Phase 1 Absorption Distribution Metabolism and Excretion of AQX-1125 (ADME)

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: AQX-1125 Oral Tablet; Drug: [14C]-AQX-1125 IV; Drug: [14C]-AQX-1125 Oral Solution

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AQX-1125 Oral Tablet; AQX-1125 - Oral Tablet	Drug: AQX-1125 Oral Tablet; 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.
Experimental: [14C]-AQX-1125 IV; Radiolabelled AQX-1125 - Intravenous	Drug: [14C]-AQX-1125 IV; 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.; Other Names: Radiolabelled AQX-1125 IV
Experimental: [14C]-AQX-1125 Oral Solution; Radiolabelled AQX-1125 - Oral Solution	Drug: [14C]-AQX-1125 Oral Solution; 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.; Other Names: Radiolabelled AQX-1125 Oral Solution

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aquinox Pharmaceuticals (Canada) Inc.
• Collaborators: Quotient Clinical
• Investigators: Principal Investigator: Dr.Nand Singh, MD, Quotient Clinical

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2016
• Primary Completion (Actual): January 4, 2017
• Study Completion (Actual): January 4, 2017

Study Registration Dates

• First Submitted: March 8, 2017
• First Submitted That Met QC Criteria: June 9, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): June 14, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pharmaceutical Solutions
• Other Study ID Numbers: AQX-1125-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No