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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Study Type

Interventional

Intervention

SCH 420814 10 mg

SCH 420814 100 mg

Placebo

Levodopa

Carbidopa

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Arm Label

SCH 420814 10 mg→SCH 420814 100 mg→Placebo

SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

Placebo→SCH 420814 10 mg→SCH 420814 100 mg

SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg

SCH 420814 100 mg→ SCH 420814 10 mg→Placebo

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Mean Peak Finger Tapping Score

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

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

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.

Full Information

NCT ID

NCT00845000

First Posted

February 13, 2009

Last Updated

October 9, 2018

Sponsor

Merck Sharp & Dohme LLC

Collaborators

Oregon Health and Science University

1. Study Identification

Unique Protocol Identification Number

NCT00845000

Brief Title

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

Official Title

Acute Effects of SCH 420814 on Dyskinesia and Parkinsonism in Levodopa Treated Patients

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

April 21, 2009 (Actual)

Primary Completion Date

April 30, 2010 (Actual)

Study Completion Date

May 14, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

Collaborators

Oregon Health and Science University

4. Oversight

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SCH 420814 10 mg→SCH 420814 100 mg→Placebo

Arm Type

Experimental

Arm 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.

Arm Title

SCH 420814 100 mg→Placebo→ SCH 420814 10 mg

Arm Type

Experimental

Arm 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.

Arm Title

Placebo→SCH 420814 10 mg→SCH 420814 100 mg

Arm Type

Experimental

Arm 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.

Arm Title

SCH 420814 10 mg→ Placebo→ SCH 420814 100 mg

Arm Type

Experimental

Arm 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.

Arm Title

SCH 420814 100 mg→ SCH 420814 10 mg→Placebo

Arm Type

Experimental

Arm 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.

Arm Title

Placebo→ SCH 420814 100 mg→SCH 420814 10 mg

Arm Type

Experimental

Arm 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.

Intervention Type

Drug

Intervention Name(s)

SCH 420814 10 mg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

SCH 420814 100 mg

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo capsule, oral, at hour 0 of treatment period

Intervention Type

Drug

Intervention Name(s)

Levodopa

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Carbidopa

Intervention Description

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

Primary Outcome Measure Information:

Title

Mean Peak Dyskinesia Score

Description

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.

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

Secondary Outcome Measure Information:

Title

Mean Peak Finger Tapping Score

Description

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.

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

Title

Mean Peak Tremor Score

Description

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.

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

Title

Mean Peak Walking Speed

Description

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.

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

No

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Parkinson Disease

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial