Efficacy and Safety of Phentermine/Topiramate in Youth With Hypothalamic Obesity

NCT06299891 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PhT_HypOb_Protocol_Clean_07-05
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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 6-28-year-old individuals with HO.

Conditions

Hypothalamic Obesity; Hypothalamic Tumor; Craniopharyngioma

Keywords

Hypothalamic Lesion; Drug Intervention; Hypothalamic Obesity; Phentermine/Topiramate

Outcome Measures

Primary Outcomes (1)

• Treatment-emergent adverse events

  Incidence of treatment-emergent adverse events including any during withdrawal in study drug vs. placebo.

  From baseline to completion of week 28

Secondary Outcomes (8)

• Maximum tolerated dose

  Week 0 to 28

• % change in BMI

  Week 0 to 28

• Proportion of individuals who experience 5% decrease in BMI

  Week 0 to 28

• Proportion of individuals who experience 2.5% decrease in BMI

  Week 0 to 28

• Change in body fat mass

  Week 0 to 28

Study Arms (2)

Drug Intervention

EXPERIMENTAL

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.

Drug: Phentermine / Topiramate Extended Release Oral Capsule [Qsymia]

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Phentermine / Topiramate Extended Release Oral Capsule [Qsymia] DRUG

To assess safety and maximum tolerated dose as well as efficacy on weight loss of Phentermine/Topiramate in individuals with hypothalamic obesity.

Drug Intervention

Placebo OTHER

To assess safety and maximum tolerated dose as well as efficacy on weight loss of placebo treatment in individuals with hypothalamic obesity.

Also known as: Matching blinded placebo capsules

Placebo

Eligibility Criteria

• Age: 6 Years - 28 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and Females; Ages 6-28 years (inclusive)
• History of rapid weight gain related to tumor onset or treatment, as assessed by an experienced endocrinologist (for example, change in BMI z-score \> 0.2 and/or BMI +5% during the first 6 months following tumor treatment)
• Obesity (BMI \> 95th%ile for age/sex using CDC 2000 reference for under 18; BMI \> 30 kg/m2 for 18+ years)
• Recent evidence of hypothalamic injury by brain MRI with central review; \>6 months status-post definitive therapy (surgery, chemotherapy, or radiation); no major operations/surgeries planned during the study period.
• Stable on pituitary replacement\* and/or appetite-modulating medications (including stimulants) for at least 2 months. \*Adjustments of less than 25% (\<25%) are permitted to hydrocortisone, growth hormone or thyroid hormone. Sex steroids and DDAVP are exempt.
• Post-menarchal females must use a highly effective form of contraception, unless hypogonadotropic hypogonadism is documented. All participating females of child-bearing potential will have pregnancy testing as outlined in the protocol.
• Participants must be able to communicate well with the investigative team, must comply with requirements of the study, and be able to provide written informed consent and/or assent for individuals less than 18y with consent of a parent/legal guardian.

You may not qualify if:

• Contraindication to Phentermine, Topiramate, or Qsymia as assessed using current package inserts. Including: History of glaucoma and known hyperthyroidism.
• Known history of nephrolithiasis (kidney stones).
• Current clinical diagnosis of anorexia nervosa or bulimia nervosa in the medical record.
• Known history of metabolic acidosis, low bicarbonate on screening laboratory assessment (below lower limit of normal), or clinically significant bone disease requiring medication (beyond calcium and/or vitamin D).
• Current or recent (\<14 days) use of monoamine oxidase inhibitor.
• Known hypersensitivity to sympathomimetic amines.
• Clinically significant cardiovascular conditions, as defined as any of the following: i) abnormal blood pressure, defined as: under 13y, 95th%ile +12 mm Hg or \> 140/90, whichever is lower; 13y and older, \> 140/90 ; ii) history of cardiac arrhythmia or arrhythmia detected on screening ECG; iii) history of heart failure and/or cardiomyopathy; iv) prolonged QTc interval (QTc \> 460 msec), and/or long QT syndrome phenotype and/or positive genotype for long QT syndrome pathogenic; v) history of cardiac disease including coronary artery disease.
• Females who are pregnant, breastfeeding, or planning to become pregnant during the trial.
• "Brittle" diabetes insipidus (in the opinion of the referring endocrinologist, e.g. requiring frequent hospitalizations and/or frequent abnormal sodium values).
• Diabetes mellitus requiring insulin/secretagogue. HbA1c \> 8.5% at Screening.
• Clinically significant hyperthyroidism as assessed using thyroid hormone measurements. Clinical measurements within 12 months of baseline/screening may be used to assess this criterion.
• History of clinically significant hypokalemia (low potassium) or current clinically significant hypokalemia (low potassium) on baseline/screening labs.
• Clinically significant liver disease and/or known severe hepatic impairment. ALT \> 3 x Upper Limit of Normal (ULN) AST \> 3 x ULN
• Clinically significant kidney disease. GFR\<60 ml/min/1.73m2
• History of seizure in the 12 months prior to Screening.

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• Children's Hospital of Philadelphia: collaborator

Study Sites (2)

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Seattle Children's

Seattle, Washington, 98101, United States

RECRUITING

MeSH Terms

Conditions

Sexual Infantilism; Hypothalamic Neoplasms; Craniopharyngioma

Interventions

Phentermine; Qsymia

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Christian L Roth, MD

  University of Washington, Dept. of Pediatrics

  PRINCIPAL INVESTIGATOR

• Shana E McCormack, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christian L Roth, MD

CONTACT

1-206-987-5428; christian.roth@seattlechildrens.org

Stephanie Purdy

CONTACT

1-206-987-2540; stephanie.purdy@seattlechildrens.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Eligible subjects will be assigned treatment using a sex-stratified permuted-block randomization (1:1) to drug vs. placebo for 28 weeks with varying block sizes constructed by the study statistician.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Two-center, double-blind (participant and assessor), randomized, parallel-arm placebo-controlled 28-week clinical trial, comparing changes related to active drug (Qsymia®) vs. placebo (matched capsules).

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 8, 2024
• Study Start: March 1, 2025
• Primary Completion: February 28, 2026
• Study Completion (Estimated): May 31, 2026
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)