Clinical trial NCT01227265: Placebo Controlled Study of Preladenant in Participants With Moderate to Severe Parkinson's Disease (P07037)
Official title: A Phase 3, 12 Week, Double-blind, Placebo-controlled Efficacy and Safety Study of Preladenant in Subjects With Moderate to Severe Parkinson's Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Idiopathic Parkinson Disease
Idiopathic Parkinson's Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2010-10-25
Enrollment: 476
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 study of the efficacy and safety of preladenant in adult participants with moderate to severe Parkinson's Disease (PD). While on this study, participants will continue to take their usual, prescribed, stable regimen of levodopa (L-dopa) or L-dopa plus adjunct PD medications and will be randomized to receive 2 mg preladenant, 5 mg preladenant, or placebo, twice daily, for 12 weeks. After that, participants may choose to receive additional treatment with preladenant. The primary hypothesis is that at least the 5 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 12 in the mean "off" time.


Eligibility criteria: Inclusion Criteria:

* Each participant must have a diagnosis of idiopathic Parkinson's disease.
* Each participant must have received prior therapy with L-dopa for approximately 1 or more years immediately before Screening and must continue to have a beneficial clinical response to L-dopa.
* Each participant must have been on a stable dopaminergic treatment regimen for at least the 5 weeks immediately before Randomization. Participants receiving other adjunctive treatments (eg, dopamine agonist, anticholinergics) are permitted to enroll in this trial. Participants taking only L-dopa are permitted to enroll in this trial.
* Each participant must be experiencing motor fluctuations with or without dyskinesias within the 4 weeks immediately before Screening, must be experiencing a minimum of 2 hours/day of "off" time, and have a Hoehn \& Yahr stage between 2.5 and 4 when in the "on" state.
* Each participant, with or without the help of a caregiver, must be capable of maintaining an accurate and complete symptom diary and to adhere to dose and visit schedules.
* Each participant must 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 (below).
* All participants who are sexually active or plan to be sexually active agree to use a highly effective method of birth control while in the study and for 2 weeks after the last dose of study drug. A male participant must also not donate sperm within 2 weeks after the last dose of study drug.

Exclusion Criteria:

* A participant must not have a form of drug induced or atypical parkinsonism, a cognitive impairment, bipolar disorder, untreated major depressive disorder, schizophrenia, or other psychotic disorder; history exposure to a known neurotoxin, or any neurological features not consistent with the diagnosis of PD as assessed by the investigator.
* A participant must not have a history of repeated strokes 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.
* A participant must not have had surgery for their PD.
* A participant must not be at imminent risk of self-harm or harm to others.
* A participant must not have a systolic blood pressure (BP) ≥150 mm Hg OR diastolic BP ≥95 mm Hg at Screening and at 2 BP rechecks prior to study start.
* A participant must not have had any clinically significant cardiovascular event or procedure for 6 months prior to study start, 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.
* A participant must not have an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 x the upper limit of normal (ULN) or total bilirubin (T BIL) ≥1.5 x ULN.
* A participant must not have a history of 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.
* A participant 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.
* A participant must not have received certain prespecified medications for a prespecified time window before the trial.
* A participant must not have an average daily consumption of more than three 4 ounce glasses (118 mL) of wine or the equivalent.
* A participant 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).
* A participant must not have allergy/sensitivity to investigational product(s) or its/their excipients.
* A participant must not be breast-feeding, considering breast-feeding, pregnant, or intending to become pregnant.
* A participant must not have used preladenant ever, or any investigational drugs within 90 days immediately before Screening.

Primary outcomes:
measure: Change From Baseline in Average "Off" Time (Hours Per Day) at Week 12
timeFrame: Baseline and Week 12
measure: Number of Participants With Systolic Blood Pressure (SBP) ≥180 mmHg and 20 mmHg Increase
timeFrame: Up to Week 14
measure: Number of Participants With Diastolic Blood Pressure (DBP) ≥105 mmHg and 15 mmHg Increase
timeFrame: Up to Week 14
measure: Percentage of Participants With Suicidality
timeFrame: Up to Week 12
measure: Change From Baseline in Total Epworth Sleepiness Scale (ESS) at Week 12
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Percentage of Participants With >30% Change (Reduction) From Baseline at Week 12 in Mean "Off" Time
timeFrame: Baseline and Week 12
measure: Change From Baseline in Average "On" Time (Hours Per Day) Without Troublesome Dyskinesia at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Hauser RA, Stocchi F, Rascol O, Huyck SB, Capece R, Ho TW, Sklar P, Lines C, Michelson D, Hewitt D. Preladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned. JAMA Neurol. 2015 Dec;72(12):1491-500. doi: 10.1001/jamaneurol.2015.2268.