Drug-Drug Interaction of SHR1459 With a Strong CYP3A Index Inducer (Rifampicin)

A Single-Center, Single-Arm, Open-Label, Fixed-Sequence Phase I Drug-Drug Interaction Clinical Study of the Effect of Rifampicin on Pharmacokinetics of SHR1459 in Chinese Healthy Subjects.

This drug-drug interaction (DDI) study had been designed to investigate the effect of a strong CYP 3A index fan-inducer rifampicin on the pharmacokinetics of SHR1459 in Chinese healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects, Drug-drug Interaction, Pharmacokinetics, SHR1459
• Intervention / Treatment: Drug: Rifampin; Drug: SHR1459

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201203
      • Jiangsu HengRui Medicine Co., Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Sign the informed consent 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. Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent;
4. Body weight ≥50 kg for male and≥ 45 kg for female, and body mass index (BMI) within the range of 19 ~ 26 kg /m2 (including 19 and 26);
5. In females, documented surgical sterilization, postmenopausal status for at least 1 year (follicle stimulating hormone [FSH] > 40 mIU/mL serum at Screening), or agreement to use an approved form of contraception
6. In males, agreement to avoid sperm donation for 3 months days after the dose of SHR1459
7. Liver function test results must be below the upper limit of normal.
8. Participants must agree to refrain from donation of whole blood and other blood products from 90 days prior to screening.
9. Heart rate ≥60 bpm.
10. GFR≥90 mL/min/1.73m2.

Exclusion Criteria:

1. Loss of more than 400 mL blood during the 3 months before the trial (eg, as a blood donor)
2. Allergic constitution;
3. History of drug use, or drug abuse screening positive;
4. Alcoholic or often drinkers;
5. A smoker with 5 cigarettes per day for more than 90 days;
6. Positive serology for hepatitis B surface antigen (HBsAg) and HCV (healthy participants), anti-treponema pallidum virus (TP), or antihuman immunodeficiency virus (HIV) Type 1 and Type 2 (all subjects)
7. Use of any drugs or substances known to be inhibitors or inducers of CYP3A within 90 days from the first dose or 5 half-lives, if known, of the drugs or substances, whichever is greater, prior to SHR1459 administration and during the study.
8. A clear medical history of important primary organ diseases such as nervous system, cardiovascular system, urinary system, digestive system, respiratory system, metabolism and musculoskeletal system.
9. Abnormal clinical laboratory tests and clinical significance judged by the investigator or other clinical findings showing the following diseases, including but not limited to gastrointestinal tract, kidney, liver, nerve, blood, endocrine, tumor, lung, immune, mental or cardiovascular and cerebrovascular diseases.
10. Use of grapefruit or marmalade in 2 weeks prior to admission to the clinical unit, as reported by the subject.
11. Major surgery within 6 months before screening.
12. Woman in breastfeeding and pregnancy and with egg donation plan, and man with sperm donation plan in 6 months after follow-up in the trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rifampicin 600 mg + SHR1459 Tablets 200 mg	Drug: Rifampin; single oral dose, 600 mg, fasted.; Drug: SHR1459; single oral dose, 200 mg, fasted.
Active Comparator: SHR1459 tablets 200 mg	Drug: SHR1459; single oral dose, 200 mg, fasted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Plasma Concentration (Cmax) for SHR1459.	predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24h for Day1 and Day9
Area Under the Plasma Concentration-time Curve from 0 to any time before the last quantifiable concentration (AUC0-t) for SHR1459.	predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24h for Day1 and Day9
Area Under the Plasma Concentration-time Curve from 0 to infinite time (AUCinf) for SHR1459.	predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24h for Day1 and Day9

Secondary Outcome Measures

Outcome Measure	Time Frame
The incidence and severity of adverse events/serious adverse events (based on NCI-CTCAE 5.0): Laboratory indicators, 12-lead electrocardiogram (ECG), physical examination, vital signs, etc.	Baseline up to 14 days post last dose, up to approximately 2 month
Other pharmacokinetics parameters of SHR1459: Tmax, T1/2, CL, Vd, etc	predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24h for Day1 and Day9

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2020
• Primary Completion (Actual): December 14, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: November 10, 2020
• First Submitted That Met QC Criteria: November 25, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): January 11, 2021
• Last Update Submitted That Met QC Criteria: January 7, 2021
• Last Verified: November 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: SHR1459-I-105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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