Pulmonary Arterial HypertensionPhase 2NCT02927366
Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients
A Phase 2 study testing QCC374 in people with Pulmonary Arterial Hypertension, run by Novartis Pharmaceuticals at 5 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- QCC374
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 19 Sep 2017to 7 Jun 2018
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients 18 years of age or older with symptomatic PAH.
- Subjects with PAH belonging to one of the following subgroups of the Updated Clinical Classification Group 1 (Nice, 2013):
- Idiopathic PAH
- familial PAH
- PAH associated with connective tissue disease, congenital heart disease (surgically repaired at least 12 months prior to screening) or drug or toxin induced (for example, anorexigen use).
- Subjects must have persistent symptoms due to PAH despite therapy with at least one of the following PAH medications: an endothelin receptor antagonist, asoluble guanylate cyclase stimulator or a phosphodiesterase inhibitor. The subjects' PAH medication regimen, with typical medications including calcium channel blockers, endothelin receptor antagonists, soluble guanylate cyclase stimulators and/or phosphodiesterase inhibitors, must have been used at a stable dose and frequency for at least 12 weeks before the screening visit and during the screening period.
Show all 12Show fewer
- Diagnosis of PAH established according to the standard criteria before the screening visit:
- Resting mean pulmonary arterial pressure > 25 mmHg.
- PVR > 240 dynes s/cm5.
- Pulmonary capillary wedge pressure or left ventricular end diastolic pressure < 15 mmHg
- PVR > 400 dynes s/cm5 at the time of the baseline right heart catheterization (RHC) (if a RHC was completed within one month of the screening visit, that result may be used for inclusion).
- 6-minute walk distance greater than 150 meters at Screening. This distance must be confirmed by a second 6MWT prior to randomization. The value of the second 6MWD should be within ± 15% of the value obtained at Screening.
Who cannot join
- Subjects with clinically unstable right heart failure within the last three months (New York Heart Association (NYHA) Class IV).
- Subjects with PAH associated with portal hypertension, Human Immunodeficiency Virus (HIV) infection or unrepaired congenital systemic to pulmonary shunts
- Subjects who have received or have been scheduled to receive long-term treatment with epoprostenol or any prostacyclin within the three months prior to the screening visit or during the screening period.
- Hypotensive subjects (systemic systolic blood pressure < 85 mmHg)
- Subjects with a history of left sided heart disease, chronic left sided heart failure, congenital or acquired valvular disease and/or pulmonary venous hypertension.
- Subjects with significant obstructive (forced expiratory volume in one second [FEV1]/forced vital capacity [FVC] < 70% predicted) or restrictive (total lung capacity < 70% predicted) lung disease at screening.
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
Germany2 sites
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Heidelberg, 69120
United States1 site
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15261
United Kingdom1 site
Novartis Investigative Site
Cambridge, Cambridgeshire, CB23 3RE
About this study
Official title: A Randomized, Parallel-group, Placebo-controlled Subject and Investigator Blinded Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of QCC374 in the Treatment of Pulmonary Arterial Hypertension
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.
Read the detailed description
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.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- QCC374, Placebo Matching
- 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, QCC374
- Medical subject headings
- Pulmonary Arterial Hypertension, Hypertension, Pulmonary, Dyspnea, Dizziness, Syncope, Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QCC374Drug
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
Placebo MatchingDrug
Placebo matching to QCC374:
0.03 mg BID, 0.06 mg BID and 0.12 mg BID
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: QCC374 |
| 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)). Receives: Drug: Placebo Matching |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 16 (Day 111)
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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))
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2016 (estimated)
- Study start19 Sep 2017
- Primary completion7 Jun 2018
- Study completion7 Jun 2018
Why it stopped: Study was terminated early for strategic reasons. Only Part I of the study was completed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02927366
- Sponsor's protocol ID
- CQCC374X2201
- Other IDs
- 2016-001412-38, 2016
- Status last verified
- Feb 2020
- First submitted
- 5 Oct 2016
- Last updated
- 5 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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