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

Healthy Volunteers Clinical Trial

Official title:

An Open Labe Study to Evaluate the Drug-Drug Interaction of Itraconazole, Rifampicin and Midazolam With SIM0417/Ritonavir in Healthy Adult Chinese Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05665647
• Other study ID #: SIM0417-107
• Status: Completed
• Phase: Phase 1
• Start date: December 29, 2022
• Est. completion date: February 14, 2023

Study information

• Verified date: January 2023
• Source: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a phase 1, open-label, fixed-sequence, 2-period drug-drug interaction study which was divided into three cohorts.

Cohort 1: to evaluate the effect of the CYP3A4 inhibitor itraconazole on the pharmacokinetics of SIM0417 and ritonavir in healthy participants.

Cohort 2: to evaluate the effect of the CYP3A4 inducer rifampicin on the pharmacokinetics of SIM0417 and ritonavir in healthy participants.

Cohort 3: to evaluate the effect of SIM0417/ ritonavir on the pharmacokinetics of CYP3A4 substrate midazolam in healthy participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: February 14, 2023
• Est. primary completion date: January 26, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Fully understand the research content, process, and potential risks of this trial, voluntarily participate in the clinical trial and sign the informed consent,

2. Healthy male and female subjects aged =18 years and =45 years old.

3. Male weight =50kg, female weight =45kg, body mass index =19 kg/m2 and =28 kg/m2.

4. 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.

Exclusion Criteria:

1. 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.

2. Difficulty in venous blood collection, a history of fainting blood or needles, or those who cannot tolerate blood collection with intravenous indwelling needles.

3. With dysphagia or any history of gastrointestinal diseases that affect drug absorption.

4. Have special requirements for diet and cannot comply with the diet provided and corresponding regulations.

5. 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.

6. 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.

7. 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.

8. 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.

9. More than 5 cigarettes per day during the 3 months prior to screening.

10. Participated in any drug clinical trial as a subject within 3 months prior to screening and took the study drug.

11. 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.

12. Have a history of drug abuse or a positive drug abuse screen.

13. 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.

14. 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).

15. HBV surface antigen, HCV antibody, HIV, or syphilis are positive during screening.

16. Physical examination, vital signs, ECG, blood routine, blood biochemistry ( serum creatinine, total bilirubin> 1.0 × ULN, ALT, AST, triglyceride>1.1 ULN)), coagulation function, thyroid function, urine routine, chest X-ray, abdominal B-scan ultrasonography results were abnormal and have clinical significance (judged by the investigator).

17. Those who have been vaccinated within 1 month before screening, or have been vaccinated with a COVID-19 vaccine within 1 week before screening, or plan to be vaccinated during the treatment or within 2 weeks after the last dose of study drug.

18. Be positive in SARS-CoV-2 nucleic acid test at screening.

19. Those who had undergone major surgery within 6 months prior to screening or were scheduled to undergo surgery during the study period and were determined by the investigators to be unsuitable for inclusion.

20. Subjects have acute disease with clinical significance that judged unsuitable for inclusion judged by the investigator within 1 month before screening.

21. Females who are pregnant or breastfeeding or positive result from pregnancy test.

22. Subjects have other conditions that are not suitable for participating in this research, or the subjects may not be able to complete this research for other reasons (judged by the investigator).

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Cohort 1: SIM0417/ritonavir and itraconazole
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
• Cohort 2: SIM0417/ritonavir and rifampicin
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
• Cohort 3: SIM0417/ritonavir and midazolam
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

Locations

Country	Name	City	State
China	Shandong First Medical University	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Simcere Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax of SIM0417 in cohort 1	Cmax of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Primary	Ctrough of SIM0417 in cohort 1	Ctrough of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Primary	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
Primary	AUC0-8 of SIM0417 in cohort 1	AUC0-8 of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Primary	AUCtau of SIM0417 in cohort 1	AUCtau of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Primary	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
Primary	Cmax of SIM0417 in cohort 2	Cmax of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin	Up to Day 14
Primary	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
Primary	AUC0-8 of SIM0417 in cohort 2	AUC0-8 of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin	Up to Day 14
Primary	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
Primary	Cmax of midazolam	Cmax of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir	Up to Day 9
Primary	AUC0-t of midazolam	AUC0-t of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir	Up to Day 9
Primary	AUC0-8 of midazolam	AUC0-8 of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir	Up to Day 9
Primary	t1/2 of midazolam	t1/2 of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir	Up to Day 9
Secondary	Adverse Events of Cohort 1	Number of Participants With Adverse Events	Up to Day 26
Secondary	Adverse Events of Cohort 2	Number of Participants With Adverse Events	Up to Day 25
Secondary	Adverse Events of Cohort 3	Number of Participants With Adverse Events	Up to Day 20
Secondary	Vital Signs	Number of Participants With Clinically Notable Vital Signs	Up to Day 14
Secondary	ECG	Number of Participants With Clinically Notable Electrocardiogram (ECG) Values	Up to Day 14
Secondary	Laboratory Tests	Number of Participants With Clinically Notable Laboratory Tests	Up to Day 14
Secondary	Cmax of ritonavir in Cohort 1	Cmax of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Secondary	Ctrough of ritonavir in Cohort 1	Ctrough of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Secondary	AUC0-t of ritonavir in Cohort 1	AUC0-t of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Secondary	AUC0-8 of ritonavir in Cohort 1	AUC0-8 of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Secondary	AUCtau of ritonavir in Cohort 1	AUCtau of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Secondary	t1/2 of ritonavir in Cohort 1	t1/2 of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole	Up to Day 14
Secondary	Cmax of ritonavir in Cohort 2	Cmax of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin	Up to Day 14
Secondary	AUC0-t of ritonavir in Cohort 2	AUC0-t of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin	Up to Day 14
Secondary	AUC0-8 of ritonavir in Cohort 2	AUC0-8 of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin	Up to Day 14
Secondary	t1/2 of ritonavir in Cohort 2	t1/2 of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin	Up to Day 14