Back to resultsA Dose Finding Study of Preladenant (SCH 420814) for the Treatment of Parkinson's Disease (PD) in Japanese Patients (P06402)
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Preladenant
Placebo tablet to match Preladenant
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease
Eligibility Criteria
Inclusion Criteria:
- Must have a diagnosis of idiopathic PD based on the United Kingdom Parkinson's Disease Society Brain Bank Criteria, judged to be moderate to severe
- Must have received prior therapy with L-dopa for more than 1 year before Screening
- Must have been on a stable, optimal dopaminergic treatment regimen, defined as maximum
therapeutic effect achieved with available anti-Parkinsonian treatment, for at least the 4 weeks immediately before randomization
- If receiving one or more of the following adjunctive treatments: amantadine, anticholinergics, catechol-O-methyltransferase inhibitors, dopa decarboxylase inhibitors, dopamine agonists, entacapone, L-dopa, must have been on a stable regimen of treatment for at least the 4 weeks immediately before randomization
- Hoehn and Yahr stage must be ≥ 2.5 and ≤ 4 following optimum titration of treatment medications at Screening
- Must be experiencing motor fluctuations with or without dyskinesias following optimum titration of
treatment medications and within the 4 weeks immediately before Screening
- Must be experiencing a minimum of 2 hours/day of "off" time as estimated by the investigator
and supported by the symptom diary (Daily Diary) at the Diary Training Visit
- With or without the help of a caregiver, must be capable of maintaining an accurate and
complete symptom diary (Daily Diary) as assessed at the Diary Training Visit
- Must have results of Screening clinical laboratory tests (complete blood count [CBC], blood
chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator at Screening
- Must have results of a physical examination within normal limits or clinically acceptable limits
to the investigator
- Must be able to adhere to dose and visit schedules
- Females of child-bearing potential must have a negative serum pregnancy test (human chorionic
gonadotropin [hCG]) at Screening and must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 2 weeks after stopping the medication
Exclusion Criteria:
- Must not have a form of drug-induced or atypical parkinsonism, cognitive impairment, bipolar disorder, schizophrenia, or other psychotic disorder
- Must not have had surgery for PD
- Must not have an untreated major depressive disorder meeting Diagnostic and Statistical Manual
of Mental Disorders IV Text Revision (DSM-IV-TR) criteria
- Must not be at imminent risk of self-harm or harm to others, in the investigator's opinion based on
clinical interview
- Must not have participated in any studies using preladenant
- Must not have allergy/sensitivity to preladenant or any of its excipients
- Must not have used any investigational drugs or participated in any other clinical trial within 90 days of Screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Preladenant 2 mg
Preladenant 5 mg
Preladenant 10 mg
Placebo
Arm Description
Participants will receive preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants will receive preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants will receive preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Participants will receive a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Outcomes
Primary Outcome Measures
Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12
The "on" state is defined as the period of time during which a participant's symptoms of PD improve or disappear following treatment with levodopa (L-dopa) or dopamine agonists. The "off" state is defined as the period of time characterized by the return of symptoms (i..e. tremor, slowness, and rigidity) following treatment with L-dopa or dopamine agonists. Study participants reported their symptoms at half-hour intervals as "off", "on", or "asleep" on their daily diary for 3 days before randomization (baseline) and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "off" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
Number of Participants Who Experienced an Adverse Event (AE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Number of Participants Who Discontinued Study Treatment Due to an AE
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Secondary Outcome Measures
Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12
The proportion of responders (≥30% Reduction in "Off" Time at Week 12) was analyzed using a generalized linear mixed model with baseline mean OFF time (hours/day) as a covariate and treatment-by-time interaction as a fixed effect, and an unstructured covariance matrix was used to model the correlation among repeated measurements. Responder rates for each treatment arm are presented as are differences from placebo with 95% confidence interval.
Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12
When a participant is "on" without dyskinesias, parkinsonian symptoms have dissipated and the participant is experiencing no uncontrollable extraneous movements. Study participants reported their parkinsonian symptoms at half-hour intervals as "off", "on without dyskinesia", "on with non-troublesome dyskinesia", "on with troublesome dyskinesia", or "asleep" on their daily diary for 3 days before randomization and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "on without troublesome dyskinesia" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
Full Information
NCT ID
NCT01294800
First Posted
February 10, 2011
Last Updated
October 8, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01294800
Brief Title
A Dose Finding Study of Preladenant (SCH 420814) for the Treatment of Parkinson's Disease (PD) in Japanese Patients (P06402)
Official Title
A Phase 2, 12-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Assess the Efficacy and Safety of Preladenant in Japanese Subjects With Moderate to Severe Parkinson's Disease. (Phase 2; Protocol No. P06402)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
February 25, 2011 (Actual)
Primary Completion Date
June 1, 2013 (Actual)
Study Completion Date
June 1, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to evaluate the efficacy of a range of preladenant doses compared with placebo in participants with moderate to severe Parkinson's disease (PD) experiencing motor fluctuations and receiving a stable dose of levodopa (L-dopa), as measured by "off" time. Participants will continue to receive their stable regimen of L-dopa plus any adjunct medications during the study as prescribed by their physician. Several classes of adjunct medications may be used, including Amantadine, anticholinergics, dopa decarboxylase inhibitors, and dopamine agonists.
Primary Hypothesis: At least the 10 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 12 in the mean "off" time.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
450 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Preladenant 2 mg
Arm Type
Experimental
Arm Description
Participants will receive preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks.
Arm Title
Preladenant 5 mg
Arm Type
Experimental
Arm Description
Participants will receive preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Arm Title
Preladenant 10 mg
Arm Type
Experimental
Arm Description
Participants will receive preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Preladenant
Other Intervention Name(s)
SCH 420814, MK-3814
Intervention Description
2, 5, or 10 mg tablets taken orally twice daily (BID)
Intervention Type
Drug
Intervention Name(s)
Placebo tablet to match Preladenant
Intervention Description
tablets taken orally BID
Primary Outcome Measure Information:
Title
Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12
Description
The "on" state is defined as the period of time during which a participant's symptoms of PD improve or disappear following treatment with levodopa (L-dopa) or dopamine agonists. The "off" state is defined as the period of time characterized by the return of symptoms (i..e. tremor, slowness, and rigidity) following treatment with L-dopa or dopamine agonists. Study participants reported their symptoms at half-hour intervals as "off", "on", or "asleep" on their daily diary for 3 days before randomization (baseline) and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "off" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
Time Frame
Baseline and Week 12
Title
Number of Participants Who Experienced an Adverse Event (AE)
Description
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Time Frame
Up to 14 weeks
Title
Number of Participants Who Discontinued Study Treatment Due to an AE
Description
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to this medicinal product.
Time Frame
Up to 12 Weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12
Description
The proportion of responders (≥30% Reduction in "Off" Time at Week 12) was analyzed using a generalized linear mixed model with baseline mean OFF time (hours/day) as a covariate and treatment-by-time interaction as a fixed effect, and an unstructured covariance matrix was used to model the correlation among repeated measurements. Responder rates for each treatment arm are presented as are differences from placebo with 95% confidence interval.
Time Frame
Up to 12 Weeks
Title
Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12
Description
When a participant is "on" without dyskinesias, parkinsonian symptoms have dissipated and the participant is experiencing no uncontrollable extraneous movements. Study participants reported their parkinsonian symptoms at half-hour intervals as "off", "on without dyskinesia", "on with non-troublesome dyskinesia", "on with troublesome dyskinesia", or "asleep" on their daily diary for 3 days before randomization and for the 3 days immediately before their Week-12 visit. The mean change from baseline in "on without troublesome dyskinesia" time was based on a constrained longitudinal data analysis with treatment, time, and treatment-by-time interaction as fixed effects, and an unstructured covariance matrix was used to model the correlation among repeated measurements.
Time Frame
Baseline and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have a diagnosis of idiopathic PD based on the United Kingdom Parkinson's Disease Society Brain Bank Criteria, judged to be moderate to severe
Must have received prior therapy with L-dopa for more than 1 year before Screening
Must have been on a stable, optimal dopaminergic treatment regimen, defined as maximum
therapeutic effect achieved with available anti-Parkinsonian treatment, for at least the 4 weeks immediately before randomization
If receiving one or more of the following adjunctive treatments: amantadine, anticholinergics, catechol-O-methyltransferase inhibitors, dopa decarboxylase inhibitors, dopamine agonists, entacapone, L-dopa, must have been on a stable regimen of treatment for at least the 4 weeks immediately before randomization
Hoehn and Yahr stage must be ≥ 2.5 and ≤ 4 following optimum titration of treatment medications at Screening
Must be experiencing motor fluctuations with or without dyskinesias following optimum titration of
treatment medications and within the 4 weeks immediately before Screening
- Must be experiencing a minimum of 2 hours/day of "off" time as estimated by the investigator
and supported by the symptom diary (Daily Diary) at the Diary Training Visit
- With or without the help of a caregiver, must be capable of maintaining an accurate and
complete symptom diary (Daily Diary) as assessed at the Diary Training Visit
- Must have results of Screening clinical laboratory tests (complete blood count [CBC], blood
chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator at Screening
- Must have results of a physical examination within normal limits or clinically acceptable limits
to the investigator
Must be able to adhere to dose and visit schedules
Females of child-bearing potential must have a negative serum pregnancy test (human chorionic
gonadotropin [hCG]) at Screening and must agree to use a medically accepted method of contraception while receiving protocol-specified medication and for 2 weeks after stopping the medication
Exclusion Criteria:
Must not have a form of drug-induced or atypical parkinsonism, cognitive impairment, bipolar disorder, schizophrenia, or other psychotic disorder
Must not have had surgery for PD
Must not have an untreated major depressive disorder meeting Diagnostic and Statistical Manual
of Mental Disorders IV Text Revision (DSM-IV-TR) criteria
- Must not be at imminent risk of self-harm or harm to others, in the investigator's opinion based on
clinical interview
Must not have participated in any studies using preladenant
Must not have allergy/sensitivity to preladenant or any of its excipients
Must not have used any investigational drugs or participated in any other clinical trial within 90 days of Screening
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
Citations:
PubMed Identifier
27632893
Citation
Hattori N, Kikuchi M, Adachi N, Hewitt D, Huyck S, Saito T. Adjunctive preladenant: A placebo-controlled, dose-finding study in Japanese patients with Parkinson's disease. Parkinsonism Relat Disord. 2016 Nov;32:73-79. doi: 10.1016/j.parkreldis.2016.08.020. Epub 2016 Aug 27.
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A Dose Finding Study of Preladenant (SCH 420814) for the Treatment of Parkinson's Disease (PD) in Japanese Patients (P06402)
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