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

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

Study Overview

• Status: Terminated
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; 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).

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States
      • California Clinical Trials
  • Maryland
    • Baltimore, Maryland, United States
      • Paraxel International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Group; 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. Patients will be assessed in clinic for 30 hours following the initial oral dose of AVE8112 or placebo	Drug: Placebo
Active Comparator: AVE8112; 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	Drug: AVE8112

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD)	Continuous; Patients will be assessed for a period of 28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacodynamics	Continuous; Patients will be assesed for a period of 28 days
Pharmacokinetics	Continuous; Patients will be assessed for a period of 28 days

Collaborators and Investigators

• Sponsor: Michael J. Fox Foundation for Parkinson's Research
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: February 26, 2013
• First Submitted That Met QC Criteria: March 1, 2013
• First Posted (Estimate): March 4, 2013

Study Record Updates

• Last Update Posted (Estimate): October 6, 2015
• Last Update Submitted That Met QC Criteria: October 2, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Parkinson's disease; cognitive impairment; movement disorder
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: MJFF AVE8112 MAD PD