Dexpramipexole and Cimetidine Drug Drug Interaction (DDI)

An Open-Label Study to Assess the Effect of Cimetidine on the Pharmacokinetics of Dexpramipexole (BIIB050) in Healthy Volunteers

This study will assess the effect of cimetidine on the pharmacokinetics (PK) of dexpramipexole in healthy volunteer and evaluate the safety and tolerability of dexpramipexole when given with or without cimetidine. Additionally, this study will explore the influence of genetic variation on the PK of dexpramipexole when given with or without cimetidine.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Cimetidine plus Dexpramipexole; Drug: Dexpramipexole

Detailed Description

This is a single-center, open-label, randomized, two-period, crossover study in approximately 14 healthy subjects. The goals of this study are as follows:

To assess the effect of cimetidine on the pharmacokinetics (PK) of dexpramipexole in healthy volunteers.

To evaluate the safety and tolerability of dexpramipexole when given with or without cimetidine.

To explore the influence of genetic variation on the PK of dexpramipexole when given with or without cimetidine.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who, in the opinion of the Investigator, are healthy as determined by medical history, physical examination, and 12 lead ECG
• Adult males/females aged 18 to 55 years inclusive
• Male and female subjects of childbearing potential must practice effective contraception during the study and up to 90 days after their last dose.

Exclusion Criteria:

• History of malignant disease, including solid tumors and hematologic malignancies.
• History of clinically significant endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major diseases, as determined by the Investigator.
• Treatment with prescription medication and/or over-the-counter products and herbal-containing and/or alternative health preparations and procedures.
• Surgery within 90 days prior to check-in.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexpramipexole single dose & 12 Doses Cimetidine; 300 mg Dexpramipexole Oral Dose (to be taken in conjunction with multiple doses of Cimetidine at 400 mg per dose)	Drug: Cimetidine plus Dexpramipexole; Multiple Oral Doses
Experimental: Dexpramipexole single Dose; 300 mg Dexpramipexole Oral Dose	Drug: Dexpramipexole; Single Oral Dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of the effect of cimetidine on the PK of dexpramipexole parameters including: AUC: Area under the plasma-concentration time curve over a specified time period; Cmax: Maximum observed plasma concentration and CLr: renal clearance	pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, and 72 hours after dexpramipexole administration in each dosing period.

Secondary Outcome Measures

Outcome Measure	Time Frame
PK parameters of dexpramipexole including, but not limited to, half-life when given with or without cimetidine	pre-dose and at 15, 30, and 45 minutes, and 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, and 72 hours after dexpramipexole administration in each dosing period.

Collaborators and Investigators

• Sponsor: Knopp Biosciences

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 16, 2012
• First Submitted That Met QC Criteria: February 21, 2012
• First Posted (Estimate): February 22, 2012

Study Record Updates

• Last Update Posted (Estimate): November 25, 2014
• Last Update Submitted That Met QC Criteria: November 24, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Protective Agents; Dopamine Agonists; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Antioxidants; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Antiparkinson Agents; Anti-Dyskinesia Agents; Histamine H2 Antagonists; Pramipexole; Cimetidine
• Other Study ID Numbers: 223HV104