An Open-Label, Single-Dose, Single-Period Study to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-Paxalisib in Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- [14C]-Paxalisib Capsule
- Conditions
- Healthy
- Sponsor
- Kazia Therapeutics Limited
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- To determine the mass balance recovery after a single oral dose of carbon-14 ([14C])-Paxalisib
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
Single-centre, open-label, non-randomised study to assess the mass balance recovery, PK, metabolite profile, and metabolite identification of a single oral dose of 14C labelled paxalisib ([14C] Paxalisib) in healthy male subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy males.
- •Aged 30 to 65 years inclusive at the time of signing informed consent.
- •Body mass index (BMI) of 18.0 to 35.0 kg/m2 as measured at screening.
- •Must be willing and able to communicate and participate in the whole study.
- •Must have regular bowel movements (i.e., average stool production of ≥1 and ≤3 stools per day).
- •Must provide written informed consent.
- •Must agree to adhere to the contraception requirements defined in study protocol.
Exclusion Criteria
- •Subjects who have received any IMP in a clinical research study within the 90 days prior to Day
- •Subjects who are, or are immediate family members of, a study site or sponsor employee.
- •Evidence of current SARS-CoV-2 infection.
- •History of any drug or alcohol abuse in the past 2 years.
- •Regular alcohol consumption \>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).
- •A confirmed positive alcohol breath test at screening or admission.
- •Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
- •Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
- •Subjects with pregnant or lactating partners.
- •Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 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, shall participate in the study.
Arms & Interventions
[14C]-Paxalisib Capsule
Subjects will be dosed on the morning of Day 1 following an overnight fast of a minimum of 10 h. Subjects will remain resident in the clinical unit until 168 h post dose (Day 8) and this may be extended up to a maximum of 48 h (i.e., up to Day 10).
Intervention: [14C]-Paxalisib Capsule
Outcomes
Primary Outcomes
To determine the mass balance recovery after a single oral dose of carbon-14 ([14C])-Paxalisib
Time Frame: Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)
Mass balance recovery of total radioactivity (TR) in all excreta (urine and faeces): CumAe (amount excreted) and Cum%Ae
To provide plasma samples for metabolite profiling and structural identification
Time Frame: Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)
Collection of plasma samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites
To provide urine samples for metabolite profiling and structural identification
Time Frame: Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)
Collection of urine samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites
To provide faecal samples for metabolite profiling and structural identification
Time Frame: Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)
Collection of faecal samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites
Secondary Outcomes
- To provide hematology laboratory safety testing information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To determine the routes and rates of elimination of [14C]-Paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To identify the chemical structure of each metabolite accounting for more than 10% (in plasma) of circulating TR or metabolites in excreta (urine and faeces) that account for more than 10% of the administered radioactive dose(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To explore the Cmax pharmacokinetic (PK) parameter of paxalisib following administration of [14C] Paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To explore the Tmax pharmacokinetic (PK) parameter of paxalisib following administration of [14C] Paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To explore the Cmax pharmacokinetic (PK) of TR following administration of [14C] Paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To explore the AUC(0-last) and AUC(0-inf) pharmacokinetic (PK) parameter of paxalisib following administration of [14C] Paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To explore the Tmax pharmacokinetic (PK) of TR following administration of [14C] Paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To explore the AUC(0-last) and AUC(0-inf) pharmacokinetic (PK) of TR following administration of [14C] Paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide blood pressure vital sign safety information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To evaluate the extent of distribution of TR into blood cells(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide adverse event (AE) safety information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide heart rate vital sign safety information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide oral temperature vital sign safety information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide respiratory rate vital sign safety information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide electrocardiogram (ECG) safety information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide physical examination safety information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))
- To provide clinical chemistry laboratory safety testing information for paxalisib(Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8))