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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Nilotinib
Placebo to nilotinib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension focused on measuring Pulmonary Arterial Hypertension, Nilotinib, 6MWD, Pulmonary Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nilotinib

Placebo

Arm Description

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

Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.

Outcomes

Primary Outcome Measures

Change in Pulmonary Vascular Resistance (PVR)
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
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
Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated.

Full Information

First Posted
August 3, 2010
Last Updated
April 14, 2014
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01179737
Brief Title
Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)
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 Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated due to serious adverse event (SAE)
Study Start Date
July 2010 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
January 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
Keywords
Pulmonary Arterial Hypertension, Nilotinib, 6MWD, Pulmonary Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Nilotinib
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants were assigned to receive placebo to nilotinib to match 50 mg and 150 mg capsules during 168 days.
Intervention Type
Drug
Intervention Name(s)
Nilotinib
Intervention Description
Nilotinib capsules for oral administration at 50 mg, 150 mg twice a day and 300 mg (2 capsules of 150 mg) twice a day.
Intervention Type
Drug
Intervention Name(s)
Placebo to nilotinib
Intervention Description
Placebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day
Primary Outcome Measure Information:
Title
Change in Pulmonary Vascular Resistance (PVR)
Description
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.
Time Frame
168 days
Secondary Outcome Measure Information:
Title
Change in Six-Minute Walk Distance (6MWD) From Baseline
Description
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
Time Frame
Baseline, 168 days
Title
Total Number of Adverse Events and Serious Adverse Events
Description
Adverse events were summarized by the number of patients having any adverse event overall and presented in the safety section. Study was prematurely terminated.
Time Frame
168 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Novartis Investigative Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0391
Country
United States
Facility Name
Novartis Investigative Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Novartis Investigative Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Novartis Investigative Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2573
Country
United States
Facility Name
Novartis Investigative Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Marburg
ZIP/Postal Code
35039
Country
Germany
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
120-752
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
168752
Country
Singapore
Facility Name
Novartis Investigative Site
City
Zurich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

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

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