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AnaemiaPhase 3NCT02969655

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)

A Phase 3 study testing Daprodustat small, Daprodustat large and Darbepoetin alfa in people with Anaemia, run by GlaxoSmithKline at 50 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Daprodustat is a drug that is currently being developed as a treatment for renal anemia . This study is to evaluate the efficacy and safety of daprodustat following a switch from erythropoiesis-stimulating agent (ESA) in Japanese HD subjects with renal anemia who are currently treated with ESA. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Anaemia
What is being tested?
Daprodustat small, Daprodustat large and Darbepoetin alfa
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
271 participants
Where
50 sitesJapan
Study dates
21 Nov 2016to 2 Jul 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 16Show fewer
  • 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.

Who cannot join

  • 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
Show all 24Show fewer
  • 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.

Trial locations and contacts

50 sites in 1 country.

50 sites in 1 country

Japan50 sites

  • GSK Investigational Site

    Aichi, 441-8023

  • GSK Investigational Site

    Aichi, 446-0053

  • GSK Investigational Site

    Aichi, 446-0065

  • GSK Investigational Site

    Aichi, 454-0932

  • GSK Investigational Site

    Aichi, 455-0021

  • GSK Investigational Site

    Aichi, 462-0802

  • GSK Investigational Site

    Aichi, 486-8510

  • GSK Investigational Site

    Chiba, 276-0031

  • GSK Investigational Site

    Ehime, 790-0962

  • GSK Investigational Site

    Ehime, 792-0812

  • GSK Investigational Site

    Fukui, 918-8503

  • GSK Investigational Site

    Fukuoka, 804-0094

  • GSK Investigational Site

    Fukuoka, 811-0120

  • GSK Investigational Site

    Fukuoka, 811-0213

  • GSK Investigational Site

    Fukuoka, 818-0083

  • GSK Investigational Site

    Fukushima, 963-8002

  • GSK Investigational Site

    Fukushima, 963-8071

  • GSK Investigational Site

    Gunma, 370-0615

  • GSK Investigational Site

    Gunma, 372-0817

  • GSK Investigational Site

    Gunma, 375-0024

  • GSK Investigational Site

    Hokkaido, 004-0814

  • GSK Investigational Site

    Hokkaido, 007-0803

  • GSK Investigational Site

    Hokkaido, 073-0022

  • GSK Investigational Site

    Hokkaido, 073-0196

  • GSK Investigational Site

    Ibaraki, 300-0062

  • GSK Investigational Site

    Ibaraki, 302-0011

  • GSK Investigational Site

    Ibaraki, 305-0861

  • GSK Investigational Site

    Kagawa, 761-8024

  • GSK Investigational Site

    Kanagawa, 224-0032

  • GSK Investigational Site

    Kanagawa, 227-0046

  • GSK Investigational Site

    Kanagawa, 234-0054

  • GSK Investigational Site

    Kanagawa, 235-0045

  • GSK Investigational Site

    Kyoto, 613-0034

  • GSK Investigational Site

    Miyagi, 981-0954

  • GSK Investigational Site

    Nagano, 390-0821

  • GSK Investigational Site

    Nagano, 390-1401

  • GSK Investigational Site

    Nagano, 399-8292

  • GSK Investigational Site

    Okayama, 714-0043

  • GSK Investigational Site

    Osaka, 543-0052

  • GSK Investigational Site

    Osaka, 547-0024

  • GSK Investigational Site

    Osaka, 584-0082

  • GSK Investigational Site

    Osaka, 594-0076

  • GSK Investigational Site

    Saitama, 348-0045

  • GSK Investigational Site

    Shizuoka, 424-0012

  • GSK Investigational Site

    Tokyo, 158-0094

  • GSK Investigational Site

    Tokyo, 169-0075

  • GSK Investigational Site

    Toyama, 930-0065

  • GSK Investigational Site

    Toyama, 938-8502

  • GSK Investigational Site

    Yamagata, 990-0834

  • GSK Investigational Site

    Yamaguchi, 755-0155

Other trials in Japan

About this study

Official 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

Daprodustat is a drug that is currently being developed as a treatment for renal anemia . This study is to evaluate the efficacy and safety of daprodustat following a switch from erythropoiesis-stimulating agent (ESA) in Japanese HD subjects with renal anemia who are currently treated with ESA. The primary objective is to demonstrate non-inferiority of daprodustat to darbepoetin alfa. This study is a 52-week, Phase III, double-blind, active-controlled, parallel-group, multi-center study. The total duration of the study will be approximately 58 weeks including screening and follow-up.

Conditions
Anaemia
Being tested
Daprodustat small, Daprodustat small placebo, Daprodustat large, Daprodustat large placebo, Darbepoetin alfa
Keywords
Safety, Efficacy, Daprodustat, Chronic kidney disease
Medical subject headings
Anemia, Renal Insufficiency, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Daprodustat smallDrug

    Available as 7.0 millimeter (mm) round, standard biconvex, white film coated tablets containing 1 mg, 2 mg, or 4 mg of daprodustat as active ingredient

  • Daprodustat small placeboDrug

    Available as 7.0 mm round, standard biconvex, white film coated tablets containing no daprodustat

  • Daprodustat largeDrug

    Available as 9.0 mm round, standard biconvex, white film coated tablets containing 6 mg of daprodustat as active ingredient

  • Daprodustat large placeboDrug

    Available as 9.0 mm round, standard biconvex, white film coated tablets containing no daprodustat

  • Darbepoetin alfaDrug

    Available as 0.5 mL plastic prefilled syringes (PFS) for IV injection each containing 10, 15, 20, 30, 40 or 60 mcg of darbepoetin alfa in a clear and colorless solution.

  • Darbepoetin alfa placeboDrug

    Available as 0.5 mL plastic PFS for IV injection containing no darbepoetin alfa in a clear and colorless solution.

Study groups in NCT02969655
Study groupRoleWhat they receive
DaprodustatExperimentalSubjects will receive oral daprodustat once daily and intravenous (IV) darbepoetin alfa placebo once weekly for 52 weeks
Receives: Drug: Daprodustat small; Drug: Daprodustat large; Drug: Darbepoetin alfa placebo
Darbepoetin alfaActive comparatorSubjects will receive IV darbepoetin alfa once weekly and oral daprodustat placebo once daily for 52 weeks
Receives: Drug: Daprodustat small placebo; Drug: Daprodustat large placebo; Drug: Darbepoetin alfa

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52)

    The mean hemoglobin during the Evaluation Period was estimated by a statistical model.

    Measured: Weeks 40 to 52

Secondary outcomes (17)

  1. 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)

    The percentage of participants with observed mean Hgb within the target range during the primary efficacy evaluation period was summarized. Odds ratio was estimated using a logistic regression and provided along with its 95% CI and a one-sided p-value.

    Measured: Weeks 40 to 52

  2. Change From Baseline in Hgb (Hgb Increase Rate) at Week 4

    Change from Baseline was calculated as the post-dose Week 4 visit value minus the Baseline value.

    Measured: Baseline and Week 4

  3. Percentage of Participants by Hgb Change From Baseline Category at Week 4

    Percentage of participants within each category were provided only for daprodustat and the categories were classified into 6 (i.e., <=-2, >-2 to -1, >-1 to 0, >0 to 1, >1 to 2, >2 grams per deciliter [g/dL]). In addition, 'within 1.0 g/dL (i.e., <=-1 and >=1) and over 2.0 g/dL (i.e., <-2 and >2) categories were provided.

    Measured: Week 4

  4. Distribution of Daprodustat Dose Level by Visit

    Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Daprodustat. Median along with the interquartile range (25th and 75th percentile) has been presented.

    Measured: Day 1, Weeks 4,8,12,16,20,24,28,32,36,40,44, and 48)

  5. Distribution of Darbepoetin Alfa Dose Level by Visit

    Distribution of dose level by visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for Darbepoetin Alfa. Median along with the interquartile range (25th and 75th percentile) has been presented.

    Measured: 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

  6. Duration of Treatment Interruption Due to Hgb >13 g/dL

    Duration of treatment interruption due to Hgb >13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented for the daprodustat group.

    Measured: Up to Week 52

  7. Number of Dose Adjustments for Daprodustat

    Number of dose adjustments has been presented only for daprodustat.

    Measured: Up to Week 52

  8. Hgb Values at Each Assessment Visit

    Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.

    Measured: Baseline (Day 1), Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

  9. Change From Baseline in Hgb Values at Each Assessment Visit

    Baseline Hgb value was the value from the Day 1 visit. Change from Baseline was calcuated as the post-dose visit value minus the Baseline value. Change from Baseline Hgb values at each assessment visit for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.

    Measured: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

  10. Percentage of Participants Who Had Hgb Level Within the Target Range (10.0-12.0 g/dL) at Each Assessment Visit

    Percentage of participants with Hgb within the target range was summarized at each assessment visit by treatment group have been presented.

    Measured: Baseline (Day 1) and Weeks 4,8,12,16,20,24,28,32,36,40,44,48 and Week 52

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

    Percentage of time in Hgb target range (10.0 to 12.0 g/dL) during the primary efficacy evaluation period (Weeks 40 to 52) for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users has been presented.

    Measured: Weeks 40 to 52

  12. Number of Participants Who Had an Hgb Level of Less Than 7.5 g/dL

    If an initial Hgb value was less than 7.5 g/dL, measurement was repeated at the same study visit (using the same sample) to calculate the average. If the average met the Hgb stopping criteria, study treatment was permanently discontinued. Number of participants who had an Hgb level of less than 7.5 g/dL has been presented.

    Measured: Up to Week 52

  13. Number of Participants Who Had an Hgb Increase of More Than 2 g/dL Over Any 4 Weeks

    Number of participants who had an Hgb increase of more than 2 g/dL over any 4 weeks for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.

    Measured: Up to Week 52

  14. Number of Participants Who Had an Hgb Level of More Than 13.0 g/dL

    Number of participants who had an Hgb increase of more than 13 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.

    Measured: Up to Week 52

  15. Number of Episodes With Hgb Level of More Than 13.0 g/dL

    Number of episodes with Hgb level of more than 13.0 g/dL for hemodialysis-dependent participants with anemia associated with chronic kidney disease who were currently ESA users have been presented.

    Measured: Up to Week 52

  16. Area Under Plasma Concentration Curve From Time Zero to 4 Hours (AUC [0 - 4]) of Plasma Daprodustat

    Blood samples for Pharmacokinetic (PK) analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). NA indicates geometric co-efficient of variation could not be calculated as a single participant was analyzed. Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. PK population comprised of all daprodustat-treated participants from whom PK samples were collected and analyzed. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.

    Measured: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24

  17. Maximum Concentration (Cmax) of Plasma Daprodustat

    Blood samples for PK analysis of daprodustat were collected as the time points provided. PK parameters were calculated by standard non-compartmental analysis according to current working practices and using the currently supported version of WinNonlin (version 6.3 or higher). Data has been provided as a consolidated values for at all time-points (0,1,2,3,and 4 hours post-dose) as provided for a single value at Weeks 12 and 24 respectively. Data was not calculated for darbepoetin alfa group as the primary interest of analysis was Daprodustat and not comparator drug (darbepoetin alfa). Data is combined from Week 12 and Week 24 data.

    Measured: 0, 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Nov 2016 (estimated)
  2. Study start21 Nov 2016
  3. Primary completion2 Jul 2018
  4. Study completion2 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
271 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02969655
Sponsor's protocol ID
201754
Status last verified
Nov 2020
First submitted
17 Nov 2016
Last updated
27 Nov 2020
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study is available via the Clinical Study Data Request site.

Publications

  • Akizawa T, Nangaku M, Yonekawa T, Okuda N, Kawamatsu S, Onoue T, Endo Y, Hara K, Cobitz AR. Efficacy and Safety of Daprodustat Compared with Darbepoetin Alfa in Japanese Hemodialysis Patients with Anemia: A Randomized, Double-Blind, Phase 3 Trial. Clin J Am Soc Nephrol. 2020 Aug 7;15(8):1155-1165. doi: 10.2215/CJN.16011219. Epub 2020 Jul 28.

    PubMed 32723804

  • Natale P, Palmer SC, Jaure A, Hodson EM, Ruospo M, Cooper TE, Hahn D, Saglimbene VM, Craig JC, Strippoli GF. Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013751. doi: 10.1002/14651858.CD013751.pub2.

    PubMed 36005278

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Daprodustat small, Daprodustat large and Darbepoetin alfa in people with Anaemia, run by GlaxoSmithKline at 50 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 50 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Hemoglobin (Hgb) During the Primary Efficacy Evaluation Period (Weeks 40 to 52) (time frame: Weeks 40 to 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02969655, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.

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