Acute Haemodynamic Study of TPN171H in Patients With Pulmonary Arterial Hypertension

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 75 Years
Gender	All

More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04483115
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Vigonvita Life Sciences
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Yong Huo
Principal Investigator Affiliation	Peking University First Hospital
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry, Other
Overall Status	Recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Pulmonary Arterial Hypertension

Additional Details

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.

Arms & Interventions

Arms

Experimental: TPN171H 2.5mg group

TPN171H 2.5mg tablet + Placebo 10mg tablet

Experimental: TPN171H 5mg group

TPN171H 5mg tablet + Placebo 10mg tablet

Experimental: TPN171H 10mg group

TPN171H 10mg tablet + Placebo 5mg tablet

Placebo Comparator: Placebo group

Placebo 5mg tablet+ Placebo 10mg tablet

Active Comparator: tadalafil 20mg group

tadalafil tablet 20mg

Active Comparator: tadalafil 40mg group

tadalafil tablets 20mg *2

Interventions

Drug: - TPN171H

Tablets; Oral; Single dose

Drug: - Placebo

Tablets; Oral; Single dose

Drug: - Tadalafil

Tablets; Oral; Single dose

Contact a Trial Team

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