A Study of MK0657 in Parkinson's Disease Patients (0657-006)

A Randomized, Double-Blind, Placebo-Controlled, 2-Period Crossover Study to Evaluate Effectiveness of Single-Dose MK0657 in Combination With Levodopa on Motor Symptoms and Dyskinesias in Patients With Parkinson's Disease

In this clinical trial, the safety of MK0657 when given with levodopa will be assessed in patients with Parkinson's Disease. This study will also measure the effectiveness of MK0657, when given in combination with levodopa, to improve motor symptoms and ameliorate dyskinesias (uncontrolled movements of a part of the body) as compared to placebo.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: MK0657; Drug: Comparator: levodopa; Drug: Comparator: carbidopa; Drug: Comparator: Placebo (unspecified)

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Parkinson's Disease patients between the ages of 40 and 80 inclusive
• Patient is in general good health based on screening assessments
• Patient is willing to discontinue anti-parkinson's medications at least 8 hours prior to dosing
• Patient is levodopa responsive with levodopa-induced peak-dose dyskinesias
• Patient taking selective serotonin inhibitors (SSRIs), sleep medications and neuroleptics, have been on a stable dose for at least 30 days and has not experienced any CNS-related side effects
• Patient is not a heavy smoker or drinker

Exclusion Criteria:

• Patient has atypical Parkinson's syndrome due to drugs, identified metabolic and/or neurologic disorders, encephalitis, or other degenerative syndrome
• Patient has known intolerance or hypersensitivity to levodopa or carbidopa
• Patient has been on anticholinergics or memantine within 30 days prior to dosing
• Patients have a history of the following: seizure disorder, stroke or head trauma, pronounced cognitive impairment, psychiatric disorder, cardiovascular disease, cancer, diabetes as defined by HbA1c of greater than 8%
• Patient has a systolic BP or less than 80 mm Hg or greater than 150 mm Hg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; 7mg MK0657 capsules + >/=1.0 mg/kg/hr dose of levodopa.	Drug: MK0657; 7mg MK0657 capsules; Drug: Comparator: levodopa; levodopa >/=1.0 mg/kg/hr dose of levodopa. levodopa infusions will occur over a 2 hour period; Drug: Comparator: carbidopa; carbidopa 25mg administered 3 times: at 1 hour before levodopa infusion and at 1 and 3 hours after the start of levodopa infusion.
Other: 2; 7mg MK0657 Pbo capsules + >/=1.0 mg/kg/hr dose of levodopa.	Drug: Comparator: levodopa; levodopa >/=1.0 mg/kg/hr dose of levodopa. levodopa infusions will occur over a 2 hour period; Drug: Comparator: carbidopa; carbidopa 25mg administered 3 times: at 1 hour before levodopa infusion and at 1 and 3 hours after the start of levodopa infusion.; Drug: Comparator: Placebo (unspecified); 7mg MK0657 Pbo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy will be assessed for up to 8 hours by the Unified Parkinson's Disease Rating Scale-Motor Examination and a modified AIMS dyskinesia scale	45 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability	45 Days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Addy C, Assaid C, Hreniuk D, Stroh M, Xu Y, Herring WJ, Ellenbogen A, Jinnah HA, Kirby L, Leibowitz MT, Stewart RM, Tarsy D, Tetrud J, Stoch SA, Gottesdiener K, Wagner J. Single-dose administration of MK-0657, an NR2B-selective NMDA antagonist, does not result in clinically meaningful improvement in motor function in patients with moderate Parkinson's disease. J Clin Pharmacol. 2009 Jul;49(7):856-64. doi: 10.1177/0091270009336735. Epub 2009 Jun 2.
• Herring WJ, Assaid C, Budd K, Vargo R, Mazenko RS, Lines C, Ellenbogen A, Verhagen Metman L. A Phase Ib Randomized Controlled Study to Evaluate the Effectiveness of a Single-Dose of the NR2B Selective N-Methyl-D-Aspartate Antagonist MK-0657 on Levodopa-Induced Dyskinesias and Motor Symptoms in Patients With Parkinson Disease. Clin Neuropharmacol. 2017 Nov/Dec;40(6):255-260. doi: 10.1097/WNF.0000000000000241.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: July 24, 2007
• First Submitted That Met QC Criteria: July 24, 2007
• First Posted (Estimate): July 25, 2007

Study Record Updates

• Last Update Posted (Estimate): January 29, 2015
• Last Update Submitted That Met QC Criteria: January 28, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Aromatic Amino Acid Decarboxylase Inhibitors; Levodopa; Carbidopa
• Other Study ID Numbers: 0657-006; MK0657-006; 2007_524