The Safety, Tolerability, and Pharmacokinetics of TPN171H Tablets in Patients With Pulmonary Arterial Hypertension

NCT05948644 | Completed Phase 1

• 1 other identifier: TPN171H-04
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Exploring the safety, tolerability, and pharmacokinetic (PK) characteristics of oral TPN171H tablets in patients with Pulmonary Arterial Hypertension under continuous multiple administration conditions, providing a basis for determining the administration plan and recommended dosage in phase II clinical study.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (10)

• Incidence of Treatment-Emergent Adverse Events

  through study completion, an average of 2 years

• Q-T interval

  through study completion, an average of 2 years

• Tmax

  From time zero up to 24 hours post-dose following oral administration of TPN171H

• Cmax

  From time zero up to 24 hours post-dose following oral administration of TPN171H

• AUC0~t

  From time zero up to 24 hours post-dose following oral administration of TPN171H

• AUC0-∞

  From time zero up to 24 hours post-dose following oral administration of TPN171H

• Terminal half-life (t 1/2)

  From time zero up to 24 hours post-dose following oral administration of TPN171H

• Apparent distribution volume (Vd/F)

  From time zero up to 24 hours post-dose following oral administration of TPN171H

• Clearance rate (CL/F)

  From time zero up to 24 hours post-dose following oral administration of TPN171H

• Mean Residence Time(MRT)

  From time zero up to 24 hours post-dose following oral administration of TPN171H

Secondary Outcomes (4)

• 6- Minute Walk Distance（6-MWD）

  through study completion, an average of 2 years

• NT-proBNP

  through study completion, an average of 2 years

• The World Health Organization (WHO) functional class

  through study completion, an average of 2 years

• Borg dyspnea index

  through study completion, an average of 2 years

Study Arms (1)

TPN171H

EXPERIMENTAL

TPN171H is received 2.5mg QD for 2 consecutive weeks, then 5 mg QD for 14 consecutive weeks. If the dose is well-tolerated,TPN171H is up-titrated to 10mg QD , which will last for up to 2 years.

Drug: TPN171H

Interventions

TPN171H DRUG

TPN171H 2.5mg TPN171H 5mg TPN171H 10mg

TPN171H

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 who are able to signed the informed consent form ,understand and follow study plans and instructions;
• Patients aged 18 to 75;
• Patients with symptomatic PAH (Group1) with right heart catheterization results within the past 36 months (first category), a pulmonary vascular resistance (PVR) \> 3 Wood, a mean pulmonary artery pressure (mPVP) ≥25 mmHg and a pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg ;
• Patients have a current diagnosis of being in WHO functional class II or III;
• Targeted therapeutic drugs were not added, discontinued, or dosed within 4 weeks prior to baseline; 6.6-MWD between 100m \&450m;
• Patients who are willing to take proper contraceptive during the study and within 3 months after the study completed.

You may not qualify if:

• Patients who concomitant severe obstructive pulmonary disease(FEV1/FVC\<0.5) ;
• Total lung volume\<60% predicted;
• Systolic blood pressure below 90/60mmHg at screening;
• Left ventricular ejection fraction less than 45%, left ventricular short axis shortening rate less than 0.2;
• Lower limb diseases that affect the completion of 6-MWD testing;
• Subjects who received PDE5 inhibitors (such as sildenafil, tadalafil, vardenafil, and avanafil) within 4 weeks before baseline
• CYP3A4 enzyme inducers (such as bosentan, aprepitant, barbiturates, carbamazepine, rifampicin, pioglitazone) or inhibitors (such as cimetidine, ciprofloxacin, boceprevir-d9，telaprevir, clarithromycin, nefazodone, and ritonavir) were taken within 2 months before the start of the trial, Regular or intermittent administration of nitrates (such as nitroglycerin, isosorbide nitrate,pentaerithrityl tetranitrate ) or any form of nitric oxide donor (including nicorandil, L-arginine) and α- Receptor blocking (such as phenoxybenzamine, prazosin, terazosin,tamsulosin)
• Subjects with a clear history of allergic diseases or who have previously stopped taking either aniracetam or tadalafil due to safety or tolerable reasons;
• Previous or current drug dependence, clear history of neurological or mental disorders, such as epilepsy, dementia, psychological or other emotional issues, may invalidate informed consent or limit the subject's ability to comply with the protocol;
• Acute or chronic organic diseases (excluding breathing difficulties) prevent subjects from completing the necessary testing items required in the study (especially the 6-minute walking distance test);
• Have a history of ophthalmic diseases, such as color vision abnormalities, retinitis pigmentosa, and macular degeneration;
• Malignant tumor patients;
• Moderate or severe liver function injury and/or blood ALT and AST exceeding 1.5 times the upper limit of normal values, and blood creatinine exceeding 1.5 times the upper limit of normal values;
• Pathogenic test for HIV positive; Positive test for hepatitis B or hepatitis C; Subjects suffering from acute infectious diseases;
• Suffered from infectious diseases recently (within 1 month);

Sponsors & Collaborators

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

Study Sites (1)

Fu Zhu

Shanghai, China

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Fu Zhu

  Shanghai Xuhui Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2023
• First Posted: July 17, 2023
• Study Start: April 8, 2019
• Primary Completion: October 14, 2020
• Study Completion: October 14, 2020
• Last Updated: October 13, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)