A Study to Evaluate in Patients With Parkinsonian Type Disorders

A Phase 2 study to evaluate the safety, tolerability and initial efficacy of pramipexole ER, given with aprepitant in patients with parkinsonian type disorders

Methodology: This is an initial Phase 2, rising-dose, single-blind, out-patient, sequential-treatment study in up to 24 patients with idiopathic Parkinson's disease of about 5 months duration. All participants will have idiopathic Parkinson's disease (PD). Subjects will sign a consent form prior to any study related procedure and will complete baseline screening assessments. The study will be conducted in three parts: Part 1: All eligible patients switch from their dopaminergic treatment to the equivalent dose of pramipexole ER in the judgement of the investigator. Then, pramipexole ER is titrated alone up to the patients' optimal dose or to the protocol maximum allowed dose for Part 1 of 4.5 mg/day. Part 2: Add-on aprepitant and continue the titration of pramipexole ER from the optimal dose (or 4.5 mg/day) determined in Part 1 to the optimal dose not to exceed the protocol limit of 9.0mg/day, given in combination with aprepitant. Part 3: Maintain the dose of pramipexole ER found in Part 2 given in combination with aprepitant for 3 months with periodic safety and efficacy checks. During Parts 1 and 2, subjects will be evaluated at in-clinic visits for safety and tolerability at intervals not to exceed once weekly ± 2 days and additionally by telephone or in-clinic visits, as considered clinically appropriate, at each dose change. During Part 3, this optimal pramipexole ER/aprepitant regimen will be stably maintained for 3 months in association with monthly in-clinic laboratory and clinical evaluations. Safety and tolerability will continue to be evaluated by telephone or in-clinic visits, as deemed clinically appropriate. Pramipexole ER tablets will be administered with or without aprepitant, orally once daily in the morning. Subjects will take 1-3 pramipexole ER tablets daily. Aprepitant will be administered orally in a fixed daily dose by means of a single capsule containing 80 mg. At study completion (or at other times in accordance with Stopping Rules given below), study medications will be discontinued, and participants will be returned to their pre-admission therapeutic regimen as considered medically appropriate. Investigators will always have the option of making necessary and appropriate changes to protocol dose optimization schedules in consultation with the Sponsor. An independent DSMB will be appointed to have responsibility for safeguarding the interests of the trial subjects and assessing the safety and tolerability of the study treatments during the trial. The DSMB will meet when 10 patients complete the study and when all patients complete the study.