Last updated: 07/17/2024 17:13:06
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)
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Mean hemoglobin (Hgb) during the primary efficacy evaluation period
Timeframe: Week 40 to Week 52
Secondary outcomes:
Number of subjects with mean Hgb in the target range (10.0-12.0 grams (g)/deciliter (dL) during the primary efficacy evaluation period
Timeframe: Week 40 to Week 52
Change from baseline in Hgb at Week 4 (Hgb increase rate)
Timeframe: Baseline and Week 4
Number of subjects by Hgb change from baseline category at Week 4
Timeframe: Baseline and Week 4
Number of subjects in each dose level at each assessment visit.
Timeframe: Up to Week 52
Number of days of treatment interruption due to Hgb >13 g/dL
Timeframe: Up to Week 52
Number of dose adjustments
Timeframe: Up to Week 52
Hgb values at each assessment visit
Timeframe: Up to Week 52
Change from baseline in Hgb at each assessment visit
Timeframe: Baseline and Up to Week 52
Number of subjects who have a Hgb level within the target range (10.0 to 12.0 g/dL) at each assessment visit
Timeframe: Up to Week 52
Percentage of time in Hgb target range (10.0 to12.0 g/dL) during the primary efficacy evaluation period (Weeks 40 to 52)
Timeframe: Week 40 to Week 52
Number of subjects who have an Hgb level of less than 7.5 g/dL
Timeframe: Up to Week 52
Number of subjects who have an Hgb increase of more than 2 g/dL over any 4 weeks
Timeframe: Up to Week 52
Number of subjects who have an Hgb level of more than 13.0 g/dL
Timeframe: Up to Week 52
Number of episodes that an Hgb level of more than 13.0 g/dL
Timeframe: Up to Week 52
Area under plasma concentration curve from time zero to 4 hours (AUC [0 - 4]) of plasma daprodustat
Timeframe: 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24
Maximum concentration (Cmax) of plasma daprodustat
Timeframe: 1, 2, 3, and 4 hours post-dose at Week 12 and Week 24
Interventions:
Enrollment:
271
Primary completion date:
2018-02-07
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Tadao Akizawa, Masaomi Nangaku, Taeko Yonekawa, Nobuhiko Okuda, Shinya Kawamatsu, Tomohiro Onoue, Yukihiro Endo, Katsutoshi Hara, Alexander R Cobitz. Efficacy and safety of daprodustat compared with darbepoetin alfa in Japanese hemodialysis patients with anemia. Clin J Am Soc Nephrol. 2020;15(7)
DOI: 10.2215/CJN.16011219
Masaomi Nangaku, Tadao Akizawa, Takashi Nagakubo, Taeko Yonekawa, Toshifumi Kimura, Yukihiro Endo, Alexander Cobitz.Safety of daprodustat in patients with anemia of chronic kidney disease: a pooled analysis of phase 3 studies in Japan.Ther Apher Dial.2022;
DOI: 10.1111/1744-9987.13839
PMID: 35312234
Medical condition
Anaemia
Product
daprodustat, darbepoetin alfa
Collaborators
Not applicable
Study date(s)
November 2016 to July 2018
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
20+ years
Accepts healthy volunteers
No
- Inclusion Criteria
- Age (informed consent): >=20 years of age
Inclusion and exclusion criteria
Inclusion 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)
- 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
- 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:
- 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.
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:
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.
Liver disease (if any of the following occurs):
Trial location(s)
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Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2018-02-07
Actual study completion date
2018-02-07
Plain language summaries
Summary of results in plain language
Available language(s): Japanese, English
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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