Bioequivalence Study of Olaparib Tablets Under Fasting and Fed Conditions in Healthy Subjects

A Randomized, Open-Label, 2-formulation, Single-Dose, 2-Period Crossover Bioequivalence Study of Olaparib Tablets Under Fasting and Fed Conditions in Healthy Subjects

This Study is a Randomized, Open-Label, 2-formulation, Single-Dose, 2-Period Crossover Bioequivalence Study with a washout period of 7 days. During each session, the subjects were administered a single dose of 100 mg Olaparib Tablets (Test formulation or reference formulation ) under Fasting conditions or 150mg Olaparib Tablets (Test formulation or reference formulation ) under Fasting and Fed conditions. Venous blood samples were collected at pre-dose (0 h), and up to 72 h post dose. This study was to evaluate the bioequivalence and safety of the test formulation and the reference formulation of Olaparib Tablets in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Olaparib Tablet test formulation 100mg; Drug: Olaparib Tablet reference formulation 100mg; Drug: Olaparib Tablet test formulation 150mg; Drug: Olaparib Tablet reference formulation 150mg

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participants were fully aware of the purpose, character, methodology, and possible adverse effects of the trial, and signed an informed consent form prior to the initiation of any research procedures;
2. Healthy male aged 18 to 50 years old (including critical values);
3. Weight equal to or more than 50.0 kg and body mass index between 19 to 26.0 kg/m^2 (including critical values);
4. Participants had no history of chronic or serious diseases, including cardiovascular, respiratory, gastrointestinal, urinary, hematologic and lymphatic, endocrine, immune, psychiatric, or neurological system diseases;
5. Participants whose immediate family members had no breast, ovarian, pancreatic, prostate cancer, and other related diseases;
6. Normal or abnormal results without clinical significance on all tests including vital signs, physical examination, laboratory evaluation (hematology, urinalysis, blood biochemistry, serology, coagulation function, and urine drug screening), 12-lead electrocardiogram, chest X-ray /Chest Computed Tomography (CCT) and alcohol breath test;
7. Voluntarily signed the informed consent form, and cooperated in completing the trial according to the protocol.

Exclusion Criteria:

1. Allergic constitution or allergic history to drugs or food;
2. Participants with tablet swallowing distress;
3. Participants with a history of surgery or trauma that may affect safety or in vivo metabolism of the drug, or who had undergone surgery within 1 year prior to screening or who were scheduled to undergo surgery during the trial;
4. Participants who had used potent CYP 3A4 strong inhibitors, CYP 3A4 moderate inhibitors, CYP 3A4 strong inducers, and CYP 3A4 moderate inducers within 4 weeks prior to screening;
5. Participants who had used p-gp inhibitors within 4 weeks prior to screening;
6. Participants who had used any medicines or health products within 2 weeks prior to screening,
7. Participants with a history of drug or substance abuse within 6 months prior to screening,or a positive urine drug test during screening;
8. Participants who had used drugs within 3 months prior to screening;
9. Smoking ≥ 5 cigarettes per day on average within 3 months prior to screening,or participants who could not stop using any tobacco-based products during the trial period;
10. Participants who consumed more than 14 units of alcohol per week within the 3 months prior to screening, or who had a positive breath test for alcohol at screening,or who could not abstain from alcohol during the trial ;
11. Participants who consumed excessive amounts of tea, coffee and/or caffeine-rich beverages per day within 3 months prior to screening
12. Participants who had taken a special diet (dragon fruit, mango, grapefruit, lime, star fruit or food or drink prepared from them) within 7 days prior to screening, or participants who were unable to stop taking the above special diets during the trial;
13. Participants who had participated in other clinical trials within 3 months prior to screening;
14. Participants who had lost blood or donated more than 400 ml of blood or who had received blood transfusions or used blood products within 3 months prior to screening;
15. Participants who cannot tolerate venipuncture or with a history of fainting needle or blood;
16. Participants who are lactose intolerant;
17. Participants with special dietary requirements who could not accept a uniform diet;
18. Participants who were planning to have children, unwilling or unable to use effective contraception, or had a plan to donate sperm from 2 weeks prior to the screening until 6 months after the last dose of study drug, and who were unwilling to use non-pharmacological contraception from 2 weeks prior to the screening until one month after the last dose of study drug;
19. Any condition that the investigator considered inappropriate for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olaparib Tablet test formulation 100mg; Treatment A: During the study session, healthy subjects were administered a single dose of Olaparib Tablet test formulation100mg under Fasting conditions(test)	Drug: Olaparib Tablet test formulation 100mg; A generic product manufactured by CSPC Ouyi Pharmaceutical Co., Ltd.
Active Comparator: Olaparib Tablet reference formulation 100mg; Treatment B: During the study session, healthy subjects were administered a single dose of Olaparib Tablet reference formulation 100mg under Fasting conditions(reference for Treatment A)	Drug: Olaparib Tablet reference formulation 100mg; Olaparib Tablet reference formulation 100mg were used as a comparator drug for the bioequivalence study, manufactured by AbbVie Limited.
Experimental: Olaparib Tablet test formulation 150mg(fast); Treatment C: During the study session, healthy subjects were administered a single dose of Olaparib Tablet test formulation 150mg under Fasting conditions(test)	Drug: Olaparib Tablet test formulation 150mg; Olaparib Tablet reference formulation 150mg were used as a comparator drug for the bioequivalence study, manufactured by AbbVie Limited.
Active Comparator: Olaparib Tablet reference formulation 150mg(fast); Treatment D: During the study session, healthy subjects were administered a single dose of Olaparib Tablet reference formulation 150mg under Fasting conditions(reference for Treatment C)	Drug: Olaparib Tablet reference formulation 150mg; Olaparib Tablet reference formulation 150mg were used as a comparator drug for the bioequivalence study, manufactured by AbbVie Limited.
Experimental: Olaparib Tablet test formulation 150mg(fed); Treatment E: During the study session, healthy subjects were administered a single dose of Olaparib Tablet test formulation 150mg under Fed conditions(test)	Drug: Olaparib Tablet test formulation 150mg; Olaparib Tablet reference formulation 150mg were used as a comparator drug for the bioequivalence study, manufactured by AbbVie Limited.
Active Comparator: Olaparib Tablet reference formulation 150mg(fed); Treatment F: During the study session, healthy subjects were administered a single dose of Olaparib Tablet reference formulation 150mg under Fed conditions(reference for Treatment E)	Drug: Olaparib Tablet reference formulation 150mg; Olaparib Tablet reference formulation 150mg were used as a comparator drug for the bioequivalence study, manufactured by AbbVie Limited.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax Description: Maximum observed plasma concentration	Cmax Description: Maximum observed plasma concentration	Up to 72 hours post-dose for each period
AUC0-∞ Description: Area under the plasma concentration time curve from time zero extrapolated to infinite time	AUC0-∞ Description: Area under the plasma concentration time curve from time zero extrapolated to infinite time	Up to 72 hours post-dose for each period
AUC0-t Description: Area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration	AUC0-t Description: Area under the plasma concentration time curve from time zero to the time of the last quantifiable concentration	Up to 72 hours post-dose for each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of maximum observed plasma concentration (Tmax)	Time of maximum observed plasma concentration (Tmax)	Up to 72 hours post-dose for each period
Terminal elimination half-life (T1/2)	Terminal elimination half-life (T1/2)	Up to 72 hours post-dose for each period
Apparent total body clearance (Cl/F)	Apparent total body clearance (Cl/F)	Up to 72 hours post-dose for each period
Apparent volume of distribution (V/F)	Apparent volume of distribution (V/F)	Up to 72 hours post-dose for eachperiod
Number of participants with Adverse Events	Number of participants with Adverse Events	Up to 10 days

Collaborators and Investigators

• Sponsor: CSPC Ouyi Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2022
• Primary Completion (Actual): August 21, 2022
• Study Completion (Actual): August 21, 2022

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: HD1912BE202201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No