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

Primary Purpose

Parkinson's Disease

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

AVE8112

Placebo

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, cognitive impairment, movement disorder

Eligibility Criteria

35 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

California Clinical Trials
PARAXEL International

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo Group

AVE8112

Arm Description

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

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

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD)

Secondary Outcome Measures

Pharmacodynamics

Pharmacokinetics

Full Information

NCT ID

NCT01803945

First Posted

February 26, 2013

Last Updated

October 2, 2015

Sponsor

Michael J. Fox Foundation for Parkinson's Research

Collaborators

Sanofi

1. Study Identification

Unique Protocol Identification Number

NCT01803945

Brief Title

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

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Terminated

Why Stopped

First milestone was not met.

Study Start Date

January 2013 (undefined)

Primary Completion Date

June 2015 (Actual)

Study Completion Date

June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Michael J. Fox Foundation for Parkinson's Research

Collaborators

Sanofi

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson's Disease

Keywords

Parkinson's disease, cognitive impairment, movement disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

32 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Placebo Group

Arm Type

Placebo Comparator

Arm Description

Arm Title

AVE8112

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

AVE8112

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD)

Time Frame

Continuous; Patients will be assessed for a period of 28 days

Secondary Outcome Measure Information:

Title

Pharmacodynamics

Time Frame

Continuous; Patients will be assesed for a period of 28 days

Title

Pharmacokinetics

Time Frame

Continuous; Patients will be assessed for a period of 28 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

35 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Facility Information:

Facility Name

California Clinical Trials

City

Glendale

State/Province

California

Country

United States

Facility Name

PARAXEL International

City

Baltimore

State/Province

Maryland

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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