Comparison of Daprodustat Formulations Produced by Two Methods of Manufacture for Bioequivalence and Dissolution in Healthy Participants
Study Details
Study Description
Brief Summary
This study is comprised of two discrete Parts. Part A is a 3-period cross over evaluating relative bioavailability. Part B is a 2-period cross over evaluating bioequivalence. There will be a minimum of a 7-day washout period between treatment periods. Participants will participate in Part A or Part B, but not both. Approximately 200 participants will be included in the study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A: Daprodustat Dissolution 1/Dissolution 2/Reference
|
Drug: Daprodustat
Daprodustat will be available as oral tablets.
|
| Experimental: Part A: Daprodustat Dissolution 2/Reference/Dissolution 1
|
Drug: Daprodustat
Daprodustat will be available as oral tablets.
|
| Experimental: Part A: Daprodustat Reference/Dissolution 1/Dissolution 2
|
Drug: Daprodustat
Daprodustat will be available as oral tablets.
|
| Experimental: Part B: Daprodustat Process 1/ Process 2
|
Drug: Daprodustat
Daprodustat will be available as oral tablets.
|
| Experimental: Part B: Daprodustat Process 2/ Process 1
|
Drug: Daprodustat
Daprodustat will be available as oral tablets.
|
Outcome Measures
Primary Outcome Measures
- Part A and Part B: Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for daprodustat [Pre-dose and at 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose in each Period (Each period is 24 hours)]
Blood samples will be collected to measure AUC(0-t) at indicated time-points.
- Part A and Part B: Maximum Plasma Concentration (Cmax) for daprodustat [Pre-dose and at 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose in each Period (Each period is 24 hours)]
Blood samples will be collected to measure Cmax at indicated time-points.
Secondary Outcome Measures
- Part A and Part B: AUC From Time Zero to Infinity (AUC[0-inf]) for daprodustat [Pre-dose and at 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose in each Period (Each period is 24 hours)]
Blood samples will be collected to measure AUC(0-inf) at indicated time-points.
- Part A and Part B: Time of occurrence of Cmax (Tmax) for daprodustat [Pre-dose and at 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose in each Period (Each period is 24 hours)]
Blood samples will be collected to measure Tmax at indicated time-points.
- Part A and Part B: Terminal Elimination Half-life (T1/2) for daprodustat [Pre-dose and at 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose in each Period (Each period is 24 hours)]
Blood samples will be collected to measure T1/2 at indicated time-points.
- Part A and Part B: Oral clearance (CL/F) for daprodustat [Pre-dose and at 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose in each Period (Each period is 24 hours)]
Blood samples will be collected to measure CL/F at indicated time-points.
- Part A and Part B: Apparent Volume of Distribution (V/F) for daprodustat [Pre-dose and at 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post-dose in each Period (Each period is 24 hours)]
Blood samples will be collected to measure V/F at indicated time-points.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
-
Participants must be overtly healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests. A participant with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator and/or the Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
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Participants with body weight more than or equal to (>=) 45 kilogram (kg) and body mass index (BMI) within the range 19-31 kg per meter square (Kg/m^2).
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Male or female
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A female participant is eligible to participate if she is not breastfeeding, and at least; not pregnant as confirmed by pregnancy testing or not a woman of childbearing potential (WOCBP) or agrees to follow the contraceptive guidance during the treatment period to the follow-up visit.
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Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion Criteria:
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Participants with history of malignancy within the prior 2 years or currently receiving treatment for cancer. The only exception is localized squamous- or basal-cell carcinoma of the skin definitively treated 12 weeks or more prior to enrolment.
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Participants unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise participant safety.
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Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 30 days prior to Day 1 in this study. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
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Current enrolment or past participation (administration of last dose of investigational study treatment) within the last 30 days (or 5 half-lives, whichever is longer) before Day 1 in this study in any other clinical study involving an investigational study intervention or any other type of medical research.
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Part A participants may not participate in Part B, and Part B participants may not participate in Part A if enrolment is concurrent or overlaps.
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Participants with positive pre-study drug/alcohol screen.
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Participants with regular use of known drugs of abuse.
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Participants with a positive laboratory confirmation of Coronavirus disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
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Participants with regular alcohol consumption within 6 months prior to the study.
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Participants with urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine containing products (nicotine patches or vaporizing devices) within 6 months prior to screening.
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Participants with sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Anaheim | California | United States | 92801 |
| 2 | GSK Investigational Site | Overland Park | Kansas | United States | 66212 |
| 3 | GSK Investigational Site | Las Vegas | Nevada | United States | 89113 |
| 4 | GSK Investigational Site | Austin | Texas | United States | 78744 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 213022