Safety and Pharmacology Study of VP 20629 in Adults With Friedreich's Ataxia
Condition: Friedreich's Ataxia
MeSH terms: Ataxia; Cerebellar Ataxia; Friedreich Ataxia
Intervention: VP 20629; Placebo
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: No

Summary:

      The objectives of the study are:

        -  To evaluate the safety and tolerability of single and multiple oral doses of VP 20629 in
           subjects with Friedreich's ataxia (FA). [Primary]

        -  To characterize the pharmacokinetics of VP 20629 by investigation of the plasma
           concentration-time profile following single and multiple oral doses in subjects with FA.
           [Secondary]

        -  To investigate the pharmacodynamic effects of VP 20629 on plasma 8-isoprostane and
           malondialdehyde and urinary 8-hydroxydeoxyguanosine concentrations following multiple
           oral doses in subjects with FA. [Exploratory]
    

Eligibility criteria:

        Inclusion Criteria:

          1. Be 18 to 45 years of age (inclusive).

          2. Have a body mass index between 18 and 27 kg/m^2 (inclusive).

          3. Have a clinical presentation consistent with FA.

          4. Have a confirmed diagnosis of FA with a defined expanded guanosine, adenine, adenine
             (GAA) triplet repeat number.

          5. Have an International Cooperative Ataxia Rating Scale (ICARS) mean total score of ≤75.

          6. If female, be postmenopausal (cessation of menses ≥1 year), surgically sterile, or
             have a negative serum human chorionic gonadotropin pregnancy test within 5 days prior
             to the first dose of study drug. Women of child bearing potential must also be on an
             acceptable method of birth control, as determined by the Investigator, for 3 months
             prior to the first dose and must agree to continue use through 2 months after the last
             dose of study drug.

             If male, be surgically sterile or agree to follow an acceptable method of birth
             control as determined by the Investigator, from the screening visit through 2 months
             after the last dose of study drug.

          7. Be able to swallow capsules whole.

          8. Agree to adhere to the protocol-defined schedule of assessments and procedures.

          9. Be informed of the nature of the study and provide written informed consent before any
             study-specific procedures are performed.

        Exclusion Criteria:

          1. Have taken coenzyme Q10, idebenone, other dietary or herbal supplements (with an
             anti-oxidative effect), or over-the-counter medications (including homeopathic
             medicines and vitamins) within 1 week prior to the first dose of study drug on Day 1.

          2. If female, be pregnant or breastfeeding.

          3. Have a positive test result for human immunodeficiency virus (HIV), hepatitis B
             surface antigen, or hepatitis C antibody.

          4. Have ingested any alcohol within 48 hours before admission to the clinical study unit
             on Day -1. NOTE: Caffeine intake should be limited to 2 caffeine-containing beverages
             per day during this same time period.

          5. Have participated in an investigational drug trial within 30 days prior to the first
             dose of study drug on Day 1. NOTE: Subjects who received study drug (VP 20629 or
             placebo) in a single-dose group in this study and completed the Post-treatment Safety
             Assessment are allowed to enroll in a multiple-dose group following a 21 day washout
             period, provided they continue to meet protocol eligibility criteria. Subjects cannot
             enroll in a multiple-dose group if they have an ongoing adverse event following
             participation in a single-dose group or had a serious adverse event during a
             single-dose group (regardless of causality).

          6. Have a known hypersensitivity to any ingredient in the study formulation.

          7. Have, as determined by the Investigator and/or medical monitor, any clinically
             relevant medical or surgical condition that could interfere with the administration of
             study drug, interpretation of study results, or compromise the safety or well-being of
             the subject.

          8. Have a Columbia-Suicide Severity Rating Scale (C-SSRS) score of 4 or 5.