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

June 30, 2010
March 7, 2014
July 2010
December 2012   (final data collection date for primary outcome measure)
Change from Baseline in Mean "off" time [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
Change from Baseline to Week 12 in mean "off" time measured in hours per day [ Time Frame: Baseline, 12 weeks (Week 12 is End of Treatment) ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01155466 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Mean change from Baseline to Week 12 in "on" time without troublesome dyskinesias measured in hours per day. [ Time Frame: Baseline, 12 weeks (Week 12 is End of Treatment) ] [ Designated as safety issue: No ]
  • The proportion of Responders, where Responder is defined as a subject with at least a 30% reduction in mean "off" time from Baseline to End of Treatment (Week 12). [ Time Frame: 12 weeks (Week 12 is End of Treatment) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Placebo- and Active Controlled Study of Preladenant in Subjects With Moderate to Severe Parkinson's Disease (Study P04938)
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)

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Parkinson Disease
  • Drug: Preladenant 2 mg tablet
    one 2 mg tablet orally twice daily
    Other Name: SCH 420814
  • Drug: Preladenant 5 mg tablet
    one 5 mg tablet orally twice daily
    Other Name: SCH 420814
  • Drug: Preladenant 10 mg tablet
    one 10 mg tablet orally twice daily
    Other Name: SCH 420814
  • Drug: Placebo for Preladenant
    one tablet orally twice daily
  • Drug: Rasagiline 1 mg capsule
    one 1 mg capsule orally in AM
    Other Name: Azilect
  • Drug: Placebo for Rasagiline 1 mg capsule
    one capsule orally in AM
  • Experimental: Preladenant 2 mg
    2 mg Preladenant Tablet + Placebo for Rasagiline in AM; 2 mg Preladenant in PM
    Interventions:
    • Drug: Preladenant 2 mg tablet
    • Drug: Placebo for Rasagiline 1 mg capsule
  • Experimental: Preladenant 5 mg
    5 mg Preladenant Tablet + Placebo for Rasagiline; 5 mg Preladenant in PM
    Interventions:
    • Drug: Preladenant 5 mg tablet
    • Drug: Placebo for Rasagiline 1 mg capsule
  • Experimental: Preladenant 10 mg
    10 mg Preladenant Tablet + Placebo for Rasagiline; 10 mg Preladenant in PM
    Interventions:
    • Drug: Preladenant 10 mg tablet
    • Drug: Placebo for Rasagiline 1 mg capsule
  • Placebo Comparator: Placebo
    Placebo for preladenant + Placebo Rasagiline in AM; Placebo for preladenant in PM
    Interventions:
    • Drug: Placebo for Preladenant
    • Drug: Placebo for Rasagiline 1 mg capsule
  • Active Comparator: Rasagiline
    1 mg Rasagiline Capsule + Placebo for preladenant in AM; Placebo for preladenant in PM
    Interventions:
    • Drug: Placebo for Preladenant
    • Drug: Rasagiline 1 mg capsule
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
778
December 2012
December 2012   (final data collection date for primary outcome measure)

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
Both
30 Years to 85 Years
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01155466
P04938, 2009-015161-31, CTRI/2011/07/001896
Yes
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Not Provided
Merck Sharp & Dohme Corp.
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP