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

NCT04649723 | Completed Phase 1

• 1 other identifier: SHR1459-I-105
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects, Drug-drug Interaction, Pharmacokinetics, SHR1459

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• 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

• 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

Study Arms (2)

Rifampicin 600 mg + SHR1459 Tablets 200 mg

EXPERIMENTAL

Drug: Rifampin; Drug: SHR1459

SHR1459 tablets 200 mg

ACTIVE COMPARATOR

Drug: SHR1459

Interventions

Rifampin DRUG

single oral dose, 600 mg, fasted.

Rifampicin 600 mg + SHR1459 Tablets 200 mg

SHR1459 DRUG

single oral dose, 200 mg, fasted.

Rifampicin 600 mg + SHR1459 Tablets 200 mg; SHR1459 tablets 200 mg

Eligibility Criteria

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

You may qualify if:

• Sign the informed consent before the trial, and fully understand the trial content, process and possible adverse reactions;
• Ability to complete the study as required by the protocol;
• Healthy male or female subjects aged 18 to 45 (including 18 and 45) at the date of signing the informed consent;
• 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);
• 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
• In males, agreement to avoid sperm donation for 3 months days after the dose of SHR1459
• Liver function test results must be below the upper limit of normal.
• Participants must agree to refrain from donation of whole blood and other blood products from 90 days prior to screening.
• Heart rate ≥60 bpm.
• GFR≥90 mL/min/1.73m2.

You may not qualify if:

• Loss of more than 400 mL blood during the 3 months before the trial (eg, as a blood donor)
• Allergic constitution;
• History of drug use, or drug abuse screening positive;
• Alcoholic or often drinkers;
• A smoker with 5 cigarettes per day for more than 90 days;
• 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)
• 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.
• 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.
• 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.
• Use of grapefruit or marmalade in 2 weeks prior to admission to the clinical unit, as reported by the subject.
• Major surgery within 6 months before screening.
• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (1)

Jiangsu HengRui Medicine Co., Ltd.

Shanghai, Shanghai Municipality, 201203, China

Location

MeSH Terms

Interventions

Rifampin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To observe the effect of rifampicin on the pharmacokinetics of SHR1459 and to evaluate the safety of SHR1459, rifampicin and their coadministration in Chinese healthy subjects. The subjects will take SHR1459 at first single dose, then washout period, and take it at second single dose after multiple administration of rifampicin to get a full induction condition.

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: December 2, 2020
• Study Start: November 24, 2020
• Primary Completion: December 14, 2020
• Study Completion: December 14, 2020
• Last Updated: January 11, 2021

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)