Comparison of Daprodustat Formulations Produced by Two Methods of Manufacture for Bioequivalence and Dissolution in Healthy Participants

• ClinicalTrials.gov Identifier: NCT04640311
• Recruitment Status: Completed
• First Posted: November 23, 2020
• Last Update Posted: June 18, 2021
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

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
Anaemia	Drug: Daprodustat	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 259 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Two-part, Randomized, Double-blind, Single-dose, Crossover Study to Compare Formulations Produced by Two Methods of Manufacture for Bioequivalence and Dissolution in Healthy Adult Volunteers
• Actual Study Start Date: December 18, 2020
• Actual Primary Completion Date: May 18, 2021
• Actual Study Completion Date: May 18, 2021

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 :

1. 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 [ Time Frame: 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.
2. Part A and Part B: Maximum Plasma Concentration (Cmax) for daprodustat [ Time Frame: 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 :

1. Part A and Part B: AUC From Time Zero to Infinity (AUC[0-inf]) for daprodustat [ Time Frame: 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.
2. Part A and Part B: Time of occurrence of Cmax (Tmax) for daprodustat [ Time Frame: 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.
3. Part A and Part B: Terminal Elimination Half-life (T1/2) for daprodustat [ Time Frame: 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.
4. Part A and Part B: Oral clearance (CL/F) for daprodustat [ Time Frame: 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.
5. Part A and Part B: Apparent Volume of Distribution (V/F) for daprodustat [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.
• 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).
• Male or female
• 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.
• 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:

• 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.
• 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.
• 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.
• 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.
• 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.
• Participants with positive pre-study drug/alcohol screen.
• Participants with regular use of known drugs of abuse.
• Participants with a positive laboratory confirmation of Coronavirus disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
• Participants with regular alcohol consumption within 6 months prior to the study.
• 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.
• 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

United States, California

GSK Investigational Site

Anaheim, California, United States, 92801

United States, Kansas

GSK Investigational Site

Overland Park, Kansas, United States, 66212

United States, Nevada

GSK Investigational Site

Las Vegas, Nevada, United States, 89113

United States, Texas

GSK Investigational Site

Austin, Texas, United States, 78744

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT04640311
• Other Study ID Numbers: 213022
• First Posted: November 23, 2020
• Last Update Posted: June 18, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• URL: http://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Daprodustat; Pharmacokinetic; Bioequivalence; Bioavailability