Acute Haemodynamic Study of TPN171H in Patients with Pulmonary Arterial Hypertension

NCT04483115 | Completed Phase 2

• 1 other identifier: TPN171H-P201
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 9

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  Within 24 hours after drug administration

Secondary Outcomes (4)

• 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

Study Arms (6)

TPN171H 2.5mg group

EXPERIMENTAL

TPN171H 2.5mg tablet + Placebo 10mg tablet

Drug: TPN171H

TPN171H 5mg group

EXPERIMENTAL

TPN171H 5mg tablet + Placebo 10mg tablet

Drug: TPN171H

TPN171H 10mg group

EXPERIMENTAL

TPN171H 10mg tablet + Placebo 5mg tablet

Drug: TPN171H

Placebo group

PLACEBO COMPARATOR

Placebo 5mg tablet+ Placebo 10mg tablet

Drug: Placebo

tadalafil 20mg group

ACTIVE COMPARATOR

tadalafil tablet 20mg

Drug: Tadalafil

tadalafil 40mg group

ACTIVE COMPARATOR

tadalafil tablets 20mg \*2

Drug: Tadalafil

Interventions

TPN171H DRUG

Tablets; Oral; Single dose

Also known as: Simmerafil

TPN171H 10mg group; TPN171H 2.5mg group; TPN171H 5mg group

Placebo DRUG

Tablets; Oral; Single dose

Placebo group

Tadalafil DRUG

Tablets; Oral; Single dose

Also known as: ADCIRCA

tadalafil 20mg group; tadalafil 40mg group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Idiopathic PAH (IPAH)
• Familial PAH
• Associated PAH due to drugs or toxins
• Associated PAH due to connective tissue disease
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Vigonvita Life Sciences: lead
• Shanghai Institute of Materia Medica, Chinese Academy of Sciences: collaborator

Study Sites (9)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

Fuwai Hospital CAMS&PUMC

Beijing, Beijing Municipality, 100037, China

Location

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

Gansu Provincial Hospital

Lanzhou, Gansu, 730000, China

Location

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Wuhan, Hubei, 430030, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

First Affiliated Hospital Of Gannan Medical University

Ganzhou, Jiangxi, 341000, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

Tadalafil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Yong Huo

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: July 23, 2020
• Study Start: November 16, 2020
• Primary Completion: June 29, 2022
• Study Completion: June 29, 2022
• Last Updated: December 24, 2024

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (9)