(2R,6R)-Hydroxynorketamine for the Treatment of Neuropathic Pain

NCT05864053 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 21092004CP220059
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this randomized double blind three way (1:1:1) cross over clinical trial is to evaluate the effectiveness and duration of analgesia of a single infusion of (2R,6R)-HNK 0.5mg/kg compared with ketamine 0.5mg/kg and saline with a 5-week interval between treatments on pain, pain qualities, physical function, pain interference, sleep disturbance and quality of life in subjects with neuropathic pain of the extremities. The questions that this study will address are:

1. 1.What is the analgesic efficacy of (2R,6R)-HNK on pain intensity and pain qualities in patients with chronic (\>3 month) neuropathic pain (NP).
2. 2.What will be the effective duration of a single infusion of (2R,6R)-HNK in patients with NP.
3. 3.Will (2R,6R)-HNK reduce pain related effects including interference in daily activities of life, sleep disturbances and change the qualities of pain reported by patients.

Conditions

Pain, Neuropathic

Keywords

pain; pain, chronic; pain, neuropathic; non-opioid analgesic; ketamine; (2R,6R)-hydroxynorketamine

Outcome Measures

Primary Outcomes (1)

• Pain intensity

  Area under the pain by time curve

  35 days

Secondary Outcomes (3)

• Pain qualities

  35 days

• PainDETECT questionnaire screening scores

  5 weeks

• Analgesic consumption

  5 weeks

Study Arms (3)

Ketamine

ACTIVE COMPARATOR

Ketamine 0.5mg/kg 45 minute infusion x 1

Drug: Ketamine

(2R,6R)-hydroxynorketamine

EXPERIMENTAL

(2R,6R)-hydroxynorketamine 0.5mg/kg 45 minute infusion x 1

Drug: (2R,6R)-hydroxynorketamine

Saline

PLACEBO COMPARATOR

Saline 45 minute infusion x 1

Drug: Saline

Interventions

Saline DRUG

Saline will be administered over a 45-minute period.

Saline

Ketamine DRUG

Ketamine will be administered over a 45-minute period.

Ketamine

(2R,6R)-hydroxynorketamine DRUG

(2R,6R)-Hydroxynorketamine hydrochloride will be administered over a 45-minute period.

(2R,6R)-hydroxynorketamine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (18 to 75 years) with an established diagnosis of chronic (\> 3 month) NP of the extremities.
• Ability to read and write English sufficiently to complete study related procedures.
• A body mass index (BMI) (weight \[kg\]/height\[m \]) between 18 and 35 kg/m (inclusive) and weighs between 50 kg and 120 kg (110 - 264 pounds).
• Blood pressure with subject is in a supine position for approximately 5 minutes between 90 and 145 mmHg systolic and no higher than 90 mmHg diastolic at baseline.
• A 12-lead ECG with no clinically significant abnormality as judged by the Investigator and QTc interval ≤ 450 milliseconds at baseline.
• Resting pulse rate between 45 and 100 beats per minute.
• Clinical laboratory findings and liver function tests within the normal range, or if outside of the normal ranges, deemed not clinically significant in the opinion of the PI.
• Agree to provide written informed consent and comply with the rules regarding consumption of alcohol, caffeinated beverages, and tobacco/nicotine products during the study.
• Patients may be taking scheduled or as needed medications for their chronic neuropathic pain and agree to continue taking the scheduled medications throughout the study period.
• If the subject experiences pain relief they may elect not to take as needed medications.

You may not qualify if:

• Subjects with suspected increased intracranial or intraocular pressure.
• Subjects that have previously received ketamine for the treatment of a chronic pain diagnoses.
• Previous or current participation in any clinical study with an investigational drug, device, or biologic within 30 days.
• Subjects with severe medical illness including (but not limited to) hepatic, cardiovascular, pulmonary, renal, hematologic, endocrine, gastrointestinal, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease that in the opinion of the PI would endanger the safety of the subject or the validity of the study results.
• Clinically significant acute illness in the 2 weeks prior to dosing.
• Inability to effectively communicate with research staff.
• Subjects with known liver disease.
• Widespread pain or a diagnosis of fibromyalgia.
• Current diagnosis of mental illness.
• Pregnancy.
• Allergy to ketamine or any study drug.
• Consumption of beverages or food that contain alcohol, grapefruit, poppy seeds, Brussel sprouts, pomegranate, broccoli, char-grilled meat within 2 days prior to drug administration.
• Use of tobacco or nicotine-containing products within 4 weeks prior to drug administration.
• Poor peripheral venous access.
• Subjects in the opinion of the PI should not participate in the study.

Sponsors & Collaborators

• Rush University Medical Center: lead
• Congressionally Directed Medical Research Programs: collaborator

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

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MeSH Terms

Conditions

Neuralgia; Pain; Chronic Pain

Interventions

Ketamine; 6-hydroxynorketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Asokumar Buvanendran, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Robert J McCarthy, Pharm D

CONTACT

3125630448; robert_j_mccarthy@rush.edu

Daniel Torrez, BS

CONTACT

3129422741; daniel_torrez@rush.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Interim Chairperson, Department of Anesthesiology

Model Details: Randomized double blind three way (1:1:1) cross over clinical trial

Study Record Dates

• First Submitted: April 26, 2023
• First Posted: May 18, 2023
• Study Start: September 19, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data will be available approximately 12 months following the closure of the study.
• Access Criteria: Executed Data Use Agreement with Rush University Medical Center

Locations

US (1)