided free of charge - fruits/vegetables will be purchased by the participants. Guidance will be provided regarding the use of the meal replacement shakes at school, and participants will be encouraged to engage in family meal sessions despite eating different foods.

Group II: Phentermine/Topiramate Active Control 2 Interventions

Participants who achieve at least 5% BMI reduction at week six of the meal replacement period will be randomized (1:1) to receive either phentermine/topiramate or placebo. Participants randomized to phentermine/topiramate will start treatment at 3.75 mg/23 mg orally once daily in the morning for 14 days, then increased to 7.5 mg/46 mg orally once daily in the morning for 14 days, then be increased to 11.25 mg/69 mg orally once daily in the morning for 14 days, then increased to 15 mg/92 mg orally once daily in the morning for the remainder of the trial. Following the final study visit, participants will be down-titrated gradually by taking medication every other day for seven days before stopping treatment altogether.

Group III: Placebo Placebo Group 2 Interventions

Participants who achieve at least 5% BMI reduction at week six of the meal replacement period will be randomized (1:1) to receive either phentermine/topiramate or placebo. Participants randomized to the placebo will receive inert tablets that look like the active comparator. In order to mimic the active comparator arm, subjects randomized to the placebo arm will up titrate their placebo at the beginning of the study treatment and will down titrate as in the active comparator arm. Participants will be instructed to take the medication under the supervision of a parent/guardian and pill counts of returned product will serve as a proxy of treatment compliance.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

Phentermine/topiramate extended-release capsules (Qsymia) have been shown to be effective for weight loss, as indicated by clinical studies that demonstrate significant reductions in body weight among participants.

The combination of phentermine, an appetite suppressant, and topiramate, which may help reduce cravings, works synergistically to enhance weight loss outcomes compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine/Topiramate extended-release capsules (qsymia) for weight loss. Lonneman, DJ., Rey, JA., McKee, BD.[2021]

Phentermine/topiramate controlled-release (PHEN/TPM CR) led to significant weight loss of 8.1-10.9% in patients, compared to only 1.4-1.8% in placebo groups, and also reduced waist circumference and improved metabolic markers like blood pressure and lipid profiles.

The treatment was generally well-tolerated, with severe adverse events being similar to those in placebo groups, although common side effects included paresthesia, dry mouth, and insomnia. Long-term safety and efficacy still need further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the metabolic effects of controlled-release Phentermine/Topiramate. Kiortsis, DN.[2019]

Qsymia™, a combination of phentermine and topiramate, has been shown to produce greater weight loss than either drug alone, making it an effective treatment for obesity since its approval in 2012.

While Qsymia™ is effective, it carries potential risks such as teratogenicity, increased heart rate, psychiatric and cognitive side effects, and metabolic acidosis, which are consistent with the known side effects of its individual components.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity. Shin, JH., Gadde, KM.[2021]

In a 108-week study involving 676 overweight and obese participants with cardiometabolic disease, controlled-release phentermine/topiramate (PHEN/TPM CR) led to significant and sustained weight loss compared to placebo, with mean percentage changes in body weight of -9.3% and -10.5% for the lower and higher doses, respectively.

PHEN/TPM CR not only facilitated weight loss but also improved cardiovascular and metabolic health, showing a reduction in diabetes incidence, and was well tolerated over the study duration, with fewer adverse events reported in the second half of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year sustained weight loss and metabolic benefits with controlled-release phentermine/topiramate in obese and overweight adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Garvey, WT., Ryan, DH., Look, M., et al.[2023]

Phentermine/topiramate (Qsymia®) is a combination medication approved in July 2022 for chronic weight management in pediatric patients aged 12 and older with obesity, specifically those with a BMI in the 95th percentile or greater.

This medication works by decreasing appetite and increasing feelings of fullness, and it is also being studied for other conditions like sleep apnea and type 2 diabetes in obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine/Topiramate: Pediatric First Approval. Dhillon, S.[2022]

Qsymia™, a once-daily oral capsule combining phentermine and extended-release topiramate, has been approved in the US for treating obesity, leveraging phentermine's appetite-suppressing effects and topiramate's ability to increase feelings of fullness.

The formulation is also being explored for potential benefits in treating sleep apnea and type 2 diabetes, indicating its broader therapeutic applications beyond weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine and topiramate extended release (Qsymia™): first global approval. Cameron, F., Whiteside, G., McKeage, K.[2021]

The approval of phentermine/topiramate in 2012 led to a significant increase in the initiation rate of topiramate among patients with obesity, rising more than 2.5 times in early 2013, indicating a shift in prescribing patterns.

Despite the increased use of topiramate, it is important for healthcare providers to educate patients about the risks associated with its use, especially regarding prenatal exposure, as it lacks the same Risk Evaluation and Mitigation Strategy (REMS) that phentermine/topiramate has.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topiramate Utilization After Phentermine/Topiramate Approval for Obesity Management: Risk Minimization in the Era of Drug Repurposing. Sarayani, A., Hampp, C., Brown, JD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3814438/

Phentermine/Topiramate Extended-Release Capsules ... At week 108, rates of weight loss were 1.8% for placebo, 9.3% for 7.5/46 mg, and 10.7% for 15/92 mg. Significantly more treated patients lost 5%, 10%, 15%, and ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1071916425004622

Safety and Efficacy of Phentermine and Topiramate for ... The combination of phentermine and topiramate has demonstrated sustained weight loss of up to 13% in patients with obesity, with a favorable ...

3. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.16119

Evaluation of the efficacy and safety of controlled‐release ... This trial revealed that PHEN/TPM CR treatment led to a greater reduction in body weight and adiposity compared with placebo in Korean adults ...

4. ema.europa.eu ema.europa.eu/en/documents/other/qsiva-epar-scientific-conclusions-and-grounds-refusal-marketing-authorisation-qsiva_en.pdf

Qsiva - INN, phentermine/topiramate - EMA Treatment with Qsiva 7.5/46 mg and 15/92 mg for 28 and 56 weeks resulted in clinically relevant reductions of body weight, with a maximum effect after approx. ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00599-6/fulltext

Safety and effects of anti-obesity medications on weight ... Combination therapies, such as naltrexone/bupropion and phentermine/topiramate, exhibited superior weight-loss effects compared to monotherapies ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11743856/

Safety and effects of anti-obesity medications on weight loss ... Primary outcomes included changes in body weight, cardiometabolic indicators, psychological outcomes, and adverse events. Summary data was ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33864346/

Efficacy and Safety of Phentermine/Topiramate in Adults ... Results: Phentermine/topiramate therapy resulted in an average weight loss of 7.73 kg (95% CI: 6.60-8.85) in general compared with placebo. The weight loss was ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06299891

Efficacy and Safety of Phentermine/Topiramate in Youth ... In this pilot trial, our objective is to gather key preliminary data about phentermine/topiramate (Ph/T) that is FDA-approved for "common" obesity but has never ...