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

Herbal Interaction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05846451
• Other study ID #: 19633
• Secondary ID: U54AT008909
• Status: Recruiting
• Phase: Early Phase 1
• Start date: June 1, 2023
• Est. completion date: May 1, 2025

Study information

• Verified date: December 2023
• Source: Washington State University
• Contact: Mary Paine, PhD
• Phone: 509-358-7759
• Email: mary.paine[@]wsu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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:

1. How does kratom affect the manner in which oxycodone is metabolized (broken down and removed) by the body?

2. Does kratom change the effects oxycodone exerts on the body?

Healthy adult participants will complete four study arms, during which they will be given the following:

• 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

Description:

The primary objective of this study is to evaluate the potential for kratom to precipitate a pharmacokinetic interaction with the common opioid and dual cytochrome P450 (CYP) 3A/CYP2D6 substrate oxycodone. A secondary objective is to evaluate a potential pharmacodynamic interaction by measuring pupil diameter, the most sensitive measure of central nervous system opioid effects. To evaluate these objectives, participants will complete four arms, during which they will be administered the following:

• Arm 1: a single low dose of kratom (by mouth, as a tea)

• Arm 2: a single low dose of immediate-release oxycodone (by mouth, as a tablet)

• Arm 3: a single low dose of kratom tea and a single low dose of oxycodone

• Arm 4: daily at-home self-administration of kratom tea for four days, followed immediately by a single low dose of kratom tea and a single low dose of oxycodone in the research setting

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

• History of sleep apnea

• Any prior use of amphetamines, benzodiazepines, cocaine, MDMA, opioids, PCP, or other drugs for recreational purposes

• Use of cannabis/marijuana, hemp, THC-containing products, CBD-containing products, or CBD within the last month

• Out-of-range clinical laboratory value that the study physician considers participation in the study a health risk

• Inability to speak, read, and understand English

Related Conditions & MeSH terms

• Herbal Interaction

Intervention

Dietary Supplement:
• Kratom
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.

Drug:
• Oxycodone
Immediate-release oral tablet, 10 mg

Locations

Country	Name	City	State
United States	Washington State University College of Pharmacy and Pharmaceutical Sciences	Spokane	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Washington State University	National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Area under the pupil diameter (effect) vs. time curve (AUEC) ratio	Ratio of AUEC in presence of oxycodone+kratom to oxycodone	0-24 hours
Secondary	Oxycodone maximum plasma concentration (Cmax) ratio (presence to absence of kratom)	Ratio of Cmax of oxycodone in the presence to absence of kratom.	0-24 hours
Secondary	Oxycodone half-life ratio (presence to absence of kratom)	Ratio of half-life of oxycodone in the presence to absence of kratom	0-24 hours