Drug-Drug Interaction Study of Itraconazole, Rifampicin and Midazolam With SIM0417/Ritonavir in Healthy Participants

NCT05665647 | Completed Phase 1

• 1 other identifier: SIM0417-107
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open-label, fixed-sequence, 2-period drug-drug interaction study to evaluate the pharmacokinetic interactions of itraconazole, rifampicin, midazolam, and SIM0417/ritonavir in healthy Chinese subjects.

Conditions

Healthy Volunteers

Keywords

Drug-drug interaction

Outcome Measures

Primary Outcomes (14)

• Cmax of SIM0417 in cohort 1

  Cmax of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole

  Up to Day 14

• Ctrough of SIM0417 in cohort 1

  Ctrough of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole

  Up to Day 14

• AUC0-t of SIM0417 in cohort 1

  AUC0-t of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole

  Up to Day 14

• AUC0-∞ of SIM0417 in cohort 1

  AUC0-∞ of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole

  Up to Day 14

• AUCtau of SIM0417 in cohort 1

  AUCtau of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole

  Up to Day 14

• t1/2 of SIM0417 in cohort 1

  t1/2 of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole

  Up to Day 14

• Cmax of SIM0417 in cohort 2

  Cmax of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin

  Up to Day 14

• AUC0-t of SIM0417 in cohort 2

  AUC0-t of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin

  Up to Day 14

• AUC0-∞ of SIM0417 in cohort 2

  AUC0-∞ of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin

  Up to Day 14

• t1/2 of SIM0417 in cohort 2

  t1/2 of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin

  Up to Day 14

• Cmax of midazolam

  Cmax of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir

  Up to Day 9

• AUC0-t of midazolam

  AUC0-t of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir

  Up to Day 9

• AUC0-∞ of midazolam

  AUC0-∞ of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir

  Up to Day 9

• t1/2 of midazolam

  t1/2 of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir

  Up to Day 9

Secondary Outcomes (16)

• Adverse Events of Cohort 1

  Up to Day 26

• Adverse Events of Cohort 2

  Up to Day 25

• Adverse Events of Cohort 3

  Up to Day 20

• Vital Signs

  Up to Day 14

• ECG

  Up to Day 14

Study Arms (3)

Cohort 1: SIM0417/ritonavir and itraconazole

EXPERIMENTAL

Interaction between SIM0417/ritonavir and itraconazole

Drug: Cohort 1: SIM0417/ritonavir and itraconazole

Cohort 2: SIM0417/ritonavir and rifampicin

EXPERIMENTAL

Interaction between SIM0417/ritonavir and rifampicin

Drug: Cohort 2: SIM0417/ritonavir and rifampicin

Cohort 3: SIM0417/ritonavir and midazolam

EXPERIMENTAL

Interaction between SIM0417/ritonavir and midazolam

Drug: Cohort 3: SIM0417/ritonavir and midazolam

Interventions

Cohort 1: SIM0417/ritonavir and itraconazole DRUG

SIM0417/Ritonavir: Dose: 750 mg SIM0417 coadministered with 100 mg ritonavir once: Day1-Day2, Day9-Day10, BID; Day3,Day11(once only in the morning); Itraconazole：Dose: 200mg once；Day6-Day13, QD

Also known as: Interaction between SIM0417/ritonavir and itraconazole

Cohort 1: SIM0417/ritonavir and itraconazole

Cohort 2: SIM0417/ritonavir and rifampicin DRUG

SIM0417/Ritonavir:Dose: 750 mg SIM0417 coadministered with 100 mg ritonavir once: Day1,Day11(once only in the morning); Rifampicin：Dose: 0.6g once; Day4-Day12, QD

Also known as: Interaction between SIM0417/ritonavir and rifampicin

Cohort 2: SIM0417/ritonavir and rifampicin

Cohort 3: SIM0417/ritonavir and midazolam DRUG

SIM0417/Ritonavir: 750 mg SIM0417 coadministered with 100 mg ritonavir, Day3-Day6, BID; Day7(once only in the morning) Midazolam：Dose: 2mg once; Day1, Day6, QD

Also known as: Interaction between SIM0417/ritonavir and midazolam

Cohort 3: SIM0417/ritonavir and midazolam

Eligibility Criteria

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

You may qualify if:

• Fully understand the research content, process, and potential risks of this trial, voluntarily participate in the clinical trial and sign the informed consent,
• Healthy male and female subjects aged ≥18 years and ≤45 years old.
• Male weight ≥50kg, female weight ≥45kg, body mass index ≥19 kg/m2 and ≤28 kg/m2.
• Subjects agree to use generally accepted effective contraception from the time they sign the informed consent form. And female subjects of Cohort 1 agree to take recognized effective contraceptive measures during the study period and for the next menstrual cycle after the last dose of the study drug (male subjects up to 1 month after the last dose of the study drug ). Subjects of cohort 2 agree to take recognized effective contraceptive measures during the study period and within 1 month after the last dose of the study drug. Subjects of cohort 3 agree to take recognized effective contraceptive measures during the study period and within 3 months after the last dose of the study drug. Female subjects had been using effective contraception for 14 days prior to screening.

You may not qualify if:

• Any diseases that may affect the study results or the safety and status of the subjects, including but not limited to the central nervous system, respiratory system, cardiovascular system, alimentary system, blood and lymphatic system, endocrine system, musculoskeletal system, hepatic and kidney function obstacle.
• Difficulty in venous blood collection, a history of fainting blood or needles, or those who cannot tolerate blood collection with intravenous indwelling needles.
• With dysphagia or any history of gastrointestinal diseases that affect drug absorption.
• Have special requirements for diet and cannot comply with the diet provided and corresponding regulations.
• With specific allergic history ( asthma, urticaria, eczema, etc. ) or allergic constitution ( such as those allergic to two or more drugs, food such as milk, and pollen ) or allergic to any component of the research drug or research drug.
• With special diet ( including pitaya, mango, grapefruit, food or beverage containing caffeine, etc. ) or intense exercise taken within 48 h before the first administration of the drug.
• Taken of any prescription, non-prescription, vitamin, or herbal medicine within 4 weeks before and during the screening period and/or any vitamin, health care products were taken within 2 weeks before and during the screening period.
• During the first 3 months prior to screening or from the screening period to the first administration period, alcohol was often consumed, i.e., more than 2 units of alcohol per day ( 1 unit = 360 mL beer or 45 mL spirits with 40 % alcohol or 150 mL wine ); or alcohol breath test positive.
• More than 5 cigarettes per day during the 3 months prior to screening.
• Participated in any drug clinical trial as a subject within 3 months prior to screening and took the study drug.
• With blood donation or blood loss greater than 200 mL within 3 months prior to screening, or blood transfusion or blood products were received within 4 weeks.
• Have a history of drug abuse or a positive drug abuse screen.
• At the time of screening or baseline, the blood pressure in the resting state and the pulse are within the following ranges: such as systolic blood pressure \<90 mmHg or ≥140 mmHg, diastolic blood pressure \<60 mmHg or ≥90 mmHg, pulse \<55 bpm or \>100 bpm.
• Electrocardiographic QTc \> 450 msec (Fridericia formula) at screening and/or baseline, or presence of risk factors for Torsade de Pointes (eg, history of heart failure, history of hypokalemia, family with prolonged QT syndrome) history), or other abnormal clinical significance (judged by the investigator).
• HBV surface antigen, HCV antibody, HIV, or syphilis are positive during screening.

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Shandong First Medical University

Jinan, Shandong, 250014, China

Location

Related Publications (1)

• Ye PP, Yao BF, Yang Y, Yang XM, Li Q, Song LL, Chen KG, Zhou HY, Shi JY, Zhang YH, Zhao FR, Guo ZJ, Xu SS, Chen J, Goh AH, Zhu SW, Zheng Y, Zhao W. Drug-drug interactions of simnotrelvir/ritonavir: an open-label, fixed-sequence, two-period clinical trial. Clin Microbiol Infect. 2025 Jan;31(1):101-107. doi: 10.1016/j.cmi.2024.09.007. Epub 2024 Sep 18.

  PMID: 39299559 DERIVED

MeSH Terms

Interventions

Ritonavir; Itraconazole; Rifampin; Midazolam

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazoles; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring

Study Officials

• Wei Zhao

  Shandong First Medical University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: December 27, 2022
• Study Start: December 29, 2022
• Primary Completion: January 26, 2023
• Study Completion: February 14, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)