A Placebo- and Active Controlled Study of Preladenant in Subjects With Moderate to Severe Parkinson's Disease (P04938)

NCT ID: NCT01155466

Last Updated: 2018-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 778 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-14
• Study Completion Date: 2012-12-20

Brief Summary

When a patient with Parkinson's disease (PD) is initially treated with L-dopa or dopamine agonists, the symptoms of PD improve or disappear. After several years of taking L dopa or dopamine agonists, patients notice that their PD medications wear off sooner than when they first started taking them. This "wearing off" is characterized by the return of symptoms (i.e., tremor, slowness, and rigidity) and may occur over the course of a few minutes to an hour. When a patient's PD symptoms have returned, the patient is said to be in the "off" state. When the patient takes another dose of medication, and his/her PD symptoms improve or resolve, the patient is said to be in the "on" state. Antagonism of adenosine Type 2a receptors (A2a) may provide relief of PD symptoms. This trial will test the hypothesis that A2a receptor antagonism can lead to improvement in the function of PD participants taking a stable dose of L-dopa, as measured by a reduction in "off" time.

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 tablet + placebo to rasagiline capsule in AM and preladenant 2 mg tablet in PM for 12 weeks

Group Type: EXPERIMENTAL

Preladenant 2 mg tablet

Intervention Type: DRUG

one 2 mg tablet orally twice daily

Placebo to Rasagiline capsule

Intervention Type: DRUG

one capsule orally in AM

Preladenant 5 mg

Preladenant 5 mg tablet + placebo to rasagiline capsule in AM and preladenant 5 mg tablet in PM for 12 weeks

Group Type: EXPERIMENTAL

Preladenant 5 mg tablet

Intervention Type: DRUG

one 5 mg tablet orally twice daily

Placebo to Rasagiline capsule

Intervention Type: DRUG

one capsule orally in AM

Preladenant 10 mg

Preladenant 10 mg tablet + placebo to rasagiline capsule in AM and preladenant 10 mg tablet in PM for 12 weeks

Group Type: EXPERIMENTAL

Preladenant 10 mg tablet

Intervention Type: DRUG

one 10 mg tablet orally twice daily

Placebo to Rasagiline capsule

Intervention Type: DRUG

one capsule orally in AM

Placebo

Placebo to preladenant tablet + placebo to rasagiline capsule in AM and placebo to preladenant tablet in PM for 12 weeks

Group Type: PLACEBO_COMPARATOR

Placebo to Preladenant Tablet

Intervention Type: DRUG

one tablet orally twice daily

Placebo to Rasagiline capsule

Intervention Type: DRUG

one capsule orally in AM

Rasagiline 1 mg

Rasagiline 1 mg capsule + placebo to preladenant tablet in AM and placebo to preladenant tablet in PM for 12 weeks

Group Type: ACTIVE_COMPARATOR

Placebo to Preladenant Tablet

Intervention Type: DRUG

one tablet orally twice daily

Rasagiline 1 mg capsule

Intervention Type: DRUG

one 1 mg capsule orally in AM

Interventions

Preladenant 2 mg tablet

one 2 mg tablet orally twice daily

Intervention Type: DRUG

Preladenant 5 mg tablet

one 5 mg tablet orally twice daily

Intervention Type: DRUG

Preladenant 10 mg tablet

one 10 mg tablet orally twice daily

Intervention Type: DRUG

Placebo to Preladenant Tablet

one tablet orally twice daily

Intervention Type: DRUG

Rasagiline 1 mg capsule

one 1 mg capsule orally in AM

Intervention Type: DRUG

Placebo to Rasagiline capsule

one capsule orally in AM

Intervention Type: DRUG

Other Intervention Names

SCH 420814; SCH 420814; SCH 420814; Azilect

Eligibility Criteria

Inclusion Criteria

• Must have a diagnosis of moderate to severe idiopathic Parkinson's disease.
• 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
• 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 agonists, anticholinergics, entacapone) or taking only L dopa are permitted, provided the treatment regimen has been taken for at least 5 weeks prior to randomization
• 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
• Must be capable of maintaining an accurate and complete symptom diary and to adhere to dose and visit schedules with or without the help of a caregiver
• Must have results of a physical examination and screening clinical laboratory tests clinically acceptable to the investigator
• If 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. Males must also not donate sperm during the trial within 2 weeks after the last dose of study drug

Exclusion Criteria

• 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 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 a history of repeated strokes or head injuries, or a stroke within 6 months of Screening
• Must not have poorly-controlled diabetes or abnormal renal function
• Must not have had surgery for their PD
• Must not be at imminent risk of self-harm or harm to others
• Must not have sleep attacks or compulsive behavior that would interfere with the integrity of the trial or would pose a risk to the subject in participating in the trial
• Must not have a systolic blood pressure (BP) ≥150 mm Hg OR diastolic BP ≥95 mm Hg at Screening
• 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 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 a history of serologically confirmed hepatic dysfunction (defined as viral infection [Hepatitis B or C; Epstein Barr virus (EBV); cytomegalovirus (CMV)]) 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
• A female subject 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

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.

Reference Type: RESULT

PMID: 26523919 (View on PubMed)

Study Documents

Document Type: CSR Synopsis

View Document

Other Identifiers

2009-015161-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTRI/2011/07/001896

Identifier Type: REGISTRY

Identifier Source: secondary_id

MK-3814-015

Identifier Type: OTHER

Identifier Source: secondary_id

P04938

Identifier Type: -

Identifier Source: org_study_id