ADX48621 for the Treatment of Levodopa Induced Dyskinesia in Patients With Parkinson's Disease

Phase 2, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter Study to Evaluate the Safety, Tolerability and Efficacy of ADX48621 in the Treatment of Levodopa Induced Dyskinesia in Patients With Parkinson's Disease

The primary objective of the study is to evaluate the safety and tolerability of ADX48621 in Parkinson's disease patients following four weeks of dosing.

The secondary objectives of the study include the evaluation of the efficacy of ADX48621 compared with placebo in reducing levodopa induced dyskinesia in patients with Parkinson's; the evaluation of the effect of ADX48621 on symptoms of Parkinson's disease and patient ability to function, and the evaluation of the effect of coadministration of ADX48621 on L-dopa efficacy.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; Drug: ADX48621

Detailed Description

First study of ADX48621 in male and female Parkinson's disease patients with levodopa-induced dyskinesia. Four weeks, double-blind, placebo-controlled dose titration from 50 mg once daily up to 100 mg three times daily, at the start of week 4. Safety and tolerability assessed by adverse events enquiry, heart rate and blood pressure, 12-lead ECG, haematology and biochemistry. Efficacy assessments include Abnormal Involuntary Movement Scale (AIMS), Unified Parkinson's Disease rating Scale (UPDRS) patient PD symptom diaries, Hospital Anxiety Depression Scale (HADS), patient and clinician global impression of change in PD and dyskinesia (PGIC and CGIC).

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Addex Investigator Site
• France
  • Bordeaux, France
    • Addex Investigator Site
  • Clermont Ferrand, France
    • Addex Investigator Site
  • Nantes, France
    • Addex Investigator Site
  • Paris, France
    • Addex Investigator Site
  • Toulouse, France
    • Addex Investigator Site
• Germany
  • Bochum, Germany
    • Addex Investigator Site
  • Hanau, Germany
    • Addex Investigator Site
  • Hannover, Germany
    • Addex Investigator Site
  • Kassel, Germany
    • Addex Investigator Site
  • Marburg, Germany
    • Addex Investigator Site
  • Munich, Germany
    • Addex Investigator Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Addex Investigator Site
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Addex Investigator Site
  • California
    • La Jolla, California, United States, 92037
      • Addex Investigator Site
    • Los Angeles, California, United States, 90033
      • Addex Investigator Site
    • Sunnyvale, California, United States, 94085
      • Addex Investigator Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Addex Investigator Site
  • Florida
    • Boca Raton, Florida, United States, 33612
      • Addex Investigator Site
    • Tampa, Florida, United States, 33606
      • Addex Investigator Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Addex Investigator Site
  • Michigan
    • Southfield, Michigan, United States, 48034
      • Addex Investigator Site
  • New York
    • Commack, New York, United States, 11725
      • Addex Investigator Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Addex Investigator Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Addex Investigator Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• outpatient with idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria (UKPDSBBCDC)
• experiences moderately disabling dyskinesia (screening visit UPDRS 33 score≥2)
• has an mAIMS score at baseline ≥ 7 with a score ≥ 3 in at least one body area

Exclusion Criteria:

• surgical treatment for Parkinson's disease (e.g. Deep Brain Stimulation, within the last year or planned during the study)
• unstable co-existing psychiatric disease including cognitive impairment that, according to the Investigator, could interfere with the conduct of the study
• has a history of a significant medical condition that may affect the safety of the patient or preclude adequate participation in the study.
• is pregnant or breast-feeding. Female patients who are of child-bearing potential must be using adequate contraceptive methods (e.g. oral contraceptive, double-barrier method, intra-uterine device, intra-muscular hormonal contraceptive), and have a negative pregnancy test at Screening

Other protocol-defined inclusion and exclusion criteria may apply

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
Experimental: ADX48621	Drug: ADX48621; oral administration; Other Names: Dipraglurant
Placebo Comparator: ADX48621 Matching Placebo	Drug: Placebo; oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with abnormal safety and tolerability assessment parameters	Physical and neurological examination, heart rate and blood pressure, 12-lead ECG, hematology and biochemistry assessments, use of concomitant medications, adverse events and serious adverse events.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dyskinesia severity score measured by mAIMS		4 weeks
Change in Parkinson's disease severity	Patient diary at weeks 1, 2, 3 and 4, UPDRS Part III at weeks 2 and 4, UPDRS total score at week 4	4 weeks
Patient-rated and clinician-rated global impression of change in dyskinesia and Parkinson's disease		4 weeks

Collaborators and Investigators

• Sponsor: Addex Pharma S.A.
• Investigators: Study Director: Addex Pharma, Addex Pharma

Publications and helpful links

General Publications

• McFarthing K, Prakash N, Simuni T. CLINICAL TRIAL HIGHLIGHTS - DYSKINESIA. J Parkinsons Dis. 2019;9(3):449-465. doi: 10.3233/JPD-199002. No abstract available.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: April 4, 2011
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 15, 2011

Study Record Updates

• Last Update Posted (Estimate): July 16, 2012
• Last Update Submitted That Met QC Criteria: July 13, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: dyskinesia; Parkinson's disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Dyskinesias
• Other Study ID Numbers: ADX48621-201