A Placebo- and Active-Controlled Study of Preladenant in Early Parkinson's Disease (PD) (P05664)

NCT ID: NCT01155479

Last Updated: 2018-11-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 1022 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-06
• Study Completion Date: 2013-07-16

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).

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Preladenant 2 mg

Preladenant 2 mg oral tablet and placebo for rasagiline taken in the morning (AM) followed by preladenant 2 mg oral tablet taken in the evening (PM) for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Group Type: EXPERIMENTAL

Preladenant 2 mg tablet

Intervention Type: DRUG

Preladenant 2 mg oral tablet taken twice daily

Placebo for Rasagiline 1 mg capsule

Intervention Type: DRUG

Placebo for rasagiline 1 mg oral capsule taken once daily

Preladenant 5 mg

Preladenant 5 mg oral tablet and placebo for rasagiline taken in the AM followed by preladenant 5 mg taken in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Group Type: EXPERIMENTAL

Preladenant 5 mg tablet

Intervention Type: DRUG

Preladenant 5 mg oral tablet taken twice daily

Placebo for Rasagiline 1 mg capsule

Intervention Type: DRUG

Placebo for rasagiline 1 mg oral capsule taken once daily

Preladenant 10 mg

Preladenant 10 mg oral tablet and placebo for rasagiline taken in the AM followed by preladenant 10 mg taken in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Group Type: EXPERIMENTAL

Preladenant 10 mg tablet

Intervention Type: DRUG

Preladenant 10 mg oral tablet taken twice daily

Placebo for Rasagiline 1 mg capsule

Intervention Type: DRUG

Placebo for rasagiline 1 mg oral capsule taken once daily

Placebo

Placebo for preladenant and placebo for rasagiline taken in the AM followed by placebo for preladenant taken in the PM for 26 weeks (Part 1); preladenant 5 mg was taken twice daily for 26 weeks (Part 2).

Group Type: PLACEBO_COMPARATOR

Preladenant 5 mg tablet

Intervention Type: DRUG

Preladenant 5 mg oral tablet taken twice daily

Placebo for Rasagiline 1 mg capsule

Intervention Type: DRUG

Placebo for rasagiline 1 mg oral capsule taken once daily

Placebo for Preladenant

Intervention Type: DRUG

Placebo for preladenant 2 mg, 5 mg, or 10 mg oral tablet taken twice daily

Rasagiline

Rasagiline 1 mg oral capsule and placebo for preladenant taken in the AM followed by placebo for preladenant taken in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Group Type: ACTIVE_COMPARATOR

Rasagiline 1 mg capsule

Intervention Type: DRUG

Rasagiline 1 mg oral capsule taken once daily

Placebo for Preladenant

Intervention Type: DRUG

Placebo for preladenant 2 mg, 5 mg, or 10 mg oral tablet taken twice daily

Interventions

Preladenant 2 mg tablet

Preladenant 2 mg oral tablet taken twice daily

Intervention Type: DRUG

Preladenant 5 mg tablet

Preladenant 5 mg oral tablet taken twice daily

Intervention Type: DRUG

Preladenant 10 mg tablet

Preladenant 10 mg oral tablet taken twice daily

Intervention Type: DRUG

Rasagiline 1 mg capsule

Rasagiline 1 mg oral capsule taken once daily

Intervention Type: DRUG

Placebo for Rasagiline 1 mg capsule

Placebo for rasagiline 1 mg oral capsule taken once daily

Intervention Type: DRUG

Placebo for Preladenant

Placebo for preladenant 2 mg, 5 mg, or 10 mg oral tablet taken twice daily

Intervention Type: DRUG

Other Intervention Names

SCH 420814; SCH 420814; SCH 420814; Azilect

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.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 28490648 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

2009-013552-72

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-3814-024

Identifier Type: OTHER

Identifier Source: secondary_id

P05664

Identifier Type: -

Identifier Source: org_study_id