Randomized, Double-Blind, Active Placebo-Controlled Study of Ketamine to Treat Levodopa-Induced Dyskinesia

NCT ID: NCT04912115

Last Updated: 2023-11-18

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-05
• Study Completion Date: 2024-03-30

Brief Summary

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.

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.

Conditions

Dyskinesias; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

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).

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).

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: DRUG

Midazolam is a benzodiazepine used for anesthesia, procedural sedation, trouble sleeping, and severe agitation.

Interventions

Ketamine

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).

Intervention Type: DRUG

Midazolam

Midazolam is a benzodiazepine used for anesthesia, procedural sedation, trouble sleeping, and severe agitation.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients diagnosed with Parkinson's Disease as defined by the UK Parkinson's Disease Society Brain Bank Criteria

2. Signed a current IEC approved informed consent form

3. Male or female patients between ages 30-85 years

4. 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)

5. Waking day dyskinesia of > 25% determined as a score of ≥2 as per Question 4.1 on the UPDRS

6. Ambulatory or ambulatory-aided (e.g., walker or cane) and able to complete study assessments

7. 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

8. 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.

9. The subject/caregiver must demonstrate the ability to complete an accurate home diary based on training and evaluation (visit 2)

10. Subjects must have available a responsible adult caregiver/companion who will drive the subject home following infusions

11. Female subjects not of childbearing potential

12. 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

1. Diagnosis of an atypical or secondary Parkinsonian syndrome

2. Lack of documented response to levodopa

3. Hoehn and Yahr stage of 5

4. Known prior exposure to ketamine or other NMDA inhibitors within the last 30 days

5. History of neurosurgical intervention related to PD (e.g., deep brain stimulation)

6. History of seizures within two years prior to screening

7. History of transient ischemic attacks or stroke within two years prior to screening

8. History of intracerebral hemorrhage due to hypertension.

9. History of clinically significant arrhythmia or unstable angina within the past five years

10. History of myocardial infarction within 2 years prior to screening

11. History of NYHA Class 3 or 4 heart failure within 2 years prior to screening

12. Aneurysmal vascular disease (e.g., intracranial, thoracic or abdominal aorta)

13. History of hypertensive encephalopathy

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaTher Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

PharmaTher Inc.

Locations

Investigative Site #7

Tucson, Arizona, United States

Investigative Site #2

Chula Vista, California, United States

Investigative Site #1

Fountain Valley, California, United States

Investigative Site #3

Miami, Florida, United States

Investigative Site #6

Miami, Florida, United States

Investigative Site #5

Rolling Meadows, Illinois, United States

Investigative Site #4

Plymouth, Michigan, United States

Countries

United States

Other Identifiers

KET-001

Identifier Type: -

Identifier Source: org_study_id