Clinical trial NCT00406029: Dyskinesia in Parkinson's Disease (Study P04501)
Official title: A Phase 2, 12-Week, Double-Blind, Dose-Finding, Placebo-Controlled Study to Assess the Efficacy and Safety of a Range of SCH 420814 Doses in Subjects With Moderate to Severe Parkinson's Disease Experiencing Motor Fluctuations and Dyskinesias
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Movement Disorders
Central Nervous System Diseases
Neurodegenerative Diseases
Brain Diseases
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2006-12-04
Enrollment: 253
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the efficacy and safety of a range of doses of SCH 420814 (preladenant) when used together with a stable dose of L-dopa/dopa decarboxylase inhibitor to treat Parkinson's disease. In this study, we will be comparing 3 doses (1 mg, 2 mg, and 5 mg taken twice a day) of preladenant with placebo (sugar pill). Following an Interim Analysis (temporary hold for new enrollment-ongoing subjects will continue on treatment) to review drug safety, a new dose group of 10 mg (taken twice a day) may be added.

Approximately 160 participants will be randomized in this study in approximately 22 study centers worldwide for the first part of this study. Following the Interim Analysis, 40 new participants may be added, for a total of 200 participants. The study is double blind, which means neither you nor your study doctor will know whether you are receiving the study medication or placebo.


Eligibility criteria: Inclusion Criteria:

* Participants must be 30 years of age, of either sex and of any race, with a diagnosis of moderate to severe idiopathic Parkinson's disease for at least 5 years.
* Women of childbearing potential must have a negative serum pregnancy test at Visit 2 (Week -1). If participant is postmenopausal (not surgically induced), she must be postmenopausal by history for at least 2 years before study entry. If not, proper birth control must be used.

Note: Acceptable methods of birth control include oral or injectable hormonal contraceptive, medically prescribed intrauterine device (IUD), and double-barrier method (eg, condom in combination with spermicide). Bilateral tubal ligation is an acceptable method of birth control for this study.

* Participants' clinical laboratory tests (complete blood count \[CBC\], blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor.

Exclusion Criteria:

* Participants with any form of drug-induced or atypical parkinsonism, cognitive impairment (Mini-Mental State Examination \[MMSE\] score \<=23), a history of Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) diagnosed major depression, unstable mild depression or psychosis, or participants taking tolcapone will be excluded. (Participants with mild depression who are well controlled on a stable dose of an antidepressant medication for at least 4 weeks before screening will be eligible.)
* All participants with a severe or ongoing unstable medical condition will be excluded including those with a history of poorly controlled diabetes, obesity associated with metabolic syndrome, uncontrolled hypertension, cerebrovascular disease, or any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, renal failure, history of abnormal renal function, seizures, alcohol/drug dependence, or previous surgery for Parkinson's disease.
* Average daily consumption of more than two 4-oz (120 mL) glasses of wine or their equivalent.
* Because it is not known whether preladenant passes into breast milk and because the effects, if any, of preladenant on the developing human are unknown, women who are breastfeeding or who are considering breastfeeding are excluded from this trial.
* Participants with allergy/sensitivity to study drug or its excipients.
* Participants with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
* Participants who have used any other investigational drugs within 30 days of Screening.
* Participants who are participating in any other clinical study.

Primary outcomes:
measure: Change From Baseline to Endpoint of 12 Weeks in the 3-day Average of Awake Time Per Day Spent in the "Off" State
timeFrame: Baseline (Week -1) and up to 12 weeks
Secondary outcomes:
measure: Change From Baseline in Awake Time Per Day Spent in the "Off" State at Each Visit
timeFrame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in Awake Time Per Day Spent in the "on" State
timeFrame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in Awake Time Per Day Spent in the "on" State (no Dyskinesias)
timeFrame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in Awake Time Per Day Spent in the "on" State (With Troublesome Dyskinesias)
timeFrame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in Awake Time Per Day Spent in the "on" State (Without Troublesome Dyskinesias)
timeFrame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in Absolute Duration of Dyskinesias
timeFrame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in Total Sleep Time
timeFrame: Baseline (Week -1) and Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in Frequency of Sleep Attacks at Week 2
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Week 2
measure: Change From Baseline in Frequency of Sleep Attacks at Week 4
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Week 4
measure: Change From Baseline in Frequency of Sleep Attacks at Week 6
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Week 6
measure: Change From Baseline in Frequency of Sleep Attacks at Week 8
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Week 8
measure: Change From Baseline in Frequency of Sleep Attacks at Week 10
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Week 10
measure: Change From Baseline in Frequency of Sleep Attacks at Week 12
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Week 12
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Part 1
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in UPDRS Part 2
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in UPDRS Part 3 (1 Hour Post-dose)
timeFrame: Baseline (predose Day 1) and 1 hour postdose at Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in UPDRS Part 3 (2 Hours Post-dose)
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12
measure: Change From Baseline in UPDRS Part 4
timeFrame: Baseline (predose Day 1) and 2 hours postdose at Weeks 2, 4, 6, 8, 10, 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Hauser RA, Cantillon M, Pourcher E, Micheli F, Mok V, Onofrj M, Huyck S, Wolski K. Preladenant in patients with Parkinson's disease and motor fluctuations: a phase 2, double-blind, randomised trial. Lancet Neurol. 2011 Mar;10(3):221-9. doi: 10.1016/S1474-4422(11)70012-6.