An Open, Parallel, Single-dose Phase I Clinical Study to Evaluate the Pharmacokinetics and Safety of TQ05105 Tablets in Patients With Different Levels of Renal Function
Overview
- Phase
- Phase 1
- Intervention
- TQ05105
- Conditions
- Myelofibrosis
- Sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Peak concentration (Cmax)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
This is an open, open-label, parallel, single-dose, phase I clinical study designed to evaluate the pharmacokinetic (PK) profile of TQ05105 tablet in patients with renal impairment after a single dose, and to evaluate the urinary excretion of the drug in these patients after a single dose, as well as to evaluate the safety of the drug in these patients after a single dose.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All subjects are required to meet all of the following criteria for inclusion in this study:
- •Understand the content, process and possible adverse reactions of the trial, be able to complete the study in accordance with the requirements of the trial protocol, and voluntarily sign the informed consent;
- •Participants (including their partners) voluntarily used effective contraception within 6 months from screening until the last use of study drug;
- •Participants aged 18 \~ 75 ;
- •Body mass index (BMI) and 18 or 32 kg/m2 or less, and the male weight 50 kg or greater, female weight 45 kg or more;
- •For renal impairment subjects, also required meet all of the following criteria for inclusion in this study:
- •Subjects with moderate to severe renal insufficiency and end-stage renal disease were required to meet the diagnostic criteria for chronic kidney disease;
- •Stable renal function: creatinine detection of at least two intervals of 3 days (30 days before the screening test results for the first time acceptable) inside and outside school or in our test result, and two detecting serum creatinine results before and after the fluctuation (calculation formula: (second results - 1)) / 1 time is less than 30%;
- •During the screening period, the individual glomerular filtration rate (GFR, mL/min, using the modification of diet in renal disease (MDRD) formula, based on the results of the second serum creatinine test) was classified as follows: 60≤GFR≤89 mL/min (Group A, mild renal dysfunction, Chronic kidney disease (CKD) 2 period), or 30≤GFR≤59 mL/min (Group B, moderate renal dysfunction, CKD 3 period), or 15≤GFR≤29 mL/min (Group C, severe renal dysfunction, CKD 4 period).
- •For normal subjects, also required meet all of the following criteria for inclusion in this study:
Exclusion Criteria
- •All subjects were not eligible for the study if they met any of the following criteria:
- •Individuals with an allergy disposition, or those with a history of allergic reactions to polymyxin-type drugs (including polymyxin B, polymyxin sulfate, and polymyxin E monosodium salt);
- •Participants who have had any type of treatment or untreated malignant tumor (excluding basal cell carcinoma of the skin) within the past 5 years or at baseline;
- •Participants who have had a serious digestive, respiratory, nervous, hematological, endocrine, tumor, immune, psychological, or cardiovascular disease within the past year and are deemed unfit for the study by the investigator;
- •Participants who have had a major illness or surgery within the past 4 weeks or plan to undergo surgery during the study period;
- •Participants who have donated blood (or lost blood) of at least 400 mL within the past 3 months or have received blood products;
- •Participants who have smoked an average of more than 10 cigarettes per day within the past 3 months;
- •Participants who have consumed an average of more than 14 units (female subjects) or 21 units (male subjects) of alcohol per week within the past 3 months (1 unit = 285 mL of beer, 25 mL of distilled spirits, or 100 mL of wine);
- •Participants who have consumed a special diet (including dragon fruit, mango, grapefruit, and/or xanthine diet, chocolate) and/or consumed excessive tea, coffee, grapefruit/grapefruit juice, and/or caffeine-containing beverages (an average of 8 cups or more per day, 200 mL per cup) within the past 2 weeks;
- •Participants who have consumed any alcoholic beverages within 48 hours of receiving the study drug or who have a positive breath alcohol test;
Arms & Interventions
Mild Renal Impairment(GFR:60~89 mL/min)
15 mg orally , single dose
Intervention: TQ05105
Moderate Renal Impairment(GFR:30~59 mL/min)
10 mg orally , single dose
Intervention: TQ05105
Severe Renal Impairment(GFR:15~29 mL/min)
5 mg orally , single dose
Intervention: TQ05105
Normal(GFR≥90mL/min)
15 mg orally , single dose
Intervention: TQ05105
Outcomes
Primary Outcomes
Peak concentration (Cmax)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
Maximum plasma drug concentration of TQ05105 and TQ12550
Area under the concentration-time curve (AUC)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
Area under the plasma concentration-time curve of TQ05105 and TQ12550
Time-to-maximum concentration( Tmax) of TQ05105 and TQ12550
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
Time-to-maximum concentration
Plasma half life (t1/2)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
The time it takes for the concentration or amount in the body of that drug to be reduced by exactly one-half of TQ05105 and TQ12550
Total body clearance (CLt)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
Total body clearance of TQ05105 and TQ12550
Renal clearance (CLr)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
Renal clearance of TQ05105 and TQ12550
Apparent volume of distribution (Vd/F)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
Volume of distribution based on the terminal phase of TQ05105 and TQ12550
Terminal elimination rate (λz)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
First-order rate constant associated with the terminal (log-linear) elimination phase of TQ05105 and TQ12550
Mean residence time (MRT)
Time Frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration
The average time that the drug stays in the body of TQ05105 and TQ12550
Secondary Outcomes
- Amount Excreted in Urine as Unchanged Drug or Metabolite (Ae0-24)(Before administration, 0~ 3, 3~6， 6~9, 9~12, 12~16, 16~24, 24~36, 36~48 hours after administration)
- Adverse event rate(Baseline up to 72 hours)