Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary hypertension (PH),, Increase blood pressure in the pulmonary artery, Increased blood pressure in the pulmonary vein, Increased blood pressure in the lung vasculature, Shortness of breath, Dizziness, Fainting, Leg swelling, Cough, Angina pector
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.
Interventions
DRUGQCC374
0.015mg and 0.06mg
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period | Two years | Patients with all (serious and non-serious) adverse events, serious adverse events and death were reported |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach the Maximum Plasma Concentration (Tmax) | 16 Weeks | 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. |
| Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) | 16 weeks | 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. |
| Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) | 16 Weeks | 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 |
| Maximum Observed Plasma Concentration (Cmax) | 16 weeks | 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 |
| Change in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 112) Using Echocardiography | Two Years | Key Right Ventricular (RV) function endpoints such as Tricuspid Annular Peak Systolic Velocity (TA S') were assessed with echocardiography. Only descriptive analysis performed. |
| Change From Baseline in RV Tei Index at Week 16 (Day 112) Using Echocardiography | 16 weeks | 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. |
| Change From Baseline in RV Fractional Area Change at Week 16 (Day 112) Using Echocardiography | 16 weeks | 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. |
| Change From Baseline in Six Minute Walk Distance (6MWD) | 16 weeks | 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. |
Countries
Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study 0.12mg
-active patients will continue at the dose they finished on the QCC374X2201 study | 3 |
| Arm2 Subjects randomized to placebo in the QCC374X2201 core study completed a titration scheme similar to that of the active arm in QCC374X2201 core study protocol | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Study Terminated By Sponsor | 2 | 2 |
Baseline characteristics
| Characteristic | Arm 1 | Arm2 | Total |
|---|---|---|---|
| Age, Continuous | 40.3 Years STANDARD_DEVIATION 4.93 | 58.0 Years STANDARD_DEVIATION 9.9 | 47.4 Years STANDARD_DEVIATION 11.41 |
| Race/Ethnicity, Customized White | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 2 |
| other Total, other adverse events | 1 / 3 | 2 / 2 |
| serious Total, serious adverse events | 1 / 3 | 0 / 2 |
Outcome results
Primary
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
Time frame: Two years
Population: Safety set includes all participants who received at least one dose of study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 | Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period | Participant with AE | 2 Participants |
| Arm 1 | Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period | Participants with serious AE | 1 Participants |
| Arm 2 | Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period | Participant with AE | 2 Participants |
| Arm 2 | Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events (SAEs) in Patients With PAH Over a Two Year Period | Participants with serious AE | 0 Participants |
Secondary
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
Time frame: 16 Weeks
Population: Participants from the Pharmacokinetic (PK) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PK concentration measurement, with data available for analysis were considered.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm 1 | Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) | QCC374: Day 1, Dose Level 0.03 mg | 134 h*pg/mL |
| Arm 1 | Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) | QCC374: Day 112, Dose Level 0.12 mg | 566 h*pg/mL |
Secondary
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.
Time frame: 16 weeks
Population: Participants from the Pharmacokinetic (PK) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PK concentration measurement, with data available for analysis were considered
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm 1 | Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) | QCC374: Day 1, Dose Level 0.03 mg | 118 h*pg/mL |
| Arm 1 | Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) | QCC374: Day 112, Dose Level 0.12 mg | 526 h*pg/mL |
Secondary
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.
Time frame: 16 weeks
Population: Participants from the Pharmacodynamic (PD) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PD assessment, with data available for analysis were considered.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1 | Change From Baseline in RV Fractional Area Change at Week 16 (Day 112) Using Echocardiography | 23.91 Percentage change |
Secondary
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.
Time frame: 16 weeks
Population: Participants from the Pharmacodynamic (PD) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PD assessment, with data available for analysis were considered
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1 | Change From Baseline in RV Tei Index at Week 16 (Day 112) Using Echocardiography | 0.84 Index |
Secondary
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.
Time frame: 16 weeks
Population: Participants from the Pharmacodynamic (PD) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PD assessment, with data available for analysis were considered.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 | Change From Baseline in Six Minute Walk Distance (6MWD) | 452 Meter | Standard Deviation 104.65 |
Secondary
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.
Time frame: Two Years
Population: Participants from the Pharmacodynamic (PD) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PD assessment, with data available for analysis were considered
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1 | Change in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 112) Using Echocardiography | 10.90 cm/s |
Secondary
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
Time frame: 16 weeks
Population: Participants from the Pharmacokinetic (PK) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PK concentration measurement, with data available for analysis were considered
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm 1 | Maximum Observed Plasma Concentration (Cmax) | QCC374: Day 1, Dose Level 0.03 mg | 82 pg/mL |
| Arm 1 | Maximum Observed Plasma Concentration (Cmax) | QCC374: Day 112, Dose Level 0.12 mg | 664 pg/mL |
Secondary
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.
Time frame: 16 Weeks
Population: Participants from the Pharmacokinetic (PK) analysis set, defined as all randomized participants who received at least one dose of study drug and one evaluable PK concentration measurement, with data available for analysis were considered.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm 1 | Time to Reach the Maximum Plasma Concentration (Tmax) | QCC374: Day 1, Dose Level 0.03 mg | 0.250 hour |
| Arm 1 | Time to Reach the Maximum Plasma Concentration (Tmax) | QCC374: Day 112, Dose Level 0.12 mg | 0.0330 hour |