Evaluating a Potential Pharmacokinetic Kratom-oxycodone Interaction Concurrent With Clinical Endpoints

NCT05846451 | Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 19633U54AT008909
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to investigate whether the botanical product kratom affects how the body processes the opioid drug oxycodone. The main research questions to be answered are two-fold:

• Kratom (as a tea)
• A single dose of oxycodone (as a tablet)
• Kratom tea and a single dose of oxycodone
• Kratom tea for four days, then kratom tea and a single dose of oxycodone

Conditions

Herbal Interaction

Keywords

pharmacokinetic; pharmacokinetics; pharmacodynamic; pharmacodynamics; kratom; oxycodone; natural product; botanical product; natural product-drug interaction; mitragynine

Outcome Measures

Primary Outcomes (1)

• Oxycodone area under the concentration vs. time curve (AUC) ratio (presence to absence of kratom)

  Ratio of the AUC of oxycodone in the presence to absence of kratom.

  0-24 hours

Secondary Outcomes (3)

• Area under the pupil diameter (effect) vs. time curve (AUEC) ratio

  0-24 hours

• Oxycodone maximum plasma concentration (Cmax) ratio (presence to absence of kratom)

  0-24 hours

• Oxycodone half-life ratio (presence to absence of kratom)

  0-24 hours

Study Arms (4)

Arm 1

EXPERIMENTAL

Sixteen non-naive\* participants (8 males, 8 females) will be administered a single low dose (2 g) of a well-characterized kratom product by mouth as a tea. Pupil diameter will be measured from 0-12 hours. A washout of at least 10 days will separate Arms 1 and 2. \*Non-naive subjects are defined as intermittent users who consume 2-8 g kratom at least once per month but no more than three times daily within the last six months prior to screening and are willing to abstain for several weeks

Dietary Supplement: Kratom

Arm 2

ACTIVE COMPARATOR

The same 16 participants will be administered a single low dose (10 mg) of immediate-release oxycodone by mouth as a tablet. Plasma, pupil diameter measurements, and urine will be collected from 0-24 hours. A washout of at least 2 days will separate Arms 2 and 3.

Drug: Oxycodone

Arm 3

EXPERIMENTAL

The same 16 participants will be administered a single low dose (2 g) of kratom as a tea. After 15 minutes, the subjects will be administered a single low dose (10 mg) of oxycodone as a tablet by mouth. Plasma, pupil diameter measurements, and urine will be collected from 0-24 hours. A washout of at least 10 days will separate Arms 3 and 4.

Dietary Supplement: Kratom; Drug: Oxycodone

Arm 4

EXPERIMENTAL

The same 16 participants will self-administer a single low dose (2 g) of kratom as a tea once daily at home. On the fifth day, subjects will return to the research setting, where they will be administered a single low dose (2 g) of kratom, followed 15 minutes later by a single low dose (10 mg) of oxycodone by mouth. Plasma, pupil diameter measurements, and urine will be collected from 0-24 hours.

Dietary Supplement: Kratom; Drug: Oxycodone

Interventions

Kratom DIETARY_SUPPLEMENT

Kratom (Moon Kratom Yellow Indonesian, lot 51) is supplied as a dry leaf powder in clear plastic bags, each weighing 5 kg. Two grams of kratom dry leaf powder will be stirred into 240 mL of hot water to make a tea. The tea will be cooled to 50 degrees Celsius before administration. Participants will drink the tea within 15 minutes.

Arm 1; Arm 3; Arm 4

Oxycodone DRUG

Immediate-release oral tablet, 10 mg

Arm 2; Arm 3; Arm 4

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females, aged from 21-45 years and healthy
• Body weight between 130 and 250 pounds (60-115 kg) and body mass index between 19 and 30
• Not taking any medications (prescription and non-prescription) or dietary supplements/botanical products known to alter the pharmacokinetics of either oxycodone or kratom
• Willing to abstain from consuming dietary supplements/botanical products and fruit juices for several weeks
• Willing to abstain from cannabis/marijuana, hemp, and THC- and/or CBD-containing products for several weeks
• Willing to abstain from consuming caffeinated beverages or other caffeine-containing products the evening before and morning of any inpatient visit
• Willing to abstain from consuming alcoholic beverages for one day prior to any inpatient visit
• Willing to use an additional method of contraception that does not include oral contraceptive pills, patches, or other hormonal methods (such as abstinence, copper IUD, or condoms)
• Have consumed kratom previously and tolerated it well without any unpleasant effects
• Willing to abstain from kratom for several weeks
• Have consumed any opioid previously and tolerated it well without any unpleasant effects or addiction
• 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
• Geographically located within a 40-mile radius of Spokane and have the time to participate

You may not qualify if:

• Males and females under the age of 21 or over the age of 45
• People who weigh less than 130 pounds or more than 250 pounds
• People with a body mass index less than 19 or greater than 30
• Any current major illness or chronic illness including but not limited to kidney disease, hepatic disease, diabetes mellitus, hypertension, coronary artery disease, chronic obstructive pulmonary disease, cancer, or HIV/AIDS
• No previous exposure to kratom
• No previous exposure to an opioid
• History of anemia or any other significant hematologic disorder
• History of substance abuse, dependence, or 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)
• Pregnant or nursing
• History of allergy or intolerance to kratom, other opioids, or oxycodone
• Taking concomitant medications, both prescription and non-prescription (including dietary supplements/botanical products), known to alter the pharmacokinetics of kratom or oxycodone
• 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

Sponsors & Collaborators

• Washington State University: lead
• National Center for Complementary and Integrative Health (NCCIH): collaborator

Study Sites (1)

Washington State University College of Pharmacy and Pharmaceutical Sciences

Spokane, Washington, 99202, United States

RECRUITING

MeSH Terms

Interventions

mitragynine; Oxycodone

Intervention Hierarchy (Ancestors)

Codeine; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Central Study Contacts

Mary Paine, PhD

CONTACT

509-358-7759; mary.paine@wsu.edu

Deena Hadi, BS

CONTACT

509-368-6692; deena.hadi@wsu.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 26, 2023
• First Posted: May 6, 2023
• Study Start: June 1, 2023
• Primary Completion: May 1, 2025
• Study Completion: May 1, 2025
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)