An Open Label, Single-Dose, Single-Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-APX001 in Healthy Male Subjects After Oral and Intravenous Dosing
Overview
- Phase
- Phase 1
- Intervention
- [14C]-APX001 Oral Solution
- Conditions
- Fungal Infection
- Sponsor
- Basilea Pharmaceutica
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- Mass balance recovery as measured by mass unit equiv/g after a single oral or single intravenous (IV) dose of carbon-14 (14C)-labelled APX001 ([14C]-APX001).
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a single-center, open-label, non-randomized, single dose study in healthy male subjects. It was planned to enroll 2 cohorts of 5 subjects (10 subjects in total), with the target of achieving data in 4 evaluable subjects per cohort. Five subjects were to receive a single oral dose of APX001 and not more than (NMT) 3.1 megabecquerel (MBq) (84.0 microcurie [μCi]) 14C in the fed state. Five subjects were to receive a single IV administration containing APX001 and NMT 3.4 MBq (93.0 μCi) 14C in the fed state.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy males
- •Aged 30 to 65 years of age
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
- •Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination)
- •Must have been willing and able to communicate and participate in the whole study
- •Must have had regular bowel movements (i.e. average stool production of ≥1 and
- •≤3 stools per day)
- •Must have provided written informed consent
- •Must have adhered to the contraception requirements defined in Section 9.4 of the protocol (Appendix 16.1.1)
Exclusion Criteria
- •Subjects who had received any IMP in a clinical research study within the previous 3 months or a similar 14C radioactive clinical trial within the previous 12 months
- •Subjects who were study site employees, or immediate family members of a study site or sponsor employee
- •Subjects who had previously been enrolled in this study.
- •History of any drug or alcohol abuse in the past 2 years
- •Regular alcohol consumption in males \>21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type)
- •Current smokers and those who had smoked within the last 12 months. A breath carbon monoxide (CO) reading of greater than 10 ppm at screening and admission
- •Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months
- •Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeded 5 millisieverts (mSv) in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, was to participate in the study
- •Subjects who did not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator at screening
- •Clinically significant abnormality on electrocardiogram (ECG) as judged by the investigator
Arms & Interventions
Cohort A
\[14C\]-APX001 Oral Solution
Intervention: [14C]-APX001 Oral Solution
Cohort B
\[14C\]-APX001 Solution for Infusion
Intervention: [14C]-APX001 Solution for Infusion
Outcomes
Primary Outcomes
Mass balance recovery as measured by mass unit equiv/g after a single oral or single intravenous (IV) dose of carbon-14 (14C)-labelled APX001 ([14C]-APX001).
Time Frame: 3 weeks
Profiling of metabolites of [14C]-APX001 in plasma and excreta.
Time Frame: 3 weeks
Plasma, urine and feces samples from subjects dosed with \[14C\]-APX001 were analyzed using high resolution, accurate mass liquid chromatography tandem mass spectrometry (LC-MS/MS) with in-line fraction collection and off-line counting to obtain \[14C\]-radiochromatographic profiles and provide information on the nature of the radioactive components present, including chemical structure identification.
Secondary Outcomes
- Elimination pathway of [14C]-APX001 following a single oral or single IV dose of [14C]-APX001.(3 weeks)
- Extent of distribution of total radioactivity into blood cells following a single oral or single IV dose of [14C]-APX001.(3 weeks)