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

NCT00845000 | Completed Phase 1 Results

• 2 other identifiers: P05550MK-3814-023
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Mean Peak Dyskinesia Score

  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.

  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

Secondary Outcomes (3)

• Mean Peak Finger Tapping Score

  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

• Mean Peak Tremor Score

  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

• Mean Peak Walking Speed

  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

Study Arms (6)

SCH 420814 10 mg→SCH 420814 100 mg→Placebo

EXPERIMENTAL

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

SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

EXPERIMENTAL

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

Placebo→SCH 420814 10 mg→SCH 420814 100 mg

EXPERIMENTAL

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

SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg

EXPERIMENTAL

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

SCH 420814 100 mg→ SCH 420814 10 mg→Placebo

EXPERIMENTAL

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

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg

EXPERIMENTAL

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

Interventions

SCH 420814 10 mg DRUG

one 10-mg capsule, orally, at hour 0 of treatment period

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg; Placebo→SCH 420814 10 mg→SCH 420814 100 mg; SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg; SCH 420814 10 mg→SCH 420814 100 mg→Placebo; SCH 420814 100 mg→ SCH 420814 10 mg→Placebo; SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

SCH 420814 100 mg DRUG

single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg; Placebo→SCH 420814 10 mg→SCH 420814 100 mg; SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg; SCH 420814 10 mg→SCH 420814 100 mg→Placebo; SCH 420814 100 mg→ SCH 420814 10 mg→Placebo; SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

Placebo DRUG

Placebo capsule, oral, at hour 0 of treatment period

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg; Placebo→SCH 420814 10 mg→SCH 420814 100 mg; SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg; SCH 420814 10 mg→SCH 420814 100 mg→Placebo; SCH 420814 100 mg→ SCH 420814 10 mg→Placebo; SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

Levodopa DRUG

levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg; Placebo→SCH 420814 10 mg→SCH 420814 100 mg; SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg; SCH 420814 10 mg→SCH 420814 100 mg→Placebo; SCH 420814 100 mg→ SCH 420814 10 mg→Placebo; SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

Carbidopa DRUG

one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg; Placebo→SCH 420814 10 mg→SCH 420814 100 mg; SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg; SCH 420814 10 mg→SCH 420814 100 mg→Placebo; SCH 420814 100 mg→ SCH 420814 10 mg→Placebo; SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Oregon Health and Science University: collaborator

MeSH Terms

Conditions

Parkinson Disease

Interventions

2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine; Levodopa; Carbidopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Methyldopa; Hydrazines

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2009
• First Posted: February 16, 2009
• Study Start: April 21, 2009
• Primary Completion: April 30, 2010
• Study Completion: May 14, 2010
• Last Updated: November 7, 2018
• Results First Posted: July 21, 2016

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share