Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001412-38 | EudraCT Number |
Not provided
Not provided
Not provided
Study was terminated early for strategic reasons. Only Part I of the study was completed.
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This was a non-confirmatory, randomized, placebo controlled, subject and investigator blinded study of QCC374 in PAH subjects. The study was planned to have 2 Parts: Part 1, an initial safety cohort with a 0.03 mg bid starting dose, and Part 2, a larger cohort with a 0.06 mg bid starting dose. However, due to early study termination following Part 1, Part 2 was not completed. Both study parts were comprised of four phases: a screening period for up to 28 days, a titration period of 2 weeks, a stable dose period of 14 weeks and safety follow-up period for 28 days. At the end of the treatment period of 16 weeks, eligible patients were given the option to participate in a separate long-term extension study (CQCC374X2201E1 (NCT02939599)), where all patients were treated with an individual optimal dose of QCC374.
The decision for early termination was based on changes in Novartis strategy, and was not based on any safety concerns regarding QCC374. Only Part 1 of the study was completed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| QCC374 | Experimental | Adult patients with pulmonary arterial hypertension (PAH) on QCC374. All patients were initiated at 0.03 mg BID (Day 1-3), and were up-titrated to next higher dose 0.06 mg BID (Day 4) and increased to 0.12 mg BID (Day 7-14). |
|
| Placebo | Placebo Comparator | Adult patients with pulmonary arterial hypertension (PAH) on placebo matching to QCC374 doses (0.03 mg BID (Day 1-3), 0.06 mg BID (Day 4) and 0.12 mg BID (Day 7-14)). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QCC374 | Drug | 0.03 mg (2 capsules of 0.015 mg) BID 0.06 mg (1 capsule of 0.06 mg) BID 0.12 mg (2 capsules of 0.06 mg) BID |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 (Day 111) | The efficacy of 16 weeks of QCC374 administration in subjects with Pulmonary Arterial Hypertension (PAH) was assessed by measuring changes from baseline in Pulmonary Vascular Resistance (PVR). PVR is derived from the CO measurement in dyn·s/cm5 and can be calculated as 80 multiplied by (Mean Arterial Pressure - Mean Pulmonary Artery Wedge Pressure) divided by Cardiac Output. A higher negative number in Pulmonary Vascular Resistance indicates improvement. Only descriptive analysis performed. | Baseline, Week 16 (Day 111) |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Six Minute Walk Distance (6MWD) Over Time | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| 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
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Part 1 consisted of 8 subjects, randomized in a 6:2 ratio to QCC374 or placebo. The planned bid dose levels in Part 1 were 0.03 mg, 0.06 mg and 0.12 mg. Subjects began dosing at 0.03 mg bid.
This study was conducted in 5 centers in 4 countries: Germany (2), Korea (1), UK (1) and USA (1).
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| ID | Title | Description |
|---|---|---|
| FG000 | QCC374 | Adult patients with pulmonary arterial hypertension (PAH) on QCC374. All patients were initiated at 0.03 mg BID (Day 1-3), and were up-titrated to next higher dose 0.06 mg BID (Day 4) and increased to 0.12 mg BID (Day 7-14). |
| FG001 | Placebo | Adult patients with pulmonary arterial hypertension (PAH) on placebo matching to QCC374 doses (0.03 mg BID (Day 1-3), 0.06 mg BID (Day 4) and 0.12 mg BID (Day 7-14)). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | QCC374 | Adult patients with pulmonary arterial hypertension (PAH) on QCC374. All patients were initiated at 0.03 mg BID (Day 1-3), and were up-titrated to next higher dose 0.06 mg BID (Day 4) and increased to 0.12 mg BID (Day 7-14). |
| BG001 | Placebo |
| 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 | Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 16 (Day 111) | The efficacy of 16 weeks of QCC374 administration in subjects with Pulmonary Arterial Hypertension (PAH) was assessed by measuring changes from baseline in Pulmonary Vascular Resistance (PVR). PVR is derived from the CO measurement in dyn·s/cm5 and can be calculated as 80 multiplied by (Mean Arterial Pressure - Mean Pulmonary Artery Wedge Pressure) divided by Cardiac Output. A higher negative number in Pulmonary Vascular Resistance indicates 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 | dyn*s/cm5 | Baseline, Week 16 (Day 111) |
|
Adverse Events and Serious Adverse Events were collected for the maximum duration of participants' treatment exposure plus any follow up period, approximately 5 months.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | QCC374 | Adult patients with pulmonary arterial hypertension (PAH) on QCC374. All patients were initiated at 0.03 mg BID (Day 1-3), and were up-titrated to next higher dose 0.06 mg BID (Day 4) and increased to 0.12 mg BID (Day 7-14). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Syncope | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dental Caries | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
Due to the limited number of subjects with the available data at Week 16 (Day 111), for the primary and secondary efficacy endpoints, it is not possible to draw any meaningful treatment comparisons.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | 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 | Jun 3, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 19, 2017 | Jun 3, 2019 | SAP_001.pdf |
| 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
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| Placebo Matching | Drug | Placebo matching to QCC374: 0.03 mg BID, 0.06 mg BID and 0.12 mg BID |
|
| Baseline, Day 28, Day 56, Day 84 and Day 111 |
| Change From Baseline in Cardiac Output (CO) at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including Cardiac Output (CO). All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. CO was measured in triplicate using the thermodilution technique. Direct Fick could be used only after discussion and approval by the Sponsor. In all cases, the same technique was to be used at baseline and week 16. . A higher positive number in Cardiac Output indicates improvement. Only descriptive analysis performed. | Baseline, Week 16 (Day 111) |
| Change From Baseline in Cardiac Index at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including Cardiac Index. All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. A higher negative number in Cardiac Index indicates improvement. Only descriptive analysis performed. | Baseline, Week 16 (Day 111) |
| Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including mean Pulmonary Capillary Wedge Pressure (PCWP). All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. Pressure measurements were made in the PA, PA wedge, right ventricle (RV) and right atrium (RA) and determined at the end of normal expiration. The PCWP was recorded as the mean of three measurements. Only descriptive analysis performed. | Baseline, Week 16 (Day 111) |
| Change From Baseline in Systemic Vascular Resistance (SVR) at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including Systemic Vascular Resistance (SVR). All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. SVR is derived from the CO measurement in dyn·s/cm5 and can be calculated as 80 multiplied by (Mean Arterial Pressure - Mean Venous Pressure or CVP)) divided by Cardiac Output. A higher negative number in Mean Systemic Vascular Resistance indicates improvement. Only descriptive analysis performed. | Baseline, Week 16 (Day 111) |
| Change From Baseline in RV Fractional Area Change and RV Free Wall Average Peak Long Strain at Week 16 (Day 111) Using Echocardiography | Key Right Ventricular (RV) function endpoints such as RV fractional area change (RV FAC) and RV Free Wall Average Peak Long Strain (RV FWPLS) were assessed with echocardiography. A higher number in RV FAC and a lower number in RV FWPLS indicate an improvement. Only descriptive analysis performed. | Baseline, Week 16 (Day 111) |
| Change From Baseline in RV Tei Index at Week 16 (Day 111) 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. | Baseline, Week 16 (Day 111) |
| Change From Baseline in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 111) 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. | Baseline, Week 16 (Day 111) |
| Change From Baseline in Tricuspid Annular Plane Sys Excursion (TAPSE) at Week 16 (Day 111) Using Echocardiography | Key Right Ventricular (RV) function endpoints such as Tricuspid Annular Plane Sys Excursion (TAPSE) were assessed with echocardiography. A higher number in TAPSE indicates an improvement. Only descriptive analysis performed. | Baseline, Week 16 (Day 111) |
| Maximum Observed Plasma Concentration (Cmax) for QCC374 and Its Metabolite QCM441 | 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. | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
| Time to Reach the Maximum Plasma Concentration (Tmax) for QCC374 and Its Metabolite QCM441 | 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. | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
| Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) for QCC374 and Its Metabolite QCM441 | 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. | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
| Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) for QCC374 and Its Metabolite QCM441 | 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. | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
| Dresden |
| 01307 |
| Germany |
| Novartis Investigative Site | Heidelberg | 69120 | Germany |
| Novartis Investigative Site | Seoul | 03722 | South Korea |
| Novartis Investigative Site | Cambridge | Cambridgeshire | CB23 3RE | United Kingdom |
Adult patients with pulmonary arterial hypertension (PAH) on placebo matching to QCC374 doses (0.03 mg BID (Day 1-3), 0.06 mg BID (Day 4) and 0.12 mg BID (Day 7-14)). |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Ethiology of Pulmonary Arterial Hypertension (PAH) | Count of Participants | Participants |
|
| Time from Pulmonary Arterial Hypertension (PAH) diagnosis | Median | Full Range | Years |
|
Adult patients with pulmonary arterial hypertension (PAH) on QCC374. All patients were initiated at 0.03 mg BID (Day 1-3), and were up-titrated to next higher dose 0.06 mg BID (Day 4) and increased to 0.12 mg BID (Day 7-14).
| OG001 | Placebo | Adult patients with pulmonary arterial hypertension (PAH) on placebo matching to QCC374 doses (0.03 mg BID (Day 1-3), 0.06 mg BID (Day 4) and 0.12 mg BID (Day 7-14)). |
|
|
| Secondary | Change From Baseline in Six Minute Walk Distance (6MWD) Over Time | 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 | Baseline, Day 28, Day 56, Day 84 and Day 111 |
|
|
|
| Secondary | Change From Baseline in Cardiac Output (CO) at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including Cardiac Output (CO). All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. CO was measured in triplicate using the thermodilution technique. Direct Fick could be used only after discussion and approval by the Sponsor. In all cases, the same technique was to be used at baseline and week 16. . A higher positive number in Cardiac Output indicates 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 | L/min | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Change From Baseline in Cardiac Index at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including Cardiac Index. All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. A higher negative number in Cardiac Index indicates 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 | L/min/m2 | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including mean Pulmonary Capillary Wedge Pressure (PCWP). All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. Pressure measurements were made in the PA, PA wedge, right ventricle (RV) and right atrium (RA) and determined at the end of normal expiration. The PCWP was recorded as the mean of three measurements. 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 | mmHg | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Change From Baseline in Systemic Vascular Resistance (SVR) at Week 16 (Day 111) | The Right Heart Catheterization (RHC) assessment was performed to assess several hemodynamic variables in pulmonary hypertension, including Systemic Vascular Resistance (SVR). All hemodynamic parameters were assessed when the patient was in a stable hemodynamic rest state (as demonstrated by three consecutive CO measurements within 10% of each other) while the patient was breathing ambient air or oxygen. SVR is derived from the CO measurement in dyn·s/cm5 and can be calculated as 80 multiplied by (Mean Arterial Pressure - Mean Venous Pressure or CVP)) divided by Cardiac Output. A higher negative number in Mean Systemic Vascular Resistance indicates 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 | dynes*Sec*cm5 | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Change From Baseline in RV Fractional Area Change and RV Free Wall Average Peak Long Strain at Week 16 (Day 111) Using Echocardiography | Key Right Ventricular (RV) function endpoints such as RV fractional area change (RV FAC) and RV Free Wall Average Peak Long Strain (RV FWPLS) were assessed with echocardiography. A higher number in RV FAC and a lower number in RV FWPLS indicate 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 | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Change From Baseline in RV Tei Index at Week 16 (Day 111) 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 | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Change From Baseline in Tricuspid Annular Peak Systolic Velocity (TA S') at Week 16 (Day 111) 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 | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Change From Baseline in Tricuspid Annular Plane Sys Excursion (TAPSE) at Week 16 (Day 111) Using Echocardiography | Key Right Ventricular (RV) function endpoints such as Tricuspid Annular Plane Sys Excursion (TAPSE) were assessed with echocardiography. A higher number in TAPSE 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 | cm | Baseline, Week 16 (Day 111) |
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) for QCC374 and Its Metabolite QCM441 | 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 | Geometric Mean | Geometric Coefficient of Variation | pg/mL | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
|
|
|
| Secondary | Time to Reach the Maximum Plasma Concentration (Tmax) for QCC374 and Its Metabolite QCM441 | 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 | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
|
|
|
| Secondary | Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) for QCC374 and Its Metabolite QCM441 | 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 | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
|
|
|
| Secondary | Area Under the Plasma Concentration Time Curve From 0 to the End of a Dosing Interval (AUCtau) for QCC374 and Its Metabolite QCM441 | 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 | Geometric Mean | Geometric Coefficient of Variation | h*pg/mL | Day 1 and 112 (0.00, 0.05, 0.15, 0.30, 1.00, 2.00, 4.00, 8.00 and 12.00 hours post-dose)) |
|
|
|
| 0 |
| 6 |
| 1 |
| 6 |
| 6 |
| 6 |
| EG001 | Placebo | Adult patients with pulmonary arterial hypertension (PAH) on placebo matching to QCC374 doses (0.03 mg BID (Day 1-3), 0.06 mg BID (Day 4) and 0.12 mg BID (Day 7-14)). | 0 | 2 | 0 | 2 | 1 | 2 |
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Gastrointestinal Disorder | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Systematic Assessment |
|
| Hangover | General disorders | MedDRA (21.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Systematic Assessment |
|
| Otitis Media | Infections and infestations | 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 |
|
| Dysgeusia | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Head Discomfort | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (21.0) | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue 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 |
| Chge from BL at Day 28 |
|
|
| Chge from BL at Day 56 |
|
|
| Chge from BL at Day 84 |
|
|
| Chge from BL at Day 111 |
|
|
| Average Cardiac Output at Day 111 |
|
|
| Cardiac Output 1 at Baseline |
|
|
| Cardiac Output 1 at Day 111 |
|
|
| Cardiac Output 2 at Baseline |
|
|
| Cardiac Output 2 at Day 111 |
|
|
| Cardiac Output 3 at Baseline |
|
|
| Cardiac Output 3 at Day 111 |
|
|
| Cardiac Index at Day 111 |
|
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| PCWP at Day 111 |
|
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| SVR at Day 111 |
|
|
| RV FAC at Day 111 |
|
|
| RV FWPLS at Baseline |
|
|
| RV FWPLS at Day 111 |
|
|
| RV Tei Index at Day 111 |
|
|
| TA S' at Day 111 |
|
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| TAPSE at Day 111 |
|
|
| QCC374: Day 112, Dose Level 0.06 mg |
|
|
| QCC374: Day 112, Dose Level 0.12 mg |
|
|
| QCM441: Day 1, Dose Level 0.03 mg |
|
|
| QCM441: Day 112, Dose Level 0.06 mg |
|
|
| QCM441: Day 112, Dose Level 0.12 mg |
|
|
| QCC374: Day 112, Dose Level 0.06 mg |
|
|
| QCC374: Day 112, Dose Level 0.12 mg |
|
|
| QCM441: Day 1, Dose Level 0.03 mg |
|
|
| QCM441: Day 112, Dose Level 0.06 mg |
|
|
| QCM441: Day 112, Dose Level 0.12 mg |
|
|
| QCC374: Day 112, Dose Level 0.06 mg |
|
|
| QCC374: Day 112, Dose Level 0.12 mg |
|
|
| QCM441: Day 1, Dose Level 0.03 mg |
|
|
| QCM441: Day 112, Dose Level 0.06 mg |
|
|
| QCM441: Day 112, Dose Level 0.12 mg |
|
|
| QCC374: Day 112, Dose Level 0.06 mg |
|
|
| QCC374: Day 112, Dose Level 0.12 mg |
|
|
| QCM441: Day 1, Dose Level 0.03 mg |
|
|
| QCM441: Day 112, Dose Level 0.06 mg |
|
|
| QCM441: Day 112, Dose Level 0.12 mg |
|
|