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NCT Number: NCT07583407

Pharmacokinetics of Kava and Kratom Alone and in Combination

This study is being conducted to evaluate how different formulations of the Feel Free® Tonic containing Kava, Kratom, or a combination of both are processed in the body in healthy adults. The goal is to compare the pharmacokinetic profiles and safety of the combined herbal formulation with Kava alone and Kratom alone to better understand how these ingredients behave when taken individually versus together.

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Key information

Conditions

Herb-Herb Interaction Pharmacokinetics

Age range

21 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

ApexTrials

Guelph, Ontario, N1G 0B4, Canada

Location status: Recruiting

Location contact

Anthony Bier, MD, CCFP(EM)

PRINCIPAL_INVESTIGATOR

Katie Keene, H.BSc., CCRP

CONTACT

[email protected]

226-706-2545

About this study

This is a randomized, double blind, 3 period crossover pharmacokinetic study in healthy adults designed to compare the pharmacokinetic profiles of a combined Kava and Kratom formulation with Kava alone and Kratom alone under fasted conditions. The primary objective is to evaluate systemic exposure and key pharmacokinetic parameters following each treatment. Secondary objectives include the assessment of safety and tolerability across all study products. The investigational products are oral liquid herbal supplements containing Kava, Kratom, or a combination of both. The study will also explore subjective effects, well-being, mood, and participant perceptions of the study products. Each participant will receive all three treatments in a randomized sequence with washout periods between dosing, allowing within subject comparison of pharmacokinetic outcomes.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adults who are between 21 - 55 years of age (inclusive) at the time of signing the informed consent.
  • In otherwise good general health, as deemed by the investigator (based on review of medical history, vital signs, laboratory safety tests, and physical examination performed at screening and/or before the first dose of study product).
  • Are able to consume the study product completely within the specified timeframe.
  • Not currently using, defined as ≤ 3 uses in the past 3 months prior to Visit 2, any nicotine-containing products (patches, gums, vapes, etc.), kava products, and/or kratom products, and willing to abstain starting 14 days prior to Visit 2 and throughout the study.
  • Have a BMI range of 18.5 - 29.9 kg/m2 at screening and Visit 2.
  • Agree to follow the restrictions on concomitant treatments.
  • Agree to follow the restrictions on lifestyle.
  • Have maintained consistent dietary habits, including supplement intake, and lifestyle for the last 3 months before screening and agree to maintain them throughout the study (unless required per the restrictions)
  • Individuals with childbearing potential must agree to comply with the following requirements:
  • Have a negative pregnancy test at screening and on Day 1 of each treatment period prior to administration of study product.
  • Use a highly effective method of contraception from at least 14 days prior to the first dose through 30 days after the last dose of study product.
  • Individuals with the potential to impregnate others must agree to use a highly effective method of contraception, from at least 14 days prior to the first dose through 30 days after the last dose of study product.
  • Male-born participants must agree to abstain from sperm donation, and female-born participants must agree to abstain from ovum donation, from Screening through at least 30 days after the last dose of study product.
  • Agree to abstain from alcohol consumption for 48 hours prior to, and for the entire duration of, each treatment period.
  • Willing and able to agree to the requirements and restrictions of this study, be willing to give voluntary consent, be able to understand and read the questionnaires, and carry out all study-related procedures.
  • Must have suitable veins for repeated venipuncture.
  • Willing and able to attend video conference calls with study coordinators.
  • Agrees not to donate blood until 3 months after study completion.

Exclusion criteria

  • Individuals who are lactating, planning to become pregnant during the study, or pregnant as confirmed by a positive pregnancy test during study visits.
  • Have a known sensitivity, intolerability, or allergy to any of the study products, their excipients, or rescue medication.
  • Demonstrates a positive urine drug screen test for compounds listed in Table 8 4 at the Screening Visit or Visit 2, a positive urine cotinine test at the Screening Visit or Visit 2, or a positive breath alcohol test at Screening Visit or Visit 2.
  • Have abnormal respiratory rate (RR) or SpO2 measurements at Screening or Baseline at the discretion of the investigator.
  • Screening laboratory results showing liver enzyme levels [Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatase (ALP), Gamma-Glutamyl Transferase (GGT), total bilirubin] ≥ 2 times the upper limit of normal (ULN), or any other clinically significant abnormal safety laboratory values as per the Investigator's discretion.
  • Have hemoglobin below 135 g/L for males or 125 g/L for females, or hematocrit below 0.39 l/l for males or 0.33 l/l for females at screening.
  • Demonstrates a positive screen for HIV at screening.
  • Is currently enrolled in another clinical trial or has received/used an investigational product in another research study within 28 days before Visit 2.
  • Individuals with any abnormality, obstruction, or disorder of the gastrointestinal tract that may preclude swallowing (e.g., dysphagia) or impair gastrointestinal motility, digestion, or absorption (e.g., known intestinal malabsorption, celiac disease, inflammatory bowel disease [including Crohn's disease or ulcerative colitis], chronic pancreatitis, or steatorrhea). In addition, any history of gastrointestinal surgery or anatomical abnormality that, in the opinion of the Investigator, may affect the oral absorption of the study product.
  • Have been diagnosed with Type I/Type II diabetes or thyroid disease
  • High BP at the Screening Visit or Visit 2 (≥140 systolic or ≥90 diastolic mmHg)
  • Have low BP (<90 systolic or <60 diastolic mmHg) at Baseline unless deemed clinically insignificant by the investigator and the participant is asymptomatic.
  • Have a history of heart disease, blood-clotting disorders, renal or hepatic impairment/disease, liver injury or any clinically significant liver or kidney disorder, as determined by the Investigator.
  • Have known genetic polymorphisms of CYP450 enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2B6, and/or CYP3A4.
  • Individuals with active asthma or a history of clinically significant asthma exacerbation (i.e., requiring systemic corticosteroids, emergency department intervention, or hospitalization) within the past 12 months.
  • Individuals receiving treatment for, or who have been hospitalized in the last 12 months for, psychiatric disorders (e.g., Major Depressive Disorder, Bipolar I/II, Generalized Anxiety Disorder, Schizophrenia, or other psychotic disorders), particularly when the diagnosis is established using accepted gold-standard diagnostic methods (e.g., structured clinical interviews), or with complications such as suicidal ideation or behavior.
  • Have current use of medications, including psychiatric pharmacotherapy, that are predominantly metabolized via CYP enzymes (e.g., CYP3A4, CYP2D6, CYP1A2) and/or have CNS depressant or opioid-like effects, or act on central receptors such as μ- and δ-opioid, serotonergic 5-HT2A, post-synaptic alpha-2 adrenergic, or GABA receptors, where such treatment may create clinically significant pharmacokinetic or pharmacodynamic interactions with study treatments, including antidepressants, antipsychotics, mood stabilizers, anxiolytics, or benzodiazepines.
  • Have a history of cancer with recovery occurring within 5 years prior to the Screening visit, except for localized skin cancer without metastases (e.g., completely excised basal cell carcinoma or squamous cell carcinoma of the skin) or in situ cervical cancer (e.g., adequately treated carcinoma in situ of the cervix).
  • Reports significant blood loss or blood donation totalling between 101 mL to 449 mL of blood within 30 days before baseline or a blood donation of more than 450 mL within 90 days before Visit 2.
  • Reports donating plasma (e.g., plasmapheresis) within 15 days before Visit 2.
  • Major surgery in 3 months before screening or planned major surgery during the study.
  • History of alcohol or substance abuse (e.g., opioids, kratom) (including having been hospitalized for such an in-patient or out-patient intervention program).
  • Evidence of addictive tendency as indicated by an LDQ score ≥21.
  • Use of anxiolytic or sleep aids (natural health products or drugs) in the 4 weeks before Visit 2.
  • Currently consumes more than two (2) standard alcoholic beverages per day on average for 4 weeks.

Note: A standard alcoholic beverage is defined as 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of liquor.

  • Excessive caffeine intake, defined as habitual consumption of >500 mg per day.
  • Any other medical conditions, including active infections, or use of medications/supplements/therapies that, in the opinion of the investigator, may adversely affect the participant's ability to complete the study or its measures, pose a significant risk to the participant or compromise the quality of study data.

Treatment and study plan

Kava and Kratom Herbal Supplement

Dietary Supplement

Half- Strength Feel Free Classic Tonic (TP1)

Kava Herbal Supplement

Dietary Supplement

Kava Only Variant - Feel Free Tonic (TP2)

Kratom Herbal Supplement

Dietary Supplement

Kratom Only Variant - Feel Free Tonic (TP3)

Primary outcomes

  1. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Kavain

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    AUC0-24 for kavain following single-dose administration of Kava alone or combined Kava and Kratom

  2. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Dihydrokavain

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    AUC0-24 for dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

  3. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for Mitragynine

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    AUC0-24 for mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  4. Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) for 7-Hydroxymitragynine

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    AUC0-24 for 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

Secondary outcomes

  1. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for Kavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-72 for kavain following single-dose administration of Kava alone or combined Kava and Kratom

  2. Maximum Observed Plasma Concentration (Cmax) for Kavain

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

    Peak plasma concentration of kavain following single-dose administration of Kava alone or combined Kava and Kratom

  3. Time to Maximum Plasma Concentration (Tmax) for Kavain

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    Time to reach maximum observed plasma concentration of kavain following single-dose administration of Kava alone or combined Kava and Kratom

  4. Terminal Elimination Half-Life (T½) for Kavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Terminal elimination half-life of kavain following single-dose administration of Kava alone or combined Kava and Kratom

  5. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for Dihydrokavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-72 for dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

  6. Maximum Observed Plasma Concentration (Cmax) for Dihydrokavain

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

    Peak plasma concentration of dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

  7. Time to Maximum Plasma Concentration (Tmax) for Dihydrokavain

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    Time to reach maximum observed plasma concentration of dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

  8. Terminal Elimination Half-Life (T½) for Dihydrokavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Terminal elimination half-life of dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

  9. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for Mitragynine

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-72 for mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  10. Maximum Observed Plasma Concentration (Cmax) for Mitragynine

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

    Peak plasma concentration of mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  11. Time to Maximum Plasma Concentration (Tmax) for Mitragynine

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    Time to reach maximum observed plasma concentration of mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  12. Terminal Elimination Half-Life (T½) for Mitragynine

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Terminal elimination half-life of mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  13. Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC0-72) for 7-Hydroxymitragynine

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-72 for 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  14. Maximum Observed Plasma Concentration (Cmax) for 7-Hydroxymitragynine

    Time frame: Day 1 of each treatment period (0-12 hours post-dose)

    Peak plasma concentration of 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  15. Time to Maximum Plasma Concentration (Tmax) for 7-Hydroxymitragynine

    Time frame: Day 1 and Day 2 of each treatment period (0-24 hours post-dose)

    Time to reach maximum observed plasma concentration of 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  16. Terminal Elimination Half-Life (T½) for 7-Hydroxymitragynine

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Terminal elimination half-life of 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  17. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Kavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-∞ for kavain following single-dose administration of Kava alone or combined Kava and Kratom

  18. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Kavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Ratio of exposure from 0-24 hours relative to total exposure for kavain.

  19. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Dihydrokavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-∞ for Dihydrokavain following single-dose administration of Kava alone or combined Kava and Kratom

  20. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Dihydrokavain

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Ratio of exposure from 0-24 hours relative to total exposure for Dihydrokavain.

  21. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Mitragynine.

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-∞ for mitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  22. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for Mitragynine

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Ratio of exposure from 0-24 hours relative to total exposure for mitragynine.

  23. Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for 7-Hydroxymitragynine.

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    AUC0-∞ for 7-Hydroxymitragynine following single-dose administration of Kratom alone or combined Kava and Kratom

  24. Ratio of area under the plasma concentration from 0 to 24 Hours (AUC0-24) to area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) for 7-Hydroxymitragynine

    Time frame: Day 1 to Day 4 of each treatment period (0-72 hours post-dose)

    Ratio of exposure from 0-24 hours relative to total exposure for 7-Hydroxymitragynine.

  25. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Kavain

    Time frame: Day 14 of each treatment period

    AUC0-12,ss for Kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  26. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Kavain

    Time frame: Day 14 of each treatment period

    Cmax,ss for kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  27. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Kavain

    Time frame: Day 14 of each treatment period

    Tmax,ss of kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  28. Terminal Elimination Half-Life at Steady State (T½,ss) for Kavain

    Time frame: Day 14 of each treatment period

    T½,ss for kavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  29. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Kavain

    Time frame: Day 14 of each treatment period

    AUC0-∞,ss for kavain following multiple-day dosing administration of Kava alone or combined Kava and Kratom

  30. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for Kavain

    Time frame: Day 14 of each treatment period

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for kavain.

  31. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Dihydrokavain

    Time frame: Day 14 of each treatment period

    AUC0-12,ss for dihydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  32. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Dihydrokavain

    Time frame: Day 14 of each treatment period

    Cmax,ss for dyhydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  33. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Dihydrokavain

    Time frame: Day 14 of each treatment period

    Tmax,ss of dihydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  34. Terminal Elimination Half-Life at Steady State (T½,ss) for Dihydrokavain

    Time frame: Day 14 of each treatment period

    T½,ss for dihydrokavain following a multiple-day dosing of Kava alone or combined Kava and Kratom

  35. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Dihydrokavain

    Time frame: Day 14 of each treatment period

    AUC0-∞,ss for dihydrokavain following multiple-day dosing administration of Kava alone or combined Kava and Kratom

  36. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for Dihydrokavain

    Time frame: Day 14 of each treatment period

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for dihydrokavain.

  37. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for Mitragynine

    Time frame: Day 14 of each treatment period

    AUC0-12,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  38. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for Mitragynine

    Time frame: Day 14 of each treatment period

    Cmax,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  39. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for Mitragynine

    Time frame: Day 14 of each treatment period

    Tmax,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  40. Terminal Elimination Half-Life at Steady State (T½,ss) for Mitragynine

    Time frame: Day 14 of each treatment period

    T½,ss for mitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  41. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for Mitragynine

    Time frame: Day 14 of each treatment period

    AUC0-∞,ss for mitragynine following multiple-day dosing administration of Kratom alone or combined Kava and Kratom

  42. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for Mitragynine

    Time frame: Day 14 of each treatment period

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for mitragynine.

  43. Area under the curve at steady state from 0 to 12 hours (AUC0-12,ss) for 7-Hydroxymitragynine

    Time frame: Day 14 of each treatment period

    AUC0-12,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  44. Maximum Observed Plasma Concentration at steady state (Cmax,ss) for 7-Hydroxymitragynine

    Time frame: Day 14 of each treatment period

    Cmax,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  45. Time to Maximum Plasma Concentration at Steady State (Tmax,ss) for 7-Hydroxymitragynine

    Time frame: Day 14 of each treatment period

    Tmax,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  46. Terminal Elimination Half-Life at Steady State (T½,ss) for 7-Hydroxymitragynine

    Time frame: Day 14 of each treatment period

    T½,ss for 7-Hydroxymitragynine following a multiple-day dosing of Kratom alone or combined Kava and Kratom

  47. Area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞) for 7-Hydroxymitragynine

    Time frame: Day 14 of each treatment period

    AUC0-∞,ss for 7-Hydroxymitragynine following multiple-day dosing administration of Kratom alone or combined Kava and Kratom

  48. Ratio of area under the plasma concentration at steady state from 0 to 12 Hours (AUC0-12,ss) to area under the plasma concentration time curve extrapolated to infinity at steady state (AUC0-∞,ss) for 7-Hydroxymitragynine

    Time frame: Day 14 of each treatment period

    Ratio of exposure from 0-12 hours relative to total exposure at steady state for 7-Hydroxymitragynine.

Other outcomes

  1. Modified Drug Effects Questionnaire (DEQ)

    Time frame: Days 1 and 14 of each treatment period

    To assess the effect of TP on subjective drug effects compared to comparator. This non-validated questionnaire consists of 4 questions scored from 0 to 100, that assesses the participants subjective experience after consuming the TP.

  2. Overall Well Being, Health, and Pain

    Time frame: Pre-dose Day 1 to Pre-dose Days 7 and 14 of each treatment period

    To assess the effect of TP on overall well-being, health, and pain compared to comparator. This non-validated questionnaire consists of 4 questions scored from 0 to 100, that assesses overall quality of life with questions specifically on physical health and pain. Higher scores indicate better overall well-being, health, and pain.

  3. Ecological Momentary Assessment (EMA) Survey

    Time frame: Days 2, 4, 6, 8, 10, 12, and 14 of each treatment period

    To assess the effect of TP on mood compared to comparator. A non-validated questionnaire consisting of 13 questions assessing the participants emotional and mental/physical states they are feeling "right now." This questionnaire uses bipolar visual analogue scales in which participants how they feel "right now" on lines between two opposite feelings or physical sensations.

  4. Study Product Perception & Attitude Survey

    Time frame: Days 7 and 14 of each treatment period

    To assess the effect of TP on study product perceptions and attitudes compared to comparator. A non-validated questionnaire consisting of multiple items assessing participants' subjective experiences with the study product, including effects on daily functioning, energy, sleep, mood, mild stress/anxiety, focus, mild pain, muscle recovery, tolerability, and product quality. Items are scored on a 5#point Likert scale ranging from "Strongly Disagree" to "Strongly Agree." Higher scores indicate more favorable perceptions of the study product (except for the side effects item, where higher scores indicate greater perceived side effects).

  5. Appraisal of Effects Survey

    Time frame: Days 2, 4, 6, 8, 10, 12, and 14

    To assess participant-reported perceptions of the effects of the study product compared to comparator. A non-validated, self-administered questionnaire consisting of multiple items assessing participants' subjective experiences with the study product, including overall effect on how they feel, liking of the product, pain, muscle fatigue, mental focus/concentration, and calmness/stress. Items are scored using a 100-point visual analogue scale ranging from "Not at all" (0) to "Extremely" (100). Higher scores indicate greater perceived effects of the study product.

  6. Safety Assessments - Incidence of Treatment-Emergent Adverse Events

    Time frame: From first dose through follow-up visit

    Number and percentage of participants experiencing treatment-emergent adverse events from first dose through follow-up.

  7. Safety Assessment: Change in Subjective Opiate Withdrawal Scale (SOWS)

    Time frame: Day 1 and Day 14 of each treatment period

    To test the safety of TP by assessing the change in SOWS. This validated questionnaire is used to assess participants intensity of potential opioid withdrawal symptoms. Items are scored on a 5-point Likert scale ranging from 0 ('Not at all') to 4 ('Extremely'). Higher scores indicate higher potential withdrawal symptoms.

  8. Safety Assessment: Change in Clinical Opiate Withdrawal Scale (COWS)

    Time frame: Day 1 and Day 14 of each treatment period

    To test the safety of TP by assessing the change in COWS. This validated questionnaire is used to assess common signs and symptoms of opiate withdrawal. Items are scored from 0 to 48. Higher scores indicate higher withdrawal symptoms.

  9. Safety Assessments - Electrocardiogram (ECG)

    Time frame: Screening, and Day 1, and Day 14 of each treatment period

    To assess cardiac function based on the change in ECG intervals.

  10. Safety Assessments - Vitals (Heart Rate)

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

    Change in Heart Rate (beats per minute) from baseline to each study visit.

  11. Safety Assessments - Vitals (Blood Pressure)

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

    Change in Blood Pressure (mmHg) from baseline to each study visit.

  12. Safety Assessments - Vitals (Respiratory Rate)

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

    Change in Respiratory Rate (breaths per minute) from baseline to each study visit.

  13. Safety Assessments - Vitals (Oxygen Saturation)

    Time frame: Screening, and from Days 1, 2, 3, 4 and 14 of each treatment period

    Change in Oxygen Saturation (SpO2) from baseline to each study visit.

  14. Safety Assessments - Vitals (Body Temperature)

    Time frame: Screening, and from Day 1 to Day 14 of each treatment period

    Change in body temperature (°C) from baseline to each study visit.

  15. Safety Assessments - Weight (Change from Baseline)

    Time frame: Day 1 to Day 14 of each treatment period

    Change from baseline in body weight (kg)

  16. Safety Assessments - Body Mass Index (BMI - Change from Baseline)

    Time frame: Day 1 to Day 14 of each treatment period

    Change from baseline in body mass index (kg/m²)

  17. Safety Assessments - Height

    Time frame: Screening only

    Height (cm) measured at screening only used for calculating body mass index (kg/m²)

  18. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Hemoglobin)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in hemoglobin (g/L)

  19. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Hematocrit)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in hematocrit (%)

  20. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Red Blood Cell Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in red blood cell count (×10E^12/L).

  21. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Red Cell Distribution Width)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in red cell distribution width.

  22. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Corpuscular Volume)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in mean corpuscular volume (fL).

  23. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Corpuscular Hemoglobin)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in mean corpuscular hemoglobin (pg).

  24. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Corpuscular Hemoglobin Concentration)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in mean corpuscular hemoglobin concentration (g/L).

  25. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - White Blood Cell Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in white blood cell count (×10^9/L).

  26. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Neutrophil Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Neutrophil Count (×10^9/L).

  27. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Eosinophil Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Eosinophil Count (×10^9/L).

  28. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Basophil Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Basophil Count (×10^9/L).

  29. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Lymphocyte Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Lymphocyte Count (×10^9/L).

  30. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Monocyte Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Monocyte Count (×10^9/L).

  31. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Platelet Count)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Platelet Count (×10^9/L).

  32. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Mean Platelet Volume)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in mean platelet volume (fL)

  33. Safety Assessments - Laboratory Tests (Number of participants with abnormal Hematology values - Blood Smear Findings)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in blood smear findings.

  34. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Blood Urea Nitrogen)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in blood urea nitrogen (mmol/L).

  35. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Creatinine)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in creatinine (umol/L)

  36. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Estimated Glomerular Filtration Rate)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in estimated glomerular filtration rate (ml/min/1.7m^2).

  37. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Albumin)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in albumin (g/L).

  38. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Random Glucose)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in random glucose (mmol/L).

  39. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Fasting Glucose)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in fasting glucose (mmol/L).

  40. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Total Protein)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in total protein (g/L).

  41. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Sodium)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Sodium (mmol/L).

  42. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Potassium)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Potassium (mmol/L).

  43. Safety Assessments - Laboratory Tests (Number of participants with abnormal Clinical Chemistry values - Chloride)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Chloride (mmol/L).

  44. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Aspartate Transaminase)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Aspartate Transaminase (AST) in U/L.

  45. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Alanine Transaminase)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Alanine Transaminase (ALT) in mmol/L.

  46. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Gamma-Glutamyl Transferase)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Gamma-Glutamyl Transferase(GGT) in U/L.

  47. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Total Bilirubin)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Total Bilirubin in µmol/L.

  48. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Direct Bilirubin)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Direct Bilirubin in µmol/L.

  49. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Total Bile Acids)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Total Bile Acids in µmol/L.

  50. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - International Normalized Ratio)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in International Normalized Ratio (INR).

  51. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Glutamate dehydrogenase )

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Glutamate dehydrogenase (GLDH) in U/L.

  52. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Coproporphyrin-I)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Coproporphyrin-I (CP-I) concentration.

  53. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Coproporphyrin-III)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Coproporphyrin-I (CP-III) concentration.

  54. Safety Assessments - Laboratory Tests (Number of participants with abnormal Liver Function Test values - Alkaline Phosphatase)

    Time frame: Baseline to Day 14 of each treatment period

    To assess the safety of TP through the change from baseline to each study visit in Alkaline Phosphatase (ALP) in U/L.

Study contacts

Contact information is provided by the study sponsor or research team.

Ambreen Atif, MD

CONTACT

[email protected]

519-341-3367 ext. 129

Stephanie Recker

CONTACT

[email protected]

519-341-3367 ext. 109

Sponsors and collaborators

Lead sponsor

Botanic Tonics, LLC

Industry

Collaborators

  • Nutrasource Pharmaceutical and Nutraceutical Services, Inc.

Registry information

Official study title

A Randomized, Double-Blind, 3-Period Crossover, Pharmacokinetic Study in Healthy Adults to Compare Combined Kava and Kratom Supplementation With Kava or Kratom Alone Under Fasted Conditions

Important dates

Study start
2026
Primary completion
2026
Study completion
2026
First posted
May 13, 2026
Registry last updated
May 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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