Evaluation of the PK Profile of Firibastat Following Administration of Firibastat Prototype Tablet Formulations

Study Overview
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Brief Summary
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This is a single-centre, open-label, non-randomised, period fixed sequence study designed to investigate the PK and safety of Firibastat (QGC001) modified release (MR) prototype tablet formulations and compare this to a reference Firibastat (QGC001) immediate release (IR) capsule formulation in healthy male subjects. It is planned to enrol 12 subjects to receive single oral doses of investigational medicinal product (IMP).

Detailed Description
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Subjects will be screened for eligibility to participate in the study up to 28 days before dosing and for each treatment period they will be admitted to the clinical unit on the evening prior to IMP administration (Day -1). On the morning of Day 1, subjects will receive IMP in the fasted state (or following a FDA standard high-fat breakfast, if applicable) and will remain on site until 48 h post-dose. Between the periods, an interim analysis and review of safety and PK data from dosed regimens will be performed in order to determine which Firibastat (QGC001) MR prototype tablet formulation and dose to administer in subsequent periods. A follow-up phone call will take place 7 to 10 days post-final dose to ensure the ongoing wellbeing of the subjects.

Official Title
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A Study in Healthy Subjects Designed to Evaluate the Pharmacokinetic Profile of Firibastat (QGC001) and Active Metabolites Following Administration of Firibastat (QGC001) Prototype Tablet Formulations

Conditions
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Healthy Males

Intervention / Treatment
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* Drug: Firibastat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index of 18.0 to 32.0 kg/m2 Must adhere to the contraception requirements Exclusion Criteria: Subjects who have received any IMP in a clinical research study within the previous 3 months Subjects with pregnant partners History of any drug or alcohol abuse in the past 2 years Clinically significant abnormal biochemistry, haematology or urinalysis Subjects with BP <90/50 mmHg at screening

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: Basic Science
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Firibastat prototype tablet formulations<br>Firibastat (QGC001) 500 mg modified release prototype tablet formulations or immediate release capsule formulation - 1 tablet or 1 capsule administered per period | Drug: Firibastat<br>* Firibastat (QGC001) 500 mg<br>* Other names: QGC001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profiles of Firibastat (QGC001) and active métabolites of modified release prototype tablet formulations. Assessment of the Maximum Plasma Concentration. | [Cmax] | 3 months | 
| Pharmacokinetic (PK) profiles of Firibastat (QGC001) and active métabolites of modified release prototype tablet formulations. Assessment of the time at which the Cmax is observed. | [Tmax] | 3 months | 
| Pharmacokinetic (PK) profiles of Firibastat (QGC001) and active métabolites of modified release prototype tablet formulations. Assessment of the Areas Under the Curve. | [AUC0-24, AUC0-last and AUC0-inf] | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative bioavailability of Firibastat (QGC001) modified release prototype tablet formulations compared to the immediate release capsule formulation | [AUC0-24 MR / AUC0-24 IR] | 3 months | 
| Safety and tolerability of single doses of Firibastat (QGC001) by assessing safety haematology and chemistry laboratory tests aggregated as number of patients outside normal ranges. | Basophils, Eosinophils, Haematocrit, Haemoglobin, Lymphocytes, Mean Cell, Haemoglobin, Mean Cell Haemoglobin Concentration, Mean Cell Volume, Monocytes, Neutrophils, Platelet Count, Red Blood Cell Count, White Blood Cell Count | 3 months | 
| Safety and tolerability of single doses of Firibastat (QGC001) by assessing chemistry laboratory tests aggregated as number of patients outside normal ranges. | Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Bicarbonate, Bilirubin (Total), Calcium, Chloride, Creatine Kinase, Gamma Glutamyl Transferase, Glucose (Fasting), Potassium, Phosphate (Inorganic), Protein (Total), Sodium, Urea | 3 months | 
| Safety and tolerability of single doses of Firibastat (QGC001) by assessing urinalysis aggregated as number of patients outside normal ranges. | Bilirubin, Blood, Glucose, Ketones, Leukocytes, Nitrites, pH, Protein, Specific gravity, Urobilinogen | 3 months | 
| Safety and tolerability of single doses of Firibastat (QGC001) by assessing vital signs | Blood pressure (mmHg) | 3 months | 
| Safety and tolerability of single doses of Firibastat (QGC001) by assessing vital signs | Heart rate (bpm) | 3 months | 
| Safety and tolerability of single doses of Firibastat (QGC001) by assessing AEs | Adverse events will be recorded from the time of providing written informed consent until discharge from the study at the follow-up visit. During each study visit the subject will be questioned directly regarding the occurrence of any adverse medical event according to the source schedule. | 3 months | 
| Safety and tolerability of single doses of Firibastat (QGC001) by assessing Twelve-lead ECGs | P wave, T wave, QRS complex, QT interval, RR interval, PR segment, ST segment, | 3 months |