Parkinson's DiseasePhase 2NCT01294800

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

A Phase 2 study testing Preladenant in people with Parkinson's Disease, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 30 to 85 years
Conditions the study is for: Parkinson's Disease
What is being tested?: Preladenant
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 450 participants
Where: No sites listed yet
Study dates: 25 Feb 2011to 1 Jun 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 30 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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

Who cannot join

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

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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

About this study

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)

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
Being tested: Preladenant, Placebo tablet to match Preladenant
Keywords: Parkinson's disease
Medical subject headings: Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PreladenantDrug
Also called SCH 420814, MK-3814
2, 5, or 10 mg tablets taken orally twice daily (BID)
Placebo tablet to match PreladenantDrug
tablets taken orally BID

Study groups in NCT01294800
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Placebo tablet to match Preladenant

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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.
Measured: Up to 12 Weeks

Secondary outcomes (2)

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.
Measured: Up to 12 Weeks
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.
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

25 Feb 20111 Jun 2013

First posted14 Feb 2011 (estimated)
Study start25 Feb 2011
Primary completion1 Jun 2013
Study completion1 Jun 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 450 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01294800
Sponsor's protocol ID: P06402
Other IDs: MK-3814-026
Status last verified: Oct 2018
First submitted: 10 Feb 2011
Last updated: 8 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

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.
PubMed 27632893

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01294800
Acronym / sponsor ID: P06402
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 450 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 25 Feb 2011 (actual)
Primary completion: 1 Jun 2013 (actual)
Study completion: 1 Jun 2013 (actual)
First posted: 14 Feb 2011 (estimated)
Results: Posted 11 Oct 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
Preladenant 2 mg	Experimental	Drug: PreladenantParticipants will receive preladenant 2 mg taken orally twice daily (BID), one tablet in the morning and one tablet in the evening, for 12 weeks.
Preladenant 5 mg	Experimental	Drug: PreladenantParticipants will receive preladenant 5 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Preladenant 10 mg	Experimental	Drug: PreladenantParticipants will receive preladenant 10 mg taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.
Placebo	Placebo comparator	Drug: Placebo tablet to match PreladenantParticipants will receive a placebo to preladenant tablet taken orally BID, one tablet in the morning and one tablet in the evening, for 12 weeks.

Who may qualify

Ages: 30 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

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

Key exclusion criteria (9 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PreladenantAlso: SCH 420814, MK-38142, 5, or 10 mg tablets taken orally twice daily (BID)	Drug	Preladenant 10 mg, Preladenant 2 mg, Preladenant 5 mg
Placebo tablet to match Preladenanttablets taken orally BID	Drug	Placebo

Primary outcome

Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12
Time frame: Baseline and 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)
Time frame: Up to 14 weeks
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
Time frame: Up to 12 Weeks
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.

2 secondary outcomes

Percentage of Participants With ≥30% Reduction in "Off" Time at Week 12
Time frame: Up to 12 Weeks
Change From Baseline in Mean "On" Time Without Troublesome Dyskinesias (Hours Per Day) at Week 12
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 11 Oct 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Preladenant 2 mg	111	100
Preladenant 5 mg	113	103
Preladenant 10 mg	113	96
Placebo	113	97

Primary outcome: Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12

Time frame: Baseline and Week 12. Mean (Standard Deviation). Unit: Hours/Day

Measure	Preladenant 2 mg n = 98	Preladenant 5 mg n = 101	Preladenant 10 mg n = 93	Placebo n = 90
Value	-1.2 (2.3)	-1.0 (2.6)	-0.9 (2.2)	-0.5 (3.0)

Preladenant 2 mg vs Placebo: Difference in Least Squares Mean: -0.7 (95% CI -1.37 to 0.02), p = 0.0564, Constrained longitudinal data analysis
Preladenant 5 mg vs Placebo: Difference in Least Squares Mean: -0.5 (95% CI -1.16 to 0.22), p = 0.1844, Constrained longitudinal data analysis
Preladenant 10 mg vs Placebo: Difference in Least Squares Mean: -0.3 (95% CI -1.04 to 0.36), p = 0.3386, Constrained longitudinal data analysis

Population analysed: Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment; had endpoint data subsequent to at least one dose of study treatment; and had baseline data for those analyses requiring baseline data.

Primary outcome: Number of Participants Who Experienced an Adverse Event (AE)

Time frame: Up to 14 weeks. Number. Unit: Participants

Measure	Preladenant 2 mg n = 111	Preladenant 5 mg n = 113	Preladenant 10 mg n = 113	Placebo n = 113
Value	53	60	69	55

Population analysed: All Participants as Treated population, which included all participants who received at least one dose of study drug

Primary outcome: Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to 12 Weeks. Number. Unit: Participants

Measure	Preladenant 2 mg n = 111	Preladenant 5 mg n = 113	Preladenant 10 mg n = 113	Placebo n = 113
Value	6	6	12	5

Population analysed: All Participants as Treated population, which included all participants who received at least one dose of study drug

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 14 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Preladenant 2 mg	9 of 111 (8.1%)	19 of 111 (17.1%)	Not reported
Preladenant 5 mg	5 of 113 (4.4%)	23 of 113 (20.4%)	Not reported
Preladenant 10 mg	7 of 113 (6.2%)	25 of 113 (22.1%)	Not reported
Placebo	3 of 113 (2.7%)	14 of 113 (12.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 27632893Hattori 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.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Preladenant in people with Parkinson's Disease, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Mean "Off" Time (Hours Per Day) at Week 12 (time frame: Baseline and Week 12). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01294800, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2018.