Long-term Extension Study of the Safety and Pharmacokinetics of QCC374 in PAH Patients

Study Overview
=================
Brief Summary
-----------------
This is a long-term open-label safety extension to the Phase 2a study of inhaled QCC374 in adult patients with PAH. This study provides the patients who completed the QCC374X2201 study with the option to continue receiving QCC374. The study will monitor the long-term safety, tolerability and efficacy of QCC374 in patients with PAH.

Official Title
-----------------
Long-term, Open Label, Multicenter, Extension Study to Evaluate the Safety and Tolerability of QCC374 in Patients With Pulmonary Arterial Hypertension (PAH)

Conditions
-----------------
Pulmonary Arterial Hypertension

Intervention / Treatment
-----------------
* Drug: QCC374


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent must be obtained before any assessment is performed. Subject was enrolled in the QCC374X2201 study and completed per protocol Exclusion Criteria: Subjects who have started receiving prostacyclin (epoprostenol), prostacyclin analogs (i.e. trepostinil, iloprost, beraprost) or prostacyclin receptor agonists (i.e. selexipag) since the last study drug intake in the QCC374X2201 study. Females who are pregnant, or who plan to become pregnant during the study, or who are breastfeeding Any known factor or disease that may interfere with treatment compliance or study conduct (i.e. drug or alcohol dependence) Subjects who withdrew consent from the study QCC374X2201

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QCC374<br>placebo patients from QCC374X2201 rolled into extension study will start at 0.03mg b.i.d. or 0.06mg b.i.d. and have the opportunity to up-titrate 0.12mg -active patients will continue at the dose they finished on the QCC374X2201 study | Drug: QCC374<br>* 0.015mg and 0.06mg<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period | Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | Cmax is the maximum (peak) observed plasma drug concentration after single dose administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed | 16 weeks | 
| Time to Reach the Maximum Plasma Concentration (Tmax) | Tmax is the time to reach maximum plasma concentration after single dose administration. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed. | 16 Weeks | 
| Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) | AUClast is the area under the plasma concentration-time curve from time zero to the last measurable concentration sampling time. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed. | 16 weeks | 
| Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) | AUCtau is the area under the plasma concentration-time curve from time zero to the end of the dosing interval. PK parameters were calculated from plasma concentration-time data using non-compartmental methods. Only descriptive analysis performed | 16 Weeks | 
| Change From Baseline in Six Minute Walk Distance (6MWD) | The Six Minute Walk Test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes. The individual is able to self-pace and rest as needed as they traverse back and forth along a marked walkway. Only descriptive analysis performed. | 16 weeks | 
| Change in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 112) Using Echocardiography | Key Right Ventricular (RV) function endpoints such as Tricuspid Annular Peak Systolic Velocity (TA S') were assessed with echocardiography. Only descriptive analysis performed. | Two Years | 
| Change From Baseline in RV Tei Index at Week 16 (Day 112) Using Echocardiography | Key Right Ventricular (RV) function endpoints such as Tei Index were assessed with echocardiography. The RV Tei index is using both systolic and diastolic time intervals to evaluate the overall global dysfunction of the right ventricle in PAH patients. A lower number in RV Tei Index indicates an improvement. Only descriptive analysis performed. | 16 weeks | 
| Change From Baseline in RV Fractional Area Change at Week 16 (Day 112) Using Echocardiography | Key Right Ventricular (RV) function endpoints such as Tei Index were assessed with echocardiography. The RV Tei index is using both systolic and diastolic time intervals to evaluate the overall global dysfunction of the right ventricle in PAH patients. A lower number in RV Tei Index indicates an improvement. Only descriptive analysis performed. | 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Increase blood pressure in the pulmonary artery, Increased blood pressure in the pulmonary vein, Increased blood pressure in the lung vasculature, Shortness of breath, Fainting, Leg swelling, Cough, Angina pector, Pulmonary hypertension (PH),, Dizziness