Pharmacokinetics in End Stage Renal Disease Patients

Study Overview
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Brief Summary
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The study is a multicentre, open label, phase I, two arms study to compare pharmacokinetic of firibastat after a single oral dose of firibastat 500 mg in fourteen healthy male volunteers and in fourteen End Stage Renal Disease (ESRD) patients not yet in dialysis.

Detailed Description
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It is planned to enroll a total of 28 subjects to receive a single oral dose of investigational medicinal product (IMP): 14 ESRD patients will be enrolled in three Hungarian centres (1st arm) and 14 Healthy volunteers will be enrolled by Eurofins Optimed in Gières, France (2nd arm). Subjects will be screened for eligibility to participate in the study up to 21 days prior to the first administration. For both arm, subjects will be admitted into the Clinical Research Unit (CRU) on Day -3. On the morning of Day 1, subjects will receive a single 500 mg oral dose of firibastat following an overnight fast (i.e., at least 10 hours). Subjects will be confined to the CRU until discharge on Day 3 with PK blood sample draws for measurement of firibastat and its main metabolites being taken throughout the confinement. A follow-up post study visit will occur on Day 10 post-dose to ensure the ongoing wellbeing of the subjects.

Official Title
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A Phase I Study to Compare Pharmacokinetic Parameters of Firibastat and Its Metabolites (EC33 and QGC515) in Healthy Subjects Versus End Stage Renal Disease (ESRD) Patients After a Single Oral Administration of Firibastat 500 mg

Conditions
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Healthy Volunteers, Renal Failure

Intervention / Treatment
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* Drug: firibastat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male subjects, aged 18 to 55 years inclusive; Non-smoker subject or smoker of not more than 5 cigarettes a day; Exclusion Criteria: Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 tests); History or presence of drug or alcohol abuse (alcohol consumption > 40 grams/day);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>500 mg (2 capsules of 250 mg) | Drug: firibastat<br>* Single oral dose of 500 mg administration on Day 1<br>* Other names: QGC001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Firibastat and metabolites Concentrations | The plasma concentration data for firibastat (QGC001), EC33 and QGC515, will be analysed at each time measurement (predose, 0, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post-dose) | Day 1 to Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic and Diastolic Blood Pressure (mmHg) | Systolic and Diastolic blood pressure | Day 1 to Day 3 | 
| Heart Rate (bpm) | number of beats per minute | Day 1 to Day 3 | 
| Hematology blood sample laboratory tests aggregated as number of patients outside ranges | Hemoglobin, Hematocrit, MCH, MCHC, MCV, MPV, RBC (erythrocytes), WBC (Leucocytes), Differential Count (Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Large Unstained cells), Platelets. | Day 1 to Day 3 | 
| Biochemistry blood sample laboratory tests aggregated as number of patients outside ranges | Albumin, Alkaline Phosphatase, ALT, Amylase, AST, Bicarbonate, Bilirubin (direct, indirect and total), Calcium, Chloride, Cholesterol, Creatinine Kinase, Creatinine, gammaGT, HDLcholesterol, LDH, LDL - cholesterol, Lipase, Magnesium, Phosphate, Potassium, Protein total, Sodium, Triglycerides, Urea, Uric Acid, Glucose. | Day 1 to Day 3 | 
| Hemostasis blood sample laboratory tests aggregated as number of patients outside ranges | INR, PT, aPTT | Day 1 to Day 3 | 
| Urinalysis tests aggregated as number of patients outside ranges | pH, ketone bodies, proteins, glucose, occult blood, blood leukocytes, nitrite, bilirubin, urobilinogen, density. | Day 1 to Day 3 |