Clinical trial NCT03214588: Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adults With Friedreich Ataxia
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Evaluate Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adult Subjects With Friedreich Ataxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Friedreich Ataxia
Keywords: Drug Therapy
Lead sponsor: Neurocrine Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2017-07-11
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The drug being tested in this study is called TAK-831. TAK-831 is being tested to treat people who have Friedreich ataxia. This study will look at upper extremity (arms and hands) motor function and manual dexterity of people who take TAK-831. Efficacy evaluations also include other neurological, functional, and patient performance assessments.

The study will enroll approximately 65 participants. Participants will be randomly assigned in a 2:1:2 ratio to one of the three treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

* TAK-831 High dose
* TAK-831 Low dose
* Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient

All participants will be asked to take three tablets of high dose, low dose, or placebo twice a day for 12 weeks.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is approximately 13 weeks. Participants will make 5 visits to the clinic, and will be contacted by telephone for an exit interview no later than 7 days after their final visit or termination. Participants will also receive a safety follow-up phone call 7 to 17 days after receiving their last dose of TAK-831.

Eligibility criteria: Key Inclusion Criteria:

1. 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.

Key Exclusion Criteria:

1. Received a diagnosis of ataxic syndromes other than FRDA.
2. 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.
3. Known to be currently infected or has been infected with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus.
4. Has a known hypersensitivity to any component of the formulation of TAK-831.
5. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse.
6. 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.
7. 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.
8. 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.
9. Has a history of neuroleptic malignant syndrome, water intoxication, or paralytic ileus or other conditions that may interfere with absorption of study medication.

Primary outcomes:
measure: Change From Baseline in the Inverse Time to Complete the 9-Hole Peg Test (9-HPT-1)
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline in the Activities of Daily Living (ADL) Component Score of the Friedreich Ataxia Rating Scale (FARS)
timeFrame: Baseline and Weeks 2, 7 and 12
measure: Change From Baseline in the Inverse Time to Complete the 9-HPT-1
timeFrame: Baseline and Weeks 2 and 7
measure: Change From Baseline in the ADL Component Individual Item Scores
timeFrame: Baseline and Weeks 2, 7 and 12
measure: Change From Baseline in the Modified Friedreich Ataxia Rating Scale Neurological Examination (mFARS-neuro) Total Score
timeFrame: Baseline and Weeks 2, 7 and 12
measure: Change From Baseline in the mFARS-neuro Subscales Scores
timeFrame: Baseline and Weeks 2, 7, and 12
measure: Change From Baseline in the mFARS-neuro Individual Item Scores
timeFrame: Baseline and Weeks 2, 7, and 12
measure: Change From Baseline in the Timed 25-Foot Walk (T25FW)
timeFrame: Baseline and Weeks 2, 7 and 12
measure: Change From Baseline in the 9-HPT and T25FW Composite Score
timeFrame: Baseline and Weeks 2, 7, and 12
measure: Change From Baseline in Low-Contrast Letter Acuity (LCLA) Test Score
timeFrame: Baseline and Weeks 2, 7, and, 12
measure: Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories
timeFrame: Weeks 2, 7, and 12
measure: Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories
timeFrame: Weeks 2, 7 and 12
measure: Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories
timeFrame: Weeks 2, 7, and 12
measure: Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories
timeFrame: Weeks 2, 7, and 12
measure: Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline
timeFrame: Baseline and Weeks 2, 7, and 12
measure: Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline
timeFrame: Baseline and Weeks 2, 7, and 12
measure: Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline
timeFrame: Baseline and Week 2, 7, and 12
measure: Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories
timeFrame: Baseline and Weeks 2, 7, and 12
measure: Change From Baseline in the ADL Component Score for Upper Limb Function Items of the FARS
timeFrame: Baseline and Weeks 2, 7 and 12
measure: Number of Participants With at Least a 15 Percent (%) or at Least a 20% Reduction in 9-HPT Completion Time From Baseline
timeFrame: Baseline up to Week 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Ataxia Center
state: California
city: Gainesville
country: United States
facility: University of Florida Center for Movement Disorders
state: Florida
city: Tampa
country: United States
facility: USF College of Medicine
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
References: