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

Anaemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04640311
• Other study ID #: 213022
• Status: Completed
• Phase: Phase 1
• Start date: December 18, 2020
• Est. completion date: May 18, 2021

Study information

• Verified date: April 2022
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 259
• Est. completion date: May 18, 2021
• Est. primary completion date: May 18, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anaemia

Intervention

Drug:
• Daprodustat
Daprodustat will be available as oral tablets.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Overland Park	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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