Study to Evaluate the QTC Interval in Healthy Volunteers Dosed With Dexpramipexole (QTC = Electrocardiogram (ECG) Interval Measured From the Onset of the QRS Complex to the End of the T Wave Corrected for Heart Rate)

A Single-Center, Randomized, Blinded, Placebo- and Active-Controlled Crossover Study to Evaluate the Effect of Dexpramipexole (BIIB050) on the QTc Interval in Healthy Volunteers

To evaluate whether dexpramipexole prolongs the QTc interval when orally administered to healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Dexpramipexole; Drug: Dexpramipexole; Drug: Dexpramipexole Placebo; Drug: Moxifloxacin

Detailed Description

This is a Phase I, single-center, blinded (with respect to dexpramipexole administration), randomized, placebo- and active-controlled, 4-period crossover study in approximately 68 healthy volunteers. This thorough QT/QTc study will be conducted to formally evaluate the effect of dexpramipexole on QT prolongation.

• Study Type: Interventional
• Enrollment (Actual): 68
• 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 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 to 60 years old inclusive on Day 1.
• Subjects who, in the opinion of the Investigator, are healthy as determined by pre study medical history, physical examination, and 12 lead ECG.
• Male subjects and female subjects of childbearing potential must practice effective contraception (per protocol specifications).
• Normal systemic blood pressure defined as a systolic blood pressure of 90 to 140 mmHg and a diastolic blood pressure of 50 to 90 mmHg.

Exclusion Criteria:

• History of cardiovascular disease (e.g., hypertension, arrhythmia, heart failure, Long QT Syndrome, or other conditions/diseases causing prolongation of the QT/QTc interval), in the opinion of the Investigator.
• A prolongation of QT/QTc interval (e.g., repeated demonstration of a QT/QTc interval >450 ms before study treatment administration.
• Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTc interval changes at screening, check-in, or pre-dose on Day -1 of the first treatment period.
• Other medically significant illness.
• Clinically significant abnormal laboratory values.
• Pregnant women or women breastfeeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Moxifloxacin	Drug: Moxifloxacin; 400 mg - Oral Tablet
Experimental: Dexpramipexole	Drug: Dexpramipexole; 300 mg - Oral Tablets; Drug: Dexpramipexole; 600 mg Oral Tablets
Placebo Comparator: Dexpramipexole (placebo)	Drug: Dexpramipexole Placebo; Placebo - Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate whether a single dose of dexpramipexole prolongs the QTC interval as measured by frequent ECG measurements (using Holter monitoring) of individually corrected QT intervals (QTcI)	change from baseline

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under Curve (AUC) of dexpramipexole	pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 23 hours after dosing on Day 1 of each treatment period
Change in ECG measurements	baseline and Day 7
Cmax of dexpramipexole	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 23 hours after dosing on Day 1 of each treatment period
Tmax of dexpramipexole	pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 23 hours after dosing on Day 1 of each treatment period

Collaborators and Investigators

• Sponsor: Knopp Biosciences

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: January 9, 2012
• First Submitted That Met QC Criteria: January 17, 2012
• First Posted (Estimate): January 18, 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; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Protective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Moxifloxacin; Pramipexole
• Other Study ID Numbers: 223HV102