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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04640311

Enrollment

259

Registered

2020-11-23

Start date

2020-12-18

Completion date

2021-05-18

Last updated

2025-04-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anaemia

Keywords

Daprodustat, Pharmacokinetic, Bioequivalence, Bioavailability

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.

Interventions

DRUGDaprodustat

Daprodustat will be available as oral tablets.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
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	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	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.
Part B: AUC(0-t) 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 and 2	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.
Part A: Maximum Observed Plasma Concentration (Cmax) 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	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.
Part B: Cmax 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 and 2	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.

Secondary

Measure	Time frame	Description
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	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Part B: 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 and 2	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Part B: 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 and 2	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
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	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Part B: 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 and 2	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Part B: 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 and 2	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Part B: 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 and 2	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
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	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
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	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
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	Blood samples were collected at indicated time points to investigate the pharmacokinetics of daprodustat. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

Countries

United States

Participant flow

Recruitment details

Participants were enrolled across 4 centers in the United States. This study consisted of two parts; Part A (3-period crossover study) and Part B (2-period crossover study).

Pre-assignment details

A total of 259 participants (52 in Part A and 207 in Part B) were enrolled in the study (Safety Population: It comprised of all randomized participants who have taken at least 1 dose of study intervention).

Participants by arm

Arm	Count
Part A: Daprodustat DP 1 Process 2/Daprodustat DP 2 Process 2/Daprodustat Process 1 Participants received a single oral dose of daprodustat 4 milligrams (mg) tablets with dissolution profile (DP) 1 made by Process 2 (high shear wet granulation) in Treatment Period 1 followed by a single oral dose of daprodustat 4 mg tablets with DP 2 made by Process 2 in Treatment Period 2. Participants were administered a single oral dose of daprodustat 4 mg tablets made by reference Process 1 (twin screw granulation) in Treatment Period 3. There was a washout of at least 7 days after daprodustat dosing in Treatment Periods 1 and 2. Participants were followed up for 7 days after last dose in Treatment Period 3.	16
Part A: Daprodustat DP 2 Process 2/ Daprodustat Process 1 / Daprodustat DP 1 Process 2 Participants received a single oral dose of daprodustat 4 mg tablets with DP 2 made by Process 2 in Treatment Period 1 followed by a single oral dose of daprodustat 4 mg tablets made by reference Process 1 in Treatment Period 2. Participants were administered a single oral dose of daprodustat 4 mg tablets with DP 1 made by Process 2 in Treatment Period 3. There was a washout of at least 7 days after daprodustat dosing in Treatment Periods 1 and 2. Participants were followed up for 7 days after last dose in Treatment Period 3.	18
Part A: Daprodustat Process 1 / Daprodustat DP 1 Process 2/ Daprodustat DP 2 Process 2 Participants received a single oral dose of daprodustat 4 mg tablets made by reference Process 1 in Treatment Period 1 followed by a single oral dose of daprodustat 4 mg tablets with DP 1 made by Process 2 in Treatment Period 2. Participants were administered a single oral dose of daprodustat 4 mg tablets with DP 2 made by Process 2 in Treatment Period 3. There was a washout of at least 7 days after daprodustat dosing in Treatment Periods 1 and 2. Participants were followed up for 7 days after last dose in Treatment Period 3.	18
Part B: Daprodustat 1 mg Process 2/ Daprodustat 1 mg Process 1 Participants received a single oral dose of daprodustat 1 mg tablets made by Process 2 in Treatment Period 1 followed by a single oral dose of daprodustat 1 mg tablets made by Process 1 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	21
Part B: Daprodustat 1 mg Process 1/Daprodustat 1 mg Process 2 Participants received a single oral dose of daprodustat 1 mg tablets made by Process 1 in Treatment Period 1 followed by a single oral dose of daprodustat 1 mg tablets made by Process 2 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	19
Part B: Daprodustat 2 mg Process 2/Daprodustat 2 mg Process 1 Participants received a single oral dose of daprodustat 2 mg tablets made by Process 2 in Treatment Period 1 followed by a single oral dose of daprodustat 2 mg tablets made by Process 1 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	21
Part B: Daprodustat 2 mg Process 1/ Daprodustat 2 mg Process 2 Participants received a single oral dose of daprodustat 2 mg tablets made by Process 1 in Treatment Period 1 followed by a single oral dose of daprodustat 2 mg tablets made by Process 2 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	22
Part B: Daprodustat 4 mg Process 2/ Daprodustat 4 mg Process 1 Participants received a single oral dose of daprodustat 4 mg tablets made by Process 2 in Treatment Period 1 followed by a single oral dose of daprodustat 4 mg tablets made by Process 1 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	21
Part B: Daprodustat 4 mg Process 1/Daprodustat 4 mg Process 2 Participants received a single oral dose of daprodustat 4 mg tablets made by Process 1 in Treatment Period 1 followed by a single oral dose of daprodustat 4 mg tablets made by Process 2 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	21
Part B: Daprodustat 6 mg Process 2/Daprodustat 6 mg Process 1 Participants received a single oral dose of daprodustat 6 mg tablets made by Process 2 in Treatment Period 1 followed by a single oral dose of daprodustat 6 mg tablets made by Process 1 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	21
Part B: Daprodustat 6 mg Process 1/Daprodustat 6 mg Process 2 Participants received a single oral dose of daprodustat 6 mg tablets made by Process 1 in Treatment Period 1 followed by a single oral dose of daprodustat 6 mg tablets made by Process 2 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	21
Part B: Daprodustat 8 mg Process 2/Daprodustat 8 mg Process 1 Participants received a single oral dose of daprodustat 8 mg tablets made by Process 2 in Treatment Period 1 followed by a single oral dose of daprodustat 8 mg tablets made by Process 1 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	20
Part B: Daprodustat 8 mg Process 1/Daprodustat 8 mg Process 2 Participants received a single oral dose of daprodustat 8 mg tablets made by Process 1 in Treatment Period 1 followed by a single oral dose of daprodustat 8 mg tablets made by Process 2 in Treatment Period 2. There was a washout of at least 7 days after daprodustat dosing in Treatment Period 1. Participants were followed up for 7 days after last dose in Treatment Period 2.	20
Total	259

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG005	FG006	FG008	FG010	FG011
Part A:Treatment Period 1 (Up to 2 Days)	Physician Decision	1	0	0	0	0	0	0	0	0
Part A:Treatment Period 1 (Up to 2 Days)	Protocol Violation	0	1	0	0	0	0	0	0	0
Part A:Treatment Period 1 (Up to 2 Days)	Withdrawn by sponsor due to impact of inclement weather events	0	1	0	0	0	0	0	0	0
Part A:Treatment Period 2 (Up to 2 Days)	Adverse Event	0	0	2	0	0	0	0	0	0
Part A:Treatment Period 2 (Up to 2 Days)	Withdrawn by sponsor due to impact of inclement weather events	3	5	6	0	0	0	0	0	0
Part B:Treatment Period 1 (Up to 2 Days)	Adverse Event	0	0	0	0	0	1	0	1	0
Part B:Treatment Period 1 (Up to 2 Days)	Physician Decision	0	0	0	0	1	0	2	0	0
Part B:Treatment Period 1 (Up to 2 Days)	Withdrawal by Subject	0	0	0	1	0	1	0	0	0
Part B: Treatment Period 2(Up to 2 Days)	Withdrawal by Subject	0	0	0	0	0	0	0	0	1

Baseline characteristics

Characteristic	Total	Part A: Daprodustat DP 2 Process 2/ Daprodustat Process 1 / Daprodustat DP 1 Process 2	Part A: Daprodustat Process 1 / Daprodustat DP 1 Process 2/ Daprodustat DP 2 Process 2	Part B: Daprodustat 1 mg Process 2/ Daprodustat 1 mg Process 1	Part B: Daprodustat 1 mg Process 1/Daprodustat 1 mg Process 2	Part B: Daprodustat 2 mg Process 2/Daprodustat 2 mg Process 1	Part B: Daprodustat 2 mg Process 1/ Daprodustat 2 mg Process 2	Part A: Daprodustat DP 1 Process 2/Daprodustat DP 2 Process 2/Daprodustat Process 1	Part B: Daprodustat 4 mg Process 2/ Daprodustat 4 mg Process 1	Part B: Daprodustat 4 mg Process 1/Daprodustat 4 mg Process 2	Part B: Daprodustat 6 mg Process 2/Daprodustat 6 mg Process 1	Part B: Daprodustat 6 mg Process 1/Daprodustat 6 mg Process 2	Part B: Daprodustat 8 mg Process 2/Daprodustat 8 mg Process 1	Part B: Daprodustat 8 mg Process 1/Daprodustat 8 mg Process 2
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	259 Participants	18 Participants	18 Participants	21 Participants	19 Participants	21 Participants	22 Participants	16 Participants	21 Participants	21 Participants	21 Participants	21 Participants	20 Participants	20 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian - Central/ South Asian Heritage	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	4 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	9 Participants	0 Participants	0 Participants	1 Participants	2 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian - Mixed Race	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	9 Participants	0 Participants	1 Participants	1 Participants	0 Participants	2 Participants	2 Participants	0 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Black or African American	111 Participants	4 Participants	7 Participants	8 Participants	10 Participants	9 Participants	9 Participants	4 Participants	11 Participants	13 Participants	5 Participants	2 Participants	12 Participants	17 Participants
Race/Ethnicity, Customized Mixed Race	4 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White - Arabic/ North African Heritage	12 Participants	3 Participants	1 Participants	2 Participants	2 Participants	1 Participants	2 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized White - White/ Caucasian/ European Heritage	100 Participants	10 Participants	9 Participants	8 Participants	3 Participants	5 Participants	6 Participants	10 Participants	9 Participants	3 Participants	13 Participants	14 Participants	7 Participants	3 Participants
Sex: Female, Male Female	86 Participants	6 Participants	8 Participants	8 Participants	7 Participants	11 Participants	10 Participants	5 Participants	4 Participants	8 Participants	6 Participants	4 Participants	5 Participants	4 Participants
Sex: Female, Male Male	173 Participants	12 Participants	10 Participants	13 Participants	12 Participants	10 Participants	12 Participants	11 Participants	17 Participants	13 Participants	15 Participants	17 Participants	15 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk
deaths Total, all-cause mortality	0 / 46	0 / 45	0 / 43	0 / 39	0 / 40	0 / 42	0 / 41	0 / 42	0 / 40	0 / 42	0 / 41	0 / 40	0 / 40
other Total, other adverse events	2 / 46	3 / 45	0 / 43	1 / 39	1 / 40	3 / 42	1 / 41	3 / 42	5 / 40	6 / 42	1 / 41	5 / 40	0 / 40
serious Total, serious adverse events	0 / 46	0 / 45	0 / 43	0 / 39	0 / 40	0 / 42	0 / 41	1 / 42	0 / 40	0 / 42	0 / 41	0 / 40	0 / 40

Outcome results

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.

Time frame: 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

Population: Pharmacokinetic Population comprised of all participants in the Safety Population (All randomized participants who have taken at least 1 dose of study intervention) who had at least 1 non-missing Pharmacokinetic assessment (Non-quantifiable \[NQ\] values were considered as non-missing values).

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: Daprodustat Process 1	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	155.5 Hours*nanograms per milliliter	Geometric Coefficient of Variation 14.7
Part A: Daprodustat Process 2 Dissolution Profile 1	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	159.9 Hours*nanograms per milliliter	Geometric Coefficient of Variation 14.7
Part A: Daprodustat Process 2 Dissolution Profile 2	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	158.5 Hours*nanograms per milliliter	Geometric Coefficient of Variation 14.7

90% CI: [0.9699, 1.09]

90% CI: [0.9602, 1.081]

Primary

Part A: Maximum Observed Plasma Concentration (Cmax) Following Administration of Daprodustat

Time frame: 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

Population: Pharmacokinetic Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: Daprodustat Process 1	Part A: Maximum Observed Plasma Concentration (Cmax) Following Administration of Daprodustat	68.22 Nanograms per milliliter	Geometric Coefficient of Variation 28.7
Part A: Daprodustat Process 2 Dissolution Profile 1	Part A: Maximum Observed Plasma Concentration (Cmax) Following Administration of Daprodustat	71.06 Nanograms per milliliter	Geometric Coefficient of Variation 28.7
Part A: Daprodustat Process 2 Dissolution Profile 2	Part A: Maximum Observed Plasma Concentration (Cmax) Following Administration of Daprodustat	71.51 Nanograms per milliliter	Geometric Coefficient of Variation 28.7

90% CI: [0.9308, 1.166]

90% CI: [0.9349, 1.175]

Primary

Part B: AUC(0-t) Following Administration of Daprodustat

Time frame: 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

Population: Pharmacokinetic Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: Daprodustat Process 1	Part B: AUC(0-t) Following Administration of Daprodustat	36.97 Hours*nanograms per milliliter	Geometric Coefficient of Variation 13.5
Part A: Daprodustat Process 2 Dissolution Profile 1	Part B: AUC(0-t) Following Administration of Daprodustat	38.02 Hours*nanograms per milliliter	Geometric Coefficient of Variation 13.5
Part A: Daprodustat Process 2 Dissolution Profile 2	Part B: AUC(0-t) Following Administration of Daprodustat	83.27 Hours*nanograms per milliliter	Geometric Coefficient of Variation 17
Part B: Daprodustat 2 mg Process 2	Part B: AUC(0-t) Following Administration of Daprodustat	79.08 Hours*nanograms per milliliter	Geometric Coefficient of Variation 17
Part B: Daprodustat 4 mg Process 1	Part B: AUC(0-t) Following Administration of Daprodustat	132.9 Hours*nanograms per milliliter	Geometric Coefficient of Variation 15.4
Part B: Daprodustat 4 mg Process 2	Part B: AUC(0-t) Following Administration of Daprodustat	134.2 Hours*nanograms per milliliter	Geometric Coefficient of Variation 15.4
Part B: Daprodustat 6 mg Process 1	Part B: AUC(0-t) Following Administration of Daprodustat	249.5 Hours*nanograms per milliliter	Geometric Coefficient of Variation 16.3
Part B: Daprodustat 6 mg Process 2	Part B: AUC(0-t) Following Administration of Daprodustat	241.5 Hours*nanograms per milliliter	Geometric Coefficient of Variation 16.3
Part B: Daprodustat 8 mg Process 1	Part B: AUC(0-t) Following Administration of Daprodustat	292.8 Hours*nanograms per milliliter	Geometric Coefficient of Variation 16.3
Part B: Daprodustat 8 mg Process 2	Part B: AUC(0-t) Following Administration of Daprodustat	278.5 Hours*nanograms per milliliter	Geometric Coefficient of Variation 16.3

90% CI: [0.977, 1.083]

90% CI: [0.8914, 1.012]

90% CI: [0.9533, 1.07]

90% CI: [0.9115, 1.028]

90% CI: [0.8948, 1.011]

Primary

Part B: Cmax Following Administration of Daprodustat

Time frame: 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

Population: Pharmacokinetic Population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part A: Daprodustat Process 1	Part B: Cmax Following Administration of Daprodustat	17.90 Nanograms per milliliter	Geometric Coefficient of Variation 22.2
Part A: Daprodustat Process 2 Dissolution Profile 1	Part B: Cmax Following Administration of Daprodustat	17.39 Nanograms per milliliter	Geometric Coefficient of Variation 22.2
Part A: Daprodustat Process 2 Dissolution Profile 2	Part B: Cmax Following Administration of Daprodustat	39.20 Nanograms per milliliter	Geometric Coefficient of Variation 28.8
Part B: Daprodustat 2 mg Process 2	Part B: Cmax Following Administration of Daprodustat	35.30 Nanograms per milliliter	Geometric Coefficient of Variation 28.8
Part B: Daprodustat 4 mg Process 1	Part B: Cmax Following Administration of Daprodustat	62.05 Nanograms per milliliter	Geometric Coefficient of Variation 30.9
Part B: Daprodustat 4 mg Process 2	Part B: Cmax Following Administration of Daprodustat	60.21 Nanograms per milliliter	Geometric Coefficient of Variation 30.9
Part B: Daprodustat 6 mg Process 1	Part B: Cmax Following Administration of Daprodustat	113.4 Nanograms per milliliter	Geometric Coefficient of Variation 26.7
Part B: Daprodustat 6 mg Process 2	Part B: Cmax Following Administration of Daprodustat	109.7 Nanograms per milliliter	Geometric Coefficient of Variation 26.7
Part B: Daprodustat 8 mg Process 1	Part B: Cmax Following Administration of Daprodustat	139.5 Nanograms per milliliter	Geometric Coefficient of Variation 27.6
Part B: Daprodustat 8 mg Process 2	Part B: Cmax Following Administration of Daprodustat	120.0 Nanograms per milliliter	Geometric Coefficient of Variation 27.6

90% CI: [0.8936, 1.056]

90% CI: [0.8107, 1]

90% CI: [0.8665, 1.087]

90% CI: [0.8778, 1.066]

90% CI: [0.777, 0.9532]

Secondary