Phase 2 Clinical Study of KW-6500 in Parkinson's Disease Patients With Motor Response Complication on Levodopa Therapy

A Phase 2 Clinical Study of KW-6500 (Apomorphine Hydrochloride) in Patients With Parkinson's Disease

The purpose of this study is to evaluate the efficacy of KW-6500 versus placebo when administered as a subcutaneous injection at the individualized maintenance dose level in an OFF state in Parkinson's disease patients with motor response complications on levodopa therapy.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: apomorphine hydrochloride

Detailed Description

The efficacy of KW-6500 as a subcutaneous injection at the individualized maintenance dose level (1 mg to 6 mg per dose) when used in combination with domperidone (30 mg/day) will be evaluated in comparison with that of placebo in Parkinson's disease patients with motor response complications on levodopa therapy. The maintenance dose level for each subject will be determined using a titration scheme in 1 mg increments.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
  • Ehime
    • Toon, Ehime, Japan
  • Ibaraki
    • Tsukuba, Ibaraki, Japan
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women aged 20 years or older at the time of giving informed consent.
• Patients who have idiopathic Parkinson's disease.
• Patients who have been on a stable regimen of levodopa (at least three times daily) plus at least one other antiparkinsonian agent being administered or more frequently for at least 30 days before the preliminary evaluation and who have predictable end-of-dose wearing-off.

• Patients who meet both of the following criteria on the Modified Hoehn and Yahr Scale during the preliminary evaluation and on the day before starting study drug (Day -1).

  • Stage IV or V while in the OFF state
  • Stage II to III while in the ON state
• Patients who have experienced a 30% or more improvement in UPDRS Part 3 score when tested for responsiveness to levodopa during the baseline period.
• Patients who have at least one wearing-off episode per day and a daily average OFF time of at least two hours two days before starting study drug (Day -2) and on Day -1.
• Patients who can understand the OFF state or have a family member who can understand it.
• Patients who have given written informed consent. (Alternatively, the patient's legally acceptable representative may give written consent following the patient's oral consent, if his/her condition makes handwriting difficult.)

Exclusion Criteria:

• Patients with an illness of the cardiac, hematologic, hepatic, renal, pancreatic, metabolic, respiratory, gastrointestinal, endocrinologic, or neurologic system or a tumor that is clinically significant for their participation in the study.
• Patients with orthostatic hypotension.
• Patients with a history of drug allergies.
• Patients with a history of intolerance to morphine or its derivatives, sulfur, sulfur-containing pharmaceutical products, or sulfite.
• Patients with a history of malignant syndrome.
• Patients with a diagnosis of cancer or evidence of continued disease within five years before starting study drug.
• Patients who have been taking domperidone at a dose level of more than 30 mg/day since before the preliminary evaluation.
• Patients who do not test negative in the direct Coombs' test as part of the preliminary evaluation.
• Pregnant or lactating women, women who are planning to have children, women who test positive in the pregnancy test during the preliminary evaluation or on Day -1, or women who cannot adhere to a reliable method of contraception throughout the study.
• Patients who have received MAO inhibitors except selegiline within three months before starting study drug.
• Patients with a current or past history of mental disease or dementia (excluding psychiatric symptoms associated with Parkinson's disease).
• Patients with a Mini-Mental State Examination (MMSE) score of 23 or less on or before Day -1.
• Patients who are taking antipsychotics or dopamine antagonists.
• Patients who are receiving methyldopa, 5-HT3 receptor antagonists, or reserpine.
• Patients who are receiving papaverine.
• Patients who have had a neurosurgical operation for Parkinson's disease.
• Patients who have had transcranial magnetic stimulation (TMS) within six months before starting study drug.
• Patients with a history of drug or alcohol abuse or dependence (DSM-IV criteria) within two years before starting study drug.
• Patients previously treated with apomorphine.
• Patients who have been treated with any other investigational product within four months before starting study drug.
• Patients who, for any reason, are judged by the investigator or subinvestigator to be inappropriate for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: apomorphine hydrochloride; Apomorphine hydrochloride (started at 1 mg and titrated to a maximum of 6 mg) is subcutaneously administered.; Other Names: KW-6500
Active Comparator: KW-6500; Drug: KW-6500 (apomorphine hydrochloride (USAN))	Drug: apomorphine hydrochloride; Apomorphine hydrochloride (started at 1 mg and titrated to a maximum of 6 mg) is subcutaneously administered.; Other Names: KW-6500

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change (response ratio, raw score change, percent score change) in UPDRS (Unified Parkinson's Disease Rating Scale ) Part 3 score at the maintenance dose level	At 20 minutes after administering KW-6500 or placebo

Secondary Outcome Measures

Outcome Measure	Time Frame
The incidence of adverse events/adverse drug reactions and their nature	1 week after starting treatment

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: January 22, 2008
• First Submitted That Met QC Criteria: January 23, 2008
• First Posted (Estimate): February 7, 2008

Study Record Updates

• Last Update Posted (Actual): August 28, 2020
• Last Update Submitted That Met QC Criteria: August 27, 2020
• Last Verified: August 1, 2020

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; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Dopamine Agonists; Dopamine Agents; Emetics; Apomorphine
• Other Study ID Numbers: 6500-0702