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Safety, Pharmacokinetics and Efficacy Study of QCC374 in PAH Patients

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ClinicalTrials.gov Identifier: NCT02927366
Recruitment Status : Recruiting
First Posted : October 7, 2016
Last Update Posted : February 27, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
This is a non-confirmatory, randomized, subject and investigator blinded, placebo controlled study of QCC374 in PAH patients. The study will have 2 parts. In Part 1, an initial safety cohort, 8 subjects will be randomized in a 6:2 ratio and the starting dose will be 0.03 mg b.i.d.. In Part 2, ~ 30 subjects will be randomized in a 2:1 ratio, with a planned starting dose of 0.06 mg b.i.d.. In both Parts, subjects will be up-titrated during the first two weeks of the study to 0.12 mg b.i.d, or to their maximum tolerated dose (MTD) if their individual MTD is below 0.12 mg b.i.d. during the first two weeks of the study. The treatment duration is 16 weeks.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: QCC374 Drug: Placebo Matching Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : September 19, 2017
Estimated Primary Completion Date : December 27, 2018
Estimated Study Completion Date : December 27, 2018


Arm Intervention/treatment
Experimental: QCC374 Drug: QCC374
0.015 mg and 0.06 mg

Drug: Placebo Matching
Placebo matching

Placebo Comparator: Placebo Drug: QCC374
0.015 mg and 0.06 mg

Drug: Placebo Matching
Placebo matching




Primary Outcome Measures :
  1. Efficacy of 16 weeks of QCC374 administration in adult patients with PAH [ Time Frame: 16 weeks ]
    Percentage of the baseline PVR at week 16


Secondary Outcome Measures :
  1. Change from Baseline in Six Minute Walk Test (6MWT) [ Time Frame: 16 weeks ]
    Six Minute Walk Distance (6MWD)

  2. Change from Baseline in Right Heart Catheterization (RHC) Measurements [ Time Frame: 16 Weeks ]
    The RHC assessment is performed to assess several hemodynamic variables in pulmonary hypertension, including mean pulmonary arterial pressure (PAP), Pulmonary Capillary Wedge Pressure (PCWP), cardiac output (CO), pulmonary vascular resistance (PVR) and Systemic Vascular Resistance (SVR).

  3. Change from Baseline in Echocardiography Measurements [ Time Frame: 16 weeks ]
    Key right ventricular (RV) function endpoints with echocardiography will include but not limited to tricuspid annular peak systolic velocity (TA S'), RV Tei index and RV fractional area change.

  4. Cmax [ Time Frame: 16 weeks ]
    Cmax is the observed maximum plasma concentration following drug administration

  5. Tmax [ Time Frame: 16 weeks ]
    Tmax is the time to reach the maximum concentration after drug administration

  6. AUClast [ Time Frame: 16 weeks ]
    AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration

  7. AUCtau [ Time Frame: 16 weeks ]
    The area under the plasma (or serum or blood) concentration-time curve from time zero to the end of the dosing interval tau [mass x time / volume]



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02927366


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, Pennsylvania
Novartis Investigative Site Recruiting
Pittsburgh, Pennsylvania, United States, 15261
United States, Wisconsin
Novartis Investigative Site Recruiting
Milwaukee, Wisconsin, United States, 53215
Germany
Novartis Investigative Site Recruiting
Dresden, Germany, 01307
Novartis Investigative Site Recruiting
Giessen, Germany, 35392
Novartis Investigative Site Recruiting
Heidelberg, Germany, 69120
Novartis Investigative Site Recruiting
Munchen, Germany, 80639
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03722
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 06351
Taiwan
Novartis Investigative Site Recruiting
Tainan, Taiwan, 70421
Novartis Investigative Site Recruiting
Taipei, Taiwan, 10048
United Kingdom
Novartis Investigative Site Recruiting
Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
Sponsors and Collaborators
Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02927366     History of Changes
Other Study ID Numbers: CQCC374X2201
First Posted: October 7, 2016    Key Record Dates
Last Update Posted: February 27, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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

Additional relevant MeSH terms:
Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases