A Study to Assess the Mass Balance Recovery and Metabolite Profile & Identification of [14C]-APX001 in Healthy Males
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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
|
Outcome Measures
Primary Outcome Measures
- 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. [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 Outcome Measures
- Elimination pathway of [14C]-APX001 following a single oral or single IV dose of [14C]-APX001. [3 weeks]
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.
- Extent of distribution of total radioactivity into blood cells following a single oral or single IV dose of [14C]-APX001. [3 weeks]
Amount of radioactivity in whole blood over time was quantified by LSC and expressed in ng equivalents free drug/g.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Healthy males
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Aged 30 to 65 years of age
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Body mass index (BMI) of 18.0 to 32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator
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Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination)
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Must have been willing and able to communicate and participate in the whole study
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Must have had regular bowel movements (i.e. average stool production of ≥1 and
≤3 stools per day)
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Must have provided written informed consent
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Must have adhered to the contraception requirements defined in Section 9.4 of the protocol (Appendix 16.1.1)
Exclusion Criteria:
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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
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Subjects who were study site employees, or immediate family members of a study site or sponsor employee
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Subjects who had previously been enrolled in this study.
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History of any drug or alcohol abuse in the past 2 years
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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)
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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
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Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months
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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
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Subjects who did not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator at screening
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Clinically significant abnormality on electrocardiogram (ECG) as judged by the investigator
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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)
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Positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1 of the protocol, Appendix 16.1.1)
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Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
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Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <80 mL/min using the Cockcroft-Gault equation
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History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal (GI) disease, neurological or psychiatric disorder, as judged by the investigator
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Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
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Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever was allowed unless it was active
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Donation or loss of greater than 400 mL of blood within the previous 3 months
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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.
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Failure to satisfy the investigator of fitness to participate for any other reason
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Quotient Sciences | Ruddington | Nottingham | United Kingdom | NG11 6JS |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APX001-104