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 )

Tracking Information

• First Submitted Date: August 3, 2010
• First Posted Date: August 11, 2010
• Results First Submitted Date: January 14, 2014
• Results First Posted Date: February 27, 2014
• Last Update Posted Date: May 1, 2014
• Study Start Date: July 2010
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2014)

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.

• Original Primary Outcome Measures (submitted: August 10, 2010): Effect of nilotinib on pulmonary vascular resistance (PVR) compared to placebo [ Time Frame: 168 days for each Cohort ]

Current Secondary Outcome Measures (submitted: April 14, 2014)

• 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
• 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.

Original Secondary Outcome Measures (submitted: August 10, 2010)

• Change in Six-Minute Walk Distance (6MWD) from baseline [ Time Frame: Baseline, 168 days for each Cohort ]
• Number of patients with Adverse Events as a measure of the safety and tolerability of AMN107 [ Time Frame: 168 days for each Cohort ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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)
• 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
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Pulmonary Arterial Hypertension

Intervention

• 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

Study Arms

• 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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 14, 2014): 23
• Original Estimated Enrollment (submitted: August 10, 2010): 66
• Actual Study Completion Date: January 2013
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Germany, Korea, Republic of, Singapore, Switzerland, United States
• Removed Location Countries: Hungary, Italy

Administrative Information

• NCT Number: NCT01179737
• Other Study ID Numbers: CAMN107X2201; 2010-019883-36 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: External Affairs, Novartis Pharmaceuticals
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Novartis
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: April 2014