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

NCT04640311 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 213022
• Study Type: interventional
• Target: 259
• Locations: 1 country
• Sites: 4

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.

Conditions

Anaemia

Keywords

Daprodustat; Pharmacokinetic; Bioequivalence; Bioavailability

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (10)

• Part A: AUC From Zero Time (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) Following Administration of Daprodustat

  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

  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

  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

  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

  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

Study Arms (5)

Part A: Daprodustat Dissolution 1/Dissolution 2/Reference

EXPERIMENTAL

Drug: Daprodustat

Part A: Daprodustat Dissolution 2/Reference/Dissolution 1

EXPERIMENTAL

Drug: Daprodustat

Part A: Daprodustat Reference/Dissolution 1/Dissolution 2

EXPERIMENTAL

Drug: Daprodustat

Part B: Daprodustat Process 1/ Process 2

EXPERIMENTAL

Drug: Daprodustat

Part B: Daprodustat Process 2/ Process 1

EXPERIMENTAL

Drug: Daprodustat

Interventions

Daprodustat DRUG

Daprodustat will be available as oral tablets.

Part A: Daprodustat Dissolution 1/Dissolution 2/Reference; Part A: Daprodustat Dissolution 2/Reference/Dissolution 1; Part A: Daprodustat Reference/Dissolution 1/Dissolution 2; Part B: Daprodustat Process 1/ Process 2; Part B: Daprodustat Process 2/ Process 1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Anaheim, California, 92801, United States

Location

GSK Investigational Site

Overland Park, Kansas, 66212, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Shaddinger B, Mahar KM, Sprys M, Andrews SM, Chattoraj S, Israni R, Cobitz A. Comparison of Two Manufacturing Processes of Daprodustat for Bioequivalence and Dissolution in Healthy Volunteers: A Randomized Crossover Study. Clin Pharmacol Drug Dev. 2023 Jul;12(7):739-748. doi: 10.1002/cpdd.1257. Epub 2023 May 1.

  PMID: 37125459 BACKGROUND

MeSH Terms

Conditions

Anemia

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 23, 2020
• Study Start: December 18, 2020
• Primary Completion: May 18, 2021
• Study Completion: May 18, 2021
• Last Updated: April 10, 2025
• Results First Posted: January 26, 2023

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

US (4)