Acute Effects of Preladenant (SCH 420814) on Dyskinesia and Parkinsonism in Levodopa Treated Participants (P05550)
9 octobre 2018 mis à jour par: 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.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
12
Phase
- La phase 1
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation croisée
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
|
Expérimental: 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
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Mean Peak Dyskinesia Score
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Mean Peak Finger Tapping Score
Délai: 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
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
21 avril 2009
Achèvement primaire (Réel)
30 avril 2010
Achèvement de l'étude (Réel)
14 mai 2010
Dates d'inscription aux études
Première soumission
13 février 2009
Première soumission répondant aux critères de contrôle qualité
13 février 2009
Première publication (Estimation)
16 février 2009
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
7 novembre 2018
Dernière mise à jour soumise répondant aux critères de contrôle qualité
9 octobre 2018
Dernière vérification
1 octobre 2018
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du cerveau
- Maladies du système nerveux central
- Maladies du système nerveux
- Manifestations neurologiques
- Maladies des noyaux gris centraux
- Troubles du mouvement
- Synucleinopathies
- Maladies neurodégénératives
- Maladie de Parkinson
- Dyskinésies
- Troubles parkinsoniens
- Effets physiologiques des médicaments
- Agents neurotransmetteurs
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Agents dopaminergiques
- Agents antiparkinsoniens
- Agents anti-dyskinésie
- Inhibiteurs de la décarboxylase des acides aminés aromatiques
- Lévodopa
- Carbidopa
Autres numéros d'identification d'étude
- P05550
- MK-3814-023 (Autre identifiant: Merck Study Number)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
OUI
Description du régime IPD
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .