A Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AVE8112 in Patients With Parkinson's Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Michael J. Fox Foundation for Parkinson's Research
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Michael J. Fox Foundation for Parkinson's Research
ClinicalTrials.gov Identifier:
NCT01803945
First received: February 26, 2013
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

This is a randomized, double-blind, placebo-controlled, multiple-ascending dose study of orally administered AVE8112 in patients with Parkinson's Disease (PD).


Condition Intervention Phase
Parkinson's Disease
Drug: AVE8112
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 Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AVE8112 in Patients With Parkinson's Disease

Resource links provided by NLM:


Further study details as provided by Michael J. Fox Foundation for Parkinson's Research:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: Continuous; Patients will be assessed for a period of 28 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacodynamics [ Time Frame: Continuous; Patients will be assesed for a period of 28 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: Continuous; Patients will be assessed for a period of 28 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 32
Study Start Date: January 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Group Drug: Placebo
Active Comparator: AVE8112 Drug: AVE8112

Detailed Description:

This is a randomized, double-blind, placebo-controlled, multiple-ascending dose study of orally administered AVE8112 in patients with Parkinson's Disease (PD). Sequential cohorts of eight patients with PD will be administered ascending oral doses of AVE8112 (n=6) or placebo (n=2) once a day for 14 days. Dosing for subsequent cohorts will only proceed, and the dose level selected, after the safety and tolerability of the previous cohort has been reviewed. Doses are planned to be 1.0, 2.0, 3.0, and 4.0 mg once a day for 14 days. These are planned treatments, but doses may be modified based on safety review of previous cohort(s). In addition, cohorts may be added to reconfirm a previously administered dose, and/or a titration strategy may be employed to reach a desired dose.

Patients will be assessed in clinic for 30 hours following the initial oral dose of AVE8112 or placebo. Subsequent dosing will occur on an outpatient basis. Patients will receive telephone calls on Days 3 and 10 to monitor for adverse events (AEs) and concomitant medications, and will also be assessed in the clinic on Study Days 7 (outpatient), 14 (outpatient), and 28 (± 3 days) (Follow-up visit). Safety assessments will include physical examinations, vital signs, ECGs, clinical laboratory evaluations, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and Columbia Suicide Severity Rating Scale (C-SSRS). Pharmacodynamic assessment will include the Parkinson's Disease Cognitive Rating Scale (PD-CRS).

  Eligibility

Ages Eligible for Study:   35 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 35 to 70, inclusive, with a diagnosis of PD, currently being treated with a stable regimen (at least 4 weeks) of anti-parkinsonian drugs which include at least one L 3,4 dihydroxyphenylalanine (L DOPA)-containing therapy with or without dopamine agonist at Screening.
  • Patients must have at least two of the following: resting tremor, bradykinesia, rigidity (must have either resting tremor or bradykinesia), or gait disturbances as assessed during physical/neurological exam at the Screening visit.
  • A diagnosis of PD for 10 years or less at Screening.
  • Hoehn and Yahr stage I - III.
  • Male or female age 30 years or older at time of PD diagnosis.
  • Body Mass Index (BMI) of approximately ≥18 to ≤32 kg/m2; and a total body weight > 50 kg (l10 lbs).
  • Female patients must be of non-childbearing potential.

Exclusion Criteria:

  • Clinically significant history or evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, neurological, immunological, or psychiatric disorder(s) as determined by the Investigator or designee.
  • Female patients that are breastfeeding or female patients with a positive serum pregnancy test.
  • Use of cholinergic medications or those with cholinergic effects.
  • History of orthostatic hypotension or symptomatic drop in SBP.
  • Any subject who has advanced Parkinson's Disease.
  • Evidence of severe depression (score of >10 on Quick Inventory of Depressive Symptomatology - Self Rated [QIDS-SR]).
  • Personal and/or familial history of a significant suicide attempt.
  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: NCT01803945

Locations
United States, California
California Clinical Trials Recruiting
Glendale, California, United States
Contact: Molly Sherman    818-254-1824      
Principal Investigator: Hakop Gevorkyan, MD         
United States, Maryland
PARAXEL International Recruiting
Baltimore, Maryland, United States
Contact: Heather Karabaich    877-617-8839      
Principal Investigator: Olukemi Olugemo, MD         
Sponsors and Collaborators
Michael J. Fox Foundation for Parkinson's Research
Sanofi
  More Information

No publications provided

Responsible Party: Michael J. Fox Foundation for Parkinson's Research
ClinicalTrials.gov Identifier: NCT01803945     History of Changes
Other Study ID Numbers: MJFF AVE8112 MAD PD
Study First Received: February 26, 2013
Last Updated: March 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Michael J. Fox Foundation for Parkinson's Research:
Parkinson's disease
cognitive impairment
movement disorder

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases

ClinicalTrials.gov processed this record on September 22, 2014