An Extension Study for Patients Who Participated in the CAMN107X2201 Study - Full Text View

Purpose

This is an extension study for patients who participated in the CAMN107X2201 study.

Condition	Intervention	Phase
Pulmonary Arterial Hypertension	Drug: Nilotinib Drug: Matching placebo to Nilotinib	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Extension Study to CAMN107X2201 to Evaluate the Long-term Safety Tolerability and Efficacy of Oral Nilotinib (AMN107) in Pulmonary Arterial Hypertension (PAH)

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Nilotinib

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Reporting of Adverse Events (AE) [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
All study emergent adverse events (AEs) in the extension and core study CAMN107X2201 will be summarized and listed.

AEs starting on or after the time of the first use of study drug but not later than 7 days (30 days in case of an SAE) after the last dose of study drug will be classified as a treatment emergent AE. AEs that started during the study but before the time of the first use of study drug will be classified as a prior AE and not summarized, but included in AE listings. The same will be done for AEs that started more as a post-treatment AE.
Reporting of laboratory data [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
The Laboratory values and the change from baseline for continuous laboratory parameters will be summarized at each visit. Shift tables relative to the normal reference ranges will be used to summarize the change from baseline to each visit as well as the worst case post first dosing for each laboratory parameter. The baseline measurement will be the pre-dose measurement at Visit 2 of the core study (CAMN107X2201).
Electrocardiogram (ECG) data summarized by visit [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
All data from the ECG will be summarized by visit.
QTc at regular timepoints throughout the study [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
The Maximum post-baseline QTc value will be summarized.
Change from baseline for ECG data [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
Changes from baseline will be summarized by visit. The baseline measurement for patients entering into the extension study will be the measurement taken predose at Visit 2 in the core study CAMN107X2201.
Echocardiogram abnormalities throughout the study [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
The incidence of specified abnormalities (presence of absence of pericardial effusion, left atrial dilatation, right ventricle dilatation, right ventricle hypertrophy and any other abnormality noted on the eCRF) will be reported by visit.
Right Ventricular Systolic Pressure ( RVSP) and Left Ventricular Ejection Fraction (LVEF) measurements from Echocardiogram [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
Right Ventricular Systolic Pressure (RVSP) and Left Ventricular Ejection Fraction (LVEF) will be summarized at each visit.
Change from baseline in Echocardiogram data [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: Yes ]
Changes from baseline will be summarized. The baseline measurement for the extension will be the measurement taken during the core study CAMN107X2201.

Secondary Outcome Measures:

Summary results of Six minute walk test (6MWT) [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: No ]
A standardized Six-Minute Walk Test (6MWT) will be performed in accordance with the guidelines of the (American Thoracic Society 2003). The 6MWT should be performed indoors, along a long, flat, straight, enclosed corridor with a hard surface that is seldom traveled. The walking course must be 30 m in length.

All aspects of the 6MWT (total distance walked, number of stops, total duration of stops, oxygen saturation, systolic and diastolic blood pressure, heart rate, and Borg score) will be summarized by visit in those subjects who were able to perform.
Change from baseline in the Six minute walk test (6MWT) [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: No ]
The changes from baseline will be summarized.
Time to clinical worsening (TTCW) [ Time Frame: Week 0 through Week 160 ] [ Designated as safety issue: No ]
TTCW events are defined as all cause mortality, overnight hospitalization for worsening of PAH, a worsening of WHO functional class by at least one level, or a 15% decrease in the 6MWD as compared to baseline confirmed by two 6MWTs at two consecutive study visits, for those patients who are able to perform 6MWD.

Enrollment:	3
Study Start Date:	January 2012
Study Completion Date:	January 2013
Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Nilotinib (with matching placebo) Patients will be assigned to 50 mg, 150mg or 300 mg nilotinib (with matching placebo) according to their highest tolerated dose in the CAMN107X2201 study. Further dose escalations and reductions are allowed according to the permitted dose scheme at the discretion of the investigator. Cohort 1 patients who entered the core study extension treatment period and were treated with nilotinib will be assigned their highest tolerated nilotinib dose. Cohort 2 patients on placebo during the core study will start at 50 mg b.i.d and increase after two weeks of treatment to 150 mg b.i.d, and after an additional two weeks of treatment to 300 mg b.i.d, if tolerated. If a subject does not tolerate dose escalation, they can remain at their highest tolerated dose at the investigator's discretion. Patients treated with nilotinib will continue on their highest tolerated dose from the core study. Study treatment will remain blinded until CAMN107X2201 core database lock.	Drug: Nilotinib Nilotinib and matching placebo are capsules for oral consumption and are packaged in kits. Each kit contains of 2 bottles and each bottle will contain 70 capsules. The kits are prepared in dose levels for 50mg, 150mg and 300mg drug assignments. Drug: Matching placebo to Nilotinib Nilotinib and matching placebo are tablets for oral consumption and are packaged in kits. Each kit contains of 2 bottles and each bottle will contain 35 tablets. The kits are prepared in dose levels for 50mg, 150mg and 300mg drug assignments.

Arms

Assigned Interventions

Experimental: Nilotinib (with matching placebo)

Patients will be assigned to 50 mg, 150mg or 300 mg nilotinib (with matching placebo) according to their highest tolerated dose in the CAMN107X2201 study. Further dose escalations and reductions are allowed according to the permitted dose scheme at the discretion of the investigator.

Cohort 1 patients who entered the core study extension treatment period and were treated with nilotinib will be assigned their highest tolerated nilotinib dose.

Cohort 2 patients on placebo during the core study will start at 50 mg b.i.d and increase after two weeks of treatment to 150 mg b.i.d, and after an additional two weeks of treatment to 300 mg b.i.d, if tolerated. If a subject does not tolerate dose escalation, they can remain at their highest tolerated dose at the investigator's discretion. Patients treated with nilotinib will continue on their highest tolerated dose from the core study.

Study treatment will remain blinded until CAMN107X2201 core database lock.

Drug: Nilotinib

Nilotinib and matching placebo are capsules for oral consumption and are packaged in kits. Each kit contains of 2 bottles and each bottle will contain 70 capsules. The kits are prepared in dose levels for 50mg, 150mg and 300mg drug assignments.

Drug: Matching placebo to Nilotinib

Nilotinib and matching placebo are tablets for oral consumption and are packaged in kits. Each kit contains of 2 bottles and each bottle will contain 35 tablets. The kits are prepared in dose levels for 50mg, 150mg and 300mg drug assignments.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Written informed consent must be obtained from the patient or legal guardian, before any assessment is performed.
Patients who participated in CAMN107X2201 clinical trial and completed the study, including all end-of-study (Study Completion) assessments of the Week 48 (Day 336) in Cohort 1 and the Week 24 visit (Day 168) in Cohort 2 of the study protocol.

Exclusion Criteria:

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant UNLESS they are using two birth control methods. The two methods can be a double barrier method or a barrier method plus a hormonal method. Adequate barrier methods of contraception include: diaphragm, condom (by the partner), intrauterine device (copper or hormonal), or sponge with spermicide. Hormonal contraceptives include any marketed contraceptive agent that includes an estrogen and/or a progestational agent
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)
Patients with a pulmonary capillary wedge pressure > 15 mm Hg at time of Study Completion Assessments in CAMN107X2201. If pulmonary capillary wedge pressure is not attainable, then a left atrial pressure measurement may be used in its place.
Patients with LVEF < 45%
Patients with thrombocytopenia, platelet count < 50 x109/L (50 x 103/µL)
Patients with uncontrolled systemic arterial hypertension, systolic > 160 mm Hg or diastolic >90 mm Hg
Patients with a QTcF > 450 ms for males and > 470 ms for females in the absence of right bundle branch block (based on Visit 1 ECG if required to be performed)
[In Canada Only: Liver function tests ALT or AST > 1.5 times ULN]

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01531270

Locations

United States, Massachusetts
Novartis Investigative Site
Boston, Massachusetts, United States, 02118
United States, Ohio
Novartis Investigative Site
Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01531270 History of Changes
Other Study ID Numbers:	CAMN107X2201E1, 2010-023421-37
Study First Received:	February 8, 2012
Last Updated:	March 29, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Germany: Federal Institute for Drugs and Medical Devices Hungary: National Institute of Pharmacy Italy: The Italian Medicines Agency Korea: Food and Drug Administration Singapore: Health Sciences Authority Switzerland: Swissmedic

Keywords provided by Novartis:

pulmonary Arterial Hypertension
nilotinib
pulmonary hypertension

Additional relevant MeSH terms:

Hypertension, Pulmonary
Hypertension
Lung Diseases

Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on June 18, 2013