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NCT05981365 | COMPLETED | Sickle Cell Disease

Voxelotor CYP and Transporter Cocktail Interaction Study
Sponsor:

Pfizer

Brief Summary:

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.

Condition or disease

Sickle Cell Disease

Intervention/treatment

Voxelotor

Bupropion

Repaglinide

Flurbiprofen

Omeprazole

Midazolam

Metformin

Furosemide

Rosuvastatin

Phase

PHASE1

Detailed Description:

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.

Study Type : INTERVENTIONAL
Estimated Enrollment : 44 participants
Masking : NONE
Primary Purpose : BASIC_SCIENCE
Official 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
Actual Study Start Date : 2023-04-17
Estimated Primary Completion Date : 2023-10-04
Estimated Study Completion Date : 2023-10-04

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years to 55 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers: 1
Criteria
Inclusion Criteria
  • * 1. Males or females ≥ 18 and ≤ 55 years of age inclusive, at the time of signing the informed consent.
  • 2. 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.
  • 3. 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
  • 4. 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.
  • 5. Males must agree not to donate sperm during the study and for 30 days following last dose of study drug.
Exclusion Criteria
  • 1. Positive pregnancy test or is lactating.
  • 2. History or presence of clinically significant allergic diseases (except for untreated,
  • asymptomatic, seasonal allergies) at time of screening in the opinion of the Investigator.
  • 3. 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.
  • 4. Any signs and/or symptoms of acute illness at screening or Day -1.
  • 5. 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.
  • 6. 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.
  • 7. 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.
  • 8. 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.
  • 9. Prior exposure to voxelotor/Oxbryta® within the past month.
  • 10. Clinically significant anemia, or has donated blood or blood components exceeding 400 mL within 90 days prior to screening.
  • 11. 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.
  • 12. 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.
  • 13. Poor CYP2C9 or CYP2C19 metabolizer (determined at screening or available historical data).
  • 14. Participant has an allergy or sensitivity to voxelotor, bupropion, repaglinide, flurbiprofen, omeprazole, or midazolam.
  • Part B only
  • 15. History of statin-induced myopathy or serious hypersensitivity reaction to other 3-hydroxy-3-methylglutaryl coenzyme A, reductase inhibitors (statins).
  • 16. Heterozygous or homozygous variant allele carriers of SLCO1B1 (c.521T\>C, rs4149056), encoding the hepatic uptake transporter OATP1B1, resulting in decreased transport activity.
  • 17. Participant has an allergy or sensitivity to voxelotor, metformin, furosemide, or rosuvastatin.
Voxelotor CYP and Transporter Cocktail Interaction Study

Location Details

NCT05981365

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

Not yet recruiting

United States, Texas

ICON Early Phase Services, LLC

San Antonio, Texas, United States, 78209