Clinical Trials Register

Summary
EudraCT Number:	2017-002270-39
Sponsor's Protocol Code Number:	205270
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-12-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2017-002270-39

A.3

Full title of the trial

A 28-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center, study in recombinant human erythropoietin (rhEPO) naïve non-dialysis participants with anemia associated with chronic kidney disease to evaluate the efficacy, safety and effects on quality of life of daprodustat compared to placebo.

Estudio multicéntrico, aleatorizado, doble ciego, controlado con placebo, de grupos paralelos y de 28 semanas de duración para evaluar la eficacia, la seguridad y los efectos sobre la calidad de vida de daprodustat en comparación con placebo en participantes con anemia asociada a una nefropatía crónica que no están en diálisis y no han recibido eritropoyetina humana recombinante (EPOrh)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat in Non-Dialysis participants evaluating Hemoglobin and Quality of life (ASCEND-NHQ)

Estudio de anemia en pacientes con Nefropatía Crónica (NC): eritropoyesis inducida por un nuevo IPH(daprodustat) en participantes que no requieren diálisis para evaluar la hemoglobina y la calidad de vida (ASCEND-NHQ)

A.3.2

Name or abbreviated title of the trial where available

Anemia Studies in CKD: Erythropoiesis via a Novel PHI Daprodustat-Non Dialysis (ASCEND-NHQ)

Estudios de anemia en nefropatía crónica (NC): Eritropoyesis inducida por un nuevo IPH (daprodustat)

A.4.1

Sponsor's protocol code number

205270

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline, S.A.
B.1.3.4	Country	Spain
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline Research & Development Ltd
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline
B.5.2	Functional name of contact point	Centro de Información
B.5.3	Address:
B.5.3.1	Street Address	C/Severo Ochoa, 2 (P.T.M.)
B.5.3.2	Town/ city	Tres Cantos (Madrid)
B.5.3.3	Post code	28760
B.5.3.4	Country	Spain
B.5.4	Telephone number	902202700
B.5.5	Fax number	918070479
B.5.6	E-mail	es-ci@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Daprodustat 1mg
D.3.2	Product code	GSK1278863
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	daprodustat
D.3.9.1	CAS number	960539-70-2
D.3.9.2	Current sponsor code	GSK1278863
D.3.9.3	Other descriptive name	GSK1278863
D.3.9.4	EV Substance Code	SUB72830
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Daprodustat 2mg
D.3.2	Product code	GSK1278863
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	daprodustat
D.3.9.1	CAS number	960539-70-2
D.3.9.2	Current sponsor code	GSK1278863
D.3.9.3	Other descriptive name	GSK1278863
D.3.9.4	EV Substance Code	SUB72830
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Daprodustat 4mg
D.3.2	Product code	GSK1278863
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	daprodustat
D.3.9.1	CAS number	960539-70-2
D.3.9.2	Current sponsor code	GSK1278863
D.3.9.3	Other descriptive name	GSK1278863
D.3.9.4	EV Substance Code	SUB72830
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	4
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Daprodustat 6mg
D.3.2	Product code	GSK1278863
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	daprodustat
D.3.9.1	CAS number	960539-70-2
D.3.9.2	Current sponsor code	GSK1278863
D.3.9.3	Other descriptive name	GSK1278863
D.3.9.4	EV Substance Code	SUB72830
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Daprodustat 8mg
D.3.2	Product code	GSK1278863
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	daprodustat
D.3.9.1	CAS number	960539-70-2
D.3.9.2	Current sponsor code	GSK1278863
D.3.9.3	Other descriptive name	GSK1278863
D.3.9.4	EV Substance Code	SUB72830
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 6
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Daprodustat 10mg
D.3.2	Product code	GSK1278863
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	daprodustat
D.3.9.1	CAS number	960539-70-2
D.3.9.2	Current sponsor code	GSK1278863
D.3.9.3	Other descriptive name	GSK1278863
D.3.9.4	EV Substance Code	SUB72830
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Anaemia associated with chronic kidney disease

Anemia asociada a una nefropatía crónica.

E.1.1.1

Medical condition in easily understood language

Anaemia associated with chronic kidney disease

Anemia asociada a una nefropatía crónica.

E.1.1.2

Therapeutic area

Body processes [G] - Physiological processes [G07]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the efficacy of daprodustat to placebo on mean change in Hgb levels

Comparar la eficacia de daprodustat con la del placebo en cuanto a la variación media de los valores de Hb.

E.2.2

Secondary objectives of the trial

To compare the proportion of participants achieving increases in Hgb when treated with daprodustat versus placebo.
To compare daprodustat to placebo for health related quality-of-life

Comparar la proporción de participantes que alcanzan valores de Hb mayores al recibir daprodustat frente al tratamiento con placebo.
Comparar la calidad de vida relacionada obtenida con daprodustat y con el placebo.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Age
1. ≥18 years of age at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. CKD: Have CKD, confirmed at screening: Kidney Disease Outcomes Quality Initiative (KDOQI) CKD stages 3, 4, or 5 defined by Estimated glomerular filtration rate (eGFR) using the CKD Epidemiology Collaboration (CKD-EPI formula [Levey, 2009].
3. Hgb: Stable HemoCue Hgb from 8.5 to 10.5 at screening visit (Week -4) and from 8.5 to 10.0 g/dL at randomization (Day 1) (Section 9.1 of the study protocol).
4. IV Iron: Participants may receive up to one IV iron dose within the 8 weeks prior to screening and NO IV iron use between screening visit and randomization (Day 1).
5. Oral Iron: If needed, participant may be on stable maintenance oral iron supplementation. The type of iron and dose must not be changed for the 4 weeks prior to screening (Week -4), through the screening period, and until randomization (Day 1).
Sex
6. Male and female participants are eligible. A female participant is eligible to participate if she is not pregnant (see Section 12.4), not breastfeeding, and at leastone of the following conditions applies:
Not a woman of childbearing potential (WOCBP) as defined in Section
12.4 (Appendix 4) of the study protocol, or
A WOCBP who agrees to follow the contraceptive guidance in
Appendix 4 of the study protocol during the treatment period and for at least 4 weeks after the last dose of study treatment.
Informed Consent
7. Capable of giving signed informed consent as described in Section 12.2
Appendix 2 of the study protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Edad
1. ≥18 años de edad en el momento de firmar el consentimiento informado.
Tipo de participante y características de la enfermedad
2. Nefropatía Crónica (NC): presentar una NC, confirmada en la selección: estadios 3, 4 o 5 de NC según la Kidney Disease Outcomes Quality Initiative (KDOQI) definidos a partir de la filtración glomerular estimada (FGe) con la fórmula CKD-EPI.
3. Hemoglobina (Hb): valor de Hb mediante HemoCue estable de 8,5 a 10,5 en la visita de selección (semana -4) y de 8,5 a 10,0 g/dl en la aleatorización (día 1).
4. Hierro intravenoso (IV): los participantes podrán recibir como máximo una dosis de hierro IV en las 8 semanas previas a la selección y NO podrán recibir hierro IV entre la visita de selección y la aleatorización (día 1).
5. Hierro oral: el participante podrá tomar suplementos de hierro oral en dosis de mantenimiento estables. No se podrá variar el tipo ni la dosis de hierro en las 4 semanas previas a la selección (semana -4), ni durante todo el período de selección hasta la aleatorización (día 1).
Sexo
6. Podrán participar tanto varones como mujeres. Las mujeres podrán participar si no están embarazadas (véase la sección 12.4) ni dando de mamar, y se cumple al menos una de las condiciones siguientes:
No están en edad fértil (MEF), o
Son MEF que se comprometen a seguir las medidas anticonceptivas durante el periodo de tratamiento y durante al menos 4 semanas después de la última dosis del tratamiento del estudio.
Consentimiento informado
7. Capaces de otorgar su consentimiento informado firmado, lo que incluye el cumplimiento de los requisitos y restricciones enumerados en el documento de consentimiento informado (DCI) y en este protocolo.

E.4

Principal exclusion criteria

CKD Related Criteria
1. Dialysis: On dialysis or clinical evidence of impending need to initiate dialysis within 180 days after randomization (Day 1).
2. Kidney Transplant: Planned living-related or living-unrelated kidney transplant within 28 weeks after randomization (Day 1).
Anemia-Related Criteria
3. Transferrin saturation (TSAT) <15% (Screening only)
4. Ferritin <50 ng/mL (Screening only)
5. rhEPO or rhEPO analogues: History of rhEPO or rhEPO analogue use within the 8 weeks prior to screening and rhEPO use between screening and randomization (Day 1).
6. Transfusion: History of transfusion within the 8 weeks prior to screening and transfusion between screening and randomization (Day 1).
7. Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA)
8. Other causes of anemia: Megaloblastic anemia(untreated pernicious anemia and folate deficiency), thalassemia major, sickle cell disease or myelodysplastic syndrome
9. Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease OR clinically significant GI bleeding ≤ 8 weeks prior to screening through to randomization (Day 1)
Concomitant medication and other study treatment-related criteria
10. Severe Allergic reaction: History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product.
11. Drugs and supplements: Use of strong inhibitor of CYP2C8 (e.g.,gemfibrozil) or strong inducers of CYP2C8 (e.g., rifampin/rifampicin).
12. Ferric Citrate: Ferric citrate use within 4 weeks prior to randomization (Day 1)
Prior Clinical Study Experience
13. Other interventional study participation: Use of another investigational agent within 30 days or within five half-lives of the investigational agent (whichever is longer) or currently participating in a study of an investigational device prior to screening through to randomization (Day 1).
14. Prior treatment with daprodustat: Any prior treatment with daprodustat for a treatment duration of >30 days.
Cardiovascular Disease-Related Criteria
15. MI or acute coronary syndrome: within the 8 weeks prior to screening through to randomization. (Day 1)
16. Stroke or transient ischemic attack: within the 8 weeks prior to screening through to randomization. (Day 1)
17. Heart failure: Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system
18. QTcB (Day 1): QTcB >500 msec or QTcB >530 msec in participants with bundle branch block. There is no QTc exclusion for participants with a predominantly paced rhythm.
Other Disease Related Criteria
19. Liver Disease-Related Criteria:
- Alanine transaminase (ALT) >2x upper limit of normal (ULN) at screening(Week -4).
- Bilirubin >1.5xULN at screening (Week -4). NOTE: Isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%.
- Current unstable liver or biliary disease per investigator assessment,
generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. NOTE: Stable chronic liver disease (including asymptomatic gallstones, chronic hepatitis B or C, or Gilbert’s syndrome) is acceptable if participant otherwise meets entry criteria.
20. Malignancy: History of malignancy within the 2 years prior to screening through to randomization (Day 1), or currently receiving treatment for cancer, or complex kidney cyst (e.g. Bosniak Category II F, III or IV) > 3cm. Note: The only exception is localized squamous cell or basal cell carcinoma of the skin that has been definitively treated ≥8 weeks prior to screening.
Other Exclusion
21. Other Conditions: Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the participant at unacceptable risk, which may affect study compliance or prevent understanding of the aims or investigational procedures or possible consequences of the study.

1. Diálisis: en diálisis o con indicios clínicos de necesidad inminente de iniciar la diálisis en los 180 días siguientes a la aleatorización (día 1).
2. Trasplante renal: trasplante renal programado de un donante vivo emparentado o no emparentado en las 28 semanas siguientes a la aleatorización (día 1).
Criterios relacionados con la anemia
3. Saturación de transferrina (TSAT) < 15% (solo en la selección)
4. Ferritina < 50 ng/ml (solo en la selección)
5. rhEPO o análogos de rhEPO: uso de rhEPO o de análogos de rhEPO en las 8 semanas previas a la selección y uso de rhEPO entre la selección y la aleatorización (día 1).
6. Transfusión: antecedentes de transfusiones en las 8 semanas previas a la selección o entre la selección y la aleatorización (día 1).
7. Aplasias: antecedentes de aplasia medular o de aplasia eritrocitaria pura (AEP).
8. Otras causas de anemia: anemia megaloblástica (anemia perniciosa no tratada y carencia de ácido fólico), talasemia mayor, drepanocitosis o síndrome mielodisplásico.
9. Hemorragia digestiva: signos de úlcera gástrica, duodenal o esofágica sangrante activa O hemorragia digestiva clínicamente importante entre las 8 semanas previas a la selección y la aleatorización (día 1).
Medicación concomitante y otros criterios relacionados con el tratamiento del estudio
10. Reacción alérgica grave: antecedentes de reacciones alérgicas o anafilácticas intensas o hipersensibilidad a los excipientes del producto en investigación.
11. Medicamentos y suplementos: uso de inhibidores potentes de la CYP2C8 (p. ej., gemfibrozilo) o de inductores potentes de la CYP2C8 (p. ej., rifampicina).
12. Citrato férrico: uso de citrato férrico en las 4 semanas previas a la aleatorización (día 1).
Experiencia en estudios clínicos previos
13. Participación en otro estudio de intervención: Uso de otro fármaco en investigación en los 30 días anteriores o en un plazo previo de cinco semividas del fármaco en investigación (lo que suponga más tiempo) o participación actual en un estudio de un producto en investigación entre la selección y la aleatorización (día 1).
14. Tratamiento previo con daprodustat: cualquier tratamiento previo con daprodustat durante >30 días.
Criterios relacionados con enfermedades cardiovasculares
15. IM o síndrome coronario agudo: entre las 8 semanas previas a la selección y la aleatorización. (Día 1)
16. Ictus o accidente isquémico transitorio: entre las 8 semanas previas a la selección y la aleatorización. (Día 1)
17. Insuficiencia cardíaca: insuficiencia cardíaca crónica de clase IV según la definición del sistema de clasificación funcional de la New York Heart Association (NYHA).
18. QTcB (día 1): QTcB > 500 ms o QTcB > 530 ms en los participantes con bloqueo de rama. No se aplicará ningún criterio de exclusión basado en el QTc si el participante tiene un ritmo predominantemente regular.
Criterios relacionados con otras enfermedades
19. Criterios relacionados con enfermedades hepáticas:
- Alanina transaminasa (ALT) >2 x límite superior de la normalidad (LSN) en la selección (semana -4).
- Bilirrubina >1,5 x LSN en la selección (semana -4). NOTA: Es aceptable una bilirrubina aislada >1,5 x LSN si la bilirrubina está fraccionada y la bilirrubina directa es <35%.
- Enfermedad hepática o biliar inestable actual conforme a la evaluación del investigador, definida de forma general por la presencia de ascitis, encefalopatía, coagulopatía, hipoalbuminemia, varices esofágicas o gástricas, ictericia persistente o cirrosis. NOTA: Se aceptará la presencia de una hepatopatía estable (colelitiasis asintomática, hepatitis B o C crónica o síndrome de Gilbert) si el participante cumple los demás criterios de inclusión.
20. Neoplasias malignas: Antecedentes de neoplasia maligna en los 2 años previos al período comprendido entre la selección y la aleatorización (día 1) o tratamiento actual para el cáncer, o presencia de un quiste renal complejo (p. ej., categoría de Bosniak II F, III o IV) >3 cm. Nota: La única excepción es el carcinoma espinocelular o basocelular localizado de la piel que se haya tratado de forma definitiva ≥8 semanas antes de la selección.
Otros criterios de exclusión
21. Otros trastornos: Cualquier otro trastorno, anomalía clínica o analítica, o resultado de una exploración que el investigador considere que suponga un riesgo inaceptable para el participante, que puedan afectar al cumplimiento del estudio o que impidan comprender los objetivos, los procedimientos de investigación o las posibles consecuencias del estudio.

E.5 End points

E.5.1

Primary end point(s)

Mean change in Hgb between baseline and the Evaluation Period (EP, mean over week 24 to week 28 inclusive)

Variación media de los valores de Hb entre el momento basal y el período de evaluación (PE, media entre las semanas 24 y 28).

E.5.1.1

Timepoint(s) of evaluation of this end point

Evaluation period is mean over week 24 to week 28 inclusive.

Periodo de evaluación es la media entre las semanas 24 y 28, ambas incluida.

E.5.2

Secondary end point(s)

% of participants having a Hgb increase of ≥1.0 g/dL from baseline to EP.
Mean Change in SF-36 Vitality domain between baseline and Week 28

1. Porcentaje de participantes que logra un aumento de la Hb ≥1,0 g/dl hasta el PE.
2. Variación media en la puntuación dela vitalidad del Cuestionario (SF-36) entre el momento basal y la semana 28.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. from baseline at any post-baseline visit.
2. between baseline and Week 28

1. desde visita basal y en cualquier visita posterior a la basal.
2. entre la visita basal y la semana 28

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Brazil

Canada

France

Italy

Korea, Republic of

Mexico

Poland

Romania

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

Última visita del último paciente.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

300

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

200

F.4.2.2

In the whole clinical trial

600

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Participants will not receive any additional treatment from GSK after completion of the study. The investigator is responsible for ensuring that consideration has been given to post-study care of the participant’s medical condition.

Los participantes no recibirán ningún tratamiento adicional de GSK después de la finalización del estudio.
El investigador será responsable de garantizar que se tenga en cuenta la asistencia adecuada del sujeto después del estudio, una vez
finalizado el tratamiento del estudio.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-02-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-01-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-10-07

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Orphan Designation Number:
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