AzTrials
AzTrials

AnaemiaPhase 3NCT03029208

Anemia Studies in Chronic Kidney Disease (CKD): Erythropoiesis Via a Novel Prolyl Hydroxylase Inhibitor (PHI) Daprodustat-in Incident Dialysis (ASCEND-ID)

A Phase 3 study testing Daprodustat, Darbepoetin alfa and Iron therapy in people with Anaemia, run by GlaxoSmithKline at 111 sites in 15 countries.

Completed

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

Official record
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Trial summary

The purpose of this multi-center study is to evaluate the efficacy and safety of daprodustat in subjects with anemia associated with CKD. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Anaemia
What is being tested?
Daprodustat, Darbepoetin alfa and Iron therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
312 participants
Where
111 sitesin 15 countries
Study dates
11 May 2017to 24 Sep 2020
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 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 to 99 years of age inclusive.
  • Planning to start chronic dialysis within the next 6 weeks (from the date of the screening visit) OR have started and received dialysis (as specified below) for end-stage renal disease for a maximum of <=90 days immediately prior to randomization and is not expected to stop dialysis during the duration of the trial: HD >=2 times per week or PD >=4 times per week including incremental schedule; subjects on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD) are eligible.
  • Hemoglobin concentration as measured by HemoCue (range inclusive): 8 to 10.5 g/dL (5-6.5 millimoles per liter [mmol/L]) at screening and 8-11.0 g/dL (5 to 6.8 mmol/L) at randomization.
  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

Who cannot join

  • Planned living-related or living-unrelated kidney transplant during the study.
  • Ferritin: <=100 nanograms per milliliter (ng/mL) (<=100 micrograms per liter [mcg/L]) at screening or after IV iron supplementation.
  • Transferrin saturation (TSAT): <=20% at screening or after IV iron supplementation.
  • Vitamin B12 (cobalamin): Below the lower limit of the reference range at screening or after vitamin B12 supplementation.
  • Folate: <2.0 ng/mL (<4.5 nanomoles per liter [nmol/L]) at screening.
  • Aplasias: History of bone marrow aplasia or pure red cell aplasia (PRCA).
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  • Other causes of anemia: Untreated pernicious anemia, thalassemia major, sickle cell disease, or myelodysplastic syndrome.
  • Gastrointestinal (GI) bleeding: Evidence of actively bleeding gastric, duodenal, or esophageal ulcer disease or clinically significant GI bleeding <=10 weeks prior to screening through to randomization (Day 1).
  • Use of any Erythropoiesis-stimulating agent (ESA) treatment within 8 weeks prior to screening except for limited use as part of dialysis initiation. Note : Limited use is defined as no more than 6 weeks of short acting ESA (rhEPO or biosimilars; maximum of 20000 unit total) or long acting ESA (darbepoetin alfa [maximum of 100 mcg total] or methoxy polyethylene glycol-epoetin beta [maximum of 125 mcg total]) received before or after starting dialysis.
  • Myocardial infarction or acute coronary syndrome: <=10 weeks prior to screening through to randomization (Day 1).
  • Stroke or transient ischemic attack: <=10 weeks prior to screening through to randomization (Day 1).
  • Chronic Class IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • Current uncontrolled hypertension as determined by the Investigator that would contraindicate the use of rhEPO.
  • QT correction using Bazett's (QTcB) (Day 1): QTcB >500 milliseconds (msec), or QTcB >530 msec in subjects with bundle branch block. There is no QTc exclusion for subjects with a predominantly ventricular paced rhythm.
  • Liver disease (any one of the following): 1. Alanine transaminase (ALT) >2 times upper limit of normal (ULN) (screening only). 2. Bilirubin >1.5 times ULN (screening only) (NOTE: Isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 3. Current unstable liver or biliary disease per investigator assessment, generally defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, 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) are acceptable if subject otherwise meets entry criteria.
  • 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 (i.e. Bosniak Category II F, III or IV) >3 centimeter (cm). The only exception is localized squamous cell or basal cell carcinoma of the skin that has been definitively treated >=10 weeks prior to screening.
  • History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product or to darbepoetin alfa.
  • Use of strong Cytochrome P4502C8 (CYP2C8) inhibitors (example gemfibrozil) or strong CYP2C8 inducers (example rifampin/rifampicin).
  • Use of other investigational agent or device prior to screening through to randomization (Day 1). At screening, this exclusion applies to use of the investigational agent within 30 days or within five half-lives (whichever is longer).
  • Any prior treatment with daprodustat for treatment duration of >30 days.
  • Females only: Subject is pregnant [as confirmed by a positive serum human chorionic gonadotropin (hCG) test for females of reproductive potential (FRP) only], subject is breastfeeding, or subject is of reproductive potential and does not agree to follow one of the contraceptive options in the List of Highly Effective Methods for Avoiding Pregnancy.
  • Any other condition, clinical or laboratory abnormality, or examination finding that the investigator considers would put the subject at unacceptable risk, which may affect study compliance (example intolerance to rhEPO) or prevent understanding of the aims or investigational procedures or possible consequences of the study.

Trial locations and contacts

111 sites in 15 countries.

111 sites in 15 countries

United States36 sites

  • GSK Investigational Site

    Anaheim, California, 92801

  • GSK Investigational Site

    Augusta, Georgia, 30912

  • GSK Investigational Site

    Baltimore, Maryland, 21287

  • GSK Investigational Site

    Baton Rouge, Louisiana, 70809

  • GSK Investigational Site

    Brooklyn, New York, 11203

  • GSK Investigational Site

    Buffalo, New York, 14215

  • GSK Investigational Site

    Cerritos, California, 90703

  • GSK Investigational Site

    Chicago, Illinois, 60637

  • GSK Investigational Site

    Coral Gables, Florida, 33134

  • GSK Investigational Site

    Crystal Lake, Illinois, 60014

  • GSK Investigational Site

    Escondido, California, 92025

  • GSK Investigational Site

    Fort Wayne, Indiana, 46804

  • GSK Investigational Site

    Glendale, California, 91204

  • GSK Investigational Site

    Hampton, Virginia, 23666

  • GSK Investigational Site

    Houston, Texas, 77004

  • GSK Investigational Site

    Iowa City, Iowa, 52242

  • GSK Investigational Site

    Jackson, Mississippi, 39216

  • GSK Investigational Site

    Kansas City, Missouri, 64111

  • GSK Investigational Site

    La Palma, California, 90623

  • GSK Investigational Site

    Los Angeles, California, 90022

  • GSK Investigational Site

    Los Angeles, California, 90095

  • GSK Investigational Site

    Lufkin, Texas, 75904

  • GSK Investigational Site

    Lynwood, California, 90262

  • GSK Investigational Site

    Merrillville, Indiana, 46410

  • GSK Investigational Site

    Miami, Florida, 33126

  • GSK Investigational Site

    Miami, Florida, 33169

  • GSK Investigational Site

    Michigan City, Indiana, 46360

  • GSK Investigational Site

    Middlebury, Connecticut, 06762

  • GSK Investigational Site

    Mineola, New York, 11501

  • GSK Investigational Site

    New Orleans, Louisiana, 70112

  • GSK Investigational Site

    New York, New York, 10029

  • GSK Investigational Site

    Sacramento, California, 95825

  • GSK Investigational Site

    San Antonio, Texas, 78229

  • GSK Investigational Site

    St Louis, Missouri, 63110

  • GSK Investigational Site

    The Bronx, New York, 10461

  • GSK Investigational Site

    Whittier, California, 90603

Other trials in United States

Argentina9 sites

  • GSK Investigational Site

    Buenos Aires, 1425

  • GSK Investigational Site

    Ciudad Evita, Buenos Aires, B1778IFA

  • GSK Investigational Site

    Formosa, P3600LLD

  • GSK Investigational Site

    La Plata, Buenos Aires, B1902COS

  • GSK Investigational Site

    Mendoza, M5500AFA

  • GSK Investigational Site

    Morón, Buenos Aires, B1708DPO

  • GSK Investigational Site

    Pergamino, Buenos Aires, B2700CPM

  • GSK Investigational Site

    Pilar, Buenos Aires, 1629

  • GSK Investigational Site

    San Miguel de Tucumán, T4000AHL

Other trials in Argentina

India9 sites

  • GSK Investigational Site

    Bangalore, 560055

  • GSK Investigational Site

    Chennai, 600037

  • GSK Investigational Site

    Delhi, 110076

  • GSK Investigational Site

    Gūrgaon, 122001

  • GSK Investigational Site

    Kozhikode, 673008

  • GSK Investigational Site

    New Delhi, 110060

  • GSK Investigational Site

    Pune, 411004

  • GSK Investigational Site

    Secunderabad, 560020

  • GSK Investigational Site

    Thiruvananthapuram, 695011

Other trials in India

Russia9 sites

  • GSK Investigational Site

    Irkutsk, 664049

  • GSK Investigational Site

    Mytishchi, 141007

  • GSK Investigational Site

    Omsk, 644112

  • GSK Investigational Site

    Saint Petersburg, 191104

  • GSK Investigational Site

    Saint Petersburg, 194354

  • GSK Investigational Site

    Saint Petersburg, 196247

  • GSK Investigational Site

    Saint Petersburg, 197110

  • GSK Investigational Site

    Smolensk, 214006

  • GSK Investigational Site

    Volzhskiy, 404120

Other trials in Russia

Mexico8 sites

  • GSK Investigational Site

    Aguascalientes, 20259

  • GSK Investigational Site

    Ciudad de México, State of Mexico, 14000

  • GSK Investigational Site

    Guadalajara, Jalisco, 44600

  • GSK Investigational Site

    Mérida, Yucatán, 97130

  • GSK Investigational Site

    Mérida, Yucatán, CP 97070

  • GSK Investigational Site

    Tlalnepantla, 54055

  • GSK Investigational Site

    Torreón, Coahuila, 27000

  • GSK Investigational Site

    Zapopan, Jalisco, 45030

Other trials in Mexico

Poland8 sites

  • GSK Investigational Site

    Gdansk, 80-952

  • GSK Investigational Site

    Koło, 62-600

  • GSK Investigational Site

    Krakow, 31-826

  • GSK Investigational Site

    Lodz, 92-213

  • GSK Investigational Site

    Lodz, 96-300

  • GSK Investigational Site

    Ostróda, 14-100

  • GSK Investigational Site

    Ostrołęka, 7410

  • GSK Investigational Site

    Szczecin, 70-780

Other trials in Poland

South Korea6 sites

  • GSK Investigational Site

    Anyang-Si, Gyeonggi-do, 14068

  • GSK Investigational Site

    Bucheon-si, 14647

  • GSK Investigational Site

    Incheon, 6510

  • GSK Investigational Site

    Seoul, 05030

  • GSK Investigational Site

    Seoul, 08308

  • GSK Investigational Site

    Suwon, 16499

Other trials in South Korea

Spain5 sites

  • GSK Investigational Site

    Badalona, 08916

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Madrid, 28040

  • GSK Investigational Site

    Puerto Real, 11510

  • GSK Investigational Site

    Seville, 41009

Other trials in Spain

Italy4 sites

  • GSK Investigational Site

    Cagliari, Sardinia, 09100

  • GSK Investigational Site

    Genoa, Liguria, 16132

  • GSK Investigational Site

    Milan, Lombardy, 20153

  • GSK Investigational Site

    Pavia, Lombardy, 27100

Other trials in Italy

United Kingdom4 sites

  • GSK Investigational Site

    Birmingham, B9 5SS

  • GSK Investigational Site

    Doncaster, DN2 5LT

  • GSK Investigational Site

    London, SE5 9RS

  • GSK Investigational Site

    Middlesbrough, TS4 3BW

Other trials in United Kingdom

Australia3 sites

  • GSK Investigational Site

    Adelaide, South Australia, 5000

  • GSK Investigational Site

    Melbourne, Victoria, 3004

  • GSK Investigational Site

    St Albans, Victoria, 3021

Other trials in Australia

Canada3 sites

  • GSK Investigational Site

    Greenfield Park, Quebec, J4V 2H1

  • GSK Investigational Site

    London, Ontario, N6A 5A5

  • GSK Investigational Site

    Toronto, Ontario, M3M 0B2

Other trials in Canada

Germany3 sites

  • GSK Investigational Site

    Düsseldorf, North Rhine-Westphalia, 40210

  • GSK Investigational Site

    Kaiserslautern, Rhineland-Palatinate, 67655

  • GSK Investigational Site

    Wiesbaden, 65191

Other trials in Germany

Malaysia3 sites

  • GSK Investigational Site

    George Town, 10990

  • GSK Investigational Site

    Ipoh, 30450

  • GSK Investigational Site

    Kuala Lumpur, 59100

Other trials in Malaysia

South Africa1 site

  • GSK Investigational Site

    Cape Town, 7925

Other trials in South Africa

About this study

Official title: A 52-week Open-label (Sponsor-blind), Randomized, Active-controlled, Parallel-group, Multi-center Study to Evaluate the Efficacy and Safety of Daprodustat Compared to Recombinant Human Erythropoietin in Subjects With Anemia Associated With Chronic Kidney Disease Who Are Initiating Dialysis

The purpose of this multi-center study is to evaluate the efficacy and safety of daprodustat in subjects with anemia associated with CKD.

Conditions
Anaemia
Being tested
Daprodustat, Darbepoetin alfa, Iron therapy
Keywords
Daprodustat, recombinant human erythropoietin, darbepoetin, anemia, chronic kidney disease, dialysis, ESRD
Medical subject headings
Anemia, Renal Insufficiency, Chronic, Kidney Failure, Chronic

What participants receive

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

  • DaprodustatDrug

    Daprodustat will be supplied as film coated tablets for oral administration containing 1, 2, 4, 6, 8, or 10 mg of daprodustat. Doses of 12, 16, and 24 mg of daprodustat will be provided using multiples of these tablet strengths.

  • Darbepoetin alfaDrug

    Darbepoetin alfa will be supplied as prefilled syringes (PFS) for SC/IV injection available in strengths: 20, 30, 40, 60, 80, 100 and 150 mcg.

  • Iron therapyDrug

    Iron therapy will be administered if ferritin is <=100 ng/mL and/or TSAT is <=20%.

Study groups in NCT03029208
Study groupRoleWhat they receive
Daprodustat treated anemic subjectsExperimentalSubjects will receive oral daprodustat once daily.
Receives: Drug: Daprodustat; Drug: Iron therapy
Darbepoetin alfa treated anemic subjectsActive comparatorSubjects will receive darbepoetin alfa subcutaneously or intravenously.
Receives: Drug: Darbepoetin alfa; Drug: Iron therapy

What is being measured

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

  1. Mean Change From Baseline in Hemoglobin (Hgb) During Evaluation Period (Week 28 to Week 52)

    Blood samples were collected from participants for Hgb measurement. Hgb during the evaluation period was defined as the mean of all available post-randomization Hgb values (on and off-treatment) during the evaluation period (Week 28 to Week 52). For the primary analysis missing post-Baseline Hgb values were imputed using pre-specified multiple imputations. Change from Baseline was defined as the average of post-randomization values during the evaluation period minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. An analysis of covariance (ANCOVA) model including randomization stratification factors Baseline Hgb and treatment was performed to obtain a point estimate and two-sided 95 percent (%) confidence interval (CI) for the treatment difference (daprodustat-darbepoetin alfa).

    Measured: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 52)

Secondary outcomes (22)

  1. Average Monthly Intravenous Iron Dose (Milligrams) From Baseline to Week 52

    Total IV iron dose per participant was calculated from Day 1 to the earliest of (Week 52 visit date, first blood [red blood cells or whole blood] transfusion date and treatment stop date plus [+] 1 day) which corresponds to the time while the participant was on randomized treatment and before receiving a blood transfusion. Average monthly IV iron dose was calculated by Total IV iron dose divided by (/) (the number of days from Day 1 to the earliest of [Week 52 visit date, first blood transfusion date and treatment stop date +1] /30.4375 days). Data for participants until they underwent a red blood cells or whole blood transfusion was included in the analysis.

    Measured: Baseline (Day 1) to Week 52

  2. Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Mean Arterial Blood Pressure (MAP) at Week 52

    SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using mixed model repeated measures (MMRM) model.

    Measured: Baseline (Day 1) and Week 52

  3. Change From Baseline in SBP, DBP, MAP at End of Treatment

    SBP, DBP and MAP were measured in a semi-supine or seated position in the dialysis chair after at least a 5-minutes of rest. MAP is an average BP in an individual's arteries during a single cardiac cycle. End of treatment value for the blood pressure parameters were defined as the latest value on or before the last non-zero dose date plus (+) 1 day. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date. This analysis was carried out by using ANCOVA model.

    Measured: Baseline (Day 1) and end of treatment (last on-treatment value until Week 52)

  4. Blood Pressure (BP) Exacerbation Events Rate Per 100 Participant Years

    BP exacerbation event is defined (based on post-dialysis BP) as SBP >=25 millimeter of mercury (mmHg) increased from Baseline or SBP >=180 mmHg; or DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. The BP exacerbation events per 100 participant years was estimated using the Negative Binomial Model.

    Measured: Up to Week 52

  5. Number of Participants With at Least One Blood Pressure Exacerbation Event During Study

    BP exacerbation was defined (based on post-dialysis BP) as: SBP >=25 mmHg increased from Baseline or SBP >=180 mmHg; DBP >=15 mmHg increased from Baseline or DBP >=110 mmHg. Number of participants with at least one blood pressure exacerbation event is presented.

    Measured: Up to Week 52

  6. Change From Baseline in Post-randomization Hgb at Week 52

    Blood samples were collected from participants for Hgb measurements. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1) and Week 52

  7. Number of Hgb Responders (Hgb in the Analysis Range of 10 to 11.5 Grams/Deciliter) During Evaluation Period (Week 28 to Week 52)

    Mean Hgb during the evaluation period was defined as the mean of all evaluable Hgb values during the evaluation period (Week 28 to Week 52) including any evaluable unscheduled Hgb values that were taken during this time period. Hgb responders were defined as number of participants with a mean Hgb during the evaluation period that falls within the Hgb analysis range of 10-11.5 g/dL.

    Measured: Weeks 28 to 52

  8. Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Non-inferiority Analysis

    Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time for which Hgb was within range for a participant was calculated by dividing 'the total number of days that Hgb was within range during Weeks 28 to 52' by 'the total number of days the participant remained on treatment during Weeks 28 to 52'.

    Measured: Weeks 28 to 52

  9. Percentage of Time for Which Hgb Was Within the Analysis Range (10 to 11.5 g/dL) During Evaluation Period (Week 28 to Week 52): Superiority Analysis

    Percentage of days for which a participant's Hgb was within the analysis range of 10-11.5 g/dL (both inclusive) during the evaluation period (Week 28 to Week 52), including any unscheduled evaluable Hgb values that were taken during this time period was calculated. Percentage of time for which Hgb was within range for a participant was calculated by dividing 'the total number of days that Hgb was within range during Weeks 28 to 52' by 'the total number of days the participant remained on treatment during Weeks 28 to 52'.

    Measured: Weeks 28 to 52

  10. Number of Participants Permanently Stopping Randomized Treatment Due to Meeting Rescue Criteria

    Number of participants permanently stopping randomized treatment due to meeting rescue criteria has been presented.

    Measured: Up to Week 52

  11. Change From Baseline in Physical Component Score (PCS) Using Short Form (SF)-36 Health-related Quality of Life (HRQoL) Questionnaire at Weeks 8, 12, 28, 52

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). The PCS is an average score derived from 4 domains (physical functioning, role-physical, bodily pain and general health) representing overall physical health. PCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1), Weeks 8, 12, 28 and 52

  12. Change From Baseline in Mental Component Score (MCS) Using SF-36 HRQoL Questionnaire at Weeks 8, 12, 28, 52

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). MCS is an average score derived from 4 domains (vitality, social functioning, role-emotional and mental health) representing overall mental health. MCS ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1), Weeks 8, 12, 28 and 52

  13. Change From Baseline in SF-36 HRQoL Scores for Bodily Pain, General Health, Mental Health, Role-Emotional, Role-Physical, Social Functioning at Weeks 8, 12, 28, 52

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: bodily pain, general health, mental health, role-emotional (role limitations caused by emotional problems), role-physical (role limitations caused by physical problems), social functioning, physical functioning and vitality. Each domain is scored from 0 (poorer health) to 100 (better health). Each domain score ranges from 0 to 100, higher score indicates a better health state and better functioning. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1), Weeks 8, 12, 28 and 52

  14. Change From Baseline in Vitality Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Vitality ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1), Weeks 28 and 52

  15. Change From Baseline in Physical Functioning Domain Scores Using SF-36 HRQoL Questionnaire at Weeks 28, 52

    The SF-36 acute version 2 is a 36-item generic quality of life instrument designed to measure a participant's level of performance in the following 8 health domains: physical functioning, role-physical (role limitations caused by physical problems), social functioning, bodily pain, mental health, role-emotional (role limitations caused by emotional problems), vitality and general health. Each domain is scored from 0 (poorer health) to 100 (better health). Physical functioning ranges from 0 to 100; higher scores represent better health. Change from Baseline was calculated as post-dose visit value minus (-) Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1), Weeks 28 and 52

  16. Change From Baseline in Health Utility EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Questionnaire Score at Week 52

    EQ-5D-5L consists of 2 concepts-EQ-5D-5L descriptive system and EQ Visual Analogue Scale (EQ-VAS). EQ-5D-5L is self-assessment questionnaire, consisting of 5items covering 5 dimensions (mobility,self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by 5-point Likert scale(no problems, slight problems, moderate problems, severe problems and extreme problems). Responses for 5 dimensions together formed a 5-figure description of health state(e.g.11111 indicates no problems in all 5 dimensions). Each of these 5 figure health states were converted to a single index score by applying country-specific value set formula that attaches weights to dimensions and levels. Range for EQ-5D-5L index score is -0.594 (worst health) to 1 (full health), higher the score better the health status. Change from Baseline was calculated as post-dose visit value-Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date.

    Measured: Baseline (Day 1) and Week 52

  17. Change From Baseline in EQ Visual Analogue Scale (EQ-VAS) at Week 52

    The EQ-5D-5L consists of 2 concepts -EQ-5D-5L descriptive system and EQ-VAS. The EQ-5D-5L is a self-assessment questionnaire, consisting of five items covering five dimensions (mobility, self care, usual activities, pain/discomfort and anxiety/depression). Each dimension is measured by a five-point Likert scale (no problems, slight problems, moderate problems, severe problems, and extreme problems). The range for the EQ-5D-5L index score is 0 to 1 with '0' is worst health and '1' is full health. The EQ VAS records the respondent's self-rated health on a vertical VAS, ranging from 0 to 100, where 0 represents the worst health one can imagine and 100 represents the best health one can imagine. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1) and Week 52

  18. Change From Baseline in Chronic Kidney Disease- Anemia Symptoms Questionnaire (CKD-AQ) at Week 52

    CKD-AQ is 21-item patient reported outcome measure assessing symptoms and symptom impact in participants with anemia associated with CKD. It had 3 domains: 1.Tired/Low Energy/Weak scale consisting of 10 items; 2.Chest Pain/Shortness of Breath scale consisting of 4 items; and 3.Cognitive scale consisting of 3 items. The 4 CKD-AQ single items are: (shortness of breath, no activity), (severity-short breath, resting), (difficulty standing for long time) and (difficulty sleeping). Single-item were recorded based on a 0-100 scoring with 0=worst possible and 100=best possible score. Three domains scores were calculated as average of items in each domain and ranged from 0-100 where 0=worst possible and 100=best possible score. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1) and Week 52

  19. Change From Baseline in Patient Global Impression of Severity (PGI-S)

    The PGI-S is a 1-item questionnaire designed to assess participant's impression of disease severity on a 5-point disease severity scale (0=absent, 1=mild, 2=moderate, 3=severe, or 4=very severe). A higher score indicated worse outcome. Change from Baseline was calculated as post-dose visit value minus Baseline value. Baseline was defined as the latest non-missing pre-dose assessment on or before the randomization date.

    Measured: Baseline (Day 1), Weeks 8, 12, 28 and 52

  20. Plasma Concentration of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)

    Pharmacokinetic samples were collected at pre-dose, 0.5, 1, 2 and 3 hours post-dose on Week 4 or 8 or 12 for pharmacokinetic (PK) analysis of daprodustat (GSK1278863) and its metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13). GSK2391220, GSK2506104 and GSK2531401 are the metabolites of Daprodustat (GSK1278863). Protocol allowed participants to provide pharmacokinetic samples on Week 4 or 8 or 12. Pharmacokinetic Population comprised of participants for whom a pharmacokinetic sample was obtained and analyzed.

    Measured: Pre-dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

  21. Observed Concentration at Dosing Interval (Ctau) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)

    Pharmacokinetic samples were collected at pre-dose, 0.5, 1, 2 and 3 hours post-dose on Week 4 or 8 or 12 for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13). GSK2391220, GSK2506104 and GSK2531401 are the metabolites of Daprodustat (GSK1278863). Protocol allowed participants to provide pharmacokinetic samples on Week 4 or 8 or 12.

    Measured: Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

  22. Maximum Observed Concentration (Cmax) of Daprodustat (GSK1278863) and Its Metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13)

    Pharmacokinetic samples were collected at pre-dose, 0.5, 1, 2 and 3 hours post-dose on Week 4 or 8 or 12 for pharmacokinetic analysis of daprodustat (GSK1278863) and its metabolites GSK2391220 (M2), GSK2506104 (M3), and GSK2531401 (M13). GSK2391220, GSK2506104 and GSK2531401 are the metabolites of Daprodustat (GSK1278863). Protocol allowed participants to provide pharmacokinetic samples on Week 4 or 8 or 12.

    Measured: Pre-Dose, 0.5, 1, 2 and 3 hours post-dose; each pharmacokinetic sample was taken at Week 4 or 8 or 12

Timeline

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

  1. First posted24 Jan 2017 (estimated)
  2. Study start11 May 2017
  3. Primary completion24 Sep 2020
  4. Study completion24 Sep 2020

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
None (open label)
Enrolment
312 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03029208
Sponsor's protocol ID
201410
Other IDs
2016-000507-86, 2016
Status last verified
Sep 2021
First submitted
20 Jan 2017
Last updated
20 Oct 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • 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

  • Singh AK, Cizman B, Carroll K, McMurray JJV, Perkovic V, Jha V, Johansen KL, Lopes RD, Macdougall IC, Obrador GT, Waikar SS, Wanner C, Wheeler DC, Wiecek A, Stankus N, Strutz F, Blackorby A, Cobitz AR, Meadowcroft AM, Paul G, Ranganathan P, Sedani S, Solomon S. Efficacy and Safety of Daprodustat for Treatment of Anemia of Chronic Kidney Disease in Incident Dialysis Patients: A Randomized Clinical Trial. JAMA Intern Med. 2022 Jun 1;182(6):592-602. doi: 10.1001/jamainternmed.2022.0605.

    PubMed 35377393

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Daprodustat, Darbepoetin alfa and Iron therapy in people with Anaemia, run by GlaxoSmithKline at 111 sites in 15 countries.

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 4 inclusion and 22 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 20 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 111 sites in United States, Argentina, India, Russia, Mexico and 10 more countries. 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 20 Oct 2021). 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 Change From Baseline in Hemoglobin (Hgb) During Evaluation Period (Week 28 to Week 52) (time frame: Baseline (Pre-dose on Day 1) and evaluation period (Week 28 to Week 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 NCT03029208, 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 20 Oct 2021.

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