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

NCT01179737 | Terminated Phase 2 Results DMC

• 2 other identifiers: CAMN107X22012010-019883-36
• Study Type: interventional
• Target: 23
• Locations: 6 countries
• Sites: 13

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

Pulmonary Arterial Hypertension; Nilotinib; 6MWD; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• 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.

  168 days

Secondary Outcomes (2)

• Change in Six-Minute Walk Distance (6MWD) From Baseline

  Baseline, 168 days

• Total Number of Adverse Events and Serious Adverse Events

  168 days

Study Arms (2)

Nilotinib

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo to nilotinib

Interventions

Nilotinib 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.

Nilotinib

Placebo to nilotinib DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• World Health Organization (WHO) Functional Class II or III
• MWD ≥ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Novartis Investigative Site

Boston, Massachusetts, 02118, United States

Location

Novartis Investigative Site

Ann Arbor, Michigan, 48109-0391, United States

Location

Novartis Investigative Site

Chapel Hill, North Carolina, 27599, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44195, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37232-2573, United States

Location

Novartis Investigative Site

Calgary, Alberta, T6G 2B7, Canada

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Marburg, 35039, Germany

Location

Novartis Investigative Site

Singapore, Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, Singapore, 168752, Singapore

Location

Novartis Investigative Site

Seoul, Korea, 120-752, South Korea

Location

Novartis Investigative Site

Zurich, Switzerland, 8091, Switzerland

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharnaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2010
• First Posted: August 11, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: May 1, 2014
• Results First Posted: February 27, 2014

Record last verified: 2014-04

Locations

DE (3); SG (2); CA (1); KR (1); CH (1); US (5)