Exploring the safety, tolerability, and pharmacokinetic (PK) characteristics of oral TPN171H tablets in patients with Pulmonary Arterial Hypertension under continuous multiple administration conditions, providing a basis for determining the administration plan and recommended dosage in phase II clinical study.
This study was divided into screening period, treatment period and medication follow-up period, and the treatment period included 3 cycles. First cycle: subjects receiving the test drug 2.5mg QD for 2 consecutive weeks, PK blood collection on Day 1 and Day 7, and the subjects discharged and returned to the hospital on Day 14 for medication monitoring blood collection, safety examination and efficacy assessment. Second cycle: up to 14 weeks; the second cycle is divided into monitoring and observation cycles; subjects who complete the first cycle and examinations enter the second cycle, with a 14 day monitoring period and 12 week observation period, with the second cycle dose of 5 mg QD, subjects received PK sampling on Day 7. Third cycle:The third cycle lasts for 8 days, subjects receive 10mg QD for 8 days; subjects received PK sampling on Day 7; subjects who completed an 8-day safety observation period on Day 8 without abnormal safety tests may be discharged. After discharge into the medication follow-up period. Medication follow-up period: up to 2 years; subjects entering the follow-up period will continue to take the dose of the last treatment period, return to hospital once every 12 weeks for safety examination and efficacy assessment until the subject intolerance or withdrawal from the study or expiration of 2 years (whichever occurs first).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
TPN171H 2.5mg TPN171H 5mg TPN171H 10mg
Fu Zhu
Shanghai, China
Incidence of Treatment-Emergent Adverse Events
Time frame: through study completion, an average of 2 years
Q-T interval
Time frame: through study completion, an average of 2 years
Tmax
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
Cmax
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
AUC0~t
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
AUC0-∞
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
Terminal half-life (t 1/2)
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
Apparent distribution volume (Vd/F)
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
Clearance rate (CL/F)
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
Mean Residence Time(MRT)
Time frame: From time zero up to 24 hours post-dose following oral administration of TPN171H
6- Minute Walk Distance(6-MWD)
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Cardiopulmonary function indicators reflecting the patient's physiological state
Time frame: through study completion, an average of 2 years
NT-proBNP
Heart failure evaluation indicators to evaluate the severity of heart failure;
Time frame: through study completion, an average of 2 years
The World Health Organization (WHO) functional class
Evaluate the severity of Pulmonary Arterial Hypertension symptoms at each time point before and after taking TPN171H
Time frame: through study completion, an average of 2 years
Borg dyspnea index
to evaluate the degree of difficulty breathing in subjects after a 6-minute walk test
Time frame: through study completion, an average of 2 years