Effects of Metabolic Enzymes and Transporter Gene Polymorphisms on the Pharmacokinetics and Metabolism of Oral Abiraterone Acetate in Healthy Chinese Adults

NCT04735913 | Unknown Early Phase 1

• 1 other identifier: 20201010
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.To explore the relationship between the changes of plasma concentration of abiraterone acetate after taken orally on fasting or postprandial and gene polymorphism.
2. 2.Study of drug Metabolite profiling after oral administration of abiraterone acetate on fasting and postprandial in Chinese adults.

Conditions

Abiraterone Acetate; Gene Polymorphism; Pharmacokinetic; Metabolic Analysis; Plasma Concentration

Keywords

Abiraterone; pharmacokinetic; metabolites; plasma; gene polymorphism

Outcome Measures

Primary Outcomes (11)

• Concentrations of abiraterone in plasma

  -1h, 30min, 1h , 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 12h, 24h, 36h, 48h, 60h, 72h after administration for blood sampling

  2 months

• Cmax

  peak concentration

  2 months

• AUC0-t

  Area under curve. The linear trapezoid method is used to calculate the blood drug concentration from zero to the last measurable concentration area under the curve

  2 months

• AUC0-∞

  The area under the blood concentration-time curve from zero to infinite blood concentration

  2 months

• λz

  End phase elimination rate constant, the least square method is used to find the slope of the optimal curve for phase elimination And multiplied by 2.303

  2 months

• T1/2z

  Elimination or final half-life, 0.693/λz

  2 months

• AUC_%Extra

  \[（AUC0-∞- AUC0-t）/ AUC0-∞\]×100%, Percentage of residual area

  2 months

• Vz/F

  apparent volume of distribution, Vz/F = CLz/F /λz

  2 months

• CLz/F

  apparent clearance, CLZ /F= administration dose /AUC0-∞

  2 months

• the main metabolite of abiraterone

  The plasma, urine and feces samples were collected to assay the metabolic profile of abiraterone in vivo by UFLC-Q-Exactive Orbitrap HRMS system

  2 months

• genotyping related to abiraterone metabolism

  Mutation sites of transporter and metabolic enzyme related to abiraterone metabolism were detected through the gene detection technology service platform

  10 months

Study Arms (2)

Fasting group

OTHER

Subjects will take abiraterone acetate tablets (250 mg, produced by Patheon Ich, trade name: Zytiga®) orally on an empty stomach and their blood and plasma samples, urine and faeces samples in 72h will be collected for detection.

Drug: Abiraterone acetate tablets

Postprandial group

EXPERIMENTAL

Subjects will take abiraterone acetate tablets (250 mg, produced by Patheon Ich, trade name: Zytiga®)orally after meals and their blood and plasma samples, urine and faeces samples in 72h will be collected for detection.

Drug: Abiraterone acetate tablets

Interventions

Abiraterone acetate tablets DRUG

Subjects will take abiraterone acetate tablets (250 mg, produced by Patheon Ich, trade name: Zytiga®) orally on an empty stomach or after meals and their blood and plasma samples, urine and faeces samples in 72h will be collected for detection.

Fasting group; Postprandial group

Eligibility Criteria

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

You may qualify if:

• Age: Healthy male subjects aged 18 to 65 years
• Weight: weight ≥50.0kg, 19 ≤ BMI ≤ 26 kg/m2, BMI=weight (kg) / height2(m2)
• Fully aware of the purpose, nature, method and possible adverse reactions of the study, and sign informed consent prior to the commencement of any study procedure on a voluntarily base.
• Be able to communicate well with the investigator and understand and abide by the terms of the study requirements.

You may not qualify if:

• Clinical laboratory examination is abnormal and clinically significant.
• Vital signs examination is abnormal and clinically significant, or there are other diseases of clinical significance（Including but not limited to gastrointestinal tract, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardio-cerebrovascular disease）or other specific systemic disease.
• Electrocardiogram is abnormal and clinically significant.
• HbsAg, Anti - HCV, TPPA, or HIV antibody positive.
• History of allergy to abiraterone acetate tablets or its ingredients and analogs
• The number of daily smoking \>5 during 3 months before the trial.
• Alcoholics or regular drinkers in the 6 months prior to the trial, that is drinking more than 14 units per week (1 Unit =360mL beer or 45mL 40% liquor or 150mL wine)
• Positive for drug, has a history of drug abuse in the past five years or has used drugs in the 3 months prior to the trial.
• Positive for alcohol screening or use of any alcoholic product within 24 hours prior to taking the study drug.
• Blood donation or massive blood loss within 3 months prior to taking the study drug (\>450mL).
• Take any xanthine rich beverage, food, grapefruit fruit or products that contain grapefruit in 48 hours before the trial.
• Take in chocolate or any food or drink containing caffeine in 48 hours before the trial.
• A history of dysphagia or any gastrointestinal disease that affect drug absorption.
• Have taken the study drug or participated in the drug or medical device within three months before this trial.
• There are major changes in diet or exercise habits recently.

Sponsors & Collaborators

• Zhongnan Hospital: lead

Study Sites (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430000, China

Location

MeSH Terms

Interventions

Abiraterone Acetate

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: February 3, 2021
• Study Start: May 5, 2020
• Primary Completion: August 20, 2020
• Study Completion: July 1, 2022
• Last Updated: January 3, 2022

Record last verified: 2021-12

Locations

CN (1)