Phase 1 Absorption Distribution Metabolism and Excretion of AQX-1125

Study Overview
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Brief Summary
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This study is conducted to evaluate the absolute bioavailability, metabolism and elimination pathways of AQX-1125 in healthy male and female subjects.

Detailed Description
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This is a single-centre, open-label, non-randomised, 2-part, sequential dose study in healthy male and female subjects. It is planned to enrol a single cohort of 8 healthy subjects (4 male and 4 female) who will participate in Part 1 and Part 2 of the study. In Part 1, each subject will receive a single oral dose of AQX-1125 followed by an IV microtracer dose of carbon-14-AQX-1125 ([14C]-AQX-1125). In Part 2, each subject will receive a single oral dose of [14C]-AQX-1125.

Official Title
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An Open-Label,2-Part Sequential Dose Study Designed to Assess the Absolute Bioavailability, Mass Balance Recovery, Metabolite Profile and Identification of Metabolite Structure for [14C]-AQX-1125 in Healthy Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: AQX-1125 Oral Tablet
* Drug: [14C]-AQX-1125 IV
* Drug: [14C]-AQX-1125 Oral Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Healthy females of non-child bearing potential BMI 18.0 to 35 kg/m2 Exclusion Criteria: History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine) Current smokers and those who had smoked within the last 12 months; this included cigarettes, e-cigarettes and nicotine replacement products. Positive cotinine test result at screening and each admission Clinically significant abnormal clinical chemistry, haematology, urinalysis or electrocardiogram (ECG)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AQX-1125 Oral Tablet<br>AQX-1125 - Oral Tablet | Drug: AQX-1125 Oral Tablet<br>* Part 1: Subjects will receive a single oral dose of AQX-1125 followed by [14C]-AQX-1125 IV Microtracer dose. In Part 2 subjects receive [14C]-AQX-1125 oral solution.<br>|
| Experimental: [14C]-AQX-1125 IV<br>Radiolabelled AQX-1125 - Intravenous | Drug: [14C]-AQX-1125 IV<br>* Part 1: Subjects will receive a single oral dose of AQX-1125 followed by [14C]-AQX-1125 IV Microtracer dose. In Part 2 subjects receive [14C]-AQX-1125 oral solution.<br>* Other names: Radiolabelled AQX-1125 IV;|
| Experimental: [14C]-AQX-1125 Oral Solution<br>Radiolabelled AQX-1125 - Oral Solution | Drug: [14C]-AQX-1125 Oral Solution<br>* Part 1: Subjects will receive a single oral dose of AQX-1125 followed by [14C]-AQX-1125 IV Microtracer dose. In Part 2 subjects receive [14C]-AQX-1125 oral solution.<br>* Other names: Radiolabelled AQX-1125 Oral Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute bioavailability (F) of AQX-1125 |  | 0 - 96 hrs | 
| Mass balance recovery of total radioactivity in urine, faeces and all excreta | Measure amount excreted (Ae) | 0 -168 hrs | 
| Mass balance recovery of total radioactivity in urine, faeces and all excreta | Measure Ae as a percentage of the administered dose (%Ae) | 0 -168 hrs | 
| Mass balance recovery of total radioactivity in urine, faeces and all excreta | Cumulative recovery of Ae (Cum Ae) | 0 -168 hrs | 
| Mass balance recovery of total radioactivity in urine, faeces and all excreta | Cum Ae expressed as a percentage of the administered dose (Cum %Ae) | 0 -168 hrs | 
| Metabolite profiling and structural identification in plasma, urine and faeces to estimate the routes and rates of elimination of [14-C]-AQX-1125 |  | 0 -168 hrs | 
| Measure Ae total radioactivity for urine and faeces |  | 0-168 hrs | 
| Measure %Ae total radioactivity for urine and faeces |  | 0-168 hrs | 
| Measure Cum Ae (total) for urine and faeces |  | 0-168 hrs | 
| Measure Cum% Ae (total) for urine and faeces |  | 0-168 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration | Cmax | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | Tmax | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | Tlag | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | AUC (0-24) | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | AUC (0-last) | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | AUC (0-inf) | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | AUC % extrap | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | lambda-z | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | T1/2 | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | CL/F | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | Vz/F | 0 -96 hrs | 
| Measure PK parameters of total radioactivity in plasma following oral administration: | MRT | 0 -96 hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of Cmax | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of Tmax | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of Tlag | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of AUC(0-24) | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of AUC(0-last) | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of AUC(0-inf) | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of AUC%extrap | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of lambda-z | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of T1/2 | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of CL/F | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of Vz/F | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 1) | Measurement of MRT | 0-96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of Cmax | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of Tmax | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of Tlag | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of AUC(0-24) | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of AUC(0-last) | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of AUC(0-inf) | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of AUC%extrap | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of lambda-z | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of T1/2 | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of CL | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of Vz | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of VSS | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following IV administration (Part 1) | Measurement of MRT | 0 - 96 hrs | 
| Safety and tolerability assessments based on adverse events, safety laboratory tests, vital signs, physical examinations, ECGs and AEs (Part 1) |  | 0 - 96 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of Cmax | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of Tmax | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of Tlag | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of AUC(0-24) | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of AUC(0-last) | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of AUC(0-inf) | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of AUC%extrap | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of lambda-z | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of T1/2 | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of CL/F | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of Vz/F | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of F | 0 -168 hrs | 
| PK parameters of AQX-1125 in plasma following oral administration (Part 2) | Measurement of MRT | 0 -168 hrs | 
| Measure plasma whole blood concentration ratios for total radioactivity (Part 2) |  | 0 -168 hrs | 
| Chemical structure of major metabolites of [14-C]-AQX-1125 | Major metabolites classified as >10% of the AUC of total radioactivity in plasma and >10% dose excreted in urine and faeces following oral administration (Part 2) | 0 -168 hrs | 
| Safety and tolerability assessments based on adverse events, safety laboratory tests, vital signs and ECG (Part 2) |  | 0 -168 hrs |