Dyskinesia in Parkinson's Disease (Study P04501)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00406029
First received: November 30, 2006
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

The purpose of the study is to assess the efficacy and safety of a range of doses of SCH 420814 when used together with a stable dose of L-dopa/dopa decarboxylase inhibitor to treat Parkinson's disease. SCH 420814 is a drug that may prove to be effective in treating Parkinson's disease, and therefore we are currently gathering data to allow us to gain approval from the Food and Drug Administration (FDA) and/or other Health Authorities, so that SCH 420814 can be used to treat patients in the future. In this study, we will be comparing 3 doses (1 mg, 2mg, and 5 mg taken twice a day) of SCH 420814 with placebo (sugar pill). Following an Interim Analysis (temporary hold for new enrollment-ongoing subjects will continue on treatment) to review drug safety, a new dose group of 10 mg (taken twice a day) may be added.

Whether you will receive SCH 420814 or placebo will be decided by a process called randomization (as in the flip of a coin). Your chance of receiving the investigational drug, SCH 420814, is 75% in the first phase of the study (with a 1mg, 2mg, 5mg dose, or placebo dose arm). After 40 patients complete 12 weeks of treatment there will be an Interim Analysis which will determine the safety of the drug. If the 5 mg arm is found to be safe, then the 10 mg arm will also be added to the study. Your chance of receiving study drug (1mg, 2mg, 5mg, 10 mg, or placebo) with the 10 mg arm is 80%. If the 5 mg arm is found to be not safe, then the 10 mg arm will not be added and the 5 mg arm will also be dropped from the study. Your chance of receiving study drug (1mg, 2 mg, or placebo arm) will be 67%.

Approximately 160 subjects will be randomized in this study in approximately 22 study centers worldwide for the first part of this study. Following the Interim Analysis, we may add 40 new patients, for a total of 200 patients. The study is double blind, which means neither you nor your study doctor will know whether you are receiving the study medication or placebo.


Condition Intervention Phase
Parkinson Disease
Movement Disorders
Central Nervous System Diseases
Neurodegenerative Diseases
Brain Diseases
Drug: SCH 420814
Drug: Placebo
Drug: L-dopa
Drug: Other Parkinson's Disease treatments
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, 12-Week, Double-Blind, Dose-Finding, Placebo-Controlled Study to Assess the Efficacy and Safety of a Range of SCH 420814 Doses in Subjects With Moderate to Severe Parkinson's Disease Experiencing Motor Fluctuations and Dyskinesias

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Mean change from Baseline to endpoint of 12 weeks of treatment in the 3-day average (based on subject diaries) of time in hours per day spent in the "off" state [ Time Frame: 12-week double-blind treatment period ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mean change from Baseline in "off" time per day; "on" time per day (no dyskinesias; with and w/o troublesome dyskinesias); awake time per day in the "on" state; absolute time of dyskinesias, total sleep time, frequency of sleep attacks, and UPDRS [ Time Frame: 12-week double-blind treatment period ] [ Designated as safety issue: Yes ]
    UPDRS = Unified Parkinson's Disease Rating Scale


Enrollment: 253
Study Start Date: November 2006
Study Completion Date: November 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SCH 420814 1 mg twice daily Drug: SCH 420814
1 mg twice daily
Other Name: Preladenant
Drug: L-dopa
Participants must receive L-dopa as part of their usual ongoing treatment for Parkinson's Disease. L-dopa is often administered concomitantly with a dopa decarboxylase inhibitor (e.g., carbidopa).
Drug: Other Parkinson's Disease treatments
Participants may also receive other drugs as part of their usual ongoing treatment for Parkinson's Disease, such as dopamine agonists (e.g., pramipexole) and/or the catechol-O-methyl transferase (COMT) inhibitor entacapone.
Experimental: SCH 420814 2 mg twice daily Drug: SCH 420814
2 mg twice daily
Other Name: Preladenant
Drug: L-dopa
Participants must receive L-dopa as part of their usual ongoing treatment for Parkinson's Disease. L-dopa is often administered concomitantly with a dopa decarboxylase inhibitor (e.g., carbidopa).
Drug: Other Parkinson's Disease treatments
Participants may also receive other drugs as part of their usual ongoing treatment for Parkinson's Disease, such as dopamine agonists (e.g., pramipexole) and/or the catechol-O-methyl transferase (COMT) inhibitor entacapone.
Experimental: SCH 420814 5 mg twice daily Drug: SCH 420814
5 mg twice daily
Other Name: Preladenant
Drug: L-dopa
Participants must receive L-dopa as part of their usual ongoing treatment for Parkinson's Disease. L-dopa is often administered concomitantly with a dopa decarboxylase inhibitor (e.g., carbidopa).
Drug: Other Parkinson's Disease treatments
Participants may also receive other drugs as part of their usual ongoing treatment for Parkinson's Disease, such as dopamine agonists (e.g., pramipexole) and/or the catechol-O-methyl transferase (COMT) inhibitor entacapone.
Placebo Comparator: Placebo twice daily Drug: Placebo
twice daily
Drug: L-dopa
Participants must receive L-dopa as part of their usual ongoing treatment for Parkinson's Disease. L-dopa is often administered concomitantly with a dopa decarboxylase inhibitor (e.g., carbidopa).
Drug: Other Parkinson's Disease treatments
Participants may also receive other drugs as part of their usual ongoing treatment for Parkinson's Disease, such as dopamine agonists (e.g., pramipexole) and/or the catechol-O-methyl transferase (COMT) inhibitor entacapone.
Experimental: SCH 420814 10 mg twice daily
Following an interim analysis, a new dose group of 10 mg BID may be added after 40 subjects completed the trial.
Drug: SCH 420814
Following an interim analysis, a new dose group of 10 mg BID may be added after 40 subjects completed the trial.
Other Name: Preladenant
Drug: L-dopa
Participants must receive L-dopa as part of their usual ongoing treatment for Parkinson's Disease. L-dopa is often administered concomitantly with a dopa decarboxylase inhibitor (e.g., carbidopa).
Drug: Other Parkinson's Disease treatments
Participants may also receive other drugs as part of their usual ongoing treatment for Parkinson's Disease, such as dopamine agonists (e.g., pramipexole) and/or the catechol-O-methyl transferase (COMT) inhibitor entacapone.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be 30 years of age, of either sex and of any race, with a diagnosis of moderate to severe idiopathic Parkinson's disease for at least 5 years.
  • Women of childbearing potential must have a negative serum pregnancy test at Visit 2. If subject is postmenopausal (not surgically induced), she must be postmenopausal by history for at least 2 years before study entry. If not, proper birth control must be used.

Note: Acceptable methods of birth control include oral or injectable hormonal contraceptive, medically prescribed intrauterine device (IUD), and double-barrier method (eg, condom in combination with spermicide). Bilateral tubal ligation is an acceptable method of birth control for this study.

  • Subjects' clinical laboratory tests (complete blood count [CBC], blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator/sponsor.

Exclusion Criteria:

  • Subjects with any form of drug-induced or atypical parkinsonism, cognitive impairment (Mini-Mental State Examination [MMSE] score <=23), a history of Diagnostic and Statistical Manual of Mental Disorders IV (DSM IV) diagnosed major depression, unstable mild depression or psychosis, or subjects taking tolcapone will be excluded. (Subjects with mild depression who are well controlled on a stable dose of an antidepressant medication for at least 4 weeks before screening will be eligible.)
  • All subjects with a severe or ongoing unstable medical condition will be excluded including those with a history of poorly controlled diabetes, obesity associated with metabolic syndrome, uncontrolled hypertension, cerebrovascular disease, or any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, renal failure, history of abnormal renal function, seizures, alcohol/drug dependence, or previous surgery for Parkinson's disease.
  • Average daily consumption of more than two 4-oz (120 mL) glasses of wine or their equivalent.
  • Because it is not known whether SCH 420814 passes into breast milk and because the effects, if any, of SCH 420814 on the developing human are unknown, women who are breastfeeding or who are considering breastfeeding are excluded from this trial.
  • Subjects with allergy/sensitivity to study drug or its excipients.
  • Subjects with any clinically significant condition or situation, other than the condition being studied that, in the opinion of the investigator, would interfere with the study evaluations or optimal participation in the study.
  • Subjects who have used any other investigational drugs within 30 days of Screening.
  • Subjects who are participating in any other clinical study.
  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

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00406029     History of Changes
Other Study ID Numbers: P04501, Preladenant
Study First Received: November 30, 2006
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Brain Diseases
Central Nervous System Diseases
Dyskinesias
Movement Disorders
Nervous System Diseases
Parkinson Disease
Neurodegenerative Diseases
Neurologic Manifestations
Signs and Symptoms
Parkinsonian Disorders
Basal Ganglia Diseases
Levodopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 11, 2014