Clinical TrialHealthy VolunteersCompleted

Assessing the Pharmacokinetics and Drug Interaction Liability of Kratom, an Opioid-like Natural Product

Non-randomised, crossover Phase I study (n=15 actual) in healthy volunteers assessing the effect of a 2 g kratom tea on CYP3A4 (midazolam) and CYP2D6 (dextromethorphan) probe pharmacokinetics.

Target Enrollment
15 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

This healthy-volunteer crossover study evaluates whether a well-characterized kratom product (2 g oral tea) alters the pharmacokinetics of validated probe drugs for CYP3A4 (midazolam) and CYP2D6 (dextromethorphan).

Arm 1 administers kratom alone; Arm 2a gives the probe cocktail alone; Arm 2b gives kratom plus the probe cocktail, with a 7-day washout between relevant arms. Primary analyses will assess midazolam pharmacokinetics; secondary analyses include dextromethorphan and kratom constituent PK to inform PBPK modelling.

Study Arms & Interventions

Kratom only

experimental

Single low dose of well-characterized kratom administered as a tea to non-naïve users.

Interventions

  • Compound2 g
    via Oral• single dose• 1 doses total

    2 g dry leaf powder stirred into 240 mL hot water, cooled to 50°C, drink within 10 minutes.

Probe cocktail

experimental

Oral validated probe drugs to assess CYP2D6 and CYP3A4 activity (no kratom).

Interventions

  • Compound30 mg
    via Oral• single dose

    Dextromethorphan HBr: 2 × 15 mg liquid capsules (30 mg total).

  • Compound2.5 mg
    via Oral• single dose

    Midazolam HCl: 1.25 mL of 2 mg/mL syrup (2.5 mg total).

Kratom + cocktail

experimental

Kratom (2 g tea) given with the probe cocktail to assess interaction effects.

Interventions

  • Compound2 g
    via Oral• single dose

    Kratom tea as in Arm 1.

  • Compound30 mg
    via Oral• single dose

    Dextromethorphan HBr: 2 × 15 mg capsules.

  • Compound2.5 mg
    via Oral• single dose

    Midazolam HCl: 1.25 mL of 2 mg/mL syrup.

Participants

Ages
18 – 55
Sexes
Male & Female

Inclusion Criteria

  • Not taking any medications (prescription and non-prescription) or dietary/herbal supplements known to alter the pharmacokinetics of either study drug or kratom constituents
  • Willing to abstain from consuming dietary/herbal supplements, including kratom, and citrus juices for several weeks
  • Willing to abstain from consuming caffeinated beverages or other caffeine-containing products the evening before and morning of the first day of a study arm
  • Willing to abstain from consuming any alcoholic beverages for one day prior to any study day, during the 14-hour inpatient days, and for the 5 and/or 1 outpatient visit(s) following 14-hour visit
  • Willing to use an acceptable method of contraception that does not include oral contraceptive pills or patches (such as abstinence, copper IUD, condom)
  • Have the time to participate
  • Are non-naïve kratom users (intermittent users who are not trying to quit but willing to abstain for several weeks)
  • Carry a CYP2D6 genotype designated as having an intermediate, extensive, or ultra-extensive metabolizer phenotype
  • Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for the subject to comply with the requirements of the study

Exclusion Criteria

  • Men and women under the age of 18 or over the age of 55
  • Unwilling to abstain from kratom for several weeks
  • Any current major illness or chronic illness such as (but not limited to) kidney disease, hepatic disease, diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, cancer, or HIV/AIDS
  • History of anemia or any other significant hematologic disorder
  • History of drug or alcohol addiction or major psychiatric illness
  • A need for chronic opioid analgesics
  • Use of opioid analgesics 3 weeks prior to initiation of the study
  • An imminent likely need for opioid analgesics (e.g., planned dental or surgical procedure)
  • Female and pregnant or nursing
  • Have a history of allergy to dextromethorphan, midazolam, or related drugs
  • Have a history of intolerance or allergy to kratom or opioids
  • Taking concomitant medications, both prescription and non-prescription (including dietary supplements/herbal products), known to alter the pharmacokinetics of either study drug or kratom constituents
  • Carry a CYP2D6 genotype designated as having a poor metabolizer phenotype
  • Presence of a condition or abnormality that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data

Study Details

  • Status
    Completed
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment15 participants
  • Timeline
    Start: 2019-10-09
    End: 2022-08-31
  • Topic
    Healthy Volunteers

Locations

Washington State University College of Pharmacy and Pharmaceutical Sciences — Spokane, Washington, United States

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