Hepatic Impairment and Renal Impairment Study of SIM0417 Combined With Ritonavir

NCT05731804 | Unknown Phase 1

• 1 other identifier: SIM0417-105
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, nonrandomized, open-label, parallel controlled Phase I clinical study to evaluate the Pharmacokinetics, Safety and Tolerability of SIM0417 combined with ritonavir after a single dose in subjects with mild and moderate renal impairment, moderate hepatic impairment, normal renal function, and normal hepatic function. It is divided into Part A (subjects with mild/moderate renal impairment and subjects with normal renal function) and Part B (subjects with moderate hepatic impairment and subjects with normal hepatic function).

Conditions

Renal Impairment; Hepatic Impairment

Outcome Measures

Primary Outcomes (6)

• Cmax of SIM0417 in Part A

  Cmax of SIM0417 in Part A when SIM0417 combined with ritonavir

  Up to 48 hours from SIM0417 administration

• AUC0-t of SIM0417 in Part A

  AUC0-t of SIM0417 in Part A when SIM0417 combined with ritonavir

  Up to 48 hours from SIM0417 administration

• AUC0-∞ of SIM0417 in Part A

  AUC0-∞ of SIM0417 in Part A when SIM0417 combined with ritonavir

  Up to 48 hours from SIM0417 administration

• Cmax of SIM0417 in Part B

  Cmax of SIM0417 in Part B when SIM0417 combined with ritonavir

  Up to 48 hours from SIM0417 administration

• AUC0-t of SIM0417 in Part B

  AUC0-t of SIM0417 in Part B when SIM0417 combined with ritonavir

  Up to 48 hours from SIM0417 administration

• AUC0-∞ of SIM0417 in Part B

  AUC0-∞ of SIM0417 in Part B when SIM0417 combined with ritonavir

  Up to 48 hours from SIM0417 administration

Secondary Outcomes (19)

• Tmax of SIM0417 in Part A

  Up to 48 hours from SIM0417 administration

• t1/2 of SIM0417 in Part A

  Up to 48 hours from SIM0417 administration

• CL/F of SIM0417 in Part A

  Up to 48 hours from SIM0417 administration

• Vz/F of SIM0417 in Part A

  Up to 48 hours from SIM0417 administration

• Ae of SIM0417 in Part A

  Up to 96 hours from SIM0417 administration

Study Arms (6)

Cohort 1 of Part A

EXPERIMENTAL

Subjects with mild renal impairment(SIM0417 600 mg; Ritonavir100 mg )

Drug: SIM0417 600 mg; Ritonavir100 mg

Cohort 2 of Part A

EXPERIMENTAL

Subjects with moderate renal impairment(SIM0417 375 mg; Ritonavir100 mg )

Drug: SIM0417 375 mg; Ritonavir100 mg

Cohort 3 of Part A

EXPERIMENTAL

Subjects with normal renal function(SIM0417 600 mg; Ritonavir100 mg )

Drug: SIM0417 600 mg; Ritonavir100 mg

Cohort 4 of Part A

EXPERIMENTAL

Subjects with normal renal function(SIM0417 375 mg; Ritonavir100 mg )

Drug: SIM0417 375 mg; Ritonavir100 mg

Cohort 5 of Part B

EXPERIMENTAL

Subjects with moderate hepatic impairment (SIM0417 750 mg; Ritonavir100 mg )

Drug: SIM0417 750 mg; Ritonavir100 mg

Cohort 6 of Part B

EXPERIMENTAL

Subjects with normal hepatic function(SIM0417 750 mg; Ritonavir100 mg )

Drug: SIM0417 750 mg; Ritonavir100 mg

Interventions

SIM0417 600 mg; Ritonavir100 mg DRUG

SIM0417 is single dosed, and ritonavir is administered 12 hours before SIM0417 administration (-12 hours), at the time of SIM0417 administration (0 hour), 12 hours (12 hours) after SIM0417 administration, and 24 hours (24 hours) after SIM0417 administration.

Cohort 1 of Part A; Cohort 3 of Part A

SIM0417 375 mg; Ritonavir100 mg DRUG

SIM0417 is single dosed, and ritonavir is administered 12 hours before SIM0417 administration (-12 hours), at the time of SIM0417 administration (0 hour), 12 hours (12 hours) after SIM0417 administration, and 24 hours (24 hours) after SIM0417 administration.

Cohort 2 of Part A; Cohort 4 of Part A

SIM0417 750 mg; Ritonavir100 mg DRUG

SIM0417 is single dosed, and ritonavir is administered 12 hours before SIM0417 administration (-12 hours), at the time of SIM0417 administration (0 hour), 12 hours (12 hours) after SIM0417 administration, and 24 hours (24 hours) after SIM0417 administration.

Cohort 5 of Part B; Cohort 6 of Part B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ● PartA:
• All subjects
• Fully understand the study content, process, and potential risks of this trial, and voluntarily sign the informed consent.
• Male and female subjects aged ≥18 years and ≤75 years old.
• Male subjects weigh ≥50 kg, female subjects weigh ≥45 kg; BMI ≥ 18 and ≤ 28 kg/m\^2.
• The results of screening and baseline blood pregnancy examination of women of childbearing potential are negative, and they are willing to take effective contraceptive measures during the trial and within 3 months after the last administration of the investigational product, or have postmenopause or surgical sterilization; male subjects have no fertility plan during the trial and within 3 months after the last administration of the investigational product and voluntarily take effective contraceptive measures or have surgical sterilization.
• Subjects with renal impairment
• Glomerular filtration rate should meet the following criteria ( eGFR = eGFR（CKD-EPI）× BSA / 1.73): Mild renal impairment ( CKD2 ) 60-89 mL/min (both values included; Moderate renal impairment ( CKD3 ) 30-59 mL/min (both values included).
• The renal function status is stable, and the GFR results of the two tests before administration (at least 3 days interval ) must be in the same CKD stage.
• No medication within 14 days before enrollment, or with a stable medication regimen for the treatment of renal impairment or other comorbidities (the type, dose or frequency of medication has not been adjusted for at least 2 weeks).
• Total bilirubin, ALT and AST ≤ 2 ×ULN.
• Be in acceptable physical condition except for renal impairment and complications, according to medical history inquiry, physical examination, vital signs, laboratory tests (Hematology, blood biochemistry, urinalysis, coagulation function, thyroid function ), 12-lead ECG, chest radiograph, thyroid ultrasound, abdominal ultrasound(judged by the investigator).
• Subjects with normal renal function
• Age-matched (±10 years), weight-matched (±15kg), and gender-matched with subjects in the renal impairment group.
• Glomerular filtration rate( eGFR = eGFR（CKD-EPI）× BSA / 1.73)≥ 90 mL / min.

You may not qualify if:

• ● PartA:
• All subjects
• Breastfeeding women.
• Those with allergies, including a history of severe drug allergy or drug allergy; or may be allergic to the study drug or any excipients of the study drug.
• Difficulties in venous blood collection.
• With severe infection, trauma, major surgical operation, digestive system surgery, and affecting drug absorption within 4 weeks before screening.
• Within six months before screening, patients with myocardial infarction, severe/unstable angina pectoris, symptomatic congestive heart failure ( NYHA II-IV ), or history of supraventricular or ventricular arrhythmia or left ventricular impairment which was Clinically significant and requiring treatment or intervention.
• Participated in clinical trials of any drug intervention within 3 months before screening.
• Blood donation ≥ 400 mL within 3 months before screening, or received blood transfusion or blood products within 1 month before the screening.
• Those who are addicted to smoking or drinking within 3 months before screening, and who cannot stop smoking and drinking during the test, or those who have a positive breath test for alcohol. (Remarks: addicted to Smoking is defined as ≥5 cigarettes/day; alcoholism is defined as daily drinking exceeding the following standard amounts: 570 mL of beer, 750 mL of light beer, 200 mL of red wine or 60 mL of white wine, each containing about 20 g of alcohol ).
• With Drug abuse history or a positive drug abuse screen.
• Used any CYP3A4 potent inducer within 28 days before the first administration.
• Special diets ( including pitayas, mangoes, grapefruit, caffeine-containing foods or drinks, etc. ) or intense exercise were taken within 48 hours before the first administration of the study drug.
• Those who have been vaccinated within 1 month before screening (except for the COVID-19 vaccine), or who plan to be vaccinated during treatment / within 2 weeks after the last dose of study drug.
• lead ECG at screening, QT interval (QTcF) corrected by Fridericia formula ≥ 470 msec (female)/450 msec (male).

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Shandong Provincial Qianfoshan Hospital

Jinan, Shandong, 250014, China

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Wei Zhao

  Shandong First Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Juan Wu

CONTACT

+86 18920299268; wujuan3@simcere.com

Danny Chen

CONTACT

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: January 18, 2023
• First Posted: February 16, 2023
• Study Start: March 1, 2023
• Primary Completion: December 1, 2023
• Study Completion: December 31, 2023
• Last Updated: March 8, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)