A Placebo- and Active-Controlled Study of Preladenant in Early Parkinson's Disease (PD) (P05664)

NCT01155479 | Terminated Phase 3 Results DMC

• 3 other identifiers: P056642009-013552-72MK-3814-024
• Study Type: interventional
• Target: 1,022
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a one year, 2-part study to determine the efficacy and safety of preladenant, an adenosine type 2a (A2a) receptor antagonist. The purpose of Part 1 (first 26 weeks) is to determine if preladenant is effective in the treatment of early Parkinson's Disease. The purpose of Part 2 (second 26 weeks) is to determine if preladenant is safe and well tolerated. The primary efficacy hypothesis is that at least the 10 mg twice daily dose of preladenant is superior to placebo as measured by the change from Baseline to Week 26 in the sum of Unified Parkinson's Disease Rating Scale (UPDRS) Parts 2 and 3 scores (UPDRS2+3).

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (5)

• Change From Baseline in the Sum of Unified Parkinson's Disease Rating Scale Parts 2 and 3 Scores (UPDRS2+3)

  The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. The UPDRS Part 2 is the Activities of Daily Living (ADL) score and can range from 0-52 as determined by the physician. The UPDRS Part 3 is the Motor Examination (Total Motor Score \[TMS\]) and is defined as the total score, ranging from 0-108 as determined by the physician, of the tests given in the motor examination section. The combined scores of Parts 2 and 3 can range from 0-160 with the higher score indicating the worse condition. Change from baseline was analyzed using a constrained longitudinal analysis (cLDA) model with treatment, time, strata and treatment-by-time interaction as fixed effects and participant as a random effect.

  Baseline and Week 26

• Number of Participants With Adverse Events (AEs) in Part 1

  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.

  Day 1 to Week 26

• Number of Participants Who Discontinued Study Due to an AE in Part 1

  An 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.

  Day 1 to Week 26

• Number of Participants With Adverse Events (AEs) in Part 2

  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.

  Week 27 to Week 52

• Number of Participants Who Discontinued Study Due to an AE in Part 2

  An 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.

  Week 27 to Week 52

Secondary Outcomes (2)

• Percentage of Responders (Participants With a ≥20% Improvement in UPDRS2+3)

  Baseline and Week 26

• Change From Baseline in the UPDRS Part 2 Score (Activities of Daily Living [ADL])

  Baseline and Week 26

Study Arms (5)

Preladenant 2 mg

EXPERIMENTAL

Preladenant 2 mg oral tablet and placebo for rasagiline taken in the morning (AM) followed by preladenant 2 mg oral tablet taken in the evening (PM) for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Drug: Preladenant 2 mg tablet; Drug: Placebo for Rasagiline 1 mg capsule

Preladenant 5 mg

EXPERIMENTAL

Preladenant 5 mg oral tablet and placebo for rasagiline taken in the AM followed by preladenant 5 mg taken in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Drug: Preladenant 5 mg tablet; Drug: Placebo for Rasagiline 1 mg capsule

Preladenant 10 mg

EXPERIMENTAL

Preladenant 10 mg oral tablet and placebo for rasagiline taken in the AM followed by preladenant 10 mg taken in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Drug: Preladenant 10 mg tablet; Drug: Placebo for Rasagiline 1 mg capsule

Placebo

PLACEBO COMPARATOR

Placebo for preladenant and placebo for rasagiline taken in the AM followed by placebo for preladenant taken in the PM for 26 weeks (Part 1); preladenant 5 mg was taken twice daily for 26 weeks (Part 2).

Drug: Preladenant 5 mg tablet; Drug: Placebo for Rasagiline 1 mg capsule; Drug: Placebo for Preladenant

Rasagiline

ACTIVE COMPARATOR

Rasagiline 1 mg oral capsule and placebo for preladenant taken in the AM followed by placebo for preladenant taken in the PM for 26 weeks (Part 1) and then for another 26 weeks (Part 2).

Drug: Rasagiline 1 mg capsule; Drug: Placebo for Preladenant

Interventions

Preladenant 2 mg tablet DRUG

Preladenant 2 mg oral tablet taken twice daily

Also known as: SCH 420814

Preladenant 2 mg

Preladenant 5 mg tablet DRUG

Preladenant 5 mg oral tablet taken twice daily

Also known as: SCH 420814

Placebo; Preladenant 5 mg

Preladenant 10 mg tablet DRUG

Preladenant 10 mg oral tablet taken twice daily

Also known as: SCH 420814

Preladenant 10 mg

Rasagiline 1 mg capsule DRUG

Rasagiline 1 mg oral capsule taken once daily

Also known as: Azilect

Rasagiline

Placebo for Rasagiline 1 mg capsule DRUG

Placebo for rasagiline 1 mg oral capsule taken once daily

Placebo; Preladenant 10 mg; Preladenant 2 mg; Preladenant 5 mg

Placebo for Preladenant DRUG

Placebo for preladenant 2 mg, 5 mg, or 10 mg oral tablet taken twice daily

Placebo; Rasagiline

Eligibility Criteria

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

You may qualify if:

• Has a diagnosis of idiopathic PD for \< 5 years.
• If receiving amantadine and/or anticholinergics, must have been on a stable regimen of treatment for at least the 5 weeks immediately before Screening. (Note: Participants who are not taking any medications for PD are permitted to enroll in this trial.)
• If sexually active or plan to be sexually active, must agree to use a highly effective method of birth control while the participant is in the study and for 2 weeks after the last dose of study drug. A male participant must also not donate sperm during the trial and within 2 weeks after the last dose of study drug.

You may not qualify if:

• Must not have a form of drug-induced or atypical Parkinsonism, cognitive impairment (ie, Montreal Cognitive Assessment \[MoCA\] score \<22), bipolar disorder, untreated major depressive disorder, schizophrenia, or other psychotic disorder; history of exposure to a known neurotoxin, or any neurological features not consistent with the diagnosis of PD as assessed by the investigator.
• Must not have had surgery for PD.
• Must not have a history of repeated strokes with stepwise progression of Parkinsonism 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.
• Must not have failed to show a therapeutic response if a diagnostic levodopa (L dopa) challenge had been done with a large test dose (\>500 mg) of L dopa (if malabsorption excluded), or failed to respond to an adequate previous treatment with dopaminergic therapy.
• Must not have been treated with L dopa or dopamine agonists for 30 days or more. A participant who has been treated with L-dopa or dopamine agonists for \<30 days will be allowed to enter the study. These participants must stop taking dopaminergic medication 30 days prior to Randomization.
• Must not be at imminent risk of self-harm or harm to others.
• Must not have elevated blood pressure (BP) (systolic BP ≥150 mm Hg or diastolic BP ≥95 mm Hg) that cannot be adequately controlled with antihypertensive medication, as demonstrated by 2 BP measurements meeting acceptable BP criterion at consecutive scheduled or unscheduled visits between Screening and Randomization (a 5-6 week period), one of which must be the Randomization visit.
• Must not have had any clinically significant cardiovascular event or procedure for 6 months prior to Randomization, 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.
• Must not have an alanine aminotransferase (ALT) or aspartate amino transferase (AST) ≥ 3 x the upper limit of normal (ULN) or total bilirubin (T BIL) ≥ 1.5 x ULN.
• Must not have active 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, or a history of diagnosis of drug- or alcohol-induced hepatic toxicity or frank hepatitis.)
• 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.
• Must not have received certain prespecified medications or ingested high tyramine-containing aged cheeses (eg, Stilton) for a prespecified time window before the trial, during the trial, and for 2 weeks after the trial.
• Must not have an average daily consumption of more than three 4 ounce glasses (118 mL) of wine or the equivalent.
• 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.)
• Must not have allergy/sensitivity to investigational product(s) or its/their excipients.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Stocchi F, Rascol O, Hauser RA, Huyck S, Tzontcheva A, Capece R, Ho TW, Sklar P, Lines C, Michelson D, Hewitt DJ; Preladenant Early Parkinson Disease Study Group. Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease. Neurology. 2017 Jun 6;88(23):2198-2206. doi: 10.1212/WNL.0000000000004003. Epub 2017 May 10.

  PMID: 28490648 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; Tablets; rasagiline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2010
• First Posted: July 1, 2010
• Study Start: July 6, 2010
• Primary Completion: July 16, 2013
• Study Completion: July 16, 2013
• Last Updated: November 7, 2018
• Results First Posted: July 28, 2016

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share