Acute Haemodynamic Study of TPN171H in Patients With Pulmonary Arterial Hypertension

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: TPN171H; Drug: Placebo; Drug: Tadalafil

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100037
      • Fuwai Hospital CAMS&PUMC
  • Chongqing
    • Chongqing, Chongqing, China, 400016
      • The First Affiliated Hospital of Chongqing Medical University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Gansu Provincial Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • First Affiliated Hospital of Gannan Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TPN171H 2.5mg group; TPN171H 2.5mg tablet + Placebo 10mg tablet	Drug: TPN171H; Tablets; Oral; Single dose; Other Names: Simmerafil
Experimental: TPN171H 5mg group; TPN171H 5mg tablet + Placebo 10mg tablet	Drug: TPN171H; Tablets; Oral; Single dose; Other Names: Simmerafil
Experimental: TPN171H 10mg group; TPN171H 10mg tablet + Placebo 5mg tablet	Drug: TPN171H; Tablets; Oral; Single dose; Other Names: Simmerafil
Placebo Comparator: Placebo group; Placebo 5mg tablet+ Placebo 10mg tablet	Drug: Placebo; Tablets; Oral; Single dose
Active Comparator: tadalafil 20mg group; tadalafil tablet 20mg	Drug: Tadalafil; Tablets; Oral; Single dose; Other Names: ADCIRCA
Active Comparator: tadalafil 40mg group; tadalafil tablets 20mg *2	Drug: Tadalafil; Tablets; Oral; Single dose; Other Names: ADCIRCA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of the maximum change in pulmonary vascular resistance(PVR) to the second baseline	Within 24 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Time of maximum change in PVR	Within 24 hours after drug administration
The area under the curve for reduction in PVR	Within 24 hours after drug administration
Change in arterial oxygenation	Within 24 hours after drug administration
Change in right ventricular function	Within 24 hours after drug administration

Collaborators and Investigators

• Sponsor: Vigonvita Life Sciences
• Collaborators: Shanghai Institute of Materia Medica, Chinese Academy of Sciences

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2020
• Primary Completion (Actual): June 29, 2022
• Study Completion (Actual): June 29, 2022

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 23, 2020

Study Record Updates

• Last Update Posted (Actual): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 30, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: pulmonary arterial hypertension; PK/PD study; TPN171H; Simmerafil; Acute Haemodynamic Study
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Tadalafil
• Other Study ID Numbers: TPN171H-P201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No