Clinical trial
Phase Ib Clinical Study on the Safety, Tolerability, and Pharmacokinetics of TPN171H Tablets in the Treatment of Pulmonary Arterial Hypertension (PAH) Patients
Name
TPN171H-04
Description
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.
Trial arms
Trial start
2019-04-08
Estimated PCD
2020-10-14
Trial end
2020-10-14
Status
Completed
Phase
Early phase I
Treatment
TPN171H
TPN171H 2.5mg TPN171H 5mg TPN171H 10mg
Arms:
TPN171H
Size
10
Primary endpoint
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
Eligibility criteria
Inclusion Criteria:
1. Patients who are able to signed the informed consent form ,understand and follow study plans and instructions;
2. Patients aged 18 to 75;
3. 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 ;
4. Patients have a current diagnosis of being in WHO functional class II or III;
5. Targeted therapeutic drugs were not added, discontinued, or dosed within 4 weeks prior to baseline; 6.6-MWD between 100m \&450m;
7.Patients who are willing to take proper contraceptive during the study and within 3 months after the study completed.
Exclusion Criteria:
1. All types of PH except subtypes of Group1 specified in the inclusion criteria;
2. Patients who concomitant severe obstructive pulmonary disease(FEV1/FVC\<0.5) ;
3. Total lung volume\<60% predicted;
4. Systolic blood pressure below 90/60mmHg at screening;
5. Left ventricular ejection fraction less than 45%, left ventricular short axis shortening rate less than 0.2;
6. Lower limb diseases that affect the completion of 6-MWD testing;
7. Subjects who received PDE5 inhibitors (such as sildenafil, tadalafil, vardenafil, and avanafil) within 4 weeks before baseline
8. 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)
9. Subjects with a clear history of allergic diseases or who have previously stopped taking either aniracetam or tadalafil due to safety or tolerable reasons;
10. 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;
11. 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);
12. Have a history of ophthalmic diseases, such as color vision abnormalities, retinitis pigmentosa, and macular degeneration;
13. Malignant tumor patients;
14. 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;
15. Pathogenic test for HIV positive; Positive test for hepatitis B or hepatitis C; Subjects suffering from acute infectious diseases;
16. Suffered from infectious diseases recently (within 1 month);
17. The subject has ischemic heart disease (defined as symptomatic, requiring anti angina treatment, or having experienced myocardial infarction within the past 3 years);
18. Those who have experienced cerebrovascular events (such as transient ischemic attacks or strokes) within the past 3 months;
19. Participated in any clinical trial within 3 months prior to taking the investigational drug;
20. Pregnant or lactating women;
21. The researchers believe that subjects who are not suitable to participate in this experiment due to other reasons.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 10, 'type': 'ACTUAL'}}
Updated at
2023-10-13
1 organization
1 product
1 indication
Organization
Vigonvita Life SciencesProduct
TPN171HIndication
Pulmonary Arterial Hypertension