Cognitive Effects of Immediate Release Topiramate vs Extended Release Topiramate in Patients With Migraine

NCT03280342 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: FWA00000312-10
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Crossover, randomized, double blind: Q12h dosing in both periods; matching placebo for evening dosing during XR treatment; target dose: 100mg

Conditions

Migraine; Headache

Keywords

Migraine; Headache

Outcome Measures

Primary Outcomes (1)

• Controlled Oral Word Association Test (COWA)-generative phonemic fluency

  The primary outcome measure is the Controlled Oral Word Association (COWA: phonemic generative fluency). COWA was chosen as the primary endpoint since in previous studies of drug-induced cognitive impairment, this measure was sensitive to the effects of topiramate (Meador et al, 2003; Marino et al, 2012; Marino et al, 2015). The primary endpoint is a change in the COWA score from baseline to each post-dose assessment

  Baseline (Day 1) through Day 52

Secondary Outcomes (4)

• Measures of semantic verbal fluency

  Baseline (Day 1) through Day 52

• Digit Span Backward

  Baseline (Day 1) through Day 52

• Digit Symbol Modalities Test (SDMT)

  Baseline (Day 1) through Day 52

• Trails A & B

  Baseline (Day 1) through Day 52

Study Arms (2)

IR-TPM (Topamax)

ACTIVE COMPARATOR

IR-TPM (Topamax)

Drug: IR-TPM (Topamax); Drug: XR-TPM (Trokendi XR)

XR-TPM (Trokendi XR)

ACTIVE COMPARATOR

Drug: IR-TPM (Topamax); Drug: XR-TPM (Trokendi XR)

Interventions

IR-TPM (Topamax) DRUG

XR-TPM (Trokendi XR)

IR-TPM (Topamax); XR-TPM (Trokendi XR)

XR-TPM (Trokendi XR) DRUG

XR-TPM (Trokendi XR)

IR-TPM (Topamax); XR-TPM (Trokendi XR)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Established history of episodic migraine with or without aura, as assessed by International Headache Society criteria, for at least 6 months before screening and frequency of 3 or more headache attacks per month during the past 3 months
• Male or female, ages 18-65
• Women are required to be postmenopausal, surgically incapable of bearing children, or practicing a medically acceptable method of birth control (i.e., double barrier method, IUD, Mirena, etc) for at least 1 month before study entry through 30 days following last dose.
• If postmenopausal and on hormone replacement therapy (HRT) then must to be on a stable regimen for at least 2 months (continuous stable regimen of cyclic or non-cyclic HRT); negative pregnancy test.
• Native English speakers (due to speech and language analysis)
• Montreal Cognitive Assessment (MoCA) score equal to or greater than 26.

You may not qualify if:

• Onset of migraine occurred after age 50 years, or overuse of analgesics or migraine specific agents for the acute treatment of migraine episodes; examples of analgesic overuse included the following: more than 8 treatment episodes (episode defined as any calendar day of usage) of ergot containing medications a month; more than 8 treatment episodes of triptans a month; or more than 6 treatment episodes of potent opioids a month.
• Required, continued use of the following medications for any medical reason during the study: beta-blockers, benzodiazepines, tricyclic antidepressants, antiepileptics, calcium channel blockers, monoamine oxidase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) daily, opioids, agents for insomnia (e.g., Ambien, diphenhydramine-containing OTC products); corticosteroids, local anesthetics, botulinum toxin within last three months, or herbal preparations such as feverfew or St John's wort. However, subjects will be permitted to be on a stable regimen of a selective serotonin reuptake inhibitor or SNRI for 3 months or more for depression and/or anxiety.
• A history of nephrolithiasis
• Have previously taken topiramate
• Received an experimental drug or used an experimental or approved device for migraine prevention (e.g., TENIS unit) within 30 days of screening

Sponsors & Collaborators

• University of Minnesota: lead
• Supernus Pharmaceuticals, Inc.: collaborator

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Prism Research

Saint Paul, Minnesota, 55114, United States

Location

MeSH Terms

Conditions

Migraine Disorders; Headache

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Susan Marino, PhD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: a crossover, randomized, double blind design in conjunction with intensive pharmacokinetic sampling and multiple administrations of a neurocognitive test battery to directly compare the effects on cognition of IR-TPM to XR-TPM in adults with migraine. The dose will begin at 25mg and titrated in 25mg increments to reach target dose of 100mg.

Study Record Dates

• First Submitted: September 1, 2017
• First Posted: September 12, 2017
• Study Start: October 30, 2017
• Primary Completion: August 20, 2018
• Study Completion: September 13, 2018
• Last Updated: November 1, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)