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Phase 1 Completed N=52 Randomized Treatment

Daprodustat Bioequivalence and Food Effect Study

Source: ClinicalTrials.gov NCT03493386 ↗
Enrolled (actual)
52
Serious AEs
0.0%
Results posted
Aug 2019
Primary outcomePrimary: Part 1:Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Last Measurable Concentration (AUC[0-t]) and AUC From Zero Hours Extrapolated to Infinity AUC [0-inf] of Daprodustat — 182.8420; 179.6940; 183.0240; 179.8710 Hour*nanogram/milliliter

Summary

This is two-way crossover study to compare pharmacokinetic (PK) of daprodustat 2 milligram (mg) versus 4 mg tablets and food effect on the PK of daprodustat following single oral doses in healthy Japanese male subjects. This study will be conducted in two parts. Part 1 is the bioequivalence part in which subjects will receive single dose of 2 tablets of 2 mg daprodustat and single dose of 1 tablet of 4 mg daprodustat in crossover manner. Part 2 is Food effect part. In this part, subjects will receive single dose of 4 mg daprodustat tablet in fasting and fed state in a crossover manner. There will 5-day wash-out period between each intervention period. There will be approximately 52 subjects in Part 1 and 12 subjects in Part 2. The study will last for 6 weeks.

Outcome Measures

OutcomeResultp-value
PRIMARY
Part 1:Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Last Measurable Concentration (AUC[0-t]) and AUC From Zero Hours Extrapolated to Infinity AUC [0-inf] of Daprodustat
182.8420; 179.6940; 183.0240; 179.8710
PRIMARY
Part 1:Maximum Observed Drug Concentration (Cmax) of Daprodustat
88.8811; 85.1365
PRIMARY
Part 1:Terminal Phase Half-life (T1/2) of Daprodustat and Mean Residence Time (MRT)
3.2427; 3.2579; 2.8142; 2.9637
PRIMARY
Part 1: Time of Occurrence of Cmax (Tmax) of Daprodustat
2.000; 2.000
PRIMARY
Part 1: Percentage of AUC (0-inf) Obtained by Extrapolation (Percentage AUCex)
0.0862; 0.0836
PRIMARY
Part 1:Apparent Clearance (CL/F) of Daprodustat
21.8551; 22.2382
PRIMARY
Part 1:Apparent Oral Volume of Distribution (Vz/F) of Daprodustat
102244.3; 104522.8
PRIMARY
Part 1: Elimination Rate Constant (Kel) of Daprodustat
0.2138; 0.2128
PRIMARY
Part 2:AUC[0-t] andAUC [0-inf] of Daprodustat
142.9556; 156.4222; 143.1156; 156.5481
PRIMARY
Part 2: Cmax of Daprodustat
67.8240; 76.1944
PRIMARY
Part 2: T1/2 and MRT of Daprodustat
3.2160; 3.2389; 3.2420; 2.6695
PRIMARY
Part 2: Tmax of Daprodustat
2.750; 1.750
PRIMARY
Part 2: Percentage AUCex of Dapordustat
0.1071; 0.0723
PRIMARY
Part 2: CL/F of Daprodustat
27.9494; 25.5512
PRIMARY
Part 2: Vz/F of Daprodustat
129676.9; 119394.6
PRIMARY
Part 2: Kel of Daprodustat
0.2155; 0.2140
SECONDARY
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
3; 1; 0; 0
SECONDARY
Part 1: Change From Baseline Chemistry Paramters: Glucose, Calcium, Cholesterol, Chloride, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea.
-0.007619; -0.004270; -0.016144; -0.015834; -0.043607; 0.046747
SECONDARY
Part 1: Change From Baseline in Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Lactate Dehydrogenase and Gamma Glutamyl Transferase (GGT).
-9.5; -10.8; -2.0; -1.0; -2.1; -1.8
SECONDARY
Part 1: Change From Baseline in Chemistry Parameters; Albumin, Protein.
-2.0; -2.0; -2.3; -2.1
SECONDARY
Part 1: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate
0.268; 0.164; 2.615; 2.960; 1.7160; 1.4110
SECONDARY
Part 1:Change From Baseline in Hematology Parameter; Hematocrit
0.0005; 0.0014
SECONDARY
Part 1:Change From Baseline in Hematology Parameter; Reticulocytes
-0.0005; -0.0001
SECONDARY
Part 1: Change From Baseline in Hematology Parameters; Hemoglobin (Hb), Erythrocyte Mean Corpuscular Hb Concentration (MCHC)
1.1; 0.8; 2.1; 0.8
SECONDARY
Part 1: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils
-0.01; 0.00; 0.27; 0.25; -1.47; -0.86
SECONDARY
Part 1: Change From Baseline in Hematology Parameter Erythrocyte MCHC
0.11; 0.01
SECONDARY
Part 1: Change From Baseline in Hematology Parameter Erythrocyte Mean Corpuscular Volume (EMCV)
-0.2; -0.2
SECONDARY
Part 1: Change From Baseline in Hematology Parameters Platelets, Leukocytes
0.7; 2.0; -0.55; -0.53
SECONDARY
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes
0.018; 0.023
SECONDARY
Part 1: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)
-0.04; -0.07
SECONDARY
Part 1: Change From Baseline in Urinalysis Parameter; Specific Gravity
0.0092; 0.0088
SECONDARY
Part 1: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
-2.9; -1.5; -1.8; 0.1; -0.6; -0.4
SECONDARY
Part 1: Change From Baseline in Pulse Rate
0.0; 0.7; 0.1; 1.0
SECONDARY
Part 1: Change From Baseline in Temperature
0.23; 0.22; 0.10; 0.05
SECONDARY
Part 1: Change From Baseline in Electrocardiogram (ECG) Parameter; Mean Heart Rate (HR)
0.6; 0.2; 1.2; 0.8
SECONDARY
Part 1: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QT Duration Corrected for Heart Rate by Friderician Formula (QTcF) Interval
-3.3; -3.8; 1.4; 0.0; -2.8; -1.5
SECONDARY
Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
0; 0; 0; 0
SECONDARY
Part 2: Change From Baseline Chemistry Parameters; Glucose, Calcium, Cholesterol, Chloride, HDL Cholesterol, LDL Cholesterol, Potassium, Phosphate, Sodium, Triglycerides, and Urea
-0.425577; -0.018503; -0.076929; -0.058217; -0.172400; -0.094820
SECONDARY
Part 2: Change From Baseline in Chemistry Paremeters; ALP, ALT, AST, Creatine Kinase, Lactate Dehydrogenase, GGT
-18.9; -13.3; -3.1; -3.5; -2.8; -2.7
SECONDARY
Part 2: Change From Baseline in Chemistry Parameters; Albumin, Protein
-3.2; -1.9; -3.4; -2.6
SECONDARY
Part 2: Change From Baseline in Chemistry Parameters; Direct Bilirubin, Bilirubin, Creatinine, Urate
0.000; 0.000; 2.280; 1.425; -1.6207; -1.1050
SECONDARY
Part 2: Change From Baseline in Hematology Parameters; Hematocrit
-0.0052; -0.0025
SECONDARY
Part 2: Change From Baseline in Hematology Parameters; Reticulocytes
-0.0002; -0.0010
SECONDARY
Part 2: Change From Baseline in Hematology Parameters; Hb, Erythrocyte MCHC
-2.1; -1.2; 0.4; -0.6
SECONDARY
Part 2: Change From Baseline in Hematology Parameters; Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils
-0.04; -0.17; 0.62; -0.49; -2.31; -1.14
SECONDARY
Part 2: Change From Baseline in Hematology Parameter: EMCH
0.10; 0.03
SECONDARY
Part 2: Change From Baseline in Hematology Parameter EMCV
0.5; 0.3
SECONDARY
Part 2: Change From Baseline in Hematology Parameters Platelets, Leukocytes
-10.9; -3.2; -0.27; -0.39
SECONDARY
Part 2: Change From Baseline in Hematology Parameter Erythrocytes
-0.083; -0.044
SECONDARY
Part 2: Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH)
0.13; 0.13
SECONDARY
Part 2: Change From Baseline in Urinalysis Parameter; Specific Gravity
0.0054; 0.0013
SECONDARY
Part 2: Change From Baseline in Vital Signs; Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
-4.8; 0.2; -0.6; 2.8; 0.7; -1.3
SECONDARY
Part 2: Change From Baseline in Pulse Rate
6.1; -1.5; 4.0; 2.9
SECONDARY
Part 2: Change From Baseline in Temperature
0.28; 0.13; 0.02; 0.03
SECONDARY
Part 2: Change From Baseline in ECG Parameter; Mean Heart Rate (HR)
3.7; 0.0; 3.1; 0.6
SECONDARY
Part 2: Change From Baseline in ECG Parameter; PR Interval, QRS Interval, QT Interval, QTcF Interval
-6.2; -2.7; -4.0; -3.2; -1.5; -0.5

Eligibility Criteria

Inclusion Criteria

  • Subject must be 20 to 55 years of age inclusive, at the time of signing the informed consent.
  • Japanese subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Body weight > = 50 kilogram (kg) and body mass index (BMI) within the range 18.5 - 24.9 kilogram per meter square (kg/m^2).
  • Male subjects.
  • Subjects capable of giving signed informed consent.

Exclusion Criteria

  • History or presence of cardiovascular(CV), respiratory, hepatic, renal, gastrointestinal (GI), endocrine, haematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Abnormal blood pressure as determined by the investigator.
  • ALT >1.5x upper limit of normal (ULN).
  • Bilirubin >1.5xULN
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • QTcF > 500 millisecond (msec). The QTcF is the QT interval corrected for heart rate according to Fridericia's formula, machine-read or manually over-read. The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QT correction (QTc) for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial.
  • The values of Hgb at screening: >=16.0 gram per deciliter (g/dL).
  • History of deep vein thrombosis, pulmonary embolism or other thrombosis related condition.
  • History of myocardial infarction (MI) or acute coronary syndrome, stroke or transient ischemic attack.
  • Subjects that have undergone cholecystectomy.
  • History of malignancy within the prior 2 years or currently receiving treatment for cancer.
  • Any evidence of heart failure, as defined by the New York Heart Association (NYHA) functional classification system.
  • Past or intended use of over-the-counter or prescription medication including vitamins, diet foods and herbal medications within 14 days prior to first dosing.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrolment or past participation (that is administration of last dose of investigational study intervention) within the last 30 days (or 5 half-lives, whichever is longer) before signing of consent in this clinical study involving an investigational study intervention or any other type of medical research.
  • The subject with positive serological test for syphilis (Rapid Plasma Reagin [RPR] and Treponema pallidum haemagglutination test [TPHA]), Human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HBsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.
  • Positive pre-study drug screen.
  • Regular alcohol consumption within 6 months prior to the study defined as:for an average weekly intake of >14 units for males. One unit is equivalent to 350 milliliter (mL) of beer, 150 mL of wine or 45 mL of 80 proof distilled spirits.
  • Smoking or history of regular use of tobacco- or nicotine-containing products (example nicotine patch, electronic cigarette) within 6 months prior to screening.
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
  • History of donation of blood or blood products >= 400 mL within 3 months or >= 200 mL within 1 month prior to the first dosing day.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03493386). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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