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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Shire
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01898884
First received: July 3, 2013
Last updated: March 19, 2014
Last verified: March 2014
  Purpose

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]

Condition Intervention Phase
Friedreich's Ataxia
Drug: VP 20629
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral VP 20629 in Adult Subjects With Friedreich's Ataxia

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Incidence of adverse events and clinically relevant changes in safety laboratory testing, vital signs, and 12-lead electrocardiograms [ Time Frame: 10 days (single-dose groups) or 17 days (multiple-dose groups) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters (e.g., Cmax, Tmax, AUC, t1/2) [ Time Frame: 3 days (single-dose groups) or 10 days (multiple-dose groups) ] [ Designated as safety issue: No ]
    Blood and urine samples will be collected to assess the pharmacokinetics of VP 20629 and a potential metabolite in plasma and urine after single and multiple doses of VP 20629.


Other Outcome Measures:
  • Pharmacodynamic parameters [ Time Frame: 10 days (multiple-dose groups only) ] [ Designated as safety issue: No ]
    Blood and urine samples will be collected to measure biomarkers of oxidative stress and damage in the multiple-dose groups. These markers are plasma 8-isoprostane and malondialdehyde and urinary 8-hydroxydeoxyguanosine.


Estimated Enrollment: 56
Study Start Date: July 2013
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single dose of VP 20629 or placebo
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.
Drug: VP 20629
Other Name: Indole-3-propionic acid
Drug: Placebo
Experimental: Multiple doses of VP 20629 or placebo
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.
Drug: VP 20629
Other Name: Indole-3-propionic acid
Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01898884

Locations
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States
Contact: Brian Clemente    310-794-1225    bclemente@mednet.ucla.edu   
United States, Florida
University of South Florida Recruiting
Tampa, Florida, United States
Contact: Dr. Kelly Sullivan    813-974-5909    kbarber@health.usf.edu   
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States
Contact: Rebecca McMurray    404-728-6427    rebecca.s.mcmurray@emory.edu   
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States
Contact: Carrie Stephan    319-356-2673    carrie-stephan@uiowa.edu   
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States
Contact: Lauren Seyer    267-426-9738    seyerl@email.chop.edu   
Contact: Debbie Foerster    267-426-7584    foerster@email.chop.edu   
Sponsors and Collaborators
Shire
Investigators
Study Director: Gwendolyn Niebler, DO ViroPharma
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01898884     History of Changes
Other Study ID Numbers: 20629-100
Study First Received: July 3, 2013
Last Updated: March 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ataxia
Friedreich Ataxia
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Spinocerebellar Degenerations
Cerebellar Diseases
Brain Diseases
Central Nervous System Diseases
Spinal Cord Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Mitochondrial Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on September 18, 2014