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

August 3, 2010
April 14, 2014
July 2010
January 2013   (final data collection date for primary outcome measure)
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.
Effect of nilotinib on pulmonary vascular resistance (PVR) compared to placebo [ Time Frame: 168 days for each Cohort ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01179737 on ClinicalTrials.gov Archive Site
  • 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.
  • Change in Six-Minute Walk Distance (6MWD) from baseline [ Time Frame: Baseline, 168 days for each Cohort ] [ Designated as safety issue: No ]
  • Number of patients with Adverse Events as a measure of the safety and tolerability of AMN107 [ Time Frame: 168 days for each Cohort ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)
A 24 Week, Randomized, Double Blind, Multicenter, Placebocontrolled Efficacy, Safety, Tolerability and PK Trial of Nilotinib (Tasigna®, AMN107) in Pulmonary Arterial Hypertension (PAH)

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.

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

Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Pulmonary Arterial Hypertension
  • 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.
  • Drug: Placebo to nilotinib
    Placebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day
  • 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
    Intervention: Drug: Nilotinib
  • Placebo Comparator: Placebo
    Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.
    Intervention: Drug: Placebo to nilotinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
23
January 2013
January 2013   (final data collection date for primary outcome measure)

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

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   Germany,   Korea, Republic of,   Singapore,   Switzerland
 
NCT01179737
CAMN107X2201, 2010-019883-36
Yes
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP