A Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis (HD)-Dependent Subjects With Anemia Associated With Chronic Kidney Disease (CKD)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02969655
• Date of registration: 17/11/2016
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis (HD)-Dependent Subjects With Anemia Associated With Chronic Kidney Disease (CKD)
• Scientific title: A 52-week, Phase III, Double-blind, Active-controlled, Parallel-group, Multi-center Study to Evaluate Efficacy and Safety of Daprodustat Compared to Darbepoetin Alfa in Japanese Hemodialysis-dependent Subjects With Anemia Associated With Chronic Kidney Disease Who Are Currently ESA Users
• Date of first enrolment: November 21, 2016
• Target sample size: 271
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02969655
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Japan

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria

- Age (informed consent): >=20 years of age

- Dialysis: On HD or hemodiafiltration (HDF) given three times weekly for at least 12
weeks prior to screening

- ESAs: Use of one and the same ESA for 10 weeks prior to screening

- ESA dose: Darbepoetin alfa 10 to 60 µg per week, epoetin (including biosimilars)
<=9000 international units (IU) per week, or epoetin beta pegol <=250 µg per 4 weeks

- Hgb:>=9.5 g/dL and <=12.5 g/dL. Determined at the site using an Hgb analyzer

- Iron parameters: Ferritin >100 nanogram (ng)/millilitre (mL) or transferrin saturation
(TSAT) >20 percent (screening verification only)

- Gender (screening verification only): Female or male

Females: Not pregnant [demonstrated to be negative for human chorionic gonadotropin (hCG)
in serum], not breast-feeding, and meet at least one of the following:

• Females of non-childbearing potential are defined as follows:

Pre-menopausal with at least one of the following and no plans to utilise assisted
reproductive techniques (e.g., in vitro fertilisation or donor embryo transfer):

- History of bilateral tubal ligation or salpingectomy

- History of hysteroscopic tubal occlusion and postoperatively documented bilateral
tubal obstruction

- History of hysterectomy

- History of bilateral oophorectomy Postmenopausal defined as A) females 60 years of age
or older or B) In females < 60 years of age, 12 months of spontaneous amenorrhea [in
questionable cases a blood sample with postmenopausal follicle stimulating hormone
(FSH) and estradiol concentrations is confirmatory (see separately specified reference
ranges)]. Females on hormone replacement therapy (HRT) whose menopausal status is in
doubt will be required to use one of the most effective contraception methods if they
wish to continue their HRT during the study. Otherwise they must discontinue HRT to
allow confirmation of post-menopausal status prior to study enrolment.

• Females of childbearing potential must agree to comply with one of the contraception
methods listed as requirements in "GlaxoSmithKline (GSK) Listing of Most Effective
Contraceptive Methods for Females of Childbearing Potential from 28 days prior to the
first dose of study medication until the completion of the follow-up visit.

- Informed consent: Written informed consent, including adherence to the requirements
and conditions specified in the consent form and the protocol, must be obtained from
each subject.

Exclusion Criteria

CKD-related criteria

- Kidney transplant: Planned living-related kidney transplant during the study

Anemia-related criteria

- Aplasia: History of bone-marrow hypoplasia or pure red cell aplasia

- Other causes of anemia: pernicious anemia, thalassemia, sickle cell anemia, or
myelodysplastic syndromes

- Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or
esophageal ulcer disease OR clinically significant GI bleeding within 10 weeks prior
to screening or during a period from screening to Day 1

Cardiovascular disease-related criteria

- Myocardial infarction, acute coronary syndrome, stroke, or transient ischemic attack:
Diagnosed within 10 weeks prior to screening or during a period from screening to Day
1

- Heart failure: Chronic Class IV heart failure, as defined by the New York Heart
Association (NYHA) functional classification system

- Corrected QT (QTc) Interval (screening verification only): QTc >500 milliseconds
(msec); or QTc >530 msec in subjects with bundle branch block Note: QT interval
corrected using the Bazett's formula (QTcB) will be used, and electrocardiogram (ECG)
can be mechanically or manually read

Other disease-related criteria:

- Liver disease (if any of the following occurs):

- Alanine transaminase (ALT) >2 upper limit of normal (ULN)

- Bilirubin >1.5×ULN (isolated bilirubin >1.5 ULN is acceptable if bilirubin is
fractionated and direct bilirubin is <35 percent)

- Current unstable active liver or biliary disease (generally defined by the onset
of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric
varices, persistent jaundice, or cirrhosis)

- Malignancy: History of malignancy within 2 years prior to screening, currently
receiving treatment for cancer, or complex kidney cyst >3 centimeters (cm) (II F, III
or IV based on the Bosniak classification)

Concomitant medication and other study treatment-related criteria

- Iron: Planned use of intravenous iron during the screening phase or during a period
from Day 1 to Week 4

- Severe allergic reactions: History of severe allergic or anaphylactic reactions or
hypersensitivity to excipients in the investigational product.

- Drugs and supplements: Use or planned use of any prescription or non-prescription
drugs or dietary supplements that are prohibited during the study period [prohibited
medications: strong inducers and inhibitor of Cytochrome P450 (CYP) 2C8].

- Prior investigational product exposure: Use of an investigational agent within 30 days
or five half lives of the investigational agent (whichever is longer)

- Prior treatment with daprodustat: Any prior treatment with daprodustat for a treatment
duration of >30 days

General health-related criteria

- Other conditions: Any other condition, clinical or laboratory abnormality, or
examination finding that the investigator (or subinvestigator) considers would put the
subject at unacceptable risk, which may affect study compliance or prevent
understanding of the aims or investigational procedures or possible consequences of
the study.



Age minimum: 20 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Anaemia

Intervention(s)

Drug: Daprodustat large placebo

Drug: Daprodustat small

Drug: Daprodustat large

Drug: Daprodustat small placebo

Drug: Darbepoetin alfa

Drug: Darbepoetin alfa placebo

Primary Outcome(s)

Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) [Time Frame: Weeks 40 to 52]

Secondary Outcome(s)

Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat [Time Frame: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24]

Percentage of Participants by Hgb Change From Baseline Category at Week 4 [Time Frame: Week 4]

Percentage of Participants With Mean Hgb in the Target Range (10.0-12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) [Time Frame: Weeks 40 to 52]

Change From Baseline in Hgb (Hgb Increase Rate) at Week 4 [Time Frame: Baseline and Week 4]

Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit [Time Frame: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

Change From Baseline in Hgb Values at Each Assessment Visit [Time Frame: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

Distribution of Daprodustat Dose Level by Visit [Time Frame: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48)]

Percentage of Time in Hgb Target Range (10.0 to 12.0 g/dL) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) [Time Frame: Weeks 40 to 52]

Maximum Concentration (Cmax) of Plasma Daprodustat [Time Frame: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24]

Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks [Time Frame: Up to Week 52]

Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL [Time Frame: Up to Week 52]

Number of Dose Adjustments for Daprodustat [Time Frame: Up to Week 52]

Number of Episodes With Hgb Level of More Than 13.0 g/dL [Time Frame: Up to Week 52]

Distribution of Darbepoetin Alfa Dose Level by Visit [Time Frame: Day 1, Weeks 2,4,6,8,10,12,14,16,18,20,22,24,26,28,30,32,34,36,38,40,42,44,46,48, and 50]

Hgb Values at Each Assessment Visit [Time Frame: Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52]

Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL [Time Frame: Up to Week 52]

Duration of Treatment Interruption Due to Hgb >13 g/dL [Time Frame: Up to Week 52]

Secondary ID(s)

201754

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/11/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02969655