Not provided
Not provided
Not provided
Not provided
Not provided
Study was terminated early for strategic reasons. Only Part I of the study was completed.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| QCC374 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QCC374 | Drug | 0.015mg and 0.06mg |
|
| 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 |
| 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Pittsburgh | Pennsylvania | 15261 | United States | ||
| Novartis Investigative Site |
Not provided
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicatrials.com | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1 | Subjects randomized in the QCC374X2201 core study continued on QCC374 at their highest stable dose, in this extension study |
| FG001 | Arm 2 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Arm2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Safety set includes all participants who received at least one dose of study drug | Posted | Number | Participants | Two years |
|
through study completion an average of 4.5 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | QCC374 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pulmonary arterial hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (21.0) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 8627788300 | Novartis.email@novartis.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 7, 2018 | Nov 1, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Dec 4, 2017 | Nov 1, 2019 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| D006976 | Hypertension, Pulmonary |
| D004417 | Dyspnea |
| D004244 | Dizziness |
| D013575 | Syncope |
| D003371 | Cough |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 |
| Dresden |
| 01307 |
| Germany |
| Novartis Investigative Site | Heidelberg | 69120 | Germany |
| Novartis Investigative Site | Cambridge | Cambridgeshire | CB23 3RE | United Kingdom |
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 |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
|
|
| 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 | 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 | Posted | Median | Full Range | pg/mL | 16 weeks |
|
|
|
| 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. | 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. | Posted | Median | Full Range | hour | 16 Weeks |
|
|
|
| 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. | 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 | Posted | Median | Full Range | h*pg/mL | 16 weeks |
|
|
|
| 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 | 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. | Posted | Median | Full Range | h*pg/mL | 16 Weeks |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | Meter | 16 weeks |
|
|
|
| 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. | 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 | Posted | Mean | Standard Deviation | cm/s | Two Years |
|
|
|
| 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. | 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 | Posted | Mean | Standard Deviation | Index | 16 weeks |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | Percentage change | 16 weeks |
|
|
|
| 0 |
| 3 |
| 1 |
| 3 |
| 1 |
| 3 |
| EG001 | QCC374 Arm 2 | 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 | 0 | 2 | 0 | 2 | 2 | 2 |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (21.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (21.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| D002318 |
| Cardiovascular Diseases |
| D012120 | Respiration Disorders |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012678 | Sensation Disorders |
| D009461 | Neurologic Manifestations |
| D014474 | Unconsciousness |
| D003244 | Consciousness Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009422 | Nervous System Diseases |