Phase 1 Absorption Distribution Metabolism and Excretion of AQX-1125

Healthy Volunteer Clinical Trial

— ADME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03185195
• Other study ID #: AQX-1125-103
• Status: Completed
• Phase: Phase 1
• First received: March 8, 2017
• Last updated: June 9, 2017
• Start date: November 22, 2016
• Est. completion date: January 4, 2017

Study information

• Verified date: June 2017
• Source: Aquinox Pharmaceuticals (Canada) Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: January 4, 2017
• Est. primary completion date: January 4, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

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.
• [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.
• [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.

Locations

Country	Name	City	State
United Kingdom	Quotient Clinical	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
Aquinox Pharmaceuticals (Canada) Inc.	Quotient Clinical

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute bioavailability (F) of AQX-1125		0 - 96 hrs
Primary	Mass balance recovery of total radioactivity in urine, faeces and all excreta	Measure amount excreted (Ae)	0 -168 hrs
Primary	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
Primary	Mass balance recovery of total radioactivity in urine, faeces and all excreta	Cumulative recovery of Ae (Cum Ae)	0 -168 hrs
Primary	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
Primary	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
Primary	Measure Ae total radioactivity for urine and faeces		0-168 hrs
Primary	Measure %Ae total radioactivity for urine and faeces		0-168 hrs
Primary	Measure Cum Ae (total) for urine and faeces		0-168 hrs
Primary	Measure Cum% Ae (total) for urine and faeces		0-168 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration	Cmax	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	Tmax	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	Tlag	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	AUC (0-24)	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	AUC (0-last)	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	AUC (0-inf)	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	AUC % extrap	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	lambda-z	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	T1/2	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	CL/F	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	Vz/F	0 -96 hrs
Primary	Measure PK parameters of total radioactivity in plasma following oral administration:	MRT	0 -96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of Cmax	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of Tmax	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of Tlag	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of AUC(0-24)	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of AUC(0-last)	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of AUC(0-inf)	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of AUC%extrap	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of lambda-z	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of T1/2	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of CL/F	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of Vz/F	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 1)	Measurement of MRT	0-96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of Cmax	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of Tmax	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of Tlag	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of AUC(0-24)	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of AUC(0-last)	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of AUC(0-inf)	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of AUC%extrap	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of lambda-z	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of T1/2	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of CL	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of Vz	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of VSS	0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following IV administration (Part 1)	Measurement of MRT	0 - 96 hrs
Secondary	Safety and tolerability assessments based on adverse events, safety laboratory tests, vital signs, physical examinations, ECGs and AEs (Part 1)		0 - 96 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of Cmax	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of Tmax	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of Tlag	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of AUC(0-24)	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of AUC(0-last)	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of AUC(0-inf)	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of AUC%extrap	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of lambda-z	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of T1/2	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of CL/F	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of Vz/F	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of F	0 -168 hrs
Secondary	PK parameters of AQX-1125 in plasma following oral administration (Part 2)	Measurement of MRT	0 -168 hrs
Secondary	Measure plasma whole blood concentration ratios for total radioactivity (Part 2)		0 -168 hrs
Secondary	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
Secondary	Safety and tolerability assessments based on adverse events, safety laboratory tests, vital signs and ECG (Part 2)		0 -168 hrs