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

• Conditions: evodopa induced dyskinesia in Parkinson's disease patients; MedDRA version: 14.0Level: PTClassification code 10013916Term: DyskinesiaSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2010-022517-25-AT
• Lead Sponsor: Addex Pharma SA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-17
• Last Update Posted: 20 May 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

1. willing and able to provide written informed consent.
2. age 30 to 75 years, inclusive.
3. outpatient with idiopathic PD according to the UK Parkinson’s Disease Society Brain Bank Clinical Diagnosis Criteria (UKPDSBBCDC).
4. on an optimized PD treatment regimen with a stable dose of anti-parkinsonian medication for at least four weeks before the Screening Visit (levodopa, DDIs, COMT inhibitors, dopamine agonists and MAO-B inhibitors).
5. treated with a daily L-dopa dose (immediate or extended release formulation) between 300 and 1500 mg divided into a minimum of three doses per day.
6. experiences dyskinesia for at least three months prior to study entry.
7. experiences moderately disabling dyskinesia (screening visit UPDRS 33 score = 2).
8. has an mAIMS score at baseline = 7 with a score = 3 in at least one body area.
9. has the ability to communicate adequately with the study staff and to comply with the requirements of the entire study, with the help of a carer if applicable.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. has more than 4 hours, i.e. 8 missing or incorrectly completed entries in the Screening diary.
2. surgical treatment for Parkinson’s disease (e.g. Deep Brain Stimulation, within the last year or planned during the study).
3. unstable co-existing psychiatric disease including cognitive impairment that, according to the Investigator, could interfere with the conduct of the study.
4. has a known clinically significant allergy or known hypersensitivity to drugs that, in the opinion of the Investigator, may affect the patient’s safety.
5. has clinically significant abnormal laboratory parameters at screening, in particular, liver or renal functions tests greater than 1.5 times the upper limit of normal (ULN) or any other clinically significant biochemical or hematological abnormality as determined by the Investigator.
6. is taking or has taken less then 4 weeks prior to Screening excluded drugs: NMDA antagonists including amantadine and memantine as well as amphetamines, cocaine, topiramate, sodium valproate, apomorphine, MAO-A inhibitors, dopamine antagonists including metoclopramide, phenothiazines and any antipsychotics, potent inhibitors of CYP1A2, i.e. fluvoxamine or fluoroquinolone antibiotics, potent inhibitors of CYP2C8, i.e. gemfibrozil.
7. has known or suspected human immunodeficiency virus (HIV) or hepatitis B or C.
8. has a history of a significant medical condition that may affect the safety of the patient or preclude adequate participation in the study, including but not limited to orthostatic hypotension causing syncope, uncontrolled ischemic heart disease, uncontrolled brady- or tachyarrhythmias, coronary obstructive pulmonary disease, chronic obstructive pulmonary disease, arrhythmias, diabetes and epilepsy.
9. 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.
10. has received any investigational drug within 30 days of Screening.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of ADX48621 in Parkinson’s disease patients following four weeks of dosing;Secondary Objective: To evaluate the efficacy of ADX48621 compared with placebo in reducing levodopa induced dyskinesia in patients with Parkinson’s disease.<br><br>To evaluate the effect of ADX48621 on symptoms of Parkinson’s disease and patient ability to function.<br><br>To evaluate the effect of co-administration of ADX48621 on L-dopa efficacy.<br>;Primary end point(s): Safety and tolerability<br>;Timepoint(s) of evaluation of this end point: Week 4

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy, primary efficacy variable: dyskinesia severity measured by mAIMS AUC0-3;Timepoint(s) of evaluation of this end point: Week 4