Acute Haemodynamic Study of TPN171H in Patients With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

Official title:

Multi-center, Randomized，Placebo and Positive Controlled Clinical Study of TPN171H Tablets on Acute Haemodynamics in Patients With Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04483115
• Other study ID #: TPN171H-P201
• Status: Completed
• Phase: Phase 2
• Start date: November 16, 2020
• Est. completion date: June 29, 2022

Study information

• Verified date: December 2021
• Source: Vigonvita Life Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a phase IIa proof-of-concept study to evaluate the effect of single-dose TPN171H tablets on acute haemodynamic parameters in patients with pulmonary arterial hypertension.The trial is expected to include 60 patients, divided into 6 groups, according to 1:1:1:1:1:1 into the placebo group and the test drugs 2.5mg, 5mg, 10mg group, tadalafil tablets 20mg, 40mg group, each group 10 cases.

Description:

This study is a multi-center, randomized, placebo and positive controlled phase IIa proof-of-concept study to evaluate the effect of single-dose TPN171H tablets on acute hemodynamic parameters in patients with pulmonary arterial hypertension.The trial is expected to include 60 patients, divided into 6 groups, according to 1:1:1:1:1:1 into the placebo group and the test drugs 2.5mg, 5mg, 10mg group, tadalafil tablets 20mg, 40mg group, each group 10 cases. During the screening period, the tube placement period, and the observation period, the patients will conduct various inspections and evaluation observations as required.

The Swan-Ganz floating catheter and echocardiography were used to evaluate the efficacy of TPN171H; PK parameters: including Tmax, Cmax, AUC0-t , t1/2,CL/F, Vz/F, λz; Safety evaluation indicators include: vital signs, physical examination, laboratory examination (blood routine, blood biochemistry, blood gas analysis), 12-lead ECG, adverse events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: June 29, 2022
• Est. primary completion date: June 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients aged 18 to 75;

• Patients who have voluntarily decided to participate in this study, and signed the informed consent form;

• Patients who are able to understand and follow study plans and instructions;

• Patients with symtomatic PAH (Group1), a pulmonary vascular resistance (PVR) > 3 Wood, a mean pulmonary artery pressure (mPVP) =25 mmHg and a pulmonary artery wedge pressure (PAWP) = 15 mmHg either due to:

1. Idiopathic PAH (IPAH)

2. Familial PAH

3. Associated PAH due to drugs or toxins

4. Associated PAH due to connective tissue disease

5. Associated PAH due to congenital heart disease, if patients underwent surgical correction more than 1 year prior to screening

• Have a current diagnosis of being in WHO functional class II or III;

• Patients who are willing to take proper contraceptive during the study and within 3 months after the study completed.

Exclusion Criteria:

• All types of PH except subtypes of Group1 specified in the inclusion criteria;

• Moderate to severe COPD (FEV1 < 60% predicted);

• Moderate to severe restrictive lung disease (FVC < 70% predicted);

• Pre-treatment with PAH therapy within the last 1 months before the screening visit (including endothelin receptor antagonists, PDE5 inhibitors, guanylate cyclase agonist and prostacycline analogues);

• A "positive" response to acute vasodilator testing;

• Coagulation dysfunction (defined as activated partial thromboplastin time and international normalized ratio are both >1.5 times upper limit normal) or patients with potential bleeding risk;

• Hepatic dysfunction indicated by: serum bilirubin>3 times upper limit normal, ALT and AST>2.5 times upper limit normal;

• Renal insufficiency (creatinine clearance<30 mL/min);

• Systolic blood pressure<90 mmHg at screening;

• QT prolongation at screening, whose values (QTcF) exceeding 450 msec in males and 470 msec in females;

• Have enrolled in/or have a plan of an exercise training program for pulmonary rehabilitation before the screening visit/or during the study;

• Patients who have a recent (within 3 months) history of abusing alcohol or illicit drugs;

• Body weight<40 kg;

• Patients who have participated in a clinical study involving another investigational drug within 1 month before the screening visit;

• For any other reasons that affect compliance with the study protocol, especially the long-term monitoring of floating catheters, according to the decision of investigators;

• HBV, HCV, HIV or Tp infection;

• Patients with gastrointestinal, urinary, reproductive, immunologic, endocrine, or central nervous system disease that, in the opinion of the investigator, will affect the study;

• Have a history of malignancies within 2 years, except for a cured basal cell or skin squamous cell carcinoma;

• Pregnant women, or breast feeding women;

• Patients with hypersensitivity to iloprost or any of the excipients.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• TPN171H
Tablets; Oral; Single dose
• Placebo
Tablets; Oral; Single dose
• Tadalafil
Tablets; Oral; Single dose

Locations

Country	Name	City	State
China	Fuwai Hospital CAMS&PUMC	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	First Affiliated Hospital Of Gannan Medical University	Ganzhou	Jiangxi
China	Gansu Provincial Hospital	Lanzhou	Gansu
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
China	Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology	Wuhan	Hubei

Sponsors (2)

Lead Sponsor	Collaborator
Vigonvita Life Sciences	Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of the maximum change in pulmonary vascular resistance(PVR) to the second baseline		Within 24 hours after drug administration
Secondary	Time of maximum change in PVR		Within 24 hours after drug administration
Secondary	The area under the curve for reduction in PVR		Within 24 hours after drug administration
Secondary	Change in arterial oxygenation		Within 24 hours after drug administration
Secondary	Change in right ventricular function		Within 24 hours after drug administration