Placebo Controlled Study of Preladenant in Participants W... | NCT01227265

NCT01227265

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2010-020112-11	EudraCT Number
MK-3814-028	Other Identifier	Merck Study Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Preladenant 2 mg	Experimental	Participants received 2 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.	Drug: Preladenant
Preladenant 5 mg	Experimental	Participants received 5 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.	Drug: Preladenant
Placebo	Placebo Comparator	Participants received preladenant-matching placebo as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extention trial or return for a follow-up visit two (2) weeks later.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Preladenant	Drug	Preladenant 2 mg or 5 mg oral tablet taken twice daily	Preladenant 2 mg Preladenant 5 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Average "Off" Time (Hours Per Day) at Week 12	The "on" state is defined as the period of time during which a patient's symptoms of PD improve or disappear following treatment with 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 (cLDA) with treatment, time, and treatment-by-time interaction as fixed effects and subject as random effect.	Baseline and Week 12
Number of Participants With Systolic Blood Pressure (SBP) ≥180 mmHg and 20 mmHg Increase	The number of participants with Systolic Blood Pressure (SBP) ≥180 mmHg and 20 mmHg increase was reported. Participants lie supine at rest for 5 minutes, then have a single BP measurement taken (ie, 1 reading). Participants then stand for 3 minutes at rest, followed by a single BP measurement (1 reading) in the standing position.	Up to Week 14
Number of Participants With Diastolic Blood Pressure (DBP) ≥105 mmHg and 15 mmHg Increase	The number of participants with Diastolic Blood Pressure (DBP) ≥105 mmHg and 15 mmHg increase was reported. Participants lie supine at rest for 5 minutes, then have a single BP measurement taken (ie, 1 reading). Participants then stand for 3 minutes at rest, followed by a single BP measurement (1 reading) in the standing position.	Up to Week 14
Percentage of Participants With Suicidality	The percentage of participants with suicidality using the Columbia - Suicide Severity Rating Scale (C-SSRS) was reported. The C-SSR was used in this study only for the purpose of safety monitoring by measuring the incidence of different types of suicidality categories during treatment. The assessment was done by the nature of the responses, not by a numbered scale. Participants who reported at least one occurrence of suicidal behavior or suicidal ideation were counted as having experienced suicidality. Suicidal behavior included suicide attempt, aborted attempt, interrupted attempt, or preparatory behavior. Suicidal ideation included a wish to die or active suicidal thought with or without method, intent or plan.

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With >30% Change (Reduction) From Baseline at Week 12 in Mean "Off" Time	A participant with at least a 30% reduction in mean "off" time from Baseline to End of Treatment (Week 12) is considered as "responder". The "on" state is defined as the period of time during which a patient's symptoms of PD improve or disappear following treatment with 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 and for the 3 days immediately before their Week 12 visit.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Each participant must have a diagnosis of idiopathic Parkinson's disease.
Each participant must have received prior therapy with L-dopa for approximately 1 or more years immediately before Screening and must continue to have a beneficial clinical response to L-dopa.
Each participant must have been on a stable dopaminergic treatment regimen for at least the 5 weeks immediately before Randomization. Participants receiving other adjunctive treatments (eg, dopamine agonist, anticholinergics) are permitted to enroll in this trial. Participants taking only L-dopa are permitted to enroll in this trial.
Each participant must be experiencing motor fluctuations with or without dyskinesias within the 4 weeks immediately before Screening, must be experiencing a minimum of 2 hours/day of "off" time, and have a Hoehn & Yahr stage between 2.5 and 4 when in the "on" state.
Each participant, with or without the help of a caregiver, must be capable of maintaining an accurate and complete symptom diary and to adhere to dose and visit schedules.
Each participant must have results of Screening clinical laboratory tests drawn within 5 weeks prior to Randomization clinically acceptable to the investigator and not within the parameters specified for exclusion (below).
All participants who are sexually active or plan to be sexually active agree to use a highly effective method of birth control while in the study and for 2 weeks after the last dose of study drug. A male participant must also not donate sperm within 2 weeks after the last dose of study drug.

Exclusion Criteria:

A participant must not have a form of drug induced or atypical parkinsonism, a cognitive impairment, bipolar disorder, untreated major depressive disorder, schizophrenia, or other psychotic disorder; history exposure to a known neurotoxin, or any neurological features not consistent with the diagnosis of PD as assessed by the investigator.
A participant must not have a history of repeated strokes or head injuries, or a stroke within 6 months of Screening; poorly controlled diabetes; abnormal renal function; or a severe or ongoing unstable medical condition.
A participant must not have had surgery for their PD.
A participant must not be at imminent risk of self-harm or harm to others.
A participant must not have a systolic blood pressure (BP) ≥150 mm Hg OR diastolic BP ≥95 mm Hg at Screening and at 2 BP rechecks prior to study start.
A participant must not have had any clinically significant cardiovascular event or procedure for 6 months prior to study start, including, but not limited to, myocardial infarction, angioplasty, unstable angina, or heart failure; and a participant must not have heart failure staged New York Heart Association Class III or IV.
A participant must not have an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 x the upper limit of normal (ULN) or total bilirubin (T BIL) ≥1.5 x ULN.
A participant must not have a history of serologically confirmed hepatic dysfunction (defined as viral infection [Hepatitis B, C, or E; Epstein-Barr virus (EBV); cytomegalovirus (CMV)]) or a history of diagnosis of drug- or alcohol- induced hepatic toxicity or frank hepatitis.
A participant must not have a history within the past 5 years of a primary or recurrent malignant disease with the exception of adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or in situ prostate cancer with a normal prostate-specific antigen (PSA) post resection.
A participant must not have received certain prespecified medications for a prespecified time window before the trial.
A participant must not have an average daily consumption of more than three 4 ounce glasses (118 mL) of wine or the equivalent.
A participant must not have a severe or ongoing unstable medical condition (eg, any form of clinically significant cardiac disease, symptomatic orthostatic hypotension, seizures, or alcohol/drug dependence).
A participant must not have allergy/sensitivity to investigational product(s) or its/their excipients.
A participant must not be breast-feeding, considering breast-feeding, pregnant, or intending to become pregnant.
A participant must not have used preladenant ever, or any investigational drugs within 90 days immediately before Screening.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
26523919	Result	Hauser RA, Stocchi F, Rascol O, Huyck SB, Capece R, Ho TW, Sklar P, Lines C, Michelson D, Hewitt D. Preladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned. JAMA Neurol. 2015 Dec;72(12):1491-500. doi: 10.1001/jamaneurol.2015.2268.

ID	Title	Description
FG000	Preladenant 2 mg	Participants received 2 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.
FG001	Preladenant 5 mg	Participants received 5 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.
FG002	Placebo	Participants received preladenant-matching placebo as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extention trial or return for a follow-up visit two (2) weeks later.

ID	Title	Description
BG000	Preladenant 2 mg	Participants received 2 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.
BG001	Preladenant 5 mg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Average "Off" Time (Hours Per Day) at Week 12

The "on" state is defined as the period of time during which a patient's symptoms of PD improve or disappear following treatment with 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 (cLDA) with treatment, time, and treatment-by-time interaction as fixed effects and subject as random effect.

Full Analysis Set (FAS): All randomized participants remaining after participants were excluded for failure to receive at least one dose of study treatment, lack of any post-randomization endpoint data subsequent to at least 1 dose of study treatment, or lack of Baseline data for those analyses requiring Baseline data.

Posted

Mean

Standard Error

hours per day

Baseline and Week 12

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Preladenant 2 mg	Participants received 2 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases

OG000	Preladenant 2 mg	Participants received 2 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.
OG001	Preladenant 5 mg	Participants received 5 mg as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extension trial or return for a follow-up visit two (2) weeks later.
OG002	Placebo	Participants received preladenant-matching placebo as a single oral dose twice daily for 12 weeks. Participants could then enroll in an extention trial or return for a follow-up visit two (2) weeks later.