A Drug-drug Interaction Trial of Rifampicin Pharmacokinetics Effect on Fluzoparib

A Single Center, Single Arm, Open and Fixed Sequence Study to Investigate the Pharmacokinetic Effects of Rifampicin on Fluzoparib in Healthy Male Subjects

The primary objective of the study was to assess the effect of repeated oral doses of Rifampicin on the pharmacokinetic profile of a single dose of Fluzoparib.

The secondary objective of the study was to assess the safety of Fluzoparib given alone versus Fluzoparib coadministered with Rifampicin.

Study Overview

• Status: Completed
• Conditions: Healthy Male Subjects
• Intervention / Treatment: Drug: Fluzoparib; Drug: Rifampicin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • First Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Sign the informed consent form before the trial and fully understand the trial content, process and possible adverse reactions;
2. Ability to complete the study as required by the protocol;
3. Age on the date of signing the informed consent form is 18 to 50 years old (including both ends) and is limited to male subjects only;
4. Male subjects are willing to have no birth plans in the next 6 months and voluntarily take effective contraception;
5. The fasting weight is not less than 50kg, and the body mass index (BMI) is in the range of 18 kg/m2 to 28 kg/m2 (including both ends);
6. Health status: no medical history of heart, liver, kidney, digestive tract, nervous system, mental abnormalities and metabolic abnormalities;
7. Accepted physical examination results (vital signs, physical examination) and routine laboratory examination (blood routine, blood biochemistry, urine routine, etc.), 12-lead ECG, X-chest, abdominal B-ultrasound, etc. or no clinical significance if abnormal.
8. Creatinine clearance (CLCr) ≥ 80 mL/min, and creatinine is less than or equal to the upper limit of normal

Exclusion Criteria:

1. Participate in blood donation within 3 months before screening and donate blood volume ≥400mL or blood loss ≥400mL, participate in blood donation within 1 month before screening and donate blood volume ≥200mL or blood loss ≥200mL, or receive blood transfusion;
2. Allergic constitution, including a history of severe drug allergy or drug allergy; a history of allergies to fluzoparib capsule or its excipients;
3. with drug and/or alcohol abuse history, or alcohol, nicotine and drug screening positives, or drug abuse in the past five years or used drugs 3 months before the trial; and could not prohibit smoking and alcohol during the trial period ;
4. with medical history of cardiovascular disease such as myocarditis, coronary heart disease, pathological arrhythmia, and stroke;
5. Pulmonary diseases, including invasive lung disease, pneumonia, dyspnea, etc.;
6. Chronic kidney disease, renal insufficiency, history of renal anemia;
7. have a history of dysphagia or any history of gastrointestinal disease that affects drug absorption;
8. any uncontrolled peptic ulcer, colitis, pancreatitis, etc.;
9. Anyone who has undergone any surgery within the first 6 months of screening; has undergone any surgery that affects gastrointestinal absorption (including gastrectomy, bowel resection, stomach reduction, etc.);
10. with acute disease that has been clinically determined by the investigator occurred within 1 month before screening;
11. Other important organ diseases such as the nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolic and musculoskeletal system with clear medical history (such as uncontrolled diabetes, high blood pressure, etc.), enabling investigators considered unsuitable for participation in the study;
12. Those who have taken any clinical trial drugs within 3 months;
13. Take any drug that affects liver metabolism within 28 days before taking the investigational drug;
14. Take any prescription or over-the-counter medication within 14 days before taking the investigational drug;
15. Take any vitamin products or herbs within 14 days before taking the investigational drug;
16. Clinical laboratory tests are abnormal and clinically significant, or other clinical findings indicate the following diseases, including but not limited to gastrointestinal, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardiovascular disease;
17. combined with other viral infections (anti-HCV, anti-HIV positive, HBsAg positive) or combined with syphilis infection;
18. The subject refused to discontinue any beverage containing methylxanthine, such as caffeine (coffee, tea, cola, chocolate, etc.) or alcoholic beverages or any juice, 48 hours before the investigational drug was administered until the end of the study;
19. Strenuous exercise, or other factors affecting drug absorption, distribution, metabolism, excretion, etc.;
20. The investigator believes that the subjects are not eligible to participate in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifampicin + Fluzoparib	Drug: Fluzoparib; single dose on Day 1 and Day 12; Drug: Rifampicin; QD on Day 5-14 for 10 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration (Cmax) of Fluzoparib	Day 1 to Day 15
Area under the plasma concentration versus time curve (AUC) of Fluzoparib	Day 1 to Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Laboratory indicators, 12-lead electrocardiogram (ECG), physical examination, vital signs, adverse events (NCI-CTC AE 5.0), etc.	Up to Day 22

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2019
• Primary Completion (Actual): September 16, 2019
• Study Completion (Actual): September 16, 2019

Study Registration Dates

• First Submitted: July 3, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 26, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin
• Other Study ID Numbers: FZPL-I-110

Drug and device information, study documents

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