Phentermine-Topiramate + Lifestyle Intervention for Obesity

Overseen By Lisa L Morselli, MD PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Diabetes, Hypertension, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how combining a lifestyle intervention with the medication Phentermine-Topiramate can aid individuals with obesity. Researchers aim to understand how different bodies react to weight loss, particularly changes in metabolism (how the body uses energy). Participants will join a program featuring meal replacements and lifestyle coaching to support weight loss. The trial seeks individuals with a BMI of 30 or higher who do not have diabetes, heart, or kidney issues, and who do not use tobacco or recreational drugs. As an unphased trial, this study offers a unique opportunity to contribute to understanding obesity treatment and potentially benefit from personalized weight loss strategies.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have any of the listed conditions like diabetes, hypertension, or heart disease, you would not be eligible 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, used in this trial, has been well-studied. One study found that this treatment helped patients with obesity lose up to 13% of their body weight. Most people tolerated the treatment well. However, some possible side effects require attention. For example, one source mentions that phentermine-topiramate may cause a serious rash called Stevens-Johnson Syndrome, which includes symptoms like blisters and peeling skin.

Overall, while the treatment has been effective for weight loss, participants should discuss any concerns and monitor for side effects with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Phentermine-Topiramate treatment combined with a lifestyle intervention for obesity because it offers a dual approach to weight loss. Unlike current options that often focus solely on lifestyle changes or medication, this combination targets weight loss through both medication and structured lifestyle support. The meal replacement program, paired with lifestyle coaching, provides a hands-on, supportive method to maintain reduced calorie intake, which is not typically included in standard treatments. Additionally, the use of Phentermine-Topiramate, a combination drug, is designed to enhance weight loss more effectively than single medications by addressing multiple pathways involved in appetite and weight regulation. This comprehensive approach could lead to more effective and sustainable weight loss outcomes for individuals struggling with obesity.

What evidence suggests that Phentermine-Topiramate and Lifestyle Intervention could be effective for obesity?

Studies have shown that phentermine-topiramate, one of the treatments in this trial, helps people lose weight. In one study, participants taking this medication lost up to 10.7% of their starting weight after just over two years. Another study found that this treatment led to more weight loss than a placebo, a pill with no active medicine. Across different studies, participants consistently lost more weight with phentermine-topiramate than without it. These findings suggest that phentermine-topiramate can effectively manage obesity when combined with lifestyle changes, another component of this trial. ^{3 6 7 8 9}

Who Is on the Research Team?

Lisa L Morselli, MD PhD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for individuals with a BMI of 30 or higher, from any ethnic background. It's not suitable for those with heart disease, active cancer, post-transplant patients, weight over 400 lbs., HIV/AIDS, pregnant or breastfeeding women, smokers, and people with liver or kidney disease, diabetes (type 1 or type 2), or hypertension.

Inclusion Criteria

BMI > or = 30 any ethnicity

Exclusion Criteria

I have diabetes.

I have liver disease.

I have heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are enrolled in a weight loss program based on lifestyle changes, including a 6-month subscription to a calorie-reduced meal replacement program with lifestyle coaching

6 months

Every 2 months (in-person)

Follow-up

Participants are monitored for changes in metabolic rate and hormone levels after weight loss

12 months

Every 6 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lifestyle Intervention with Meal Replacement Program
• Phentermine-Topiramate

Trial Overview The study tests if phentermine-topiramate combined with lifestyle changes affects metabolic adaptation after weight loss differently than just lifestyle changes and meal replacements. Researchers are looking at how the body adjusts its energy use during and after dieting.

How Is the Trial Designed?

Group I: lifestyle intervention Experimental Treatment 1 Intervention

Participants will be enrolled in a weight loss program based on lifestyle changes. They will be given a 6-month subscription to a calorie-reduced meal replacement program that also offers lifestyle coaching.

Lifestyle Intervention with Meal Replacement Program is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Meal Replacement Program for:

• Weight Loss
• Obesity Management
• Metabolic Syndrome

Approved in European Union as Total Meal Replacement for:

• Weight Loss
• Obesity Management
• Type 2 Diabetes Management

Approved in Canada as Full Meal Replacement for:

• Weight Loss
• Obesity Management
• Metabolic Syndrome

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

The FDA has approved lorcaserin and the combination of phentermine and extended-release topiramate (phentermine/topiramate ER) for obesity treatment, expanding options beyond orlistat and supporting long-term weight management alongside lifestyle changes.

Phentermine/topiramate ER has been shown to result in greater weight loss compared to using phentermine or topiramate alone, and it may also improve cardiometabolic risk factors, although more long-term safety data is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of obesity and cardiometabolic risk - role of phentermine/extended release topiramate. Sweeting, AN., Tabet, E., Caterson, ID., et al.[2021]

In two 56-week trials involving 751 and 1623 patients, phentermine/topiramate significantly improved health-related quality of life (HRQOL) in individuals with obesity, with improvements in both obesity-specific and physical HRQOL measures.

While weight loss (BMI reduction) was the primary factor driving these HRQOL improvements, reductions in depressive symptoms also played a significant role, indicating that both weight and mental health are important in enhancing quality of life for patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in two randomized controlled trials of phentermine/topiramate for obesity: What mediates improvement? Kolotkin, RL., Gadde, KM., Peterson, CA., et al.[2019]

Phentermine-topiramate extended release (ER) has been shown to help obese individuals lose an average of 10% of their initial weight, which is about 8% more than a placebo, and it also reduces the risk of developing type 2 diabetes and improves cardiovascular disease risk factors.

While effective for weight loss, phentermine-topiramate ER can increase heart rate and poses risks for women of child-bearing age due to potential harm to infants, highlighting the need for careful monitoring and consideration in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination phentermine and topiramate extended release in the management of obesity. Alfaris, N., Minnick, AM., Hopkins, CM., et al.[2018]

In a 56-week phase 3 trial involving 2487 overweight or obese adults, the combination of phentermine and topiramate significantly reduced body weight compared to placebo, with participants losing an average of 8.1 kg and 10.2 kg for the lower and higher doses, respectively.

The treatment was effective in achieving at least 5% weight loss in 62% of participants on the lower dose and 70% on the higher dose, while common side effects included dry mouth and paraesthesia, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Gadde, KM., Allison, DB., Ryan, DH., et al.[2022]

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]

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]

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]

The fixed drug combination of phentermine and extended-release topiramate (Qsymia™) is the first FDA-approved combination therapy for obesity in over two decades, showing significant potential for effective weight loss.

Clinical trials demonstrated that over 50% of participants achieved and maintained at least a 10% weight loss from baseline for up to 2 years, indicating robust efficacy for long-term obesity management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine and topiramate for the management of obesity: a review. Cosentino, G., Conrad, AO., Uwaifo, GI.[2021]

In a 12-week open-label trial with 10 participants suffering from binge-eating disorder (BED) and obesity, phentermine-topiramate significantly reduced weight, binge-eating episodes, and overall eating disorder severity.

The treatment was generally safe, with no serious adverse events reported, although dysgeusia (altered taste) was the most common side effect, suggesting that phentermine-topiramate may be a promising option for managing BED in overweight individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Phentermine-Topiramate Extended Release for the Treatment of Binge Eating Disorder: An Open-Label, Prospective Study. Guerdjikova, AI., Williams, S., Blom, TJ., et al.[2020]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3260065/

Two-year sustained weight loss and metabolic benefits with ... PHEN/TPM CR was clearly effective in all BMI categories and produced greater weight loss than did placebo (P ≤ 0.0061). However, a significant treatment effect ...

3. hcp.qsymia.com hcp.qsymia.com/efficacy-and-safety/results-over-time/

Weight-Management Results with Qsymia® in Adult Patients On average, adult patients achieved significant weight loss across doses of Qsymia at 56 weeks · Clinical results at 56 weeks: Qsymia 15/92 mg with diet and ...

4. 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 ...

5. 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 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. ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/022580s021lbl.pdf

QSYMIA (phentermine and topiramate - accessdata.fda.gov The data described herein reflects exposure to QSYMIA in two 1-year, randomized, double-blind, placebo- controlled, multicenter clinical trials and two ...

7. 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 ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6261426/

Safety and tolerability of new-generation anti-obesity ... To date, the overall safety data for liraglutide are reassuring, with no new safety signals emerging from the 3-year SCALE Obesity and Prediabetes trial [41].

9. qsymia.com qsymia.com/patient/resources/safety-information

Safety Information Qsymia may cause a severe rash with blisters and peeling skin, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson Syndrome).