Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity

NCT04881799 | Active Not Recruiting Early Phase 1 Results FDA Drug

• 1 other identifier: PEDS-2021-29785
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

As the prevalence of obesity rises in the U.S., so does the incidence of pediatric type 2 diabetes (T2D), which is associated with more aggressive disease progression than in adults. From 2002-2012, the incidence of T2D in youth increased by 7% annually in the U.S. Compared to adults. T2D in adolescents is a much more progressive and recalcitrant disease, characterized by more rapid deterioration of β-cell function and earlier incidence of exogenous insulin dependence and diabetes-related comorbidities. A potential factor that drives the rapid progression of adolescent T2D is obesity (body mass index \[BMI\] \>95th percentile. Effective and safe treatments targeting both obesity and β-cell dysfunction are needed for pediatric T2D. In 2012, the FDA approved the use of Phentermine/Topiramate for the treatment of obesity in adults. This orally-administered medication is available in mid- (phentermine 7.5 mg; topiramate 46 mg) and high- (phentermine 15 mg; topiramate 92 mg) doses, administered once per day. In a meta-analysis, phentermine/topiramate was shown to be one of the most effective obesity medication currently available. A large dose-ranging trial in adults evaluating phentermine and topiramate as monotherapies vs. phentermine/topiramate demonstrated superior efficacy of the combination with an acceptable safety profile. Results from a large phase III clinical trial demonstrated placebo-subtracted weight loss of \>9% with treatment for one year at the top dose. Importantly, a separate trial demonstrated that the treatment effect is durable out to at least two years.41 The most common side effects in these trials were paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. Improvements were noted in blood pressure, lipids, glucose, insulin, HOMA-IR, C-reactive protein, and adiponectin.

Conditions

Pediatric Obesity

Outcome Measures

Primary Outcomes (1)

• Change in Body Mass Index

  The percent change in body mass index (BMI) from Baseline to Month 6 will be calculated. BMI is defined as a person's weight in kilograms divided by the square of height in meters. The Phase 1 (double-blind) portion of the study was six months and data were collected at the end of the 6 month double-blind phase.

  6 Months

Study Arms (2)

Placebo -> Qsymia

PLACEBO COMPARATOR

Participants randomized to placebo during the blinded treatment period who subsequently received study drug during the open-label extension.

Drug: Phentermine/Topiramate (Qsymia); Drug: Placebo

Qsymia -> Qsymia

EXPERIMENTAL

Participants randomized to study drug during the blinded treatment period who continued receiving study drug during the open-label extension.

Drug: Phentermine/Topiramate (Qsymia)

Interventions

Phentermine/Topiramate (Qsymia) DRUG

Oral pill taken once in the morning. Treatment will initiate with 3.75 mg/23 mg for 14 days, then increased to 7.5 mg/46 mg for 14 days, then increased to 11.25 mg/69 mg for 14 days then increased to the final dose of 15 mg/92 mg.

Placebo -> Qsymia; Qsymia -> Qsymia

Placebo DRUG

Matching placebo taken orally once in the morning.

Placebo -> Qsymia

Eligibility Criteria

• Age: 12 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ages 12 to \</= 20 years at study entry
• Obesity (BMI \>/= the 95th percentile for age and sex)
• HgbA1c \>/= 6.5% at type 2 diabetes diagnosis
• Negative diabetes auto-antibodies
• English-speaking and Spanish speaking
• For participants of child-bearing potential: when sexually active, agreement to use two forms of highly effective contraception (oral contraceptive pill, IUD, implant, and/or condoms) during study participation

You may not qualify if:

• Pregnancy or lactation
• Newly-initiated or change in dose of weight altering medication within past 6 months, including SGLT-2 inhibitors and DPP-IV inhibitors, liraglutide 1.8 mg and exenatide ER.
• Current use of sulfonylureas
• Previous metabolic/bariatric surgery
• Current use of a stimulant medication
• History of glaucoma
• Current or recent (\< 14 days) use of monoamine oxidase inhibitor or carbonic anhydrase inhibitors
• Known hypersensitivity to sympathomimetic amines
• Any history of treatment with growth hormone
• any history of bulimia nervosa
• Major psychiatric disorder as determined by the local medical monitor
• Unstable and clinically-diagnosed (defined as documented in the medical record, if available) depression or PHQ-9 score of \>/= 15
• Any history of active suicide attempt, a "yes" answer to Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) on the "Suicidal Ideation" portion of the C-SSR, or a "yes" to answer to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS
• History of suicidal ideation or self-harm within the previous 30 days or a "yes" answer to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the "Suicidal Behavior" portion of the C-SSRS and the ideation or behavior occurred within the past month.
• Current pregnancy or plans to become pregnant during study participation

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

MeSH Terms

Conditions

Pediatric Obesity

Interventions

Phentermine; Topiramate; Qsymia

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Megan Bensignor
• Organization: University of Minnesota

moberle@umn.edu

612-626-3809

Study Officials

• Megan Bensignor, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants during the first six months of the study will be randomized to receive either phentermine/topiramate or placebo. Neither the participant, care provider, investigator or study team will know whether the participant is receiving phentermine/topiramate or placebo.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a pilot, pragmatic, randomized trial with a 6-month placebo-controlled period followed by a 6-month open label extension investigating the effects of phentermine/topiramate on BMI, insulin sensitivity, and glycemic control compared to placebo plus standard treatment (metformin + insulin) in adolescents with T2D. Individuals, when randomized to phentermine/topiramate therapy will initiate treatment at 3.75 mg/23 mg orally once daily in the morning for 14 days. It will then be increased to 7.5 mg/46 mg orally once daily in the morning for 14 days. It will the be increased to 11.25 mg/69 mg orally once daily in the morning for 14 days and finally to 15 mg/92 mg orally once daily in the morning.

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 11, 2021
• Study Start: July 7, 2022
• Primary Completion: October 27, 2025
• Study Completion (Estimated): October 27, 2026
• Last Updated: May 22, 2026
• Results First Posted: May 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: 10 years after completion of the study

Locations

US (1)