The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Voxelotor CYP and Transporter Cocktail Interaction Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05981365
Recruitment Status : Completed
First Posted : August 8, 2023
Last Update Posted : February 2, 2024
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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 Intervention/treatment Phase
Sickle Cell Disease Drug: Voxelotor Drug: Bupropion Drug: Repaglinide Drug: Flurbiprofen Drug: Omeprazole Drug: Midazolam Drug: Metformin Drug: Furosemide Drug: Rosuvastatin Phase 1

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
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 : April 17, 2023
Actual Primary Completion Date : October 4, 2023
Actual Study Completion Date : October 4, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions
Drug Information available for: Voxelotor

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Part A
To evaluate the effect of multiple doses of voxelotor on the plasma pharmacokinetics (PK) of a single dose of bupropion, repaglinide, flurbiprofen, omeprazole, and midazolam
 Drug: Voxelotor
Drug drug interaction
Other Name: Oxbryta

Drug: Bupropion
Drug drug interaction
Other Name: Wellbutrin

Drug: Repaglinide
Drug drug interaction
Other Name: Prandin

Drug: Flurbiprofen
Drug drug interaction
Other Name: Ansaid

Drug: Omeprazole
Drug drug interaction
Other Name: Prilosec

Drug: Midazolam
Drug drug interaction
Other Name: Dormicum
Experimental: Part B
To evaluate the effect of multiple doses of voxelotor on the plasma PK of a single dose of metformin, furosemide, and rosuvastatin
 Drug: Voxelotor
Drug drug interaction
Other Name: Oxbryta

Drug: Metformin
Drug drug interaction
Other Name: Glucophage

Drug: Furosemide
Drug drug interaction
Other Name: Lasix

Drug: Rosuvastatin
Drug drug interaction
Other Name: Crestor


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Part A- Maximum observed plasma concentration (Cmax) for bupropion [ Time Frame: Up to 81 Days ]
  2. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for bupropion [ Time Frame: Up to 81 Days ]
  3. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for bupropion [ Time Frame: Up to 81 Days ]
  4. Part A- Maximum observed plasma concentration (Cmax) for repaglinide [ Time Frame: Up to 81 Days ]
  5. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for repaglinide [ Time Frame: Up to 81 Days ]
  6. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for repaglinide [ Time Frame: Up to 81 Days ]
  7. Part A- Maximum observed plasma concentration (Cmax) for flurbiprofen [ Time Frame: Up to 81 Days ]
  8. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for flurbiprofen [ Time Frame: Up to 81 Days ]
  9. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for flurbiprofen [ Time Frame: Up to 81 Days ]
  10. Part A- Maximum observed plasma concentration (Cmax) for omeprazole [ Time Frame: Up to 81 Days ]
  11. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for omeprazole [ Time Frame: Up to 81 Days ]
  12. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for omeprazole [ Time Frame: Up to 81 Days ]
  13. Part A- Maximum observed plasma concentration (Cmax) for midazolam [ Time Frame: Up to 81 Days ]
  14. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for midazolam [ Time Frame: Up to 81 Days ]
  15. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for midazolam [ Time Frame: Up to 81 Days ]
  16. Part B- Maximum observed plasma concentration (Cmax) for metformin [ Time Frame: Up to 68 Days ]
  17. Part B- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for metformin [ Time Frame: Up to 68 Days ]
  18. Part B- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for metformin [ Time Frame: Up to 68 Days ]
  19. Part B- Maximum observed plasma concentration (Cmax) for furosemide [ Time Frame: Up to 68 Days ]
  20. Part B- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for furosemide [ Time Frame: Up to 68 Days ]
  21. Part B- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for furosemide [ Time Frame: Up to 68 Days ]
  22. Part B- Maximum observed plasma concentration (Cmax) for rosuvastatin [ Time Frame: Up to 68 Days ]
  23. Part B- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for rosuvastatin [ Time Frame: Up to 68 Days ]
  24. Part B- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for rosuvastatin [ Time Frame: Up to 68 Days ]

Secondary Outcome Measures :
  1. Part A- Maximum observed plasma concentration (Cmax) for 6-hydroxybupropion [ Time Frame: Up to 81 Days ]
  2. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for 6-hydroxybupropion [ Time Frame: Up to 81 Days ]
  3. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for 6-hydroxybupropion [ Time Frame: Up to 81 Days ]
  4. Part A- Maximum observed plasma concentration (Cmax) for 5-hydroxyomeprazole [ Time Frame: Up to 81 Days ]
  5. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for 5-hydroxyomeprazole [ Time Frame: Up to 81 Days ]
  6. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for 5-hydroxyomeprazole [ Time Frame: Up to 81 Days ]
  7. Part A- Maximum observed plasma concentration (Cmax) for 1-hydroxymidazolam [ Time Frame: Up to 81 Days ]
  8. Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for 1-hydroxymidazolam [ Time Frame: Up to 81 Days ]
  9. Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for 1-hydroxymidazolam [ Time Frame: Up to 81 Days ]
  10. Part A- The time that Cmax is observed (tmax) for bupropion in plasma [ Time Frame: Up to 81 Days ]
  11. Part A- The time that Cmax is observed (tmax) for 6-hydroxybupropion in plasma [ Time Frame: Up to 81 Days ]
  12. Part A- The time that Cmax is observed (tmax) for repaglinide in plasma [ Time Frame: Up to 81 Days ]
  13. Part A- The time that Cmax is observed (tmax) for flurbiprofen in plasma [ Time Frame: Up to 81 Days ]
  14. Part A- The time that Cmax is observed (tmax) for omeprazole in plasma [ Time Frame: Up to 81 Days ]
  15. Part A- The time that Cmax is observed (tmax) for 5-hydroxyomeprazole in plasma [ Time Frame: Up to 81 Days ]
  16. Part A- The time that Cmax is observed (tmax) for midazolam in plasma [ Time Frame: Up to 81 Days ]
  17. Part A- The time that Cmax is observed (tmax) for 1-hydroxymidazolam in plasma [ Time Frame: Up to 81 Days ]
  18. Part A- terminal elimination half-life (t½) for bupropion in plasma [ Time Frame: Up to 81 Days ]
  19. Part A- terminal elimination half-life (t½) for 6-hydroxybupropion in plasma [ Time Frame: Up to 81 Days ]
  20. Part A- terminal elimination half-life (t½) for repaglinide in plasma [ Time Frame: Up to 81 Days ]
  21. Part A- terminal elimination half-life (t½) for flurbiprofen in plasma [ Time Frame: Up to 81 Days ]
  22. Part A- terminal elimination half-life (t½) for omeprazole in plasma [ Time Frame: Up to 81 Days ]
  23. Part A- terminal elimination half-life (t½) for 5-hydroxyomeprazole in plasma [ Time Frame: Up to 81 Days ]
  24. Part A- terminal elimination half-life (t½) for midazolam in plasma [ Time Frame: Up to 81 Days ]
  25. Part A- terminal elimination half-life (t½) for 1-hydroxymidazolamin plasma [ Time Frame: Up to 81 Days ]
  26. Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for bupropion [ Time Frame: Up to 81 Days ]
  27. Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for omeprazole [ Time Frame: Up to 81 Days ]
  28. Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for midazolam [ Time Frame: Up to 81 Days ]
  29. Part B- The time that Cmax is observed (tmax) for metformin in plasma [ Time Frame: Up to 68 Days ]
  30. Part B- The time that Cmax is observed (tmax) for furosemide in plasma [ Time Frame: Up to 68 Days ]
  31. Part B- The time that Cmax is observed (tmax) for rosuvastatin in plasma [ Time Frame: Up to 68 Days ]
  32. Part B- terminal elimination half-life (t½) for metformin in plasma [ Time Frame: Up to 68 Days ]
  33. Part B- terminal elimination half-life (t½) for furosemide in plasma [ Time Frame: Up to 68 Days ]
  34. Part B- terminal elimination half-life (t½) for rosuvastatin in plasma [ Time Frame: Up to 68 Days ]
  35. Part A- Incidence of Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Up to 81 Days ]
  36. Part B- Incidence of Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Up to 68 Days ]
  37. Part A- Incidence of clinically significant changes in clinical laboratory tests, physical examination findings, and vital signs [ Time Frame: Up to 81 Days ]
  38. Part B- Incidence of clinically significant changes in clinical laboratory tests, physical examination findings, and vital signs [ Time Frame: Up to 68 Days ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05981365


Locations
Layout table for location information
United States, Texas
ICON Early Phase Services, LLC
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
Pfizer
Investigators
Layout table for investigator information
Study Director: Pfizer CT.gov Call Center Pfizer
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05981365    
Other Study ID Numbers: GBT440-0122
C5341029 ( Other Identifier: Alias Study Number )
First Posted: August 8, 2023    Key Record Dates
Last Update Posted: February 2, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Drug drug interaction
Additional relevant MeSH terms:
Layout table for MeSH terms
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Metformin
Repaglinide
Flurbiprofen
Furosemide
Midazolam
Bupropion
Omeprazole
Rosuvastatin Calcium
 Hypoglycemic Agents
Physiological Effects of Drugs
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action