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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01155466
First received: June 30, 2010
Last updated: March 7, 2014
Last verified: March 2014
  Purpose

When a patient with Parkinson 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 (ie, 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 Parkinson's disease (PD) symptoms. This trial will test the hypothesis that A2a receptor antagonism can lead to improvement in the function of PD subjects, as measured by a reduction in "off" time.


Condition Intervention Phase
Parkinson Disease
Drug: Preladenant 2 mg tablet
Drug: Preladenant 5 mg tablet
Drug: Preladenant 10 mg tablet
Drug: Placebo for Preladenant
Drug: Rasagiline 1 mg capsule
Drug: Placebo for Rasagiline 1 mg capsule
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, 12-Week, Double-Blind, Double-Dummy, Placebo- and Active-Controlled Efficacy and Safety Study of Preladenant in Subjects With Moderate to Severe Parkinson's Disease (Phase 3;Protocol No. P04938)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Change from Baseline in Mean "off" time [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants with >30% Reduction in Mean "off" Time [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Change from Baseline in Mean "on" time without Troublesome Dyskinesia [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]

Enrollment: 778
Study Start Date: July 2010
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Preladenant 2 mg
2 mg Preladenant Tablet + Placebo for Rasagiline in AM; 2 mg Preladenant in PM
Drug: Preladenant 2 mg tablet
one 2 mg tablet orally twice daily
Other Name: SCH 420814
Drug: Placebo for Rasagiline 1 mg capsule
one capsule orally in AM
Experimental: Preladenant 5 mg
5 mg Preladenant Tablet + Placebo for Rasagiline; 5 mg Preladenant in PM
Drug: Preladenant 5 mg tablet
one 5 mg tablet orally twice daily
Other Name: SCH 420814
Drug: Placebo for Rasagiline 1 mg capsule
one capsule orally in AM
Experimental: Preladenant 10 mg
10 mg Preladenant Tablet + Placebo for Rasagiline; 10 mg Preladenant in PM
Drug: Preladenant 10 mg tablet
one 10 mg tablet orally twice daily
Other Name: SCH 420814
Drug: Placebo for Rasagiline 1 mg capsule
one capsule orally in AM
Placebo Comparator: Placebo
Placebo for preladenant + Placebo Rasagiline in AM; Placebo for preladenant in PM
Drug: Placebo for Preladenant
one tablet orally twice daily
Drug: Placebo for Rasagiline 1 mg capsule
one capsule orally in AM
Active Comparator: Rasagiline
1 mg Rasagiline Capsule + Placebo for preladenant in AM; Placebo for preladenant in PM
Drug: Placebo for Preladenant
one tablet orally twice daily
Drug: Rasagiline 1 mg capsule
one 1 mg capsule orally in AM
Other Name: Azilect

  Eligibility

Ages Eligible for Study:   30 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 are taking only L dopa are permitted to enroll in this trial
  • 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; poorly controlled diabetes; abnormal renal function; or a severe or ongoing unstable medical condition

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

Additional Information:
No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01155466     History of Changes
Other Study ID Numbers: P04938, 2009-015161-31, CTRI/2011/07/001896
Study First Received: June 30, 2010
Last Updated: March 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Idiopathic Parkinson Disease
Idiopathic Parkinson's Disease

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Rasagiline
Monoamine Oxidase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014