A Study to Assess the Mass Balance Recovery and Metabolite Profile & Identification of [14C]-APX001 in Healthy Males

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

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.

Study Overview

• Status: Completed
• Conditions: Fungal Infection
• Intervention / Treatment: Drug: [14C]-APX001 Oral Solution; Drug: [14C]-APX001 Solution for Infusion

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Sciences

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Healthy males
2. Aged 30 to 65 years of age
3. Body mass index (BMI) of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
4. Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination)
5. Must have been willing and able to communicate and participate in the whole study

6. Must have had regular bowel movements (i.e. average stool production of ≥1 and

   ≤3 stools per day)

7. Must have provided written informed consent
8. Must have adhered to the contraception requirements defined in Section 9.4 of the protocol (Appendix 16.1.1)

Exclusion Criteria:

1. 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
2. Subjects who were study site employees, or immediate family members of a study site or sponsor employee
3. Subjects who had previously been enrolled in this study.
4. History of any drug or alcohol abuse in the past 2 years
5. 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)
6. 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
7. Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months
8. 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
9. Subjects who did not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator at screening
10. Clinically significant abnormality on electrocardiogram (ECG) as judged by the investigator
11. Clinically significant abnormal biochemistry, hematology or urinalysis at screening as judged by the investigator (laboratory parameters are listed in Appendix 1 of the protocol, Appendix 16.1.1)
12. Positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1 of the protocol, Appendix 16.1.1)
13. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
14. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <80 mL/min using the Cockcroft-Gault equation
15. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal (GI) disease, neurological or psychiatric disorder, as judged by the investigator
16. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
17. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever was allowed unless it was active
18. Donation or loss of greater than 400 mL of blood within the previous 3 months
19. Subjects who were taking, or had taken, any prescribed or over-the-counter drug (other than 4 g per day paracetamol) or herbal remedies in the 14 days before IMP administration (see Section 11.4 of the protocol, Appendix 16.1.1). Exceptions may have applied on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI and sponsor's medical monitor.
20. Failure to satisfy the investigator of fitness to participate for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; [14C]-APX001 Oral Solution	Drug: [14C]-APX001 Oral Solution; Total dose containing NMT 3.1 MBq (84.0 µCi) 14C
Experimental: Cohort B; [14C]-APX001 Solution for Infusion	Drug: [14C]-APX001 Solution for Infusion; Total dose containing NMT 3.4 MBq (93.0 µCi) 14C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).		3 weeks
Profiling of metabolites of [14C]-APX001 in plasma and excreta.	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.	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Elimination pathway of [14C]-APX001 following a single oral or single IV dose of [14C]-APX001.	Amount of radioactivity recovered from urine and feces over time was measured by liquid scintillation counting (LSC) and expressed as a percentage of administered radioactivity.	3 weeks
Extent of distribution of total radioactivity into blood cells following a single oral or single IV dose of [14C]-APX001.	Amount of radioactivity in whole blood over time was quantified by LSC and expressed in ng equivalents free drug/g.	3 weeks

Collaborators and Investigators

• Sponsor: Basilea Pharmaceutica
• Investigators: Study Director: Marc Engelhardt, Basilea Pharmaceutica International Ltd, Allschwil

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2018
• Primary Completion (Actual): September 26, 2018
• Study Completion (Actual): September 26, 2018

Study Registration Dates

• First Submitted: October 1, 2020
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Pharmaceutical Solutions
• Other Study ID Numbers: APX001-104; C4791004 (Other Identifier: Alias Study Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No