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Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)

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ClinicalTrials.gov Identifier: NCT01179737
Recruitment Status : Terminated (Study was terminated due to serious adverse event (SAE))
First Posted : August 11, 2010
Results First Posted : February 27, 2014
Last Update Posted : May 1, 2014
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months treatment with nilotinib will significantly reduce pulmonary artery resistance.

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Nilotinib Drug: Placebo to nilotinib Phase 2

Detailed Description:
The purpose of this trial was to establish the safety, tolerability and PK of nilotinib in this population and to test the hypothesis that 6 months

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A 24 Week, Randomized, Double Blind, Multicenter, Placebocontrolled Efficacy, Safety, Tolerability and PK Trial of Nilotinib (Tasigna®, AMN107) in Pulmonary Arterial Hypertension (PAH)
Study Start Date : July 2010
Actual Primary Completion Date : January 2013
Actual Study Completion Date : January 2013

Arm Intervention/treatment
Experimental: Nilotinib
Participants in cohort 1 were assigned to receive nilotinib 50 mg during 14 days, followed by 150 mg during 14 days, followed by 300 mg during 140 days. Participants in cohort 2 were assigned to receive nilotinib 300 mg during 168 days
Drug: Nilotinib
Nilotinib capsules for oral administration at 50 mg, 150 mg twice a day and 300 mg (2 capsules of 150 mg) twice a day.

Placebo Comparator: Placebo
Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.
Drug: Placebo to nilotinib
Placebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day

Primary Outcome Measures :
  1. Change in Pulmonary Vascular Resistance (PVR) [ Time Frame: 168 days ]
    Change in pulmonary vascular resistance is measured via right heart catheter assessment according to local hospital procedures. It assesses several prognostic hemodynamic variables in pulmonary hypertension, including Pulmonary Vascular Resistance (PVR). Study was prematurely terminated and not powered for efficacy.

Secondary Outcome Measures :
  1. Change in Six-Minute Walk Distance (6MWD) From Baseline [ Time Frame: Baseline, 168 days ]
    During standardized walk course participants are connected to a portable pulse oximeter via a finger probe and instructed to walk at a comfortable speed for as far as they could manage in 6 minutes. Study was prematurely terminated and efficacy data were not analyzed or summarized

  2. Total Number of Adverse Events and Serious Adverse Events [ Time Frame: 168 days ]
    Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated.

Information from the National Library of Medicine

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

Inclusion Criteria:

  • World Health Organization (WHO) Functional Class II or III
  • 6MWD ≥ 150 m and ≤ 450 m at screening
  • Current diagnosis of PAH according to Dana Point 2008 Meeting
  • Inadequate clinical response on one or more class(es) of PAH drug
  • Stabilization of pulmonary hypertension medications for ≥ 2 months on approved therapeutic dose of at least one PAH drug and still symptomatic with WHO functional Class II or III performance.

Exclusion Criteria:

  • Women of child-bearing potential not practicing birth control
  • In treatment with chronic nitric oxide therapy
  • Pre-existing lung disease
  • Use of drugs prolonging the QT interval or strong CYP3A4 inhibitors
  • Long QT syndrome or QTc > 450 ms males; > 470 ms females.
  • WHO Class IV
  • Pulmonary capillary wedge pressure > 15 mm Hg
  • Other diagnosis of PAH in WHO Diagnostic Group 1
  • PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV) or other miscellaneous causes (WHO Diagnostic Class V, which includes sarcoidosis, histiocytosis X, lymphangiomatosis, compression of pulmonary vessels)
  • Thrombocytopenia < 50 x109/L (50 x 103/µL)
  • Uncontrolled systemic arterial hypertension, systolic > 160 mm Hg or diastolic >90 mm Hg
  • Any advanced, severe, or unstable disease of any type that may interfere with the primary and secondary endpoint evaluations.

Other protocol-defined inclusion/exclusion criteria may apply

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): NCT01179737

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United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02118
United States, Michigan
Novartis Investigative Site
Ann Arbor, Michigan, United States, 48109-0391
United States, North Carolina
Novartis Investigative Site
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Novartis Investigative Site
Cleveland, Ohio, United States, 44195
United States, Tennessee
Novartis Investigative Site
Nashville, Tennessee, United States, 37232-2573
Canada, Alberta
Novartis Investigative Site
Calgary, Alberta, Canada, T6G 2B7
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Marburg, Germany, 35039
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 120-752
Novartis Investigative Site
Singapore, Singapore, 119074
Novartis Investigative Site
Singapore, Singapore, 168752
Novartis Investigative Site
Zurich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01179737    
Obsolete Identifiers: NCT01531270
Other Study ID Numbers: CAMN107X2201
2010-019883-36 ( EudraCT Number )
First Posted: August 11, 2010    Key Record Dates
Results First Posted: February 27, 2014
Last Update Posted: May 1, 2014
Last Verified: April 2014
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Pulmonary Arterial Hypertension
Pulmonary Hypertension
Additional relevant MeSH terms:
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Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases