Dexpramipexole Japanese PK Study

A Single and Multiple Dose, Open-Label Study of the Pharmacokinetics, Safety, and Tolerability of Dexpramipexole (BIIB050) in Healthy Japanese and Caucasian Subjects

This is a single and multiple dose, open-label study to evaluate the pharmacokinetics (PK), safety, and tolerability of dexpramipexole administered orally to adult Japanese and Caucasian healthy subjects.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Single dose reduced; Drug: Single dose standard; Drug: Multiple Dose; Drug: Multiple Dose

Detailed Description

The study is designed to evaluate the influence of ethnic factors on dexpramipexole safety, tolerability, and PK. Subjects will be admitted to the clinical unit on Day -1 (the day prior to first dosing) and will remain in the clinical unit under observation until discharge. All subjects will have a final follow up visit. Whilst resident in the clinic, subjects will receive 4 treatments: The first 3 treatments comprise Part A of the study and the final treatment group comprises Part B.

Part A:

Treatment 1: Dose 1 (reduced) of dexpramipexole; a single dose Treatment 2: Dose 2 (standard) dexpramipexole; a single dose Treatment 3: Dose 3 (standard) dexpramipexole; 5 doses administered at 12 hour intervals Part B: Dose 4 (standard) dexpramipexole; 5 doses administered at 12 hour intervals There will be a minimum washout of 3 days between treatments.

For all subjects, prior to proceeding to the next treatment group, safety and tolerability data will be reviewed.

Caucasian subjects will be matched individually (on a 1:1 basis) to Japanese subjects with respect to gender and age and if possible BMI.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who are able and willing to give written informed consent.
• Adult Japanese and Caucasian males/females aged 18 to 60 years inclusive and between 18 and 30 kg/m2 body mass index (BMI), inclusive.
• Male and female subjects will be enrolled on the study. Male subjects and female subjects of childbearing potential, must practice effective contraception during the study and be willing and able to continue contraception for 1 month (females) or 3 months (males) after their last dose of study treatment
• Japanese subjects must be born in Japan and have both parents and four grandparents of Japanese descent.
• Japanese subjects must have lived outside of Japan for no more than 5 years.
• Japanese subjects must not have significant changes with regard to diet; i.e., their diet must not have significantly changed since leaving Japan.
• Caucasian subjects will be matched individually (on a 1:1 basis) to Japanese subjects with respect to gender and age, and if possible BMI.

Exclusion Criteria:

• Subjects who do not conform to the above inclusion criteria.
• Female subjects who are pregnant, trying to become pregnant or lactating.
• Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders.
• Subjects who have a clinically relevant surgical history.
• Subjects who have previously received dexpramipexole or pramipexole.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment 1 (Part A); Dexpramipexole single dose (reduced dose)	Drug: Single dose reduced; Treatment 1 (Part A)
Experimental: Treatment 2 (Part A); Dexpramipexole single dose (Standard dose)	Drug: Single dose standard; Treatment 2 (Part A)
Experimental: Treatment 3 (Part A); Dexpramipexole multiple dosing	Drug: Multiple Dose; Treatment 3 (Part A); Drug: Multiple Dose; Part B
Experimental: Treatment for Part B; Dexpramipexole multiple dosing	Drug: Multiple Dose; Treatment 3 (Part A); Drug: Multiple Dose; Part B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax of dexpramipexole	pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours after dosing on Days 1 and 5 in Treatments 1 and 2, and after the fifth dose on Day 11 in Treatment 3 for Parts A & B.
AUC of dexpramipexole	pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours after dosing on Days 1 and 5 in Treatments 1 and 2, and after the fifth dose on Day 11 in Treatment 3 for Parts A & B.

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in clinical laboratory tests	pre-dose to 72 hrs post-dose in each dose group and again at follow-up (14 hrs post last dose)
ECG changes	pre-dose to 72 hrs post-dose in each dose group and again at follow-up (14 hrs post last dose)
Vital Sign changes	pre-dose to 72 hrs post-dose in each dose group and again at follow-up (14 hrs post last dose)
Adverse Event monitoring	pre-dose to 72 hrs post-dose in each dose group and again at follow-up (14 hrs post last dose)

Collaborators and Investigators

• Sponsor: Knopp Biosciences
• Collaborators: Biogen

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: July 28, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (Estimate): August 26, 2011

Study Record Updates

• Last Update Posted (Actual): June 22, 2021
• Last Update Submitted That Met QC Criteria: June 16, 2021
• 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
• Other Study ID Numbers: 223HV101