Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich Ataxia

NCT03214588 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TAK-831-1501U1111-1189-7951
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 6

Brief Summary

The purpose of this study is to evaluate the efficacy of TAK-831 versus placebo on upper extremity (arm and hands) motor function and manual dexterity. This study will also evaluate the efficacy of TAK-831 versus placebo on activities of daily living (ADL) and other secondary assessments.

Conditions

Friedreich Ataxia

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Inverse Time to Complete the 9-Hole Peg Test (9-HPT-1)

  The 9-HPT-1 is a measure of timed upper extremity (arm and hand) function and manual dexterity. The participant picks up pegs 1 at a time (9 in total), using 1 hand only, and places them into holes on the board as quickly as possible, in any order until all holes are filled. Then, without pausing, the participant removes the pegs 1 at a time and returns them as quickly as possible. Each participant performs this task twice with each hand separately. Results on both tests are then averaged for an overall task completion time and the inverse transform is performed. A positive change from Baseline indicates improvement. Change from Baseline in 9-HPT-1 was analyzed using mixed model for repeated measures (MMRM) analysis of covariance (ANCOVA) with Baseline 9-HPT-1 as a covariate; pooled site, visit, treatment, and ambulation status (randomization factor) as fixed factors; and treatment-by-visit and Baseline 9-HPT-1-by-visit interactions.

  Baseline and Week 12

Secondary Outcomes (19)

• Change From Baseline in the Activities of Daily Living (ADL) Component Score of the Friedreich Ataxia Rating Scale (FARS)

  Baseline and Weeks 2, 7 and 12

• Change From Baseline in the Inverse Time to Complete the 9-HPT-1

  Baseline and Weeks 2 and 7

• Change From Baseline in the ADL Component Individual Item Scores

  Baseline and Weeks 2, 7 and 12

• Change From Baseline in the Modified Friedreich Ataxia Rating Scale Neurological Examination (mFARS-neuro) Total Score

  Baseline and Weeks 2, 7 and 12

• Change From Baseline in the mFARS-neuro Subscales Scores

  Baseline and Weeks 2, 7, and 12

Study Arms (3)

Placebo

PLACEBO COMPARATOR

TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.

Drug: TAK-831 Placebo

TAK-831 75 mg

EXPERIMENTAL

TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.

Drug: TAK-831

TAK-831 300 mg

EXPERIMENTAL

TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.

Drug: TAK-831

Interventions

TAK-831 DRUG

TAK-831 tablets

TAK-831 300 mg; TAK-831 75 mg

TAK-831 Placebo DRUG

TAK-831 placebo matching tablets

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• \. Has a genetically-confirmed diagnosis (homozygous for guanine-adenine-adenine \[GAA\] repeat expansions in the frataxin gene \[FXN\] in the affected range of Friedreich ataxia \[FRDA\] or a compound heterozygous expansion with a point mutation or deletion), with an established disease stage of 2 to 5, inclusive, as determined by the Functional Staging for Ataxia, at Screening.

You may not qualify if:

• Received a diagnosis of ataxic syndromes other than FRDA.
• Has a history of cancer, except basal cell carcinoma or in situ cervical cancer that has been in remission for greater than or equal to (\>=5) years prior to first dose of study drug.
• Known to be currently infected or has been infected with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
• Has a known hypersensitivity to any component of the formulation of TAK-831.
• Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse.
• Has taken any excluded medication, or has had insufficient washout of medications or is unable or unwilling to discontinue medications as required by the protocol.
• If male, the participant intends to donate sperm during the course of this study or for 95 days after the last dose of study drug.
• If female, the participant is of childbearing potential and lactating, pregnant (positive prerandomization serum pregnancy test), or plans to become pregnant before participating in the study, during the study, or within 35 days after last dose of the study drug, or intending to donate ova during such time period.
• Has a history of neuroleptic malignant syndrome, water intoxication, or paralytic ileus or other conditions that may interfere with absorption of study medication.

Sponsors & Collaborators

• Neurocrine Biosciences: lead
• Takeda: collaborator

Study Sites (6)

UCLA Ataxia Center

Los Angeles, California, 90095, United States

Location

University of Florida Center for Movement Disorders

Gainesville, Florida, 32607, United States

Location

USF College of Medicine

Tampa, Florida, 33612, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43220, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Friedreich Ataxia

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Neurocrine Medical Information
• Organization: Neurocrine Biosciences

medinfo@neurocrine.com

877-641-3461

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 11, 2017
• Study Start: November 8, 2017
• Primary Completion: December 27, 2018
• Study Completion: December 27, 2018
• Last Updated: June 14, 2021
• Results First Posted: December 19, 2019

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)