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Acute Haemodynamic Study of TPN171H in Patients With Pulmonary Arterial Hypertension

Primary Purpose

Pulmonary Arterial Hypertension

Status

Completed

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

TPN171H

Placebo

Tadalafil

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring pulmonary arterial hypertension, Acute Haemodynamic Study, PK/PD study, TPN171H, Simmerafil

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Peking Union Medical College Hospital
Peking University First Hospital
Fuwai Hospital CAMS&PUMC
The First Affiliated Hospital of Chongqing Medical University
Gansu Provincial Hospital
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
The Second Xiangya Hospital of Central South University
First Affiliated Hospital Of Gannan Medical University
Shanghai Pulmonary Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

TPN171H 2.5mg group

TPN171H 5mg group

TPN171H 10mg group

Placebo group

tadalafil 20mg group

tadalafil 40mg group

Arm Description

TPN171H 2.5mg tablet + Placebo 10mg tablet

TPN171H 5mg tablet + Placebo 10mg tablet

TPN171H 10mg tablet + Placebo 5mg tablet

Placebo 5mg tablet+ Placebo 10mg tablet

tadalafil tablet 20mg

tadalafil tablets 20mg *2

Outcomes

Primary Outcome Measures

Percentage of the maximum change in pulmonary vascular resistance(PVR) to the second baseline

Secondary Outcome Measures

Time of maximum change in PVR

The area under the curve for reduction in PVR

Change in arterial oxygenation

Change in right ventricular function

Full Information

NCT ID

NCT04483115

First Posted

July 15, 2020

Last Updated

June 30, 2022

Sponsor

Vigonvita Life Sciences

Collaborators

Shanghai Institute of Materia Medica, Chinese Academy of Sciences

1. Study Identification

Unique Protocol Identification Number

NCT04483115

Brief Title

Acute Haemodynamic Study of TPN171H in Patients With Pulmonary Arterial Hypertension

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

November 16, 2020 (Actual)

Primary Completion Date

June 29, 2022 (Actual)

Study Completion Date

June 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vigonvita Life Sciences

Collaborators

Shanghai Institute of Materia Medica, Chinese Academy of Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Arterial Hypertension

Keywords

pulmonary arterial hypertension, Acute Haemodynamic Study, PK/PD study, TPN171H, Simmerafil

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TPN171H 2.5mg group

Arm Type

Experimental

Arm Description

TPN171H 2.5mg tablet + Placebo 10mg tablet

Arm Title

TPN171H 5mg group

Arm Type

Experimental

Arm Description

TPN171H 5mg tablet + Placebo 10mg tablet

Arm Title

TPN171H 10mg group

Arm Type

Experimental

Arm Description

TPN171H 10mg tablet + Placebo 5mg tablet

Arm Title

Placebo group

Arm Type

Placebo Comparator

Arm Description

Placebo 5mg tablet+ Placebo 10mg tablet

Arm Title

tadalafil 20mg group

Arm Type

Active Comparator

Arm Description

tadalafil tablet 20mg

Arm Title

tadalafil 40mg group

Arm Type

Active Comparator

Arm Description

tadalafil tablets 20mg *2

Intervention Type

Drug

Intervention Name(s)

TPN171H

Other Intervention Name(s)

Simmerafil

Intervention Description

Tablets; Oral; Single dose

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Tablets; Oral; Single dose

Intervention Type

Drug

Intervention Name(s)

Tadalafil

Other Intervention Name(s)

ADCIRCA

Intervention Description

Tablets; Oral; Single dose

Primary Outcome Measure Information:

Title

Percentage of the maximum change in pulmonary vascular resistance(PVR) to the second baseline

Time Frame