An Open Labe Study to Evaluate the Drug-Drug Interaction of Itraconazole, Rifampicin and Midazolam With SIM0417/Ritonavir in Healthy Adult Chinese Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Healthy Volunteers
- Sponsor
- Jiangsu Simcere Pharmaceutical Co., Ltd.
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- AUC0-t of SIM0417 in cohort 1
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Detailed 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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/m
- •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
- •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.
Outcomes
Primary Outcomes
AUC0-t of SIM0417 in cohort 1
Time Frame: Up to Day 14
AUC0-t of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
AUC0-t of SIM0417 in cohort 2
Time Frame: Up to Day 14
AUC0-t of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Cmax of SIM0417 in cohort 1
Time Frame: Up to Day 14
Cmax of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
t1/2 of midazolam
Time Frame: Up to Day 9
t1/2 of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
Ctrough of SIM0417 in cohort 1
Time Frame: Up to Day 14
Ctrough of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
AUC0-∞ of SIM0417 in cohort 2
Time Frame: Up to Day 14
AUC0-∞ of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin
Cmax of midazolam
Time Frame: Up to Day 9
Cmax of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
AUC0-t of midazolam
Time Frame: Up to Day 9
AUC0-t of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
AUC0-∞ of SIM0417 in cohort 1
Time Frame: Up to Day 14
AUC0-∞ of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
Cmax of SIM0417 in cohort 2
Time Frame: Up to Day 14
Cmax of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin
t1/2 of SIM0417 in cohort 2
Time Frame: Up to Day 14
t1/2 of SIM0417 when SIM0417/ritonavir is single dosed administration or combined with rifampicin
AUCtau of SIM0417 in cohort 1
Time Frame: Up to Day 14
AUCtau of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
t1/2 of SIM0417 in cohort 1
Time Frame: Up to Day 14
t1/2 of SIM0417 when SIM0417/ritonavir is multiple administered or combined with itraconazole
AUC0-∞ of midazolam
Time Frame: Up to Day 9
AUC0-∞ of midazolam when midazolam is single dosed administration or combined with SIM0417/ritonavir
Secondary Outcomes
- Adverse Events of Cohort 1(Up to Day 26)
- AUC0-t of ritonavir in Cohort 1(Up to Day 14)
- t1/2 of ritonavir in Cohort 1(Up to Day 14)
- Laboratory Tests(Up to Day 14)
- Adverse Events of Cohort 3(Up to Day 20)
- ECG(Up to Day 14)
- Cmax of ritonavir in Cohort 1(Up to Day 14)
- Ctrough of ritonavir in Cohort 1(Up to Day 14)
- t1/2 of ritonavir in Cohort 2(Up to Day 14)
- AUC0-t of ritonavir in Cohort 2(Up to Day 14)
- AUC0-∞ of ritonavir in Cohort 1(Up to Day 14)
- Cmax of ritonavir in Cohort 2(Up to Day 14)
- Adverse Events of Cohort 2(Up to Day 25)
- Vital Signs(Up to Day 14)
- AUCtau of ritonavir in Cohort 1(Up to Day 14)
- AUC0-∞ of ritonavir in Cohort 2(Up to Day 14)