Clinical trial NCT01803945: A Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AVE8112 in Patients With Parkinson's Disease
Official title: A Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AVE8112 in Patients With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
cognitive impairment
movement disorder
Lead sponsor: Michael J. Fox Foundation for Parkinson's Research
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2013-03-04
Enrollment: 32
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Continuous; Patients will be assessed for a period of 28 days
Secondary outcomes:
measure: Pharmacodynamics
timeFrame: Continuous; Patients will be assesed for a period of 28 days
measure: Pharmacokinetics
timeFrame: Continuous; Patients will be assessed for a period of 28 days
Other outcomes:
Locations:
city: Glendale
country: United States
facility: California Clinical Trials
state: California
city: Baltimore
country: United States
facility: PARAXEL International
state: Maryland
Study officials:
References: