A Dose Finding Study of Preladenant (SCH 420814) for the Treatment of Parkinson's Disease (PD) in Japanese Patients (P06402)

NCT01294800 | Completed Phase 2 Results DMC

• 2 other identifiers: P06402MK-3814-026
• Study Type: interventional
• Target: 450
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline and Week 12

• 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.

  Up to 14 weeks

• 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.

  Up to 12 Weeks

Secondary Outcomes (2)

• Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12

  Up to 12 Weeks

• Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12

  Baseline and Week 12

Study Arms (4)

Preladenant 2 mg

EXPERIMENTAL

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.

Drug: Preladenant

Preladenant 5 mg

EXPERIMENTAL

Participants will receive preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.

Drug: Preladenant

Preladenant 10 mg

EXPERIMENTAL

Participants will receive preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.

Drug: Preladenant

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo tablet to match Preladenant

Interventions

Preladenant DRUG

2, 5, or 10 mg tablets taken orally twice daily (BID)

Also known as: SCH 420814, MK-3814

Preladenant 10 mg; Preladenant 2 mg; Preladenant 5 mg

Placebo tablet to match Preladenant DRUG

tablets taken orally BID

Placebo

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 27632893 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2011
• First Posted: February 14, 2011
• Study Start: February 25, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 8, 2018
• Results First Posted: October 11, 2016

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share