Mass Balance Recovery, Metabolite Profile, and Metabolite Identification of [14C]-Paxalisib in Healthy Male Subjects

NCT05012670 | Completed Phase 1 FDA Drug

• 2 other identifiers: KZA-0084-102QSC204878
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• To determine the mass balance recovery after a single oral dose of carbon-14 ([14C])-Paxalisib

  Mass balance recovery of total radioactivity (TR) in all excreta (urine and faeces): CumAe (amount excreted) and Cum%Ae

  Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)

• To provide plasma samples for metabolite profiling and structural identification

  Collection of plasma samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites

  Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)

• To provide urine samples for metabolite profiling and structural identification

  Collection of urine samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites

  Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)

• To provide faecal samples for metabolite profiling and structural identification

  Collection of faecal samples for metabolite profiling, structural identification, and quantification analysis of paxalisib metabolites

  Day 1 to Day 8 (or up to Day 10 if discharge criteria not met at Day 8)

Secondary Outcomes (18)

• 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 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)

Other Outcomes (1)

• To assess the urine PK 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)

Study Arms (1)

[14C]-Paxalisib Capsule

EXPERIMENTAL

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).

Drug: [14C]-Paxalisib Capsule

Interventions

[14C]-Paxalisib Capsule DRUG

Each subject will receive a single dose 15 mg (NMT 3.5 MBq), administered orally in the fasted state with with 240 mL water.

Also known as: Phosphoinositide 3-kinase (PI3K) Inhibitor

[14C]-Paxalisib Capsule

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
• 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.
• Subjects who have been administered IMP in an ADME study in the last 12 months.
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
• Clinically significant abnormal clinical chemistry, haematology, or urinalysis as judged by the investigator (laboratory parameters are listed in study protocol).
• Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in study protocol)
• Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), or human immunodeficiency virus (HIV) antibody results

Sponsors & Collaborators

• Kazia Therapeutics Limited: lead
• Quotient Sciences: collaborator

Study Sites (1)

Quotient Sciences

Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Interventions

Phosphatidylinositol 3-Kinases

Intervention Hierarchy (Ancestors)

Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Philip Evans, MBChB, MRCS

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: August 19, 2021
• Study Start: August 18, 2021
• Primary Completion: March 30, 2023
• Study Completion: January 30, 2024
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)