Ketamine HCl Prolonged Release Oral Tablets for CRPS

Complex Regional Pain Syndromes Clinical Trial

Official title: A Phase 2 Single-arm, Open Label Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of Ketamine HCl Prolonged Release Tablets in Participants With Complex Regional Pain Syndrome

Status Not yet recruiting

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of Ketamine HCl Prolonged Release (PR) tablets in participants with pain due to complex regional pain syndrome (CRPS).

Additionally, this trial will explore the feasibility of the trial design through dosing compliance, clinical instruments, and efficacy signals.

Clinical Trial Description

This study will enroll patients with history of CRPS (greater than 6 months) at a single academic medical institution in the United States. All participants will be informed about the study and potential risks and will provided written informed consents prior to undergoing any study-related procedures.

There are 3 cohorts of 3+3 participants each that are assigned escalating dose levels of oral Ketamine HCl PR (1 tablet=40mg).

The daily dose of Ketamine PR for the 3 cohort is as follows:

Cohort 1 is 80 mg/day (1 tablets of 40mg twice a day); Cohort 2 is 160 mg/day (2 tablets of 40mg twice a day); Cohort 3 is 240 mg/day (3 tablets of 40mg twice a day).

Each cohort consists of 1 sentinel participant that must complete Visit 4 before the other 2 participants are enrolled. If participants withdraw from the study before completing Cycle 1 for reasons other than a dose-limiting toxicity, additional participants will be enrolled to replace them, until at least 3 successful participants have completed Cohort 1. At this time a safety review will be conducted. If there are 2 or more DLT events observed in Cohort 1, the study will stop. If there is 1 Dose Limiting Toxicity (DLT) event observed, an additional 3 participants will be enrolled in Cohort 1. If there are 2 or more DLT events observed in the additional set of participants, the study will stop. If there is ≤ 1 DLT event observed in the additional set, enrollment will open for Cohort 2.

After at least 3 participants in Cohort 2 have completed Cycle 1, a safety review will be conducted to assess the safety and tolerability of the investigational product.

If there are 2 or more DLT events observed in Cohort 2, the Maximum Tolerated Dose (MTD) will become 80mg ketamine HCl PR per day and the study will open for general enrollment. If there is 1 Dose Limiting Toxicity (DLT) event observed, an additional 3 participants will be enrolled in Cohort 2. If there are 2 or more DLT events observed in the additional set of participants, the MTD will become 80mg ketamine HCl PR per day and the study will open for general enrollment. If there is ≤ 1 DLT event observed in the additional set, enrollment will open for Cohort 3.

After at least 3 participants in Cohort 3 have completed Cycle 1, a safety review will be conducted by the SRC to assess the safety and tolerability of the investigational product. If there are 2 or more DLT events observed in Cohort 3, the Maximum Tolerated Dose (MTD) will become 160mg ketamine HCl PR per day and the study will open for general enrollment. If there is 1 Dose Limiting Toxicity (DLT) event observed, an additional 3 participants will be enrolled in Cohort 3. If there are 2 or more DLT events observed in the additional set of participants, the MTD will become 160mg ketamine HCl PR per day and the study will open for general enrollment. If there is ≤ 1 DLT event observed in the additional set, the study will open for general enrollment where the MTD is 240mg ketamine HCl PR per day. If 0 DLT events are observed in Cohort 3, the study will open for general enrollment where the MTD is 240mg ketamine HCl PR per day.

Health status assessments including physical exams, blood work, urinalysis, EKG and questionnaires to assess quality of life and pain scale measurement will be conducted at the clinic visits. The participants will also keep a daily diary to record pain levels and any additional pain medication needed.

There will be a screening visit (day -28 to -7), clinic visits at day 1, week 2, week 4, week 8, and at the end of study (EOS) visit. There will be additional telemedicine visits at week 1, week 3 and at the safety followup visit approximately 4 weeks after the EOS visit.

Definition of Dose Limiting Toxicities (DLT):

Any of the following symptoms, if they interfere with the daily life of the participant, will be considered DLTs:

• General - sedation, impaired consciousness

• Head, Ear, Eyes, Nose, Throat - horizontal, vertical or rotary nystagmus, mydriasis, excessive salivation

• Cardiovascular - hypertension, tachycardia, palpitations, arrhythmias, chest pain

• Abdominal - abdominal pain, abdominal tenderness, nausea, vomiting

• Neurological - altered mental status (disorientation), paranoia, dysphoria, anxiety, confusion, slurred speech, dizziness, ataxia, dysarthria, trismus, muscular rigidity, psychomotor, psychomimetic, or acute dystonic reactions

• Genitourinary - lower urinary tract symptoms

• Trauma - a thorough examination for evidence of trauma is needed as injuries secondary to ketamine intoxication can occur due to the diminished perception of pain.

Any of the following symptoms will always be considered DLTs:

• Respiratory - respiratory depression, apnea, laryngospasm

• Cardiovascular - hypotension, bradycardia, myocardial infarction

• Neurological - seizure, stupor, coma ;

Related Conditions & MeSH terms

• Complex Regional Pain Syndromes
• Reflex Sympathetic Dystrophy
• Syndrome

• NCT number: NCT06419985
• Study type: Interventional
• Source: University of Southern California
• Contact: Diane McIntee, MS
• Phone: 626-372-0075
• Email: dmcintee99@gmail.com
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2024
• Completion date: July 2026