Skip to main content
OpenTrials
Completed

NCT Number: NCT05981365

Voxelotor CYP and Transporter Cocktail Interaction Study

This research study is examining multiple doses of voxelotor (a study drug intended for treatment of sickle cell disease) and how it interacts with additional substrates (substrates are drugs or other substances that are metabolized by cytochrome enzymes. The substrates used in this study are FDA approved medications). The study will help to determine the safety and tolerability of the study drugs taken together, as well as the pharmacokinetics (PK) on how your body processes and responds to the combination of the study drug and substrates. Although these drugs are FDA approved, their use in this study is experimental.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

ICON Early Phase Services, LLC

San Antonio, Texas, 78209, United States

About this study

This is an open-label, fixed-sequence, 2-period evaluation study. This means the study doctor and participants in the study will know what study drugs they are taking. There will be approximately 46 healthy male and female participants between the ages of 18 - 55. There will be two parts of the study: parts A and B.

Part A will consist of 26 healthy male and female participants (at least 20% African American). For Part A, participant involvement is expected to last approximately 81 days, including a 33-day screening period and a 48-day on study period (consisting of 2 study treatment periods, a washout period lasting 7 to 14 days, and the Follow-up visit).

Part B will consist of 20 healthy male and female participants (at least 20% African American). For Part B, participant involvement is expected to last approximately 68 days, including a 33-day screening period and a 35-day on study period (consisting of 2 study treatment periods, a washout period lasting 7 to 14 days, and the Follow-up visit).

You will only be allowed to be in one part of the study.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • 1. Males or females ≥ 18 and ≤ 55 years of age inclusive, at the time of signing the informed consent.
  • No clinically significant findings as assessed by review of medical and surgical history, vital signs assessments, 12-lead electrocardiograms (ECG), physical examination, and clinical laboratory evaluations conducted at screening and day of admission. A single repeat measurement/test may be performed to confirm eligibility based upon initial vital signs, ECG, or clinical laboratory tests abnormalities.
  • Body mass Index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2, and body weight ≥ 50 kg at screening and Period 1 Day -1. BMI = weight (kg)/(height [m])2
  • Females of childbearing potential must agree to use a highly effective method of contraception or practice abstinence from 2 weeks prior to study start through 30 days after the last dose of study drug. A highly effective method of contraception is defined as one that results in a low documented failure rate when used consistently and correctly such as: condom plus use of an intrauterine device; intrauterine system or hormonal method of contraception (oral, injected, implanted, or transdermal) for their female partner; or sexual abstinence. Males must be surgically sterilized, or agree to practice true abstinence, or use acceptable contraception if sexually active with a female partner of childbearing potential, throughout the study, and for at least 30 days after the last dose of study drug.
  • Males must agree not to donate sperm during the study and for 30 days following last dose of study drug.

Exclusion criteria

  • Positive pregnancy test or is lactating.
  • History or presence of clinically significant allergic diseases (except for untreated,

asymptomatic, seasonal allergies) at time of screening in the opinion of the Investigator.

  • History or presence of conditions which, in the opinion of the Investigator, are known to interfere with the absorption, distribution, metabolism, or excretion of drugs, such as previous surgery on the gastrointestinal tract (including removal of parts of the stomach, bowel, liver, or pancreas). Participants who have a history of cholecystectomy and appendectomy are eligible for enrollment.
  • Any signs and/or symptoms of acute illness at screening or Day -1.
  • Abnormal ECG in any of the single ECGs collected at screening or Day -1, including QTcF > 430 msec for males and > 450 msec for females, or any cardiac rhythm other than sinus rhythm that is interpreted by the Investigator to be clinically significant. A single repeat measurement may be performed to re-evaluate ECG abnormalities (ie, to confirm that a participant is eligible). All the single ECGs must be not clinically significant to qualify for enrollment into the study.
  • Resting bradycardia (HR < 45 bpm) or resting tachycardia (HR > 100 bpm) at screening or Day -1. A single repeat measurement may be performed to re-evaluate vital signs abnormalities(ie, to confirm that a participant is ineligible). Each of the readings must be not clinically significant to qualify for enrollment into the study.
  • Hypertension, defined as resting (supine) systolic blood pressure (BP) > 140 mmHg or resting diastolic BP > 90 mmHg at screening or Day -1. A single repeat measurement may be performed to re-evaluate vital signs abnormalities (ie, to confirm that a participant is eligible). Each of the readings must be not clinically significant to qualify for enrollment into the study.
  • Use of prescription medications (with the exception of contraception), any over the counter drugs including herbal preparations including St. John's wort or dietary supplements, or any drugs that induce or inhibit study drug specific CYP450(s) within 14 days or 5 half-lives, whichever is longer, prior to Day -1, or requires continuing use during study participation.
  • Prior exposure to voxelotor/Oxbryta® within the past month.
  • Clinically significant anemia, or has donated blood or blood components exceeding 400 mL within 90 days prior to screening.
  • Positive screen for human immunodeficiency virus 1 (HIV-1) and HIV -2 antibodies, hepatitis A virus antibody, hepatitis B surface antigen, or hepatitis C virus antibody.
  • History or presence of contraindication to the use of midazolam including but not limited to hypersensitivity to benzodiazepines or formulation ingredients, acute narrow-angle glaucoma, myasthenia gravis, severe respiratory insufficiency, or sleep apnea syndrome.
  • Poor CYP2C9 or CYP2C19 metabolizer (determined at screening or available historical data).
  • Participant has an allergy or sensitivity to voxelotor, bupropion, repaglinide, flurbiprofen, omeprazole, or midazolam.

Part B only

  • History of statin-induced myopathy or serious hypersensitivity reaction to other 3-hydroxy-3-methylglutaryl coenzyme A, reductase inhibitors (statins).
  • Heterozygous or homozygous variant allele carriers of SLCO1B1 (c.521T>C, rs4149056), encoding the hepatic uptake transporter OATP1B1, resulting in decreased transport activity.
  • Participant has an allergy or sensitivity to voxelotor, metformin, furosemide, or rosuvastatin.

Treatment and study plan

Voxelotor

Drug

Drug drug interaction

Other names: Oxbryta

bupropion

Drug

Drug drug interaction

Other names: Wellbutrin

repaglinide

Drug

Drug drug interaction

Other names: Prandin

Flurbiprofen

Drug

Drug drug interaction

Other names: Ansaid

Omeprazole

Drug

Drug drug interaction

Other names: Prilosec

midazolam

Drug

Drug drug interaction

Other names: Dormicum

metformin

Drug

Drug drug interaction

Other names: Glucophage

Furosemide

Drug

Drug drug interaction

Other names: Lasix

Rosuvastatin

Drug

Drug drug interaction

Other names: Crestor

Primary outcomes

  1. Part A: Maximum Observed Plasma Concentration (Cmax) for Bupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

  2. Part A: Cmax for Repaglinide

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively

  3. Part A: Cmax for Flurbiprofen

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

  4. Part A: Cmax for Omeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

  5. Part A: Cmax for Midazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

  6. Part A: Area Under the Plasma Concentration-Time Curve From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUCt) for Bupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    AUCt was calculated using the linear/log trapezoidal rule.

  7. Part A: AUCt for Repaglinide

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  8. Part A: AUCt for Flurbiprofen

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  9. Part A: AUCt for Omeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  10. Part A: AUCt for Midazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  11. Part A: Area Under the Plasma Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUCinf) for Bupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  12. Part A: AUCinf for Repaglinide

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  13. Part A: AUCinf for Flurbiprofen

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  14. Part A: AUCinf for Omeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  15. Part A: AUCinf for Midazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  16. Part B: Cmax for Metformin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

  17. Part B: Cmax for Furosemide

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

  18. Part B: Cmax for Rosuvastatin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

  19. Part B: AUCt for Metformin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  20. Part B: AUCt for Furosemide

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  21. Part B: AUCt for Rosuvastatin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Day 1 and Day 4 for Treatment A and Treatment C, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  22. Part B: AUCinf for Metformin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  23. Part B: AUCinf for Furosemide

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  24. Part B: AUCinf for Rosuvastatin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

Secondary outcomes

  1. Part A: Cmax for 6-Hydroxybupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

  2. Part A: Cmax for 5-Hydroxyomeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

  3. Part A: Cmax for 1-Hydroxymidazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

  4. Part A: AUCt for 6-Hydroxybupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  5. Part A: AUCt for 5-Hydroxyomeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  6. Part A: AUCt for 1-Hydroxymidazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCt was calculated using the linear/log trapezoid rule.

  7. Part A: AUCinf for 6-Hydroxybupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  8. Part A: AUCinf for 5-Hydroxyomeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  9. Part A: AUCinf for 1-Hydroxymidazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    AUCinf was calculated as AUClast + Clast/lamda z, where AUClast: area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. Clast is the last measurable concentration and lamda z: apparent terminal elimination rate constant.

  10. Part A: Time at Which Cmax Was Observed (Tmax) for Bupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    The time that Cmax was observed.

  11. Part A: Tmax for 6-Hydroxybupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    The time that Cmax was observed for 6-Hydroxybupropion.

  12. Part A: Tmax for Repaglinide

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively

    The time that Cmax was observed for Repaglinide.

  13. Part A: Tmax for Flurbiprofen

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    The time that Cmax was observed for Flurbiprofen.

  14. Part A: Tmax for Omeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    The time that Cmax was observed for Omeprazole.

  15. Part A: Tmax for 5-Hydroxyomeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    The time that Cmax was observed for 5-Hydroxyomeprazole.

  16. Part A: Tmax for Midazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    The time that Cmax was observed for Midazolam.

  17. Part A: Tmax for 1-Hydroxymidazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    The time that Cmax was observed for 1-Hydroxymidazolam.

  18. Part A: Terminal Elimination Half-life (T½) for Bupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  19. Part A: t1/2 6-Hydroxybupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  20. Part A: T1/2 for Repaglinide

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Period 1 Day 4 and Period 2 Day 6 for Treatment B and F, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  21. Part A: T1/2 for Flurbiprofen

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  22. Part A: T1/2 for Omeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  23. Part A: T1/2 for 5-Hydroxyomeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  24. Part A: T1/2 for Midazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  25. Part A: T1/2 for 1-Hydroxymidazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  26. Part A: Ratio of Metabolite to Parent AUCt Corrected for Molecular Weight (AUCt M/P) for 6-Hydroxybupropion/Bupropion

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose on Period 1 Day 1, Period 2 Day 2 and Period 2 Day 12 for Treatment A, D and G, respectively

  27. Part A: Ratio of Metabolite to Parent AUCt Corrected for Molecular Weight for 5-Hydroxyomeprazole/Omeprazole

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

  28. Part A: Ratio of Metabolite to Parent AUCt Corrected for Molecular Weight for Hydroxymidazolam/Midazolam

    Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and E, respectively

  29. Part B: Tmax for Metformin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

  30. Part B: Tmax for Furosemide

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

  31. Part B: Tmax for Rosuvastatin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

  32. Part B: T½ for Metformin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  33. Part B: T½ for Furosemide

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

  34. Part B: T½ for Rosuvastatin

    Time frame: Predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose on Period 1 Day 1 and Period 2 Day 4 for Treatment A and Treatment C, respectively

    T½ was calculated as ln (2)/lambda z; where lamda z: apparent terminal elimination rate constant.

Other outcomes

  1. Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Time frame: From start of study drug on Day 1 up to Day 28 (for a maximum of 30 days)

    An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE: any event that was not present before exposure to study drug (voxelotor or cocktail drugs [probe substrates]) or any event already present that worsened in either intensity or frequency after exposure to study drug. An SAE was defined as an AE that at any dose resulted in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability; a congenital anomaly/birth defect; other important medical events.

  2. Part B: Number of Participants With TEAEs and SAEs

    Time frame: From start of study drug on Day 1 up to Day 18 (for a maximum of 20 days)

    An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE: any event that was not present before exposure to study drug (voxelotor or cocktail drugs [probe substrates]) or any event already present that worsened in either intensity or frequency after exposure to study drug. An SAE was defined as an AE that at any dose resulted in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability; a congenital anomaly/birth defect; other important medical events.

  3. Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Tests

    Time frame: From start of study drug on Day 1 up to Day 28 (for a maximum of 30 days)

    The following laboratory parameters were assessed: hematology: hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, red blood cell count, neutrophils, monocytes, lymphocytes, basophils and eosinophils. coagulation: prothrombin time, partial thromboplastin time, international normalized ratio. Serum Chemistry: albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, blood urea nitrogen, lactate dehydrogenase. Urinalysis: ketones, pH, protein, blood glucose, bilirubin, chloride, bicarbonate, phosphorous, potassium was assessed. Clinical significance of laboratory abnormalities was determined by investigator.

  4. Part A: Number of Participants With Clinically Significant Abnormalities in Physical Examinations

    Time frame: From start of study drug on Day 1 up to Day 28 (for a maximum of 30 days)

    A complete physical examination included cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and weight were also measured and recorded. Clinical significance of physical examinations was determined by investigator.

  5. Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs

    Time frame: From start of study drug on Day 1 up to Day 28 (for a maximum of 30 days)

    Vital signs included oral temperature, heart rate, respiratory rate (breaths per minute), and blood pressure. Blood pressure and heart rate were measured in a supine position using completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Clinical significance of vital signs was determined by investigator.

  6. Part B: Number of Participants With Clinically Significant Abnormalities in Laboratory Tests

    Time frame: From start of study drug on Day 1 up to Day 18 (for a maximum of 20 days)

    The following laboratory parameters were assessed: hematology: hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet count, red blood cell count, neutrophils, monocytes, lymphocytes, basophils and eosinophils. coagulation: prothrombin time, partial thromboplastin time, international normalized ratio. Serum Chemistry: albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, creatinine, blood urea nitrogen, lactate dehydrogenase. Urinalysis: ketones, pH, protein, blood glucose, bilirubin, chloride, bicarbonate, phosphorous, potassium was assessed. Clinical significance of laboratory abnormalities was determined by investigator.

  7. Part B: Number of Participants With Clinically Significant Abnormalities in Physical Examinations

    Time frame: From start of study drug on Day 1 up to Day 18 (for a maximum of 20 days)

    A complete physical examination included cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and weight were also measured and recorded. Clinical significance of physical examinations was determined by investigator.

  8. Part B: Number of Participants With Clinically Significant Abnormalities in Vital Signs

    Time frame: From start of study drug on Day 1 up to Day 18 (for a maximum of 20 days)

    Vital signs included oral temperature, heart rate, respiratory rate (breaths per minute), and blood pressure. Blood pressure and heart rate were measured in a supine position using completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Clinical significance of vital signs was determined by investigator.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

A Phase 1, Open-Label, Two-Part, Fixed-Sequence, Drug-Drug Interaction Study to Evaluate the Effect of Voxelotor on the Pharmacokinetics of Selected CYP and Transporter Probe Substrates in Healthy Participants

Important dates

Study start
2023
Primary completion
2023
Study completion
2023
First posted
Aug 8, 2023
Registry last updated
Nov 22, 2024

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.

Related clinical trials

Published trials that share one or more normalized conditions with this study.