Phentermine/Topiramate for Hypothalamic Obesity

Recruiting at 1 trial location

Overseen By Clinton Elfers

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Seattle Children's Hospital

Must be taking: Pituitary replacements, Appetite-modulating

Must not be taking: MAO inhibitors, Carbonic anhydrase inhibitors

Disqualifiers: Cardiovascular conditions, Diabetes, Liver disease, 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: 7

Duration: 28 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Hypothalamic obesity (HO) refers to the substantial weight gain that often complicates hypothalamic brain tumors. Children with this treatment-recalcitrant form of obesity have excess rates of metabolic sequelae compared to otherwise healthy children with similar obesity, and later experience excess mortality related to cardiometabolic disease. 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 been tested in HO. The subset of individuals with HO who experience hyperphagia or excess daytime sleepiness may benefit from the Ph/T-induced decrease in appetite and increase in alertness. Preliminary assessments of safety, adverse events, dosing (Aim 1), as well as of efficacy (% BMI loss, Aim 2) will be made in a 28-week parallel-arm double-blinded Phase 2 placebo-controlled clinical trial in 12-28-year-old individuals with HO.

Will I have to stop taking my current medications?

The trial requires that you have been stable on pituitary replacement and/or appetite-modulating medications for at least 2 months before joining. If you are on a new weight management medication, stimulant, or investigational medication, you must have been on it for at least 2 months before the trial.

What data supports the effectiveness of the drug Phentermine/Topiramate for hypothalamic obesity?

Phentermine/Topiramate, known as Qsymia, is effective for weight loss by reducing appetite and increasing fullness, and it has been approved for obesity treatment in adults and adolescents. While it is not specifically approved for hypothalamic obesity, its success in managing weight in other forms of obesity suggests potential benefits. ^{1 2 3 4 5}

Is Phentermine/Topiramate safe for humans?

Phentermine/Topiramate, also known as Qsymia, has been approved for obesity treatment in adults and adolescents, but it can have side effects like increased heart rate, mood changes, and metabolic issues. It is important to discuss these potential risks with a healthcare provider before starting the treatment. ^{1 2 3 4 6}

How is the drug Phentermine/Topiramate unique for treating hypothalamic obesity?

Phentermine/Topiramate is unique because it combines two medications: phentermine, which suppresses appetite, and topiramate, which is used for seizures and migraines, to achieve greater weight loss than either drug alone. This combination is taken once daily and is designed to decrease appetite and increase feelings of fullness, making it different from other treatments that may not target these specific mechanisms. ^{1 2 3 4 7}

Research Team

Christian L Roth, MD

Principal Investigator

University of Washington, Dept. of Pediatrics

Shana McCormack

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for young people aged 12-28 with hypothalamic obesity, often due to brain tumors like craniopharyngioma. Participants should have issues with excessive hunger or sleepiness. Key eligibility details are not provided, so it's assumed that standard health requirements and consent apply.

Inclusion Criteria

I am between 12 and 28 years old.

History of rapid weight gain related to tumor onset or treatment, as assessed by an experienced endocrinologist

I am using effective birth control or have a condition that prevents me from getting pregnant.

Exclusion Criteria

My kidney function is low (GFR under 60).

History of allergy or sensitivity to test agents. Including individuals with known aspirin allergy or hypersensitivity and/or known allergy to FD&C Yellow No. 5 (tartrazine)

My thinking or memory problems don't stop me from joining the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive phentermine/topiramate or placebo for 28 weeks with dose titration and monitoring for safety and efficacy

28 weeks

5 visits (in-person), 2 visits (remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of withdrawal effects

1 week

1 visit (remote or in-person if needed)

Treatment Details

Interventions

• Phentermine/Topiramate

Trial Overview The trial tests Phentermine/Topiramate capsules (Qsymia), which may reduce appetite and increase alertness in patients with hypothalamic obesity. It's a double-blinded study comparing the drug against a placebo over 28 weeks to see if it helps lower BMI and improve other health aspects.

Participant Groups

Group I: Drug Intervention Experimental Treatment 1 Intervention

Active drug dose escalation and adjustment: The drug had been used in adolescents with obesity before. For this trial, the FDA approved dose titration will be followed until the highest tolerable dose is reached.

Group II: Placebo Placebo Group 2 Interventions

Matching placebo using capsules matching the appearance of the active drug.

Phentermine/Topiramate is already approved in United States for the following indications:

Approved in United States as Qsymia for:

• Obesity in adults with a BMI of 27 kg/m^2 or greater and at least one weight-related comorbidity, or with a BMI of at least 30 kg/m^2

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Findings from Research

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]

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 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 combination of phentermine and topiramate (PHEN/TPM CR) has been shown to effectively promote weight loss and improve metabolic diseases associated with 'sick fat' in thousands of patients, addressing the limitations of traditional weight loss therapies.

PHEN/TPM CR is generally well-tolerated and works by targeting multiple physiological processes that contribute to body fat accumulation, making it a promising option for treating obesity and its related metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease. Bays, H.[2018]

This study protocol outlines a Phase I/IIa trial involving 30 adults with binge eating disorder (BED) and bulimia nervosa (BN) to evaluate the safety and preliminary efficacy of Qsymia, a combination of phentermine and topiramate, over a 12-week period.

The trial aims to measure the impact of Qsymia on binge eating frequency and related psychological factors, addressing the need for more effective treatments for these eating disorders, as current therapies leave many patients symptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa. Dalai, SS., Adler, S., Najarian, T., et al.[2023]

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]

References

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

Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Phentermine/Topiramate: Pediatric First Approval. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Phentermine and topiramate extended release (Qsymia™): first global approval. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease. [2018]

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

Study protocol and rationale for a randomized double-blinded crossover trial of phentermine-topiramate ER versus placebo to treat binge eating disorder and bulimia nervosa. [2023]

7. United States 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. [2023]