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

• ClinicalTrials.gov Identifier: NCT01179737
• Recruitment Status: Terminated
• First Posted: August 11, 2010
• Results First Posted: February 27, 2014
• Last Update Posted: May 1, 2014
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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.

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• 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
• 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; Nilotinib; 6MWD; Pulmonary Hypertension

Additional relevant MeSH terms:

Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Vascular Diseases; Cardiovascular Diseases; Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases