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

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

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.

Study Overview

• Status: Completed
• Conditions: Anaemia
• Intervention / Treatment: Drug: Daprodustat

• Study Type: Interventional
• Enrollment (Actual): 259
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • GSK Investigational Site
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78744
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Area Under the Concentration-time Curve (AUC) From Zero (Pre-dose) to Time of Last Quantifiable Concentration (AUC[0-t]) Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1, 2 and 3
Part B: AUC(0-t) Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1 and 2
Part A: Maximum Observed Plasma Concentration (Cmax) Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1, 2 and 3
Part B: Cmax Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods. The geometric coefficient of variation is model adjusted and is a within-participant coefficient of variation. Analysis was performed using a mixed effect model.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1 and 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: AUC From Zero Time (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1, 2 and 3
Part A: Time of Occurrence of Cmax (Tmax) Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1, 2 and 3
Part A: Terminal Phase Half-life (T1/2) Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1, 2 and 3
Part A: Apparent Clearance Following Oral Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1, 2 and 3
Part A: Apparent Volume of Distribution Following Oral Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1, 2 and 3
Part B: AUC(0-inf) Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1 and 2
Part B: Tmax Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1 and 2
Part B: T1/2 Following Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1 and 2
Part B: Apparent Clearance Following Oral Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1 and 2
Part B: Apparent Volume of Distribution Following Oral Administration of Daprodustat	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.	Pre-dose and 30 minutes, 1 Hour, 2 Hours, 2 Hours 30 Minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in Treatment Periods 1 and 2

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Actual): May 18, 2021
• Study Completion (Actual): May 18, 2021

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: April 19, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Bioequivalence; Bioavailability; Pharmacokinetic; Daprodustat
• Other Study ID Numbers: 213022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No