Phentermine/Topiramate for Hypothalamic Obesity

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Christian L Roth, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Approved in 3 Jurisdictions

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}

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.

Trial 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)

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The Children's Hospital of Philadelphia Philadelphia, PA

Seattle Children's Seattle, WA

Who Is Running the Clinical Trial?

Seattle Children's Hospital Lead Sponsor

Children's Hospital of Philadelphia Collaborator

References

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

Clinical utility of phentermine/topiramate (Qsymia™) combination for the treatment of obesity. [2021] Qsymia™ (Vivus Inc, Mountain View, CA, USA), a combination of phentermine and delayed-release topiramate, has been available in the US since September 2012 for the treatment of obesity. Phentermine is an anorexigenic agent, which is approved for the short-term treatment of obesity, while topiramate is approved for nonweight loss indications - seizure disorders and migraine prophylaxis. The amount of weight loss achieved with combination therapy is of a greater magnitude than what could be achieved with either agent alone. Adverse events that occur with the combination therapy are in line with the known side effect profiles of the constituent drugs; teratogenicity, a slight increase in heart rate, psychiatric and cognitive adverse effects, and metabolic acidosis are concerns.

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

Phentermine/Topiramate: Pediatric First Approval. [2022] Phentermine/topiramate extended-release capsule (Qsymia&#174;) is a fixed-dose combination of phentermine and topiramate, which is being developed by VIVUS (a subsidiary of Icahn Enterprises) for the treatment of obesity, sleep apnoea syndrome, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH). The once-daily formulation of phentermine (a sympathomimetic amine) and topiramate is designed to combat obesity by decreasing appetite and increasing satiety. In July 2022, phentermine/topiramate received its first approval in the USA, as an adjunct to a reduced-calorie diet and increased physical activity, for chronic weight management in pediatric patients aged &#8805;&#160;12 years with BMI in the 95th percentile or greater standardized for age and sex. Phentermine/topiramate is approved in the US and South Korea for obesity in adults. Clinical development of phentermine/topiramate for sleep apnoea syndrome and type-2 diabetes in obese patients and preclinical development for NASH is ongoing in the US. This article summarizes the milestones in the development of phentermine/topiramate leading to this pediatric first approval for chronic weight management in adolescents.

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

A review of the metabolic effects of controlled-release Phentermine/Topiramate. [2019] Very few drugs are approved for obesity treatment by regulatory agencies. Very recently phentermine/topiramate controlled-release [PHEN/TPM CR; (Qsymia®)] obtained Food and Drug Administration (FDA) approval as an addition to a reduced-calorie diet and exercise for chronic weight management. Our aim was to review the available clinical evidence on weight loss, metabolic effects and adverse events associated with use of this product.

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

Phentermine and topiramate extended release (Qsymia™): first global approval. [2021] Vivus' proprietary oral capsule containing phentermine and extended-release (ER) topiramate has been approved in the US for the treatment of obesity. Phentermine is an appetite suppressant, while topiramate is an anti-epileptic medication. The once-daily formulation, known as Qsymia™, is designed to produce weight loss by decreasing appetite and increasing satiety. The product is also in clinical development for sleep apnoea syndrome and type 2 diabetes mellitus. This article summarizes the milestones in the development of phentermine/topiramate ER leading to this first approval for obesity.

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

Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease. [2018] Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of non-surgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide D-fructose approved as a treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl/topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediate-release phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease.

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] Bulimia nervosa (BN) and binge eating disorder (BED) are associated with severe psychological and medical consequences. Current therapies are limited, leaving up to 50% of patients symptomatic despite treatment, underscoring the need for additional treatment options. Qsymia, an FDA-approved medication for obesity, combines phentermine and topiramate ER. Topiramate has demonstrated efficacy for both BED and BN, but limited tolerability. Phentermine is FDA-approved for weight loss. A rationale for combined phentermine/topiramate for BED and BN is improved tolerability and efficacy. While a prior case series exploring Qsymia for BED showed promise, randomized studies are needed to evaluate Qsymia's safety and efficacy when re-purposed in eating disorders. We present a study protocol for a Phase I/IIa single-center, prospective, double-blinded, randomized, crossover trial examining safety and preliminary efficacy of Qsymia for BED and BN.

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] Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with ≥2 weight-related comorbidities.