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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Parkinson Disease

Treatments: Drug: Levodopa; Drug: Placebo; Drug: SCH 420814 10 mg; Drug: SCH 420814 100 mg; Drug: Carbidopa

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00845000

MK-3814-023 (Other Identifier)

P05550

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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12 participants in 6 patient groups

SCH 420814 10 mg→SCH 420814 100 mg→Placebo

Experimental group

Description:

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.

Treatment:

Drug: Levodopa

Drug: Placebo

Drug: SCH 420814 100 mg

Drug: SCH 420814 10 mg

Drug: Carbidopa

SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Levodopa

Drug: Placebo

Drug: SCH 420814 100 mg

Drug: SCH 420814 10 mg

Drug: Carbidopa

Placebo→SCH 420814 10 mg→SCH 420814 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Levodopa

Drug: Placebo

Drug: SCH 420814 100 mg

Drug: SCH 420814 10 mg

Drug: Carbidopa

SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Levodopa

Drug: Placebo

Drug: SCH 420814 100 mg

Drug: SCH 420814 10 mg

Drug: Carbidopa

SCH 420814 100 mg→ SCH 420814 10 mg→Placebo

Experimental group

Description:

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.

Treatment:

Drug: Levodopa

Drug: Placebo

Drug: SCH 420814 100 mg

Drug: SCH 420814 10 mg

Drug: Carbidopa

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Levodopa

Drug: Placebo

Drug: SCH 420814 100 mg

Drug: SCH 420814 10 mg

Drug: Carbidopa