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Acute Effects of Preladenant (SCH 420814) on Dyskinesia and Parkinsonism in Levodopa Treated Participants (P05550)

This study has been completed.
Sponsor:
Collaborator:
Oregon Health and Science University
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00845000
First received: February 13, 2009
Last updated: June 9, 2016
Last verified: June 2016
  Purpose
This is a randomized, placebo-controlled, 3-period crossover, balanced, single-site, third party-blind study of preladenant (SCH 420814) in participants with Parkinson disease (PD) to be conducted in conformance with Good Clinical Practices. This trial will investigate the effects of single doses of preladenant and placebo on the dyskinesia and antiparkinsonian actions of a levodopa infusion. The study will examine 10 mg ("low dose") or 100 mg ("high dose") study drug, given as single, oral administrations in conjunction with intravenous (IV) levodopa infusion and oral carbidopa.

Condition Intervention Phase
Parkinson Disease
Drug: SCH 420814 10 mg
Drug: SCH 420814 100 mg
Drug: Placebo
Drug: Levodopa
Drug: Carbidopa
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Acute Effects of SCH 420814 on Dyskinesia and Parkinsonism in Levodopa Treated Patients

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Mean Peak Dyskinesia Score [ Time Frame: Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0 of each treatment period ] [ Designated as safety issue: No ]
    Dyskinesia was scored on a scale of 0 (absent), 1 (mild) , 2 (moderate), 3 (severe) and 4 (incapacitating) for seven body parts (face, neck, trunk, each arm and each leg) based on the worse dyskinesia noted during the entire measurement time. Scores were assessed at Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0. The dyskinesia score was the sum of the scores for the seven body parts. The peak dyskinesia score was recorded for each participant regardless of what timepoint the score was achieved. The total possible score for an individual at each timepoint could range from 0 to 28 with higher scores indicating greater effects of the dyskinesia. The mean peak dyskinesia score was calculated using the individual peak values.


Secondary Outcome Measures:
  • Mean Peak Finger Tapping Score [ Time Frame: Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0 of each treatment period ] [ Designated as safety issue: No ]
    Tapping was measured with two manual counters with keys that were depressed to register a count. The participant alternately tapped each counter using the index finger of the more affected hand for 60 seconds and was not allowed to use more than one finger to tap. The participant was instructed to tap as rapidly as possible while being timed for 60 seconds. The counts were recorded for the two counters at Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0. The peak tapping score was recorded for each participant regardless of what timepoint the score was achieved. The mean peak finger tapping score was calculated using the individual peak values.

  • Mean Peak Tremor Score [ Time Frame: Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0 of each treatment period ] [ Designated as safety issue: No ]
    Tremor was scored on a scale of 0 (absent), 1 (mild, 2 (moderate), 3 (severe) and 4 (incapacitating) for seven body parts (face, neck, trunk, each arm and each leg) based on the worse tremor observed during the time spent with participant while taking other study measurements(vital signs, drawing samples, performing the tapping and walking tasks). Scores were assessed at Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0. The tremor score was the sum of scores for seven body parts. The peak tremor score was recorded for each participant regardless of what timepoint the score was achieved. The total possible score for an individual at each timepoint could range from 0 to 28 with higher scores indicating more effects of the tremors. The mean peak tremor score was calculated using the individual peak values.

  • Mean Peak Walking Speed [ Time Frame: Hours 0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 7.0 and 8.0 of each treatment period ] [ Designated as safety issue: No ]
    Walking speed assessment began with the participant being seated in an armless chair. Then while being timed, the participant stood up with their arms crossed on their chest and walked 6 meters, turned around, returned to the chair and sat. Timing was stopped when the participant's buttocks hit the chair and the total time was recorded. If the participant could not arise in 60 seconds, 60 seconds was entered in this line of the report form and the participant was tested again but allowed to push off to get out of the chair. Sixty seconds was the maximum time allowed to complete the walking assessment, thus 60 seconds was recorded as the time if they could not complete the task within this time limit. Walking speed was assessed at Hours 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 7.0 and 8. The peak walking speed was recorded for each participant regardless of what timepoint the score was achieved. The mean peak walking speed was calculated using the individual peak values.


Enrollment: 12
Study Start Date: April 2009
Study Completion Date: May 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SCH 420814 10 mg→SCH 420814 100 mg→Placebo
Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose.
Drug: SCH 420814 10 mg
one 10-mg capsule, orally, at hour 0 of treatment period
Drug: SCH 420814 100 mg
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Drug: Placebo
Placebo capsule, oral, at hour 0 of treatment period
Drug: Levodopa
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
Drug: Carbidopa
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
Experimental: SCH 420814 100 mg→Placebo→ SCH 420814 10 mg
Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose.
Drug: SCH 420814 10 mg
one 10-mg capsule, orally, at hour 0 of treatment period
Drug: SCH 420814 100 mg
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Drug: Placebo
Placebo capsule, oral, at hour 0 of treatment period
Drug: Levodopa
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
Drug: Carbidopa
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
Experimental: Placebo→SCH 420814 10 mg→SCH 420814 100 mg
Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose.
Drug: SCH 420814 10 mg
one 10-mg capsule, orally, at hour 0 of treatment period
Drug: SCH 420814 100 mg
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Drug: Placebo
Placebo capsule, oral, at hour 0 of treatment period
Drug: Levodopa
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
Drug: Carbidopa
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
Experimental: SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg
Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose.
Drug: SCH 420814 10 mg
one 10-mg capsule, orally, at hour 0 of treatment period
Drug: SCH 420814 100 mg
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Drug: Placebo
Placebo capsule, oral, at hour 0 of treatment period
Drug: Levodopa
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
Drug: Carbidopa
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
Experimental: SCH 420814 100 mg→ SCH 420814 10 mg→Placebo
Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose.
Drug: SCH 420814 10 mg
one 10-mg capsule, orally, at hour 0 of treatment period
Drug: SCH 420814 100 mg
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Drug: Placebo
Placebo capsule, oral, at hour 0 of treatment period
Drug: Levodopa
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
Drug: Carbidopa
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
Experimental: Placebo→ SCH 420814 100 mg→SCH 420814 10 mg
Participants were to receive their assigned experimental treatment based on randomly assigned treatment sequence at Hour 0 following an overnight withdrawal of their antiparkinsonian medications of each treatment period. The levodopa infusion was to be started at Hour 1 and was to run for 2 hours. The participants were to also receive 25 mg of carbidopa at the following times: Hours 0, 2, and 4. Treatment periods were to be separated by at least 7 days but not more than 28 days washout between each dose.
Drug: SCH 420814 10 mg
one 10-mg capsule, orally, at hour 0 of treatment period
Drug: SCH 420814 100 mg
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Drug: Placebo
Placebo capsule, oral, at hour 0 of treatment period
Drug: Levodopa
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
Drug: Carbidopa
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have a diagnosis of idiopathic PD based on history, exam and any relevant laboratory tests
  • Participants must have been treated with levodopa for one or more years
  • Participants must have motor fluctuations that can be measured as a 10% change in tapping speed between "on" and "off" and concurrent motor Unified PD Rating Scale (UPDRS) must also show a 20% improvement when "on"
  • Participants must have dyskinesia when "on" measured as at least 2 in one or more body parts on scale using 0 (absent) to 4 (severe) for four limbs, trunk, neck and face (total 7 body parts and 28 points)
  • Participant must be free of any clinically significant disease that would interfere with the study evaluations
  • Female participants must be postmenopausal and/or surgically sterilized and have a negative serum pregnancy test at the screening visit and a negative urine or serum pregnancy test upon each admission to the study center
  • Premenopausal, unsterilized female participants have to agree to use a medically accepted method of contraception
  • Male participants must agree to use a medically accepted method of contraception as or abstain from sexual intercourse during the trial and for 2 months after stopping the medication.

Exclusion Criteria:

  • Female participants who are pregnant, intend to become pregnant (within 3 months of ending the study), or are lactating
  • Participants with dementia (mini-mental state examination [MMSE] <23), hallucinations, confusion, major psychiatric disorders, and unstable medical conditions
  • Participants with any stable surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
  • Participants with a positive screen for drugs of abuse
  • Participants who are positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV)
  • Participants who are currently participating in another medical interventional clinical study or have participated in a medical interventional clinical study within 30 days and who have previously received this compound.
  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.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00845000

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Oregon Health and Science University
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00845000     History of Changes
Other Study ID Numbers: P05550  MK-3814-023 
Study First Received: February 13, 2009
Results First Received: April 18, 2016
Last Updated: June 9, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Parkinson Disease
Dyskinesias
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Neurologic Manifestations
Signs and Symptoms
Levodopa
Carbidopa
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on December 08, 2016