ND

• Register: EUCTR
• Last refreshed on: 10 February 2014
• Main ID: EUCTR2010-019883-36-IT
• Date of registration: 24/09/2010
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: ND
• Scientific title: A 24 week, randomized, double blind, multicenter, placebocontrolled efficacy, safety, tolerability and PK trial of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)
• Date of first enrolment: 20/09/2010
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019883-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: yes Other specify the comparator: - same IMP used at different dosage Number of treatment arms in the trial: 2

Countries of recruitment

Canada, Germany, Hungary, Italy, Korea, Republic of, Singapore, United States

Contacts

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

• Name: Drug Regulatory Affairs
• Affiliation: NOVARTIS FARMA

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria Patients eligible for inclusion in this study have to fulfill all of the following criteria: 1. Written informed consent must be obtained before any assessment is performed 2. Male or female 18 years of age or older who are unable to bear children and females of child bearing potential not disqualified as per Exclusion Criterion 1 (below) 3. WHO Functional Class II or III 4. 6MWD = 150 m and = 450 m at screening. Distances of two consecutive 6MWTs should be within 15% of one another 5. A current diagnosis of Pulmonary Arterial Hypertension according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect (ASD, VSD or PDA), or PAH associated with diet therapies or other drugs 6. Inadequate clinical response despite stabilization on one or more class(es) of PAH drug [e.g., PDE5 inhibitor, endothelin receptor blocker, vasodilator prostaglandin (systemic, inhaled or oral)] 7. Stabilization of pulmonary hypertension medications defined as observed for = 2 months on approved therapeutic dose of at least one PAH drug and still symptomatic with WHO functional Class II or III performance.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion criteria Patients fulfilling any of the following criteria are not eligible for inclusion in this study: 1. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. UNLESS they are: ?? women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner ?? women whose partners have been sterilized by vasectomy or other means ?? using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), sponge or spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent 2. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 10 mIU/mL) 3. History of ventricular tachycardia, ventricular fibrillation or ventricular flutter 4. Use of drugs known to prolong the QT interval or known to be strong CYP3A4 inhibitors (refer to Appendix 6) 5. Untreated or inadequately controlled hypokalemia (<3.5 mmol/L) or hypomagnesemia (<0.65 mmol/L) at the screening visit (Visit 1) 6. Evidence of clinically significant left ventricular dysfunction. 7. Evidence of clinically significant hepatic impairment, including AST or ALT > 3 times the upper limit of normal (if due to bosentan therapy subject is excluded unless bosentan is discontinued and the above LFTs return to < 2 times the upper limit of normal; Subject must still be on a stable regimen including at least one approved PAH therapy at time of study drug randomization). Bilirubin > 2 times the upper limit of normal. [Canada only: AST or ALT > 1.5 times the upper limit of normal] 8. Atrial fibrillation or history of atrial fibrillation in the previous 3 months 9. Having syncope in the 3 months prior to the screening visit 10. History of previous myocardial infarction, unstable angina, or clinically significant bradycardia (<60 bpm and accompanied by clinical symptoms) 11. QRS > 120 ms or > 140 ms in the presence of bundle branch block 12. Current or history of consistently prolonged QTcF (2 or more ECGs in the prior 12 months in the absence of a right bundle branch block or QTcF>450 ms for males and > 470 ms for females at screening); family history of long QT syndrome 13. WHO Class IV 14. History of Torsades de Pointes 15. In treatment with chronic nitric oxide therapy 16. Pre-existing lung disease including parasitic diseases affecting lungs, congenital abnormalities of the lungs, COPD, thorax or diaphragm or bronchial asthma, associated with chronic hypoxia that may contribute to severity of PAH 17. With a pulmonary capillary wedge pressure > 15 mm Hg to rule out PAH secondary to left ventricular dysfunction 18. Diagnosis of pulmonary artery or vein stenosis 19. With other diagnosis of PAH in WHO Diagnostic Group 1 are excluded including congenital systemic to pulmonary shunts (large, small that are not surgically repaired), portal hypertension, HIV infection, glycogen storage disease, Gaucher’s disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders) 20. With a diagnosis of PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary t

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension (PAH)
MedDRA version: 14.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Trade Name: TASIGNA
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: nilotinib
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration number: 200-

Trade Name: TASIGNA
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: nilotinib
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration number: 150-

Trade Name: TASIGNA
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: nilotinib
Current Sponsor code: AMN107
Concentration unit: mg milligram(s)
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: Secondary objectives Key • To test the effect of nilotinib on 6 min walk distance (6MWD) relative to baseline and compared to placebo after 24 weeks of therapy. Other • Establish the safety and tolerability of nilotinib in patients with PAH including effects on QTc and platelet activation • To test the effect of nilotinib on pulmonary vascular resistance relative to baseline after 24 weeks of therapy • To test the effect of nilotinib on other hemodynamic parameters, including cardiac output/index (CO/CI), pulmonary artery pressure (PaP), pulmonary capillary wedge pressure (PCWP), systemic pressure (SAP) and resistance (SVR) • To test the effect of nilotinib on time to clinical worsening (TTCW) compared to placebo • To assess change in Borg dyspnea score during 6-min walk testing, with nilotinib as compared to placebo • To assess the pharmacokinetics of nilotinib in this patient population.

Timepoint(s) of evaluation of this end point: N.A.

Main Objective: Primary objective • To evaluate the effect of nilotinib on pulmonary vascular resistance (PVR) compared to placebo after 24 weeks of therapy

Primary end point(s): Pulmonary Vascular Resistance (PVR)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: N.D.

Secondary end point(s): N.D.

Secondary ID(s)

2010-019883-36-HU

CAMN107X2201

Source(s) of Monetary Support

Novartis Pharma Services AG