xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05981365</url>
    </required_header>
    <id_info>
      <org_study_id>GBT440-0122</org_study_id>
      <secondary_id>C5341029</secondary_id>
      <nct_id>NCT05981365</nct_id>
    </id_info>
    <brief_title>Voxelotor CYP and Transporter Cocktail Interaction Study</brief_title>
    <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</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Pfizer</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Pfizer</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This research study is examining multiple doses of voxelotor (a study drug intended for&#xD;
        treatment of sickle cell disease) and how it interacts with additional substrates (substrates&#xD;
        are drugs or other substances that are metabolized by cytochrome enzymes. The substrates used&#xD;
        in this study are FDA approved medications). The study will help to determine the safety and&#xD;
        tolerability of the study drugs taken together, as well as the pharmacokinetics (PK) on how&#xD;
        your body processes and responds to the combination of the study drug and substrates.&#xD;
        Although these drugs are FDA approved, their use in this study is experimental.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is an open-label, fixed-sequence, 2-period evaluation study. This means the study doctor&#xD;
        and participants in the study will know what study drugs they are taking. There will be&#xD;
        approximately 46 healthy male and female participants between the ages of 18 - 55. There will&#xD;
        be two parts of the study: parts A and B.&#xD;
  &#xD;
        Part A will consist of 26 healthy male and female participants (at least 20% African&#xD;
        American). For Part A, participant involvement is expected to last approximately 81 days,&#xD;
        including a 33-day screening period and a 48-day on study period (consisting of 2 study&#xD;
        treatment periods, a washout period lasting 7 to 14 days, and the Follow-up visit).&#xD;
  &#xD;
        Part B will consist of 20 healthy male and female participants (at least 20% African&#xD;
        American). For Part B, participant involvement is expected to last approximately 68 days,&#xD;
        including a 33-day screening period and a 35-day on study period (consisting of 2 study&#xD;
        treatment periods, a washout period lasting 7 to 14 days, and the Follow-up visit).&#xD;
  &#xD;
        You will only be allowed to be in one part of the study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Active, not recruiting</overall_status>
    <start_date type="Actual">April 17, 2023</start_date>
    <completion_date type="Anticipated">September 28, 2023</completion_date>
    <primary_completion_date type="Anticipated">September 28, 2023</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for bupropion</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for bupropion</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for bupropion</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for repaglinide</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for repaglinide</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for repaglinide</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for flurbiprofen</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for flurbiprofen</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for flurbiprofen</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for omeprazole</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for omeprazole</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for omeprazole</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for midazolam</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for midazolam</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for midazolam</measure>
      <time_frame>Up to 81 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- Maximum observed plasma concentration (Cmax) for metformin</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for metformin</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for metformin</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- Maximum observed plasma concentration (Cmax) for furosemide</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for furosemide</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for furosemide</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- Maximum observed plasma concentration (Cmax) for rosuvastatin</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration (AUCt) for rosuvastatin</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part B- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for rosuvastatin</measure>
      <time_frame>Up to 68 Days</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for 6-hydroxybupropion</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>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</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for 6-hydroxybupropion</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for 5-hydroxyomeprazole</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>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</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for 5-hydroxyomeprazole</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- Maximum observed plasma concentration (Cmax) for 1-hydroxymidazolam</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>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</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- area under the plasma concentration-time curve (AUC) from time 0 extrapolated to infinity (AUCinf) for 1-hydroxymidazolam</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for bupropion in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for 6-hydroxybupropion in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for repaglinide in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for flurbiprofen in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for omeprazole in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for 5-hydroxyomeprazole in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for midazolam in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- The time that Cmax is observed (tmax) for 1-hydroxymidazolam in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for bupropion in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for 6-hydroxybupropion in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for repaglinide in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for flurbiprofen in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for omeprazole in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for 5-hydroxyomeprazole in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for midazolam in plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- terminal elimination half-life (t½) for 1-hydroxymidazolamin plasma</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for bupropion</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for omeprazole</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for midazolam</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- The time that Cmax is observed (tmax) for metformin in plasma</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- The time that Cmax is observed (tmax) for furosemide in plasma</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- The time that Cmax is observed (tmax) for rosuvastatin in plasma</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- terminal elimination half-life (t½) for metformin in plasma</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- terminal elimination half-life (t½) for furosemide in plasma</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- terminal elimination half-life (t½) for rosuvastatin in plasma</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- Incidence of Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- Incidence of Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part A- Incidence of clinically significant changes in clinical laboratory tests, physical examination findings, and vital signs</measure>
      <time_frame>Up to 81 Days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part B- Incidence of clinically significant changes in clinical laboratory tests, physical examination findings, and vital signs</measure>
      <time_frame>Up to 68 Days</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">18</enrollment>
    <condition>Sickle Cell Disease</condition>
    <arm_group>
      <arm_group_label>Part A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>To evaluate the effect of multiple doses of voxelotor on the plasma PK of a single dose of metformin, furosemide, and rosuvastatin</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Voxelotor</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part A</arm_group_label>
      <arm_group_label>Part B</arm_group_label>
      <other_name>Oxbryta</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Bupropion</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part A</arm_group_label>
      <other_name>Wellbutrin</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Repaglinide</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part A</arm_group_label>
      <other_name>Prandin</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Flurbiprofen</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part A</arm_group_label>
      <other_name>Ansaid</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Omeprazole</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part A</arm_group_label>
      <other_name>Prilosec</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Midazolam</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part A</arm_group_label>
      <other_name>Dormicum</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Metformin</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part B</arm_group_label>
      <other_name>Glucophage</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Furosemide</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part B</arm_group_label>
      <other_name>Lasix</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Rosuvastatin</intervention_name>
      <description>Drug drug interaction</description>
      <arm_group_label>Part B</arm_group_label>
      <other_name>Crestor</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1. Males or females ≥ 18 and ≤ 55 years of age inclusive, at the time of signing the&#xD;
               informed consent.&#xD;
  &#xD;
               2. No clinically significant findings as assessed by review of medical and surgical&#xD;
               history, vital signs assessments, 12-lead electrocardiograms (ECG), physical&#xD;
               examination, and clinical laboratory evaluations conducted at screening and day of&#xD;
               admission. A single repeat measurement/test may be performed to confirm eligibility&#xD;
               based upon initial vital signs, ECG, or clinical laboratory tests abnormalities.&#xD;
  &#xD;
               3. Body mass Index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2, and body weight ≥ 50 kg at screening&#xD;
               and Period 1 Day -1. BMI = weight (kg)/(height [m])2&#xD;
  &#xD;
               4. Females of childbearing potential must agree to use a highly effective method of&#xD;
               contraception or practice abstinence from 2 weeks prior to study start through 30 days&#xD;
               after the last dose of study drug. A highly effective method of contraception is&#xD;
               defined as one that results in a low documented failure rate when used consistently&#xD;
               and correctly such as: condom plus use of an intrauterine device; intrauterine system&#xD;
               or hormonal method of contraception (oral, injected, implanted, or transdermal) for&#xD;
               their female partner; or sexual abstinence. Males must be surgically sterilized, or&#xD;
               agree to practice true abstinence, or use acceptable contraception if sexually active&#xD;
               with a female partner of childbearing potential, throughout the study, and for at&#xD;
               least 30 days after the last dose of study drug.&#xD;
  &#xD;
               5. Males must agree not to donate sperm during the study and for 30 days following&#xD;
               last dose of study drug.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Positive pregnancy test or is lactating.&#xD;
  &#xD;
            2. History or presence of clinically significant allergic diseases (except for untreated,&#xD;
  &#xD;
               asymptomatic, seasonal allergies) at time of screening in the opinion of the&#xD;
               Investigator.&#xD;
  &#xD;
            3. History or presence of conditions which, in the opinion of the Investigator, are known&#xD;
               to interfere with the absorption, distribution, metabolism, or excretion of drugs,&#xD;
               such as previous surgery on the gastrointestinal tract (including removal of parts of&#xD;
               the stomach, bowel, liver, or pancreas). Participants who have a history of&#xD;
               cholecystectomy and appendectomy are eligible for enrollment.&#xD;
  &#xD;
            4. Any signs and/or symptoms of acute illness at screening or Day -1.&#xD;
  &#xD;
            5. Abnormal ECG in any of the single ECGs collected at screening or Day -1, including&#xD;
               QTcF &gt; 430 msec for males and &gt; 450 msec for females, or any cardiac rhythm other than&#xD;
               sinus rhythm that is interpreted by the Investigator to be clinically significant. A&#xD;
               single repeat measurement may be performed to re-evaluate ECG abnormalities (ie, to&#xD;
               confirm that a participant is eligible). All the single ECGs must be not clinically&#xD;
               significant to qualify for enrollment into the study.&#xD;
  &#xD;
            6. Resting bradycardia (HR &lt; 45 bpm) or resting tachycardia (HR &gt; 100 bpm) at screening&#xD;
               or Day -1. A single repeat measurement may be performed to re-evaluate vital signs&#xD;
               abnormalities(ie, to confirm that a participant is ineligible). Each of the readings&#xD;
               must be not clinically significant to qualify for enrollment into the study.&#xD;
  &#xD;
            7. Hypertension, defined as resting (supine) systolic blood pressure (BP) &gt; 140 mmHg or&#xD;
               resting diastolic BP &gt; 90 mmHg at screening or Day -1. A single repeat measurement may&#xD;
               be performed to re-evaluate vital signs abnormalities (ie, to confirm that a&#xD;
               participant is eligible). Each of the readings must be not clinically significant to&#xD;
               qualify for enrollment into the study.&#xD;
  &#xD;
            8. Use of prescription medications (with the exception of contraception), any over the&#xD;
               counter drugs including herbal preparations including St. John's wort or dietary&#xD;
               supplements, or any drugs that induce or inhibit study drug specific CYP450(s) within&#xD;
               14 days or 5 half-lives, whichever is longer, prior to Day -1, or requires continuing&#xD;
               use during study participation.&#xD;
  &#xD;
            9. Prior exposure to voxelotor/Oxbryta® within the past month.&#xD;
  &#xD;
           10. Clinically significant anemia, or has donated blood or blood components exceeding 400&#xD;
               mL within 90 days prior to screening.&#xD;
  &#xD;
           11. Positive screen for human immunodeficiency virus 1 (HIV-1) and HIV -2 antibodies,&#xD;
               hepatitis A virus antibody, hepatitis B surface antigen, or hepatitis C virus&#xD;
               antibody.&#xD;
  &#xD;
           12. History or presence of contraindication to the use of midazolam including but not&#xD;
               limited to hypersensitivity to benzodiazepines or formulation ingredients, acute&#xD;
               narrow-angle glaucoma, myasthenia gravis, severe respiratory insufficiency, or sleep&#xD;
               apnea syndrome.&#xD;
  &#xD;
           13. Poor CYP2C9 or CYP2C19 metabolizer (determined at screening or available historical&#xD;
               data).&#xD;
  &#xD;
           14. Participant has an allergy or sensitivity to voxelotor, bupropion, repaglinide,&#xD;
               flurbiprofen, omeprazole, or midazolam.&#xD;
  &#xD;
               Part B only&#xD;
  &#xD;
           15. History of statin-induced myopathy or serious hypersensitivity reaction to other&#xD;
               3-hydroxy-3-methylglutaryl coenzyme A, reductase inhibitors (statins).&#xD;
  &#xD;
           16. Heterozygous or homozygous variant allele carriers of SLCO1B1 (c.521T&gt;C, rs4149056),&#xD;
               encoding the hepatic uptake transporter OATP1B1, resulting in decreased transport&#xD;
               activity.&#xD;
  &#xD;
           17. Participant has an allergy or sensitivity to voxelotor, metformin, furosemide, or&#xD;
               rosuvastatin.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>55 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Pfizer CT.gov Call Center</last_name>
      <role>Study Director</role>
      <affiliation>Pfizer</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>ICON Early Phase Services, LLC</name>
        <address>
          <city>San Antonio</city>
          <state>Texas</state>
          <zip>78209</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-0122</url>
      <description>To obtain contact information for a study center near you, click here.</description>
    </link>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>May 17, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Drug drug interaction</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anemia, Sickle Cell</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Metformin</mesh_term>
      <mesh_term>Repaglinide</mesh_term>
      <mesh_term>Flurbiprofen</mesh_term>
      <mesh_term>Furosemide</mesh_term>
      <mesh_term>Midazolam</mesh_term>
      <mesh_term>Bupropion</mesh_term>
      <mesh_term>Omeprazole</mesh_term>
      <mesh_term>Rosuvastatin Calcium</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_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.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05981365
  org study id: GBT440-0122
  secondary id: C5341029
  nct id: NCT05981365
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  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.
  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.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Part A- Maximum observed plasma concentration (Cmax) for bupropion
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part A- Maximum observed plasma concentration (Cmax) for repaglinide
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part A- Maximum observed plasma concentration (Cmax) for flurbiprofen
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part A- Maximum observed plasma concentration (Cmax) for omeprazole
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part A- Maximum observed plasma concentration (Cmax) for midazolam
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part B- Maximum observed plasma concentration (Cmax) for metformin
  time frame: Up to 68 Days
  measure: 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
  measure: 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
  measure: Part B- Maximum observed plasma concentration (Cmax) for furosemide
  time frame: Up to 68 Days
  measure: 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
  measure: 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
  measure: Part B- Maximum observed plasma concentration (Cmax) for rosuvastatin
  time frame: Up to 68 Days
  measure: 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
  measure: 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
  measure: Part A- Maximum observed plasma concentration (Cmax) for 6-hydroxybupropion
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part A- Maximum observed plasma concentration (Cmax) for 5-hydroxyomeprazole
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part A- Maximum observed plasma concentration (Cmax) for 1-hydroxymidazolam
  time frame: Up to 81 Days
  measure: 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
  measure: 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
  measure: Part A- The time that Cmax is observed (tmax) for bupropion in plasma
  time frame: Up to 81 Days
  measure: Part A- The time that Cmax is observed (tmax) for 6-hydroxybupropion in plasma
  time frame: Up to 81 Days
  measure: Part A- The time that Cmax is observed (tmax) for repaglinide in plasma
  time frame: Up to 81 Days
  measure: Part A- The time that Cmax is observed (tmax) for flurbiprofen in plasma
  time frame: Up to 81 Days
  measure: Part A- The time that Cmax is observed (tmax) for omeprazole in plasma
  time frame: Up to 81 Days
  measure: Part A- The time that Cmax is observed (tmax) for 5-hydroxyomeprazole in plasma
  time frame: Up to 81 Days
  measure: Part A- The time that Cmax is observed (tmax) for midazolam in plasma
  time frame: Up to 81 Days
  measure: Part A- The time that Cmax is observed (tmax) for 1-hydroxymidazolam in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for bupropion in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for 6-hydroxybupropion in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for repaglinide in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for flurbiprofen in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for omeprazole in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for 5-hydroxyomeprazole in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for midazolam in plasma
  time frame: Up to 81 Days
  measure: Part A- terminal elimination half-life (t½) for 1-hydroxymidazolamin plasma
  time frame: Up to 81 Days
  measure: Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for bupropion
  time frame: Up to 81 Days
  measure: Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for omeprazole
  time frame: Up to 81 Days
  measure: Part A- Ratio of metabolite to parent AUCt corrected for molecular weight (AUCt M/P) for midazolam
  time frame: Up to 81 Days
  measure: Part B- The time that Cmax is observed (tmax) for metformin in plasma
  time frame: Up to 68 Days
  measure: Part B- The time that Cmax is observed (tmax) for furosemide in plasma
  time frame: Up to 68 Days
  measure: Part B- The time that Cmax is observed (tmax) for rosuvastatin in plasma
  time frame: Up to 68 Days
  measure: Part B- terminal elimination half-life (t½) for metformin in plasma
  time frame: Up to 68 Days
  measure: Part B- terminal elimination half-life (t½) for furosemide in plasma
  time frame: Up to 68 Days
  measure: Part B- terminal elimination half-life (t½) for rosuvastatin in plasma
  time frame: Up to 68 Days
  measure: Part A- Incidence of Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
  time frame: Up to 81 Days
  measure: Part B- Incidence of Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
  time frame: Up to 68 Days
  measure: Part A- Incidence of clinically significant changes in clinical laboratory tests, physical examination findings, and vital signs
  time frame: Up to 81 Days
  measure: Part B- Incidence of clinically significant changes in clinical laboratory tests, physical examination findings, and vital signs
  time frame: Up to 68 Days
  arm group label: Part A
  arm group type: Experimental
  description: 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
  arm group label: Part B
  arm group type: Experimental
  description: To evaluate the effect of multiple doses of voxelotor on the plasma PK of a single dose of metformin, furosemide, and rosuvastatin
  intervention type: Drug
  intervention name: Voxelotor
  description: Drug drug interaction
  arm group label: Part A
  arm group label: Part B
  other name: Oxbryta
  intervention type: Drug
  intervention name: Bupropion
  description: Drug drug interaction
  arm group label: Part A
  other name: Wellbutrin
  intervention type: Drug
  intervention name: Repaglinide
  description: Drug drug interaction
  arm group label: Part A
  other name: Prandin
  intervention type: Drug
  intervention name: Flurbiprofen
  description: Drug drug interaction
  arm group label: Part A
  other name: Ansaid
  intervention type: Drug
  intervention name: Omeprazole
  description: Drug drug interaction
  arm group label: Part A
  other name: Prilosec
  intervention type: Drug
  intervention name: Midazolam
  description: Drug drug interaction
  arm group label: Part A
  other name: Dormicum
  intervention type: Drug
  intervention name: Metformin
  description: Drug drug interaction
  arm group label: Part B
  other name: Glucophage
  intervention type: Drug
  intervention name: Furosemide
  description: Drug drug interaction
  arm group label: Part B
  other name: Lasix
  intervention type: Drug
  intervention name: Rosuvastatin
  description: Drug drug interaction
  arm group label: Part B
  other name: Crestor
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 55 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Pfizer CT.gov Call Center
  role: Study Director
  affiliation: Pfizer
  facility: 
  country: United States
  url: https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-0122
  description: To obtain contact information for a study center near you, click here.
  responsible party type: Sponsor
  mesh term: Anemia, Sickle Cell
  mesh term: Metformin
  mesh term: Repaglinide
  mesh term: Flurbiprofen
  mesh term: Furosemide
  mesh term: Midazolam
  mesh term: Bupropion
  mesh term: Omeprazole
  mesh term: Rosuvastatin Calcium
  sharing ipd: No
  ipd 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.