A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Three Doses of Aplindore MR (1, 3, and 6 mg Twice Daily) in Patients With Early Parkinson Disease (APLIED)
Overview
- Phase
- Phase 2
- Intervention
- aplindore MR tablets or Placebo
- Conditions
- Early Parkinson Disease
- Sponsor
- Neurogen Corporation
- Enrollment
- 9
- Locations
- 25
- Primary Endpoint
- Mean change from baseline to end of treatment in the combined scores of Parts II and III of the UPDRS
- Status
- Terminated
- Last Updated
- 16 years ago
Overview
Brief Summary
This is a clinical trial to be conducted at multiple Parkinson Study Group (PSG) sites in the USA. Patients with early Parkinson disease will be randomly allocated to one of 4 arms in the study. The 4 arms include 3 arms with different doses of aplindore MR tablets and 1 placebo arm. The study drug will be taken twice a day (BID). The study is blinded and neither subjects, nor the investigators, will know what treatment the subject is receiving. Investigational study drug will be adjusted to the assigned dosage and then maintained at that dosage for the balance of the 12 week follow-up period. The entire study will take about 13 weeks. The study will assess the safety and tolerability of aplindore and measure how effective aplindore is in improving movement and other effects of Parkinson disease.
Detailed Description
One hundred and sixty eight patients will be randomly assigned to one of four investigational treatment regimens in this outpatient study. For active treatment arms, study drug will be titrated to the assigned dosage and then maintained for up to a 12 week follow-up period before receiving tapered doses in advance of study completion. Dosing will take place over a total of about 13 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female at least 30 years old;
- •Initial diagnosis of idiopathic PD must be within 5 years;
- •At least two of the following cardinal signs must be present: bradykinesia, resting tremor, and rigidity;
- •PD progression must be Stage 1 to 2.5 (inclusive) according to the modified Hoehn and Yahr classification system;
- •Have a score on the MoCA of at least 26;
- •Have a score on the Beck Depression Inventory II (BDI II) of less than 15;
- •Have a screening UPDRS (Part III) motor score of at least 10;
- •In good general health as determined by a thorough medical history and physical examination (including vital signs), neurological examination, 12-lead ECG, and clinical chemistry laboratory tests;
- •Females of childbearing potential must be using an acceptable method of contraception and have a negative serum pregnancy test at the screening and baseline visits. Acceptable methods of contraception are oral, intrauterine, implantable, injectable contraceptives, double barrier methods or condoms impregnated with spermicide. After screening, subjects using oral contraceptive methods of contraception must agree to add an additional method until 30 days after the last dose of study medication. Women on oral contraceptives or using cervical rings must have been using them for at least 1 month before the screening visit;
- •Male subjects with partners of childbearing potential must use adequate contraception during the study and for 3 months after the study;
Exclusion Criteria
- •History or clinical features consistent with an atypical parkinsonian syndrome;
- •History of surgical intervention for PD;
- •History of severe allergic or anaphylactic reaction to any drug;
- •History of allergies or known sensitivity, hypersensitivity, or severe adverse reaction (e.g., requiring abrupt discontinuation) to any drug similar to aplindore;
- •Taking prescription drug therapy or over the counter medication for chronic medical conditions who have not been on stable doses for at least 1 month before the screening visit;
- •Treated with L-dopa within 2 months before the baseline visit or who have had cumulative treatment exceeding 2 months;
- •Have taken dopamine agonist therapy within 1 month before the baseline visit or who have taken dopamine agonist therapy for a cumulative period exceeding 2 months;
- •Are receiving amantadine, anticholinergics, or monoamine oxidase B inhibitors who have not been taking stable doses for at least 2 months before the baseline visit;
- •A clinically significantly abnormal clinical laboratory value as judged by the investigator or a value that is disapproved by the study Clinical Monitor;
- •A decrease in either systolic blood pressure of at least 40 mmHg or a decrease in diastolic blood pressure of at least 20 mmHg following 5 minutes supine and 2 minutes standing, at or within 6 months before the baseline visit;
Arms & Interventions
1
aplindore 2 mg MR total daily dose
Intervention: aplindore MR tablets or Placebo
2
aplindore 6 mg MR total daily dose
Intervention: aplindore MR tablets or Placebo
3
aplindore 12 mg MR total daily dose
Intervention: aplindore MR tablets or Placebo
4
Placebo
Intervention: aplindore MR tablets or Placebo
Outcomes
Primary Outcomes
Mean change from baseline to end of treatment in the combined scores of Parts II and III of the UPDRS
Time Frame: 3 months
Secondary Outcomes
- The responder rate; Part II and Part III scores (separately) of the UPDRS; mean change from baseline in the modified Schwab and England Activities of Daily Living; time course in UPDRS and in modified S&E-ADL; safety and tolerability of aplindore MR(3 months)