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

This study has been terminated.
(Study was terminated due to serious adverse event (SAE))
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01179737
First received: August 3, 2010
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Pulmonary Arterial Hypertension
Drug: Nilotinib
Drug: Placebo to nilotinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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)

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in Pulmonary Vascular Resistance (PVR) [ Time Frame: 168 days ] [ Designated as safety issue: No ]
    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:
  • Change in Six-Minute Walk Distance (6MWD) From Baseline [ Time Frame: Baseline, 168 days ] [ Designated as safety issue: No ]
    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

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


Enrollment: 23
Study Start Date: July 2010
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01179737

Locations
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
Germany
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
Singapore
Novartis Investigative Site
Singapore, Singapore, 119074
Novartis Investigative Site
Singapore, Singapore, 168752
Switzerland
Novartis Investigative Site
Zurich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01179737     History of Changes
Obsolete Identifiers: NCT01531270
Other Study ID Numbers: CAMN107X2201, 2010-019883-36
Study First Received: August 3, 2010
Results First Received: January 14, 2014
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Korea: Korea FDA
Germany: Ministry of Health
Switzerland: Swissmedic
Singapore: Health Sciences Authority
Italy: The Italian Medicines Agency
Hungary: Institutional Ethics Committee

Keywords provided by Novartis:
Pulmonary Arterial Hypertension
Nilotinib
6MWD
Pulmonary Hypertension

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

ClinicalTrials.gov processed this record on July 20, 2014