Clinical TrialOpioid Use Disorder (OUD)PlaceboCompleted

A Study of Oral Ibogaine in Opioid Withdrawal

Phase I/2a randomized study (n=116) with single-ascending oral ibogaine doses (3–12 mg/kg) in healthy volunteers followed by a double-blind, placebo-controlled single-dose proof-of-concept in opioid-dependent patients for medically supervised opioid withdrawal.

Target Enrollment
116 participants
Study Type
Phase I/II interventional
Design
Randomized, double Blind

Detailed Description

Stage 1 is a single-blind, within-subject assessment in healthy volunteers using placebo (Day 1) then ibogaine (Day 2) to evaluate safety, tolerability, PK and to establish an MTD/TTD via single-ascending doses (3, 6, 9, 12 mg/kg).

Stage 2 is a randomized, double-blind, parallel-group proof-of-concept in opioid-dependent patients comparing the selected DMX-1002 dose to matching placebo for safety, tolerability and efficacy during medically supervised opioid withdrawal.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Study Arms & Interventions

DMX-1002

experimental

Single ascending dose ibogaine (DMX-1002) in Stage 1; selected dose vs placebo in Stage 2.

Interventions

  • Compound3 - 12 mg/kg
    via Oral• single dose• 1 doses total

    Single-ascending doses 3 → 6 → 9 → 12 mg/kg of ibogaine HCl (DMX-1002); starting dose 3 mg/kg; single administration per stage.

Placebo

inactive

Matching capsule placebo used in within-subject Stage 1 and parallel Stage 2.

Interventions

  • Placebo
    via Oral• single dose

    Matching microcrystalline cellulose placebo capsules.

Participants

Ages
18 – 55
Sexes
Male & Female

Inclusion Criteria

  • 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 regimens 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 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).

Exclusion Criteria

  • 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.

Study Details

  • Status
    Completed
  • Phase
    Phase IPhase II
  • Type
    interventional
  • Design
    Randomizeddouble Blind
  • Target Enrollment116 participants
  • Timeline
    Start: 2021-04-01
    End: 2023-08-10
  • Compound
    Placebo
  • Topic
    Opioid Use Disorder (OUD)

Locations

MAC Clinical Research Manchester (Early Phase Unit), Neuroscience Centre of Excellence — Manchester, Greater Mancherster, United Kingdom
Hammersmith Medicines Research (HMR) Limited — London, United Kingdom

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