Single Ascending Doses of Kratom in Healthy Nondependent Adults With Opioid Experience

Inclusion Criteria

• Provision of signed and dated informed consent form (ICF)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Healthy adult male or female
• Current nondependent, polydrug recreational user who has used opioid drugs for recreational (nontherapeutic) purposes (i.e., for psychoactive effects) and has a history of recreational use of at least 2 or more of any of the perception-altering (e.g., lysergic acid diethylamide [LSD], kratom, cannabis, dronabinol, ketamine, phencyclidine [PCP], dextromethorphan, 3,4 methylenedioxymethamphetamine [MDMA], mescaline, psilocybin, tryptamine derivatives or ring-substituted amphetamines with perception altering effects) or stimulant (e.g., cocaine, amphetamine, methamphetamine, methylphenidate, methcathinone, and other synthetic cathinones) drugs
• If male, meets one of the following criteria:
• Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from study drug administration to at least 90 days after study drug administration. An acceptable method of contraception includes one of the following:
• Abstinence from heterosexual intercourse
• Double-barrier method (e.g., male condom with spermicide or male condom with a vaginal spermicide [gel, foam, or suppository]) Or
• Is unable to procreate; defined as surgically sterile (i.e., has undergone a vasectomy at least 180 days prior to study drug administration)
• If female, meets one of the following criteria:
• Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:

a1. Abstinence from heterosexual intercourse from the Screening visit through to at least 30 days after study drug administration

a2. One of the following contraceptive methods, used from at least 28 days prior to the Screening visit through to at least 30 days after study drug administration:

• Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, or transdermal patch)
• Intrauterine device (with or without hormones)
• Male partner vasectomized at least 6 months prior to the Screening visit

a3. One of the following double-barrier contraceptive methods, used from the Screening visit through to at least 30 days study drug administration:

• Male condom plus spermicide
• Diaphragm plus spermicide
• Cervical cap plus spermicide
• Is of non-childbearing potential, defined as surgically sterile (i.e., has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation), or is in a postmenopausal state (i.e., at least 1 year without menses without an alternative medical condition prior to the Screening visit and follicle stimulating hormone levels ≥ 40 mIU/mL at Screening)
• Body mass index (BMI) within 18.0 kg/m2 to 34.0 kg/m2, inclusively at Screening
• Minimum weight of 50.0 kg at Screening
• Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs, oxygen saturation [SpO2], and respiratory rate) and/or ECG, as determined by an Investigator

Exclusion Criteria

• Difficulty swallowing capsules
• Female who is lactating
• Female who is pregnant according to the pregnancy test at Screening or prior to study drug administration
• Male with female partner who is pregnant, lactating, or planning to become pregnant during this study or within 90 days after study drug administration
• History of significant hypersensitivity to kratom or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
• Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability with the exception of cholecystectomy that is permitted at the discretion of an Investigato