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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 : September 5, 2021
Sponsor:
Collaborators:
MAC Clinical Research
ERT: Clinical Trial Technology Solutions
Information provided by (Responsible Party):
DemeRx IB, Inc.

Tracking Information
First Submitted Date  ICMJE May 13, 2021
First Posted Date  ICMJE August 31, 2021
Last Update Posted Date September 5, 2021
Actual Study Start Date  ICMJE April 1, 2021
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 31, 2021)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: August 30, 2021)
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 (and at Day 30) ]
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 31, 2021)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2021)
  • Stage 2 - Subject completion status at Day 6 (key secondary endpoint) [ Time Frame: Day 1 to 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 (and at Day 30) ]
    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 1 to 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 1 to 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
Current Other Pre-specified Outcome Measures
 (submitted: August 31, 2021)
  • 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), 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
Original Other Pre-specified Outcome Measures
 (submitted: August 30, 2021)
  • 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), 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 1 ]
    MRI of the brain
  • Safety (Stage 1 and Stage 2) - number of subjects with abnormal neurological function [ Time Frame: Day 1 ]
    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 1 ]
    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 1 to 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
 
Descriptive Information
Brief Title  ICMJE A Study of Oral Ibogaine in Opioid Withdrawal
Official Title  ICMJE Ibogaine to Determine Maximum Tolerated Dose (MTD) or Treat-to-Target Dose (TTD) for the Evaluation of Efficacy and Safety
Brief Summary Study DMX-IB 201 is a Phase 1/2a study of ibogaine consisting of an initial single ascending dose escalation stage to determine the maximum tolerated dose (MTD) or treat-to-target dose (TTD) in healthy volunteers, followed by a randomized, double-blind, placebo-controlled proof of concept stage to demonstrate the efficacy, safety and tolerability of the selected dose in opioid-dependent patients who seek medically supervised opioid withdrawal
Detailed Description Detailed description restricted as elements of this trial are part of a Phase 1 clinical trial.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Stage 1 (phase 1) is an open-label design targeting healthy volunteers who will be enrolled into 4 separate ascending dose cohorts to receive a single dose of the IMP (DMX-1002).

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)
Masking Description:
Stage 1 (phase 1) of the study is open-label. Stage 2 (phase 2a) is double-blinded. Patients will be randomized to receive either the IMP or placebo as a single dose
Primary Purpose: Treatment
Condition  ICMJE Opiate Withdrawal Syndrome
Intervention  ICMJE
  • Drug: DMX-1002
    Investigation of the safety, tolerability and pharmacokinetics (PK) in healthy volunteers (Stage 1 - open-label), and the efficacy, safety, tolerability and PK in opioid-dependent patients (Stage 2 - blinded)
    Other Name: Ibogaine Hydrochloride
  • Drug: Placebo
    Matching placebo to the IMP (DMX-1002) for Stage 2 (phase 2 a) only
    Other Name: Microcrystalline cellulose
Study Arms  ICMJE
  • Experimental: Single dose IMP (DMX-1002)

    Stage 1 (open label): treatment at one of 4 ascending dose levels (3, 6, 9 or 12 mg/kg)

    Stage 2 (blinded): MTD/TTD established in Stage 1 vs placebo (proof of concept)

    Interventions:
    • Drug: DMX-1002
    • Drug: Placebo
  • Placebo Comparator: Matching Placebo
    Placebo using capsules identical to the IMP (DMX-1002)
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 30, 2021)
110
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2023
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Important Inclusion Criteria for both Stages 1 and 2:

  • Males and females between 18 years and 55 years of age.
  • For Stage 1, healthy volunteers (who may be recreational opioid users but present without withdrawal symptoms (COWS score ≤ 2) on Day 1, prior to dosing).
  • For Stage 2, opioid-dependent subjects (DSM-IV) seeking medically supervised opioid withdrawal and presenting with an OOWS score ≥ 5 on Day 1, prior to dosing.
  • Self-report of at least 1 prior positive hallucinogen drug experience that included a meaningful altered state of consciousness. Hallucinogenic substances can include psilocybin, LSD, MDMA or other classic hallucinogens.
  • Females that are not of child-bearing potential as defined within the protocol.
  • Males who agree to use 1 of the acceptable contraceptive regiments and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration or who are unable to procreate (as defined within the protocol).
  • For Stage 1, negative urine tests for drugs of abuse (opiates, benzodiazepines, amphetamines, cannabinoids, cocaine, barbiturates, and phencyclidine), and CNS (central nervous system) prescription drugs (SSRIs [selective serotonin reuptake inhibitors], SNRIs [serotonin-norepinephrine reuptake inhibitors], mood stabilizers) both at screening and within approximately 7 days prior to dosing, and negative breath alcohol test at Day -1.
  • For Stage 2, negative blood and urine tests for methadone, buprenorphine, mitragynine, non-opioid drugs of abuse (benzodiazepines, amphetamines, cannabinoids, cocaine, barbiturates, and phencyclidine), and CNS prescription drugs (SSRIs, SNRIs, mood stabilizers) both at screening and within approximately 7 days prior to dosing, and negative breath alcohol test at Day -1.
  • Negative serology test result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C virus antibody at Screening and COVID-19 at Screening and Day -1.
  • Willing to not consume citrus fruits (such as grapefruit, Seville oranges) and/or citrus fruit products throughout the study until Day 6.
  • Willing to refrain from taking any prescription and non-prescription drugs, with the exception of hormone replacement therapy but including herbal and nutritional supplements within 2 weeks prior to Day 1 and throughout the study until Day 6.
  • CYP2D6 genotype that demonstrates gene variants of fast or intermediate metabolism (i.e. not ultra-rapid or poor).

Important Exclusion Criteria for both Stages 1 and 2:

  • Current diagnosis of opioid or other substance dependence (except caffeine) according to DSM-IV or DSM-5 definitions (Stage 1 only).
  • Any history of seizure or convulsion, including febrile convulsion in childhood or as an adult.
  • History of chronic or frequent migraines.
  • Current or recent (≤1 year) history of significant alcohol abuse (>3 units per day on a regular basis)
  • For Stage 1, drug dependency disorder.
  • For Stage 2, polydrug abuse or dependency within the past 3 years other than opioids, caffeine, and/or nicotine.
  • Personal history or presence of primary psychotic disorder (including substance-induced or due to a medical condition), bipolar affective disorder Type I or Type II, or schizophrenia (not including non-psychotic, clinically stable disorders such as depression or anxiety).
  • First or second-degree family history of primary psychotic disorder, bipolar affective disorder Type I or Type II, or schizophrenia.
  • Showing suicidal tendency as per the Columbia Suicide Severity Rating Scale (C-SSRS).
  • Any prior use of ibogaine, noribogaine or other chemically related substances or any allergy or intolerance to excipients in the ibogaine capsules.
  • History or presence of clinically significant cardiovascular disease including angina, myocardial infarction, coronary artery disease, heart failure, arrhythmias, endocarditis, syncope of unknown origin, or any other condition that, in the opinion of the investigator, may be associated with a higher risk of arrhythmias.
  • History or presence at screening (12-lead ECG and 24-hour Holter monitoring) or Day 1 (12-lead ECG) of an ECG that (1) shows QTcF interval duration >420 ms, PR interval duration >210 ms, or QRS interval duration >120 ms, obtained as an average from 3 ECG recordings, taken at least 1 minute apart after at least 10 minutes of quiet rest in the supine position; (2) shows bigeminy, trigeminy or couplets; or (3) shows, in the opinion of the investigator, any other clinically significant abnormality.
  • History or family history of prolonged QT interval.
  • Orthostatic hypotension or uncontrolled hypertension as characterized by sustained systolic elevation to ≥160 mmHg and/or diastolic elevation to ≥100 mmHg.
  • Subjects with a resting heart rate of <60 bpm on the ECG at screening.
  • Use of any prescription drugs (with the exception of hormone replacement therapy) in the 28 days prior to the first study drug administration, that are known to inhibit or induce CYP2D6 or to cause QT prolongation or, in the opinion of the investigator, would put into question the status of the participant as healthy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: M Luz +1 786 3473500 mluz@demerx.com
Contact: D Mash +1 786 3473500 dmash@demerx.com
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05029401
Other Study ID Numbers  ICMJE DMX-IB-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party DemeRx IB, Inc.
Study Sponsor  ICMJE DemeRx IB, Inc.
Collaborators  ICMJE
  • MAC Clinical Research
  • ERT: Clinical Trial Technology Solutions
Investigators  ICMJE Not Provided
PRS Account DemeRx IB, Inc.
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP