Safety and Pharmacology Study of VP 20629 in Adults With Friedreich's Ataxia

Shire

Status and phase: Completed; Phase 1

Conditions: Friedreich's Ataxia

Treatments: Drug: VP 20629; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01898884

20629-100

Details and patient eligibility

About

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]

Enrollment: 46 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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46 participants in 2 patient groups

Single dose of VP 20629 or placebo

Experimental group

Description:

Four groups of 8 subjects each will receive a single dose of VP 20629 (150 mg, 450 mg, 900 mg, or 1200 mg) or placebo.

Treatment:

Drug: Placebo

Drug: VP 20629

Multiple doses of VP 20629 or placebo

Experimental group

Description:

Three groups of 8 subjects each will receive multiple doses of VP 20629 (300 mg, 600 mg, or 900 mg total daily dose) or placebo. VP 20629 or placebo will be administered every 8 hours for 7 days with a single morning dose on Day 8.

Treatment:

Drug: Placebo

Drug: VP 20629