Clinical trial NCT01294800: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-02-14
Enrollment: 450
Sex: ALL
Minimum age (years): 30
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12
timeFrame: Baseline and Week 12
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to 14 weeks
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to 12 Weeks
Secondary outcomes:
measure: Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12
timeFrame: Up to 12 Weeks
measure: Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.