A Study of Oral Ibogaine in Opioid Withdrawal

Ibogaine to Determine Maximum Tolerated Dose (MTD) or Treat-to-Target Dose (TTD) for the Evaluation of Efficacy and Safety

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 restricted as elements of this trial are part of a Phase 1 clinical trial.

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; recreational opioid use is allowed but not required for inclusion in the study.
• 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 alcohol test.
• 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 -2.
• 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, 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 -2 (12-lead ECG) of ECGs that (1) shows QTcF interval duration >420 ms (if QTcF >420 ms prior to dosing on Day 1, subjects need not be excluded provided QTcF was ≤ 420 at Screening and Day -2 and QTcF ≤ 440 on Day 1.), 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; or (2) ECG showing ventricular 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 cardiac channelopathy or sudden cardiac death.
• Orthostatic hypotension or uncontrolled hypertension as characterized by sustained systolic elevation to ≥160 mmHg and/or diastolic elevation to ≥100 mmHg at screening or Day -2.
• Subjects with an average resting heart rate of <50 bpm on the ECG at screening.
• Use of any prescription drugs 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.