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

NCT04912115 | Suspended Phase 2 FDA Drug

• 1 other identifier: KET-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in the Unified Dyskinesia Rating Scale (UDysRS) total score from Baseline to Week 8.

  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.

  8 weeks

Secondary Outcomes (2)

• Change in total daily OFF times as assessed by subject completed 24-hour diaries, from Baseline to Week 8.

  8 weeks

• 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.

  8 weeks

Study Arms (2)

Ketamine

EXPERIMENTAL

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).

Drug: Ketamine

Midazolam

ACTIVE COMPARATOR

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).

Drug: Midazolam

Interventions

Ketamine 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).

Ketamine

Midazolam DRUG

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

Midazolam

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PharmaTher Inc.: lead

Study Sites (7)

Investigative Site #7

Tucson, Arizona, 85719, United States

Location

Investigative Site #2

Chula Vista, California, 91910, United States

Location

Investigative Site #1

Fountain Valley, California, 92708, United States

Location

Investigative Site #3

Miami, Florida, 33032, United States

Location

Investigative Site #6

Miami, Florida, 33175, United States

Location

Investigative Site #5

Rolling Meadows, Illinois, 60008, United States

Location

Investigative Site #4

Plymouth, Michigan, 48170, United States

Location

MeSH Terms

Conditions

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

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Study Director

  PharmaTher Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: May 25, 2021
• First Posted: June 3, 2021
• Study Start: October 5, 2021
• Primary Completion: December 30, 2023
• Study Completion: March 30, 2024
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

US (7)