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

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

Study Overview

• Status: Withdrawn
• Conditions: Migraine; Headache
• Intervention / Treatment: Drug: IR-TPM (Topamax); Drug: XR-TPM (Trokendi XR)

Detailed Description

The primary objective is to compare the effect of treatment with an immediate-release topiramate (IR-TPM), namely Topamax®, to an extended-release topiramate (XR-TPM), namely Trokendi XR®, regimen on cognition in adults with migraine.

The secondary objective is to determine the factors that explain inter-individual variability in cognitive response. Pharmacokinetic and demographic factors will be explored. Variability in cognitive response between individuals can be large. A population approach (nonlinear, mixed effects) will be used to determine drug exposure response relationships.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University Of Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Male or female, ages 18-65
3. 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.
4. 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.
5. Native English speakers (due to speech and language analysis)
6. Montreal Cognitive Assessment (MoCA) score equal to or greater than 26.

Exclusion Criteria:

1. 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.
2. 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.
3. A history of nephrolithiasis
4. Have previously taken topiramate
5. Received an experimental drug or used an experimental or approved device for migraine prevention (e.g., TENIS unit) within 30 days of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IR-TPM (Topamax)	Drug: IR-TPM (Topamax); XR-TPM (Trokendi XR); Drug: XR-TPM (Trokendi XR); XR-TPM (Trokendi XR)
Active Comparator: XR-TPM (Trokendi XR)	Drug: IR-TPM (Topamax); XR-TPM (Trokendi XR); Drug: XR-TPM (Trokendi XR); XR-TPM (Trokendi XR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measures of semantic verbal fluency	Change in scores from individual baseline to each post-dose assessment on measures of semantic verbal fluency (e.g., Animals)	Baseline (Day 1) through Day 52
Digit Span Backward	Change in scores from individual baseline to each post-dose assessment on measures of working memory (i.e., Digit Span Backward)	Baseline (Day 1) through Day 52
Digit Symbol Modalities Test (SDMT)	Change in scores from individual baseline to each post-dose assessment on measure of psychomotor speed	Baseline (Day 1) through Day 52
Trails A & B	Change in scores from individual baseline to each post-dose assessment on measures of executive function	Baseline (Day 1) through Day 52

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: Supernus Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Susan Marino, PhD, University Of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2017
• Primary Completion (Actual): August 20, 2018
• Study Completion (Actual): September 13, 2018

Study Registration Dates

• First Submitted: September 1, 2017
• First Submitted That Met QC Criteria: September 8, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): November 1, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Migraine; Headache
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: FWA00000312-10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No