Acute Effects of Preladenant (SCH 420814) on Dyskinesia and Parkinsonism in Levodopa Treated Participants (P05550)
9 oktober 2018 bijgewerkt door: Merck Sharp & Dohme LLC
Acute Effects of SCH 420814 on Dyskinesia and Parkinsonism in Levodopa Treated Patients
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.
Studie Overzicht
Toestand
Voltooid
Conditie
Studietype
Ingrijpend
Inschrijving (Werkelijk)
12
Fase
- Fase 1
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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.
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Crossover-opdracht
- Masker: Dubbele
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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.
|
one 10-mg capsule, orally, at hour 0 of treatment period
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Placebo capsule, oral, at hour 0 of treatment period
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
|
|
Experimenteel: 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.
|
one 10-mg capsule, orally, at hour 0 of treatment period
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Placebo capsule, oral, at hour 0 of treatment period
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
|
|
Experimenteel: 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.
|
one 10-mg capsule, orally, at hour 0 of treatment period
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Placebo capsule, oral, at hour 0 of treatment period
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
|
|
Experimenteel: 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.
|
one 10-mg capsule, orally, at hour 0 of treatment period
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Placebo capsule, oral, at hour 0 of treatment period
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
|
|
Experimenteel: 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.
|
one 10-mg capsule, orally, at hour 0 of treatment period
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Placebo capsule, oral, at hour 0 of treatment period
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
|
|
Experimenteel: 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.
|
one 10-mg capsule, orally, at hour 0 of treatment period
single oral dose of four SCH 420814 25-mg capsules at hour 0 of treatment period
Placebo capsule, oral, at hour 0 of treatment period
levodopa intravenous (IV) infusion (1 mg/kg body weight) was beginning 1 hour after study drug administration and continued for 2 hours
one 25-mg table, orally, at hours 0, 2 and 4 of each treatment period
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Mean Peak Dyskinesia Score
Tijdsspanne: 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
|
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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Mean Peak Finger Tapping Score
Tijdsspanne: 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
|
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.
|
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
Tijdsspanne: 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
|
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.
|
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
Tijdsspanne: 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
|
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.
|
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
|
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Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
21 april 2009
Primaire voltooiing (Werkelijk)
30 april 2010
Studie voltooiing (Werkelijk)
14 mei 2010
Studieregistratiedata
Eerst ingediend
13 februari 2009
Eerst ingediend dat voldeed aan de QC-criteria
13 februari 2009
Eerst geplaatst (Schatting)
16 februari 2009
Updates van studierecords
Laatste update geplaatst (Werkelijk)
7 november 2018
Laatste update ingediend die voldeed aan QC-criteria
9 oktober 2018
Laatst geverifieerd
1 oktober 2018
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Hersenziekten
- Ziekten van het centrale zenuwstelsel
- Ziekten van het zenuwstelsel
- Neurologische manifestaties
- Basale ganglia-ziekten
- Bewegingsstoornissen
- Synucleïnopathieën
- Neurodegeneratieve ziekten
- Ziekte van Parkinson
- Dyskinesieën
- Parkinson-stoornissen
- Fysiologische effecten van medicijnen
- Neurotransmitter agenten
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Dopamine-agenten
- Antiparkinson-agenten
- Middelen tegen dyskinesie
- Aromatische aminozuurdecarboxylaseremmers
- Levodopa
- Carbidopa
Andere studie-ID-nummers
- P05550
- MK-3814-023 (Andere identificatie: Merck Study Number)
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
JA
Beschrijving IPD-plan
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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