A Study of Oral Ibogaine in Opioid Withdrawal
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|ClinicalTrials.gov Identifier: NCT05029401|
Recruitment Status : Recruiting
First Posted : August 31, 2021
Last Update Posted : August 2, 2022
|Condition or disease||Intervention/treatment||Phase|
|Opiate Withdrawal Syndrome||Drug: DMX-1002 Drug: Placebo||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||116 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||
The initial Stage 1 (phase 1) design was an open label study. Following review of data from the first cohort in Stage 1, an additional 6 subjects will be recruited into Cohort 1 and the protocol has been amended to implement a multi-centre, single-blind placebo-controlled assessment of QTcF and individualized heart rate correction modeling of QTcI.
Following baseline evaluations each subject receives placebo (Day 1) followed by ibogaine (Day 2), serving as his or her own control. In addition, data is collected from the baseline assessments (Day -1) to assess QT/RR diurnal variability under normal conditions and in response to autonomic stimulus (i.e. postural changes).
Stage 2 (phase 2a) is a double-blind, placebo-controlled, parallel group design targeting opioid-dependent patients to receive a single dose of the DMX-1002 or placebo for medically supervised opioid withdrawal.
|Masking:||Double (Participant, Investigator)|
Stage 1 (phase 1) of the study is single-blind (participant blinded); patients receive one initial dose of placebo, followed by one dose of IMP on the next day, and thereby serve as their own controls.
Stage 2 (phase 2a) is double-blinded. Patients will be randomized to receive either the IMP or placebo as a single dose
|Official Title:||Ibogaine to Determine Maximum Tolerated Dose (MTD) or Treat-to-Target Dose (TTD) for the Evaluation of Efficacy and Safety|
|Actual Study Start Date :||April 1, 2021|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||October 2023|
Experimental: Single dose IMP (DMX-1002)
Stage 1 (single blind, placebo controlled): initial dose of placebo, followed by treatment at one of 4 ascending dose levels of IMP (3, 6, 9 or 12 mg/kg)
Stage 2 (blinded): MTD/TTD established in Stage 1 vs placebo (proof of concept)
Investigation of the safety, tolerability and pharmacokinetics (PK) in healthy volunteers (Stage 1 - single blind), and the efficacy, safety, tolerability and PK in opioid-dependent patients (Stage 2 - double blind)
Other Name: Ibogaine Hydrochloride
Matching placebo to the IMP (DMX-1002)
Other Name: Microcrystalline cellulose
Placebo Comparator: Matching Placebo
Placebo using capsules identical to the IMP (DMX-1002)
Matching placebo to the IMP (DMX-1002)
Other Name: Microcrystalline cellulose
- Stage 2 - Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) average score from Day 2 to Day 6 [ Time Frame: Day 2 to Day 6 ]The SOWS-Gossop is a 10-item questionnaire to evaluate opioid withdrawal symptom severity. Each item is scored on a 4-point scale. Higher scores indicate greater severity (total score range 0-40).
- Stage 2 - Subject completion status at Day 6 (key secondary endpoint) [ Time Frame: Day 6 ]Proportion of subjects who received study medication and completed the SOWS-Gossop assessment on Day 6
- Stage 2 - Objective Opiate Withdrawal Scale of Handelsman (OOWS Handelsman) average score from Day 2 to Day 6 [ Time Frame: Day 2 to Day 6 ]The OOWS-Handelsman is an interview and observation tool for assessing opioid withdrawal signs and symptoms. It contains 13 physically observable signs, rated present or absent, based on a timed period of observation of the subject by a rater. Higher scores indicate greater severity (total score range 0-13).
- Stage 2 - Subject completion status at Day 30 [ Time Frame: Day 30 ]Proportion of subjects who received study medication and completed the SOWS-Gossop assessment on Day 30
- Stage 2 - Time to drop-out through Day 30 [ Time Frame: Day 1 to Day 30 ]Time to drop-out
- Stage 2 - Daily subject-rated Visual Analog Scale for Efficacy (VAS-E) score from Day 2 to Day 6 and at Day 30 [ Time Frame: Day 2 to Day 6 and at Day 30 ]The VAS-E is a scale to quantify the state of craving a subject experienced in the previous 24 hours. The scale size is 100 mm, anchored on the left by "no craving at all" and anchored on the right by "strongest craving ever."
- Stage 2 - Clinician-rated daily Clinical Global Impression - Improvement (CGI-I) score from Day 2 to Day 6 [ Time Frame: Day 2 to Day 6 ]The CGI-I is a 7-point scale that requires the clinician to assess how much the subject's condition has improved or worsened from baseline. The ratings are: 1 - very much improved; 2 - much improved; 3 - minimally improved; 4 - no change; 5 - minimally worse; 6 - much worse; 7 - very much worse.
- Stage 2 - Hamilton Depression Rating Scale (HAM-D) score at Day 6 and Day 30 [ Time Frame: Day 6 and Day 30 ]The HAM-D is used to determine a subject's level of depression. The study uses the original 17-item scale. Higer scores indicate greater severity (total score range 0-52).
- Stage 2 - Proportion of subjects requiring clonidine for relief of withdrawal symptoms up to Day 6 [ Time Frame: Day 1 to Day 6 ]Proportion of subjects requiring clonidine for relief of withdrawal symptoms
- Safety (Stage 1 and Stage 2) - Frequency of treatment-emergent adverse events [ Time Frame: Day 1 to Day 30 ]Number of subjects with treatment-emergent adverse events
- Safety (Stage 1 and Stage 2) - number of subjects with abnormal electrocardiograms (ECG) [ Time Frame: Day 1 to Day 30 ]12-Lead ECG including heart rate (HR), QT interval corrected for HR according to Fridericia (QTcF), Individually corrected QTc interval (QTcI), HR-corrected J to T-peak interval (JTpc), PR interval, and QRS interval
- Safety (Stage 1 and Stage 2) - number of subjects with new magnetic resonance imaging (MRI) findings (in the presence of ataxia greater than 24 hours post-dose) [ Time Frame: Day 2 ]MRI of the brain
- Safety (Stage 1 and Stage 2) - number of subjects with abnormal neurological function [ Time Frame: Day 2 to Day 6 ]Neurological function
- Safety (Stage 1 and Stage 2) - number of subjects with abnormal Scale for the Assessment and Rating of Ataxia (SARA) scores [ Time Frame: Day 2 ]The SARA is a tool for assessing ataxia. It includes 8 items related to gait, stance, sitting, speech, finger-chase test, nose-finger test, fast alternating movements and heel-shin test. Total scores range from 0 (no ataxia) to 40 (most severe ataxia).
- Safety (Stage 2) - number of subjects with newly emerging suicidal ideation or behavior [ Time Frame: Day 6 and Day 30 ]Suicidality is assessed by means of the Columbia Suicide Severity Rating Scale (C-SSRS). It contains 6 "yes" or "no" questions (Q1: wish to be dead; Q2: non-specific suicidal thoughts; Q3-5: more specific suicidal thoughts and intent to act; Q6: suicidal behavior). An answer of "yes" to any of the six questions may indicate a need for referral to a trained mental health professional and an answer of "yes" to questions 4, 5 or 6 indicate high-risk.
- Pharmacokinetics (Stage 1 and Stage 2) - maximum whole blood and plasma concentrations [Cmax] of ibogaine and noribogaine [ Time Frame: 0.5 hours pre-dose up to 120 hours post-dose (Day 6) ]Whole blood and plasma concentrations
- Pharmacokinetics (Stage 1 and Stage 2) - time to reach Cmax [Tmax] for ibogaine and noribogaine [ Time Frame: 0.5 hours pre-dose up to 120 hours post-dose (Day 6) ]Tmax
- Pharmacokinetics (Stage 1 and Stage 2) - area under the concentration-time curve up to the last measurable time point (AUC0-T) for ibogaine and noribogaine [ Time Frame: 0.5 hours pre-dose up to 120 hours post-dose (Day 6) ]AUC0-T
- Pharmacokinetics (Stage 1 and Stage 2) - apparent elimination half-life (T-half) of ibogaine and noribogaine [ Time Frame: 0.5 hours pre-dose up to 120 hours post-dose (Day 6) ]T-half
- Pharmacokinetics (Stage 1) - renal clearance (CLr) of ibogaine [ Time Frame: 0.5 hours pre-dose up to 120 hours post-dose (Day 6) ]CLr
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05029401
|Contact: D Mash, PhD||+1 786 firstname.lastname@example.org|
|Contact: Project Manageremail@example.com|
|MAC Clinical Research Manchester (Early Phase Unit), Neuroscience Centre of Excellence||Active, not recruiting|
|Manchester, Greater Mancherster, United Kingdom, M13 9NQ|
|Hammersmith Medicines Research (HMR) Limited||Recruiting|
|London, United Kingdom, NW10 7EW|
|Contact: Project Manager +44 208 9614130 firstname.lastname@example.org|
|Principal Investigator: Takahiro Yamamoto, MD|