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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
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
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
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
Shandong First Medical University
Jinan, Shandong, China
Cmax of SIM0417 in cohort 1
Cmax of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
Ctrough of SIM0417 in cohort 1
Ctrough of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: 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
Time frame: Up to Day 14
AUC0-∞ of SIM0417 in cohort 1
AUC0-∞ of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
AUCtau of SIM0417 in cohort 1
AUCtau of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: 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
Time frame: Up to Day 14
Cmax of SIM0417 in cohort 2
Cmax of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Time frame: 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
Time frame: Up to Day 14
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
AUC0-∞ of SIM0417 in cohort 2
AUC0-∞ of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Time frame: 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
Time frame: Up to Day 14
Cmax of midazolam
Cmax of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
Time frame: Up to Day 9
AUC0-t of midazolam
AUC0-t of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
Time frame: Up to Day 9
AUC0-∞ of midazolam
AUC0-∞ of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
Time frame: Up to Day 9
t1/2 of midazolam
t1/2 of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
Time frame: Up to Day 9
Adverse Events of Cohort 1
Number of Participants With Adverse Events
Time frame: Up to Day 26
Adverse Events of Cohort 2
Number of Participants With Adverse Events
Time frame: Up to Day 25
Adverse Events of Cohort 3
Number of Participants With Adverse Events
Time frame: Up to Day 20
Vital Signs
Number of Participants With Clinically Notable Vital Signs
Time frame: Up to Day 14
ECG
Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Time frame: Up to Day 14
Laboratory Tests
Number of Participants With Clinically Notable Laboratory Tests
Time frame: Up to Day 14
Cmax of ritonavir in Cohort 1
Cmax of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
Ctrough of ritonavir in Cohort 1
Ctrough of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
AUC0-t of ritonavir in Cohort 1
AUC0-t of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
AUC0-∞ of ritonavir in Cohort 1
AUC0-∞ of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
AUCtau of ritonavir in Cohort 1
AUCtau of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
t1/2 of ritonavir in Cohort 1
t1/2 of ritonavir when SIM0417/ritonavir is multiple administered or combined with itraconazole
Time frame: Up to Day 14
Cmax of ritonavir in Cohort 2
Cmax of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Time frame: Up to Day 14
AUC0-t of ritonavir in Cohort 2
AUC0-t of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Time frame: Up to Day 14
AUC0-∞ of ritonavir in Cohort 2
AUC0-∞ of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Time frame: Up to Day 14
t1/2 of ritonavir in Cohort 2
t1/2 of ritonavir when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Time frame: Up to Day 14