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

NCT ID: NCT01179737

Last Updated: 2014-05-01

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-07-31

Study Completion Date

2013-01-31

Brief Summary

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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

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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

Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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

Group Type EXPERIMENTAL

Nilotinib

Intervention Type DRUG

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

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

Group Type PLACEBO_COMPARATOR

Placebo to nilotinib

Intervention Type DRUG

Placebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day

Interventions

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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.

Intervention Type DRUG

Placebo to nilotinib

Placebo to nilotinib capsules for oral administration to match 50 mg, 150 mg and 300 mg capsules twice a day

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Boston, Massachusetts, United States

Site Status

Novartis Investigative Site

Ann Arbor, Michigan, United States

Site Status

Novartis Investigative Site

Chapel Hill, North Carolina, United States

Site Status

Novartis Investigative Site

Cleveland, Ohio, United States

Site Status

Novartis Investigative Site

Nashville, Tennessee, United States

Site Status

Novartis Investigative Site

Calgary, Alberta, Canada

Site Status

Novartis Investigative Site

Hamburg, , Germany

Site Status

Novartis Investigative Site

Heidelberg, , Germany

Site Status

Novartis Investigative Site

Marburg, , Germany

Site Status

Novartis Investigative Site

Singapore, Singapore, Singapore

Site Status

Novartis Investigative Site

Singapore, Singapore, Singapore

Site Status

Novartis Investigative Site

Seoul, Korea, South Korea

Site Status

Novartis Investigative Site

Zurich, Switzerland, Switzerland

Site Status

Countries

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United States Canada Germany Singapore South Korea Switzerland

Other Identifiers

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2010-019883-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAMN107X2201

Identifier Type: -

Identifier Source: org_study_id

NCT01531270

Identifier Type: -

Identifier Source: nct_alias

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