Human Mass Balance and Biotransformation Study of [14C]Afuresertib

NCT05489744 | Completed Phase 1

• 1 other identifier: LAE002CN1001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study adopts a single-center, single-dose, non-randomized, open-label design with a proposed enrollment of 6-10 healthy male subjects. After a single oral dose of approximately 125 mg/150 µCi \[14C\]Afuresertib tablets, blood, urine and fecal specimens are collected from each subject at defined time points/periods during the trial, and PK parameters, recovery, and excretion routes of \[14C\]Afuresertib in plasma are calculated by measuring the total radioactivity. The main metabolic and elimination pathways and characteristics of Afuresertib in human, as well as circulating metabolites with close to or higher than 10% of plasma total radioactivity exposure, are also identified by plasma, urine, and fecal radioactive metabolite profiles and major metabolite structure.

Conditions

Healthy Volunteer

Keywords

Mass balance

Outcome Measures

Primary Outcomes (4)

• Quantitatively analyze total radioactivity in the excreta.

  Quantitatively analyze total radioactivity in the excreta of healthy male subjects after oral administration of \[14C\]Afuresertib to calculate the excretion of radioactivity in human body and confirm the main excretion route of the drug.

  0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.

• Pharmacokinetics (PK) analysis of radioactivity in plasma will be measured.

  The total radioactivity in collected plasma and urine specimens is determined by a liquid scintillation counter. The collected whole blood and feces homogenate specimens are combusted by an oxidation combustor, and the total radioactivity is measured and calculated by a liquid scintillation counter.

  0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.

• Identify the main biotransformation pathways and the major metabolites by HPLC-MS/MS.

  Each mixed specimen is processed by appropriate methods, and followed by the combination of HPLC and on-line or off-line isotope detector to obtain radioisotope metabolite profile. The major metabolites in plasma, urine and feces specimens are identified by HPLC-MS/MS. Cumulative recovery of total radioactivity in urine and/or feces will be measured by HPLC-MS/MS.

  0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.

• Quantitatively analyze the concentration of Afuresertib and its metabolites by the validated HPLC-MS/MS.

  Quantitatively analyze the concentration of Afuresertib and its metabolites (if applicable) in plasma using a validated HPLC-MS/MS method to obtain the PK parameters in plasma. Percentage of each metabolite in urine and feces to the dose (%dose) or percentage of circulating metabolites in plasma to total exposure AUC (% AUC).

  0-504 hours after IP taken. Phased testing is adopted in this study to determine whether specimen collection may be terminated in advance or the collection time needs to be prolonged based on the test results.

Secondary Outcomes (1)

• Safety and tolerability of Afuresertib as measured by adverse events (AEs) .

  During the screening period, at Day-2, Day-1, before dosing (within 1 hour before dosing) and at 4, 24, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312, 336, 360, 384, 408, 432, 456, 480, and 504 hours after dosing.

Study Arms (1)

125 mg [14C]Afuresertib

EXPERIMENTAL

125 mg/150 µCi \[14C\]Afuresertib (125 mg of Afuresertib containing 150 µCi of \[14C\]Afuresertib)

Drug: [14C]Afuresertib

Interventions

[14C]Afuresertib DRUG

Suspension containing approximately 125 mg of Afuresertib (containing 150 µCi of \[14C\]Afuresertib) is administered orally on an empty stomach, with approximately 240 mL of water for suspending and drug taking.

Also known as: [14C]LAE002

125 mg [14C]Afuresertib

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male adults;
• Aged 18-45 years (inclusive);
• BMI: 19-26 kg/m2 (inclusive); body weight ≥ 50 kg;
• Willing to sign the Informed Consent Form (ICF);
• Capable of communicating well with investigators and completing the entire study as required.

You may not qualify if:

• Abnormal and clinically significant results of physical examination, vital signs, laboratory tests (routine hematology, blood biochemistry, coagulation function, routine urinalysis, fecal occult blood, thyroid function), 12-lead ECG, chest X-ray, and abdominal B-mode ultrasound (liver, gallbladder, pancreas, spleen, kidney);
• Resting QT interval corrected with Fridericia's formula (QTcF) ≥ 450 ms shown on the 12-lead ECG;
• Positive for hepatitis B surface antigen or E antigen, IgG antibody against hepatitis C virus (Anti-HCV IgG), antihuman immunodeficiency virus antigen/antibody (HIV-Ag/Ab) Combo Assay, and treponema pallidum antibody;
• Clinically significant CRP abnormality in SaRS-CoV-2 infection screening or positive for SARS-CoV-2 nucleic acid test;
• Use of any drug that inhibits or induces liver drug-metabolizing enzymes within 30 d before screening (see Appendix 1 for details);
• Use of any prescription drugs, over-the-counter drugs, Chinese herbal medicines or food supplements, such as vitamins and calcium supplements, within 14 d before screening;
• History of diabetes mellitus and/or pancreatitis;
• History of any serious disease or condition that may affect the study results in the opinion of the investigators, including but not limited to disorders of the circulatory system, respiratory system, endocrine system, nervous system, digestive system, urinary system, or blood, immune, mentality, or metabolism diseases;
• History of structural heart disease, heart failure, myocardial infarction, angina pectoris, unexplained arrhythmia, torsades de pointes, ventricular tachycardia, atrioventricular block, long QT syndrome (LQTS), symptoms or family history of LQTS (indicated by genetic evidence or sudden death of close relatives due to cardiac causes at a young age);
• Reception of major surgery (included but not limited to any surgery with significant risk of bleeding, prolonged general anesthesia, or significant traumatic injury, or incisional biopsy) within 6 months before the screening period, unhealed surgical wounds;
• Allergic constitution, history of allergy to two or more substances; possibly allergic to the investigational product or its excipients as judged by the investigator;
• Hemorrhoids or perianal disease with regular/ongoing hematochezia, irritable bowel syndrome, inflammatory bowel disease.
• Habitual constipation or diarrhea;
• Alcoholism or regular alcohol consumption within 6 months before screening period, that is, drinking volume \> 14 U of alcohol per week (1 U = 360 mL beer or 45 mL spirits with 40% alcohol or 150 mL wine); breath alcohol test result \> 0 mg/100 mL during the screening period;
• Consumption of more than 5 cigarettes per day or habitual use of nicotine-containing products within 3 months before the screening period, and unable to abstain during the study;

Sponsors & Collaborators

• Laekna Limited: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

Location

Study Officials

• Liyan Miao

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 12, 2022
• First Posted: August 5, 2022
• Study Start: August 6, 2022
• Primary Completion: October 21, 2022
• Study Completion: October 21, 2022
• Last Updated: May 15, 2023

Record last verified: 2023-05

Locations

CN (1)