- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04912115
Randomized, Double-Blind, Active Placebo-Controlled Study of Ketamine to Treat Levodopa-Induced Dyskinesia
A Multi-Center, Phase II, Randomized, Double-Blind, Prospective, Active Placebo- Controlled Trial of Sub-Anesthetic Intravenous Infusion of Ketamine to Treat Levodopa- Induced Dyskinesia in Subjects With Parkinson's Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This Phase II trial is a prospective, double-blind, randomized, parallel trial-design with two arms. Subjects will be randomized to treatment with the investigational product (ketamine) or an active control (midazolam). The active control causes mild sedation and is employed to minimize unmasking of the test article.
The study is an out-patient study. However, infusion days and days involving prolonged assessments are expected to require the subject to be onsite. Subjects will return to the site for safety and efficacy evaluations. On Day 1, PK samples will be collected near the end of Infusion 1 and post-infusion to evaluate near-steady-state blood levels in all subjects. Intensive PK sampling will be conducted in all subjects prior to, during, and a few hours after Infusion 2 (Day 5 ± 2).
The primary objective of the study is to evaluate the effects of low-dose intravenous infusion of ketamine on levodopa-induced dyskinesia (LID) in patients with Parkinson's disease. All patients included in the study should meet the inclusion criteria. Half of the participants will receive ketamine, while the other half will receive active placebo (Midazolam). All participants will be assigned to either the active group or the control group randomly. During the clinical trial, both investigators and patients are double-blind except serious adverse events occurred.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Tucson, Arizona, United States, 85719
- Investigative Site #7
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California
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Chula Vista, California, United States, 91910
- Investigative Site #2
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Fountain Valley, California, United States, 92708
- Investigative Site #1
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Florida
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Miami, Florida, United States, 33032
- Investigative Site #3
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Miami, Florida, United States, 33175
- Investigative Site #6
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Illinois
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Rolling Meadows, Illinois, United States, 60008
- Investigative Site #5
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Michigan
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Plymouth, Michigan, United States, 48170
- Investigative Site #4
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients diagnosed with Parkinson's Disease as defined by the UK Parkinson's Disease Society Brain Bank Criteria
- Signed a current IEC approved informed consent form
- Male or female patients between ages 30-85 years
- At least three years of prior treatment with levodopa of at least 400 mg daily subject to a maximum of 8 divided doses per day (excluding bedtime and nighttime)
- Waking day dyskinesia of > 25% determined as a score of ≥2 as per Question 4.1 on the UPDRS
- Ambulatory or ambulatory-aided (e.g., walker or cane) and able to complete study assessments
- Have been on stable doses of all anti-Parkinson's medications for 30 days prior to entry into the study, including a levodopa preparation administered not less than three times daily, and be willing to remain on the same doses of medications throughout the course of the study
- Any other current and allowed prescription/non-prescription medications and/or nutritional supplements taken regularly must have been at a stable dose and regimen for at least 30 days prior to screening, and the patient must be willing to continue the same doses and regimens during study participation.
- The subject/caregiver must demonstrate the ability to complete an accurate home diary based on training and evaluation (visit 2)
- Subjects must have available a responsible adult caregiver/companion who will drive the subject home following infusions
- Female subjects not of childbearing potential
- Male subjects, regardless of their fertility status, with nonpregnant women of childbearing potential (WOCBP) partners must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use a highly effective (less than 1% failure rate) method of contraception (such as combination oral contraceptives, implanted contraceptives, or intrauterine devices) or effective method of contraception (such as diaphragms with spermicide or cervical sponges) for the duration of the study and until their plasma concentrations are below the level that could result in a relevant potential exposure to a possible fetus, predicted to be 90 days following the last dose of study drug
Exclusion Criteria:
- Diagnosis of an atypical or secondary Parkinsonian syndrome
- Lack of documented response to levodopa
- Hoehn and Yahr stage of 5
- Known prior exposure to ketamine or other NMDA inhibitors within the last 30 days
- History of neurosurgical intervention related to PD (e.g., deep brain stimulation)
- History of seizures within two years prior to screening
- History of transient ischemic attacks or stroke within two years prior to screening
- History of intracerebral hemorrhage due to hypertension.
- History of clinically significant arrhythmia or unstable angina within the past five years
- History of myocardial infarction within 2 years prior to screening
- History of NYHA Class 3 or 4 heart failure within 2 years prior to screening
- Aneurysmal vascular disease (e.g., intracranial, thoracic or abdominal aorta)
- History of hypertensive encephalopathy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ketamine
Ketamine will be administered as intravenous infusions with infusion rates ranging from 0.1 mg/kg/hr to 0.30 mg/kg/hr.
To maintain blinding, both active and placebo will be infused at similar infusion rates (mL/hr).
|
Ketamine is an FDA-approved N-methyl-D-aspartate (NMDA) receptor-modulating drug pharmacologically classified as an NMDA receptor antagonist (also noted to be a weak opioid receptor agonist).
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Active Comparator: Midazolam
Midazolam will be administered as intravenous infusions with infusion rates ranging from 0.009 mg/kg/hr to 0.027 mg/kg/hr.
To maintain blinding, both active and placebo will be infused at similar infusion rates (mL/hr).
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Midazolam is a benzodiazepine used for anesthesia, procedural sedation, trouble sleeping, and severe agitation.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the Unified Dyskinesia Rating Scale (UDysRS) total score from Baseline to Week 8.
Time Frame: 8 weeks
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The change from baseline to week 8 of treatment in the sum of the items comprising the Unified Dyskinesia Rating Scale (UDysRS).
The Unified Dyskinesia Rating Scale (UDysRS) is administered to assess dyskinesia.
The scoring range is 0-104, where higher score means more dyskinesia.
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8 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in total daily OFF times as assessed by subject completed 24-hour diaries, from Baseline to Week 8.
Time Frame: 8 weeks
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Change in daily "OFF"-time as assessed with patient diaries from run-in to week 8.
This is a self administered diary where patients assess their motor state every half hour during 24 hours.
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8 weeks
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Change in the UPDRS total score of part III (motor) and sum score of Questions 4.1 and 4.2 (dyskinesia) in part IV from Baseline to Week 8.
Time Frame: 8 weeks
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Change in MDS-UPDRS sum score of part III (Motor Examination) from baseline to week 8. Minimum value is 0 and maximum value is 124.
Higher score mean a worse outcome.
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8 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Study Director, PharmaTher Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Dyskinesias
- Movement Disorders
- Neurologic Manifestations
- Central Nervous System Diseases
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Ketamine
- Midazolam
Other Study ID Numbers
- KET-001
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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