simmerafil (TPN171H) / Shanghai Inst. of Materia Medica, Vigonvita Life Sci, Topharman - LARVOL DELTA

Long-term Safety of TPN171H Tablet in Erectile Dysfunction. (clinicaltrials.gov) - P3 | N=472 | Recruiting | Sponsor: Vigonvita Life Sciences | Trial completion date: Apr 2025 ➔ Aug 2025 | Trial primary completion date: Apr 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Erectile Dysfunction

Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Patients With Mild or Moderate Hepatic Impairment Versus Participants With Normal Hepatic Function: A Phase I Study. (PubMed, Clin Pharmacol Drug Dev) - "All adverse events were not serious and no participant withdrew from this study. Considering the increase in TPN171 plasma exposure, the highest dose of 5 mg TPN171 is recommended in patients with ED having mild-to-moderate HI."

Journal • P1 data • PK/PD data • Cardiovascular • Erectile Dysfunction • Hepatology • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

A Phase I Study to Evaluate the Pharmacokinetics and Safety of TPN171 (a PDE5 Inhibitor) in Adults with Renal Impairment. (PubMed, Clin Pharmacol Drug Dev) - "All adverse events were mild intensity, and no participant was discontinued in this study. In conclusion, TPN171 can be cautiously used in patients with mild to severe renal impairment."

Journal • P1 data • PK/PD data • Cardiovascular • Erectile Dysfunction • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases

Evaluation of the acute effects of single-dose TPN171 on semen quality in healthy Chinese male volunteers. (PubMed, Br J Clin Pharmacol) - P1 | "The findings indicate that a single oral dose of 10 mg TPN171 did not induce acute effects on semen quality in healthy male Chinese volunteers. The exposure of seminal plasma to TPN171 was <0.001% of the administered dose."

Journal • Erectile Dysfunction

Hemodynamic and Pharmacokinetic Interactions of TPN171 with Alcohol in Healthy Male Subjects. (PubMed, Clin Transl Sci) - "Alcohol had no influence on the pharmacokinetics of TPN171, and vice versa. Though the concomitant administration of TPN171 and alcohol induced a more pronounced increase in PR, this did not result in clinical symptoms or heart rate increase-related adverse events, indicating that the combined use was generally safe and well-tolerated."

Clinical • Journal • PK/PD data

Long-term Safety of TPN171H Tablet in Erectile Dysfunction. (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Vigonvita Life Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Erectile Dysfunction

Long-term Safety of TPN171H Tablet in Erectile Dysfunction. (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Vigonvita Life Sciences

New P3 trial • Erectile Dysfunction

Acute Hemodynamic Study Of Oral TPN171H In Patients With Pulmonary Arterial Hypertension: A Multicenter, Randomized, Controlled, Phase 2 Clinical Trial (AHA 2023) - P2 | "Methods In this multicenter, double-blind, randomized, placebo-controlled and active-controlled, phase 2 trial, we randomly assigned 60 patients with pulmonary arterial hypertension to receive single oral intake of placebo, TPN171H (2.5-mg or 5-mg or 10-mg) or Tadalafil (20-mg or 40-mg). TPN171H has potential to be a novel treatment option for patients with pulmonary arterial hypertension and warrants further investigation. This clinical trial was registered at www.ClinicalTrials.gov (Identifier: NCT04483115)."

Clinical • P2 data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Drug-Drug Interaction (DDI) Study for TPN171H (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Vigonvita Life Sciences

New P1 trial • Erectile Dysfunction

Safety and Pharmacokinetics of a Single Oral TPN171H in Healthy Elderly Subjects (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Vigonvita Life Sciences

New P1 trial • Erectile Dysfunction

The Safety, Tolerability, and Pharmacokinetics of TPN171H Tablets in Patients With Pulmonary Arterial Hypertension (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Vigonvita Life Sciences

New P1 trial • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Solid Tumor

Evaluate the Effect of TPN171H on the QT/QTc Interval in Healthy Volunteers (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Vigonvita Life Sciences | Recruiting ➔ Completed

Trial completion

Efficacy and Safety Study of TPN171H Tablets in Erectile Dysfunction. (clinicaltrials.gov) - P3 | N=765 | Completed | Sponsor: Vigonvita Life Sciences | Recruiting ➔ Completed

Trial completion • Erectile Dysfunction

Evaluate the Effect of TPN171H on the QT/QTc Interval in Healthy Volunteers (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Vigonvita Life Sciences

New P1 trial

Effect of TPN171H on Spermatogenesis (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Vigonvita Life Sciences | Recruiting ➔ Completed | Trial completion date: Apr 2023 ➔ Dec 2022 | Trial primary completion date: Apr 2023 ➔ Dec 2022

Trial completion • Trial completion date • Trial primary completion date • Erectile Dysfunction

Pharmacodynamic Study of TPN171H Tablets in Patients With Mild to Moderate Erectile Dysfunction (clinicaltrials.gov) - P2 | N=84 | Completed | Sponsor: Vigonvita Life Sciences | Recruiting ➔ Completed

Trial completion • Erectile Dysfunction

a Study to Evaluate the Pharmacokinetics and Safety of TPN171H Tablets in Patients With Renal Insufficiency and Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Vigonvita Life Sciences | Recruiting ➔ Completed | N=56 ➔ 16 | Trial completion date: Dec 2023 ➔ Oct 2022

Enrollment change • Trial completion • Trial completion date • Cardiovascular • Erectile Dysfunction • Hypertension • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases

Effect of TPN171H on Spermatogenesis (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Vigonvita Life Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Erectile Dysfunction

Effect of TPN171H on Spermatogenesis (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Vigonvita Life Sciences

New P1 trial • Erectile Dysfunction

Pharmacodynamic Study of TPN171H Tablets in Patients With Mild to Moderate Erectile Dysfunction (clinicaltrials.gov) - P2 | N=84 | Recruiting | Sponsor: Vigonvita Life Sciences | Not yet recruiting ➔ Recruiting

Enrollment open • Erectile Dysfunction

Acute Haemodynamic Study of TPN171H in Patients With Pulmonary Arterial Hypertension (clinicaltrials.gov) - P2 | N=60 | Completed | Sponsor: Vigonvita Life Sciences | Recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Jun 2022

Trial completion • Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Pharmacokinetics, mass balance, and metabolism of [C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension. (PubMed, Acta Pharmacol Sin) - "Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10."

Journal • PK/PD data • Cardiovascular • Erectile Dysfunction • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CYP2E1 • CYP3A4 • UGT1A9

TPN171H alleviates pulmonary hypertension via inhibiting inflammation in hypoxia and monocrotaline-induced rats. (PubMed, Vascul Pharmacol) - "Hypoxia and monocrotaline (MCT)-induced PH rat models were established, which were treated by oral administration of TPN171H (5, 25 mg/kg/d) or sildenafil (25 mg/kg/d). The results suggested that TPN171H significantly reduced RVSP and RVHI, and reversed pulmonary vascular remodeling in rats with both models. Furthermore, in in vivo and in vitro research, our data suggested that TPN171H remarkably suppressed cathepsin B-mediated NLRP3 inflammasome activation, which may contribute to its therapeutical function for PH."

Journal • Preclinical • Cardiovascular • Hypertension • Immunology • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • CTSB • NLRP3

Pharmacodynamic Study of TPN171H Tablets in Patients With Mild to Moderate Erectile Dysfunction (clinicaltrials.gov) - P2 | N=84 | Not yet recruiting | Sponsor: Vigonvita Life Sciences

New P2 trial • Erectile Dysfunction

A Study of the Hemodynamic Interactions of TPN171H Tablets & Alcohol in Healthy Male Subjects (clinicaltrials.gov) - P1 | N=19 | Completed | Sponsor: Vigonvita Life Sciences | Recruiting ➔ Completed

Trial completion • Erectile Dysfunction