Clinical trial NCT01155479: A Placebo- and Active-Controlled Study of Preladenant in Early Parkinson's Disease (PD) (P05664)
Official title: A Phase 3, Double-Blind, Double-Dummy, Placebo- and Active-Controlled Dose-Range-Finding Efficacy and Safety Study of Preladenant in Subjects With Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Parkinson Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-07-01
Enrollment: 1022
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a one year, 2-part study to determine the efficacy and safety of preladenant, an adenosine type 2a (A2a) receptor antagonist. The purpose of Part 1 (first 26 weeks) is to determine if preladenant is effective in the treatment of early Parkinson's Disease. The purpose of Part 2 (second 26 weeks) is to determine if preladenant is safe and well tolerated. The primary efficacy hypothesis is that at least the 10 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 26 in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) Parts 2 and 3 scores (UPDRS2+3).


Eligibility criteria: Inclusion Criteria:

* Has a diagnosis of idiopathic PD for \< 5 years.
* If receiving amantadine and/or anticholinergics, must have been on a stable regimen of treatment for at least the 5 weeks immediately before Screening. (Note: Participants who are not taking any medications for PD are permitted to enroll in this trial.)
* Must have a UPDRS Part 3 score of ≥10, a Hoehn and Yahr Stage ≤3, be ≥30 to ≤85 years of age, and have results of Screening clinical laboratory tests drawn within 5 weeks prior to randomization, clinically acceptable to the investigator, and not within the parameters specified for exclusion.
* If sexually active or plan to be sexually active, must agree to use a highly effective method of birth control while the participant is in the study and for 2 weeks after the last dose of study drug. A male participant must also not donate sperm during the trial and within 2 weeks after the last dose of study drug.

Exclusion Criteria:

* Must not have a form of drug-induced or atypical Parkinsonism, cognitive impairment (ie, Montreal Cognitive Assessment \[MoCA\] score \<22), bipolar disorder, untreated major depressive disorder, schizophrenia, or other psychotic disorder; history of exposure to a known neurotoxin, or any neurological features not consistent with the diagnosis of PD as assessed by the investigator.
* Must not have had surgery for PD.
* Must not have a history of repeated strokes with stepwise progression of Parkinsonism or head injuries, or a stroke within 6 months of screening; poorly controlled diabetes; abnormal renal function; or a severe or ongoing unstable medical condition.
* Must not have failed to show a therapeutic response if a diagnostic levodopa (L dopa) challenge had been done with a large test dose (\>500 mg) of L dopa (if malabsorption excluded), or failed to respond to an adequate previous treatment with dopaminergic therapy.
* Must not have been treated with L dopa or dopamine agonists for 30 days or more. A participant who has been treated with L-dopa or dopamine agonists for \<30 days will be allowed to enter the study. These participants must stop taking dopaminergic medication 30 days prior to Randomization.
* Must not be at imminent risk of self-harm or harm to others.
* Must not have elevated blood pressure (BP) (systolic BP ≥150 mm Hg or diastolic BP ≥95 mm Hg) that cannot be adequately controlled with antihypertensive medication, as demonstrated by 2 BP measurements meeting acceptable BP criterion at consecutive scheduled or unscheduled visits between Screening and Randomization (a 5-6 week period), one of which must be the Randomization visit.
* Must not have had any clinically significant cardiovascular event or procedure for 6 months prior to Randomization, including, but not limited to, myocardial infarction, angioplasty, unstable angina, or heart failure; and a participant must not have heart failure staged New York Heart Association Class III or IV.
* Must not have an alanine aminotransferase (ALT) or aspartate amino transferase (AST) ≥ 3 x the upper limit of normal (ULN) or total bilirubin (T BIL) ≥ 1.5 x ULN.
* Must not have active serologically-confirmed hepatic dysfunction (defined as viral infection \[Hepatitis B, C, or E; Epstein-Barr virus (EBV)\]; cytomegalovirus \[CMV\] or a history of diagnosis of drug- or alcohol-induced hepatic toxicity or frank hepatitis, or a history of diagnosis of drug- or alcohol-induced hepatic toxicity or frank hepatitis.)
* Must not have a history within the past 5 years of a primary or recurrent malignant disease with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with a normal prostate-specific antigen (PSA) post resection.
* Must not have received certain prespecified medications or ingested high tyramine-containing aged cheeses (eg, Stilton) for a prespecified time window before the trial, during the trial, and for 2 weeks after the trial.
* Must not have an average daily consumption of more than three 4 ounce glasses (118 mL) of wine or the equivalent.
* Must not have a severe or ongoing unstable medical condition (eg, any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, seizures, or alcohol/drug dependence.)
* Must not have allergy/sensitivity to investigational product(s) or its/their excipients.
* Must not be breast-feeding, considering breast-feeding, pregnant or intending to become pregnant.
* Must not have used preladenant ever, or any investigational drugs within 90 days immediately before screening.

Primary outcomes:
measure: Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3)
timeFrame: Baseline and Week 26
measure: Number of Participants With Adverse Events (AEs) in Part 1
timeFrame: Day 1 to Week 26
measure: Number of Participants Who Discontinued Study Due to an AE in Part 1
timeFrame: Day 1 to Week 26
measure: Number of Participants With Adverse Events (AEs) in Part 2
timeFrame: Week 27 to Week 52
measure: Number of Participants Who Discontinued Study Due to an AE in Part 2
timeFrame: Week 27 to Week 52
Secondary outcomes:
measure: Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3)
timeFrame: Baseline and Week 26
measure: Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL])
timeFrame: Baseline and Week 26
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Stocchi F, Rascol O, Hauser RA, Huyck S, Tzontcheva A, Capece R, Ho TW, Sklar P, Lines C, Michelson D, Hewitt DJ; Preladenant Early Parkinson Disease Study Group. Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease. Neurology. 2017 Jun 6;88(23):2198-2206. doi: 10.1212/WNL.0000000000004003. Epub 2017 May 10.