Ignite Creation Date:
2024-05-19 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06419985
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-17
First Post:
2024-05-06
Brief Title:
Ketamine HCl Prolonged Release Oral Tablets for CRPS
Sponsor:
University of Southern California
Organization:
University of Southern California
Study Overview
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
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Additionally this trial will explore the feasibility of the trial design through dosing compliance clinical instruments and efficacy signals
Detailed 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 33 participants each that are assigned escalating dose levels of oral Ketamine HCl PR 1 tablet40mg
The daily dose of Ketamine PR for the 3 cohort is as follows
Cohort 1 is 80 mgday 1 tablets of 40mg twice a day Cohort 2 is 160 mgday 2 tablets of 40mg twice a day Cohort 3 is 240 mgday 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
There are 3 cohorts of 33 participants each that are assigned escalating dose levels of oral Ketamine HCl PR 1 tablet40mg
The daily dose of Ketamine PR for the 3 cohort is as follows
Cohort 1 is 80 mgday 1 tablets of 40mg twice a day Cohort 2 is 160 mgday 2 tablets of 40mg twice a day Cohort 3 is 240 mgday 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None