Pharmacokinetic in Normal Population
Conditions
Keywords
Tafenoquine, CYP2D6, Pharmacokinetic
Brief summary
The goal of this clinical trial is to learn how people's different genetic makeups affects how their bodies convert the FDA approved drug ARAKODA (tafenoquine) to its active form. Tafenoquine is a drug that is taken to prevent malaria for people traveling to areas where there is malaria. This trial will be in healthy participants age 18-65.
Detailed description
This trial will explore the how different CYP450 2D6 phenotypes metabolize a single 300mg dose of tafenoquine. Pharmacokinetic (PK) blood and urine samples, and research samples will be obtained at specific timepoints during the 2-month study.
Interventions
Single, 300mg dose
Sponsors
State University of New York - Upstate Medical University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18-65 at the time of consent, weighing between 132 and 250 pounds 2. Ability and willingness to sign informed consent 3. Available for the study period 4. Willing to use contraception for the duration of the study 5. Agree not to take over the counter antioxidants, vitamin C or vitamin E, 2 weeks prior to dosing and 7 days post dosing
Exclusion criteria
1. Women: positive urine pregnancy test at screening or day of dosing 2. Women who are lactating or intend to become pregnant during the study period. 3. Acute or chronic clinically significant hematologic, pulmonary, cardiovascular, hepatic, or renal functional abnormality as determined by medical history, physical examination or laboratory screening. 4. History of allergic reaction to tafenoquine or primaquine. 5. Scheduled receipt of any vaccine 1 week prior to or after 4 weeks tafenoquine dosing. Routine COVID and influenza vaccination will be allowed outside of this timeframe. 6. Currently taking metformin, dofeltilide or other medication with known multidrug and toxin extrusion enzyme (MATE) metabolism. 7. Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy. 8. Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the participant from participating in the study. 9. Participants with hemoglobin, Creatinine, BUN, and Albumin of grade 2 or greater. Participants with eGFR \<90mL/min/1.73m2; ALT \>1.5x ULN, or AST \>1.5x ULN. Any exclusionary lab abnormality may be repeated once. If a repeat screening blood test is performed, only the result of the second test will be reviewed and used to determine eligibility. 10. Positive HIV, hepatitis B surface antigen or hepatitis C. 11. G6PD result not normal or \< 70% activity 12. Significant screening physical examination abnormalities or chronic medical condition that in the opinion of the investigator may impact participant safety, including BMI \> 35kg/m2 13. Participation (active or follow-up phase) or planned participation in another vaccine, or drug, in the 4 weeks prior to or during the trial 14. Beliefs that bar the administration of blood products or transfusions 15. Clinician discretion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Tafenoquine levels in blood over time | Pre-dose, 4, 8, 12, and 24 hours (Day 2) and Days, 3, 4, 5, 6, 7, 8, 15, 22, 29, and 57. |
| Tafenoquine levels in urine over time | Pre-dose, total volume collected between 0-4, 4-8, 8-12, 12-24 hours and then single void collections on Days 3, 4, 5, 6, 7, 8, 15, 22, 29, 57. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Methemoglobin Levels | Pre-dose, 4, 8, 12, and 24 hours (Day 2) and Days, 3, 4, 5, 6, 7, 8, 15, 22, 29, and 57 | Methemoglobin Levels at defined PK timepoints |
| Laboratory abnormalities | Pre-dose, Day 4 and 15 | Complete Blood Count and reticulocyte count |
| Adverse Events | From Day 1 to Day 29 | — |
| Serious Adverse Events | Day 1 to Day 57 | — |
Countries
United States
Contacts
CONTACTKeely Terrillion
PRINCIPAL_INVESTIGATORMichele Spring, MD
State University of New York - Upstate Medical University
Outcome results
None listed