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

NCT04804059 | Completed Phase 1 FDA Drug

• 2 other identifiers: APX001-104C4791004
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Fungal Infection

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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

Study Arms (2)

Cohort A

EXPERIMENTAL

\[14C\]-APX001 Oral Solution

Drug: [14C]-APX001 Oral Solution

Cohort B

EXPERIMENTAL

\[14C\]-APX001 Solution for Infusion

Drug: [14C]-APX001 Solution for Infusion

Interventions

[14C]-APX001 Oral Solution DRUG

Total dose containing NMT 3.1 MBq (84.0 µCi) 14C

Cohort A

[14C]-APX001 Solution for Infusion DRUG

Total dose containing NMT 3.4 MBq (93.0 µCi) 14C

Cohort B

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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)
• Positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1 of the protocol, Appendix 16.1.1)
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
• Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of \<80 mL/min using the Cockcroft-Gault equation
• History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal (GI) disease, neurological or psychiatric disorder, as judged by the investigator

Sponsors & Collaborators

• Basilea Pharmaceutica: lead

Study Sites (1)

Quotient Sciences

Ruddington, Nottingham, NG11 6JS, United Kingdom

Location

Related Publications (1)

• Hodges MR, Ople E, Evans P, Pantophlet AJ(, Richardson J, Williams D, Tripathy S, Tawadrous M, Jakate A. A phase 1 open label study to assess the human mass balance and metabolite profile of 14C-fosmanogepix, a novel Gwt-1 inhibitor in healthy male participants. Antimicrob Agents Chemother. 2024 Aug 7;68(8):e0027324. doi: 10.1128/aac.00273-24. Epub 2024 Jul 16.

  PMID: 39012090 DERIVED

MeSH Terms

Conditions

Mycoses

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• Marc Engelhardt

  Basilea Pharmaceutica International Ltd, Allschwil

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2020
• First Posted: March 18, 2021
• Study Start: August 17, 2018
• Primary Completion: September 26, 2018
• Study Completion: September 26, 2018
• Last Updated: May 17, 2024

Record last verified: 2024-05

Locations

GB (1)