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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 6
- 主要终点
- Change From Baseline in the Inverse Time to Complete the 9-Hole Peg Test (9-HPT-1)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-
- •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.
研究组 & 干预措施
Placebo
TAK-831 placebo-matching tablets, orally, twice daily for up to 12 weeks.
干预措施: TAK-831 Placebo (Drug)
TAK-831 75 mg
TAK-831 75 mg, tablets, orally, twice daily for up to 12 weeks.
干预措施: TAK-831 (Drug)
TAK-831 300 mg
TAK-831 300 mg, tablets, orally, twice daily for up to 12 weeks.
干预措施: TAK-831 (Drug)
结局指标
主要结局
Change From Baseline in the Inverse Time to Complete the 9-Hole Peg Test (9-HPT-1)
时间窗: Baseline and Week 12
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.
次要结局
- 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 Timed 25-Foot Walk (T25FW)(Baseline and Weeks 2, 7 and 12)
- Number of Participants by Patient Global Impression-Severity (PGI-S) (Global Severity) Score Categories Relative to Baseline(Baseline and Weeks 2, 7, and 12)
- Number of Participants by CGI-S (Upper Extremity Functional Severity) Score Categories Relative to Baseline(Baseline and Week 2, 7, and 12)
- Change From Baseline in the 9-HPT and T25FW Composite Score(Baseline and Weeks 2, 7, and 12)
- Number of Participants by CGI-I (Upper Extremity Functional Change) Score Categories(Weeks 2, 7, and 12)
- Change From Baseline in the ADL Component Score for Upper Limb Function Items of the FARS(Baseline and Weeks 2, 7 and 12)
- Number of Participants by Clinical Global Impression-Improvement (CGI-I) (Global Change) Score Categories(Weeks 2, 7, and 12)
- 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 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)
- Change From Baseline in the mFARS-neuro Individual Item Scores(Baseline and Weeks 2, 7, and 12)
- Change From Baseline in Low-Contrast Letter Acuity (LCLA) Test Score(Baseline and Weeks 2, 7, and, 12)
- Number of Participants by PGI-S (Upper Extremity Functional Severity) Score Categories(Baseline and Weeks 2, 7, and 12)
- Number of Participants With at Least a 15 Percent (%) or at Least a 20% Reduction in 9-HPT Completion Time From Baseline(Baseline up to Week 12)
- Number of Participants by Patient Global Impression-Improvement (PGI-I) (Global Change) Score Categories(Weeks 2, 7 and 12)
- Number of Participants by PGI-I (Upper Extremity Functional Change) Score Categories(Weeks 2, 7, and 12)
- Number of Participants by Clinical Global Impression-Severity (CGI-S) (Global Severity) Score Categories Relative to Baseline(Baseline and Weeks 2, 7, and 12)