Efficacy, Safety, Tolerability, Pharmacokinetics of Sotrastaurin-tacrolimus vs. Mycophenolic Acid-tacrolimus in de Novo Liver Transplant Patients

Liver Transplantation Clinical Trial

Official title:

A 24-month Randomized Multicenter Study Evaluating Efficacy, Safety, Tolerability and Pharmacokinetics of Sotrastaurin and Tacrolimus vs. a Tacrolimus/Mycophenolate Mofetil-based Control Regimen in de Novo Liver Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01128335
• Other study ID #: CAEB071B2201
• Secondary ID: 2007-001776-36
• Status: Completed
• Phase: Phase 2
• Start date: April 2010
• Est. completion date: July 2012

Study information

• Verified date: November 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety and efficacy of different doses of sotrastaurin when combined with tacrolimus for the prevention of acute rejection after de novo liver transplantation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Recipients of any race, 18 years or older

• Recipients of primary de novo orthotopic liver transplant from a deceased donor

• Recipients of a kidney with a cold ischemia time < 30 hours

• HCV-negative recipients

Exclusion criteria:

• Prior organ/cellular transplant or multiple organ transplant

• MELD-score > 35

• HCC > Milan criteria

• Donor age < 12 years

• Cold ischemia > 15 hours

• Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) or drugs with QT-prolonging properties

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Drug:
• MMF(1000mg bid) + tacrolimus + standard of care medications
MMF(1000mg bid) + tacrolimus + standard of care medications
• sotrastaurin (200mg bid) + tacrolimus + standard of care medications
sotrastaurin (200mg bid) + tacrolimus + standard of care medications
• sotrastaurin (200mg bid) + tacrolimus + standard of care medications
sotrastaurin (200mg bid) + tacrolimus + standard of care medications
• sotrastaurin (300 mg bid) + tacrolimus + standard of care medications
sotrastaurin (300 mg bid) + tacrolimus + standard of care medications

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	San Martin	Buenos Aires
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	London	Ontario
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Praha 4	Czech Republic
Finland	Novartis Investigative Site	HUS
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Chambray les Tours
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Strasbourg
France	Novartis Investigative Site	Villejuif
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Regensburg
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Pisa	PI
Spain	Novartis Investigative Site	L'Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Zurich
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigative Site	Rochester	Minnesota
United States	Novartis Investigative Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Canada,  Czechia,  Finland,  France,  Germany,  Italy,  Spain,  Switzerland, 

References & Publications (1)

Pascher A, De Simone P, Pratschke J, Salamé E, Pirenne J, Isoneimi H, Bijarnia M, Krishnan I, Klupp J. Protein kinase C inhibitor sotrastaurin in de novo liver transplant recipients: a randomized phase II trial. Am J Transplant. 2015 May;15(5):1283-92. do — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of primary efficacy failure defined as composite efficacy endpoint (treated BPAR of Banff grade = 1, graft loss, or death) in the different treatment arms.		Month 6
Secondary	Evaluate renal allograft function post-transplantation (estimated GFR by MDRD equation; estimated creatinine clearance by Cockcroft-Gault formula; serum creatinine).		Months 3, 6, 12, and 24
Secondary	Occurrence of primary efficacy failure defined as composite efficacy endpoint (treated BPAR of Banff grade = 1, graft loss, or death) in the different treatment arms.		Months 12, 24
Secondary	Occurrence of rejection requiring T-cell depleting antibody, occurrence of treated biopsy-proven acute rejections of Banff grade = 1 that is steroid-resistant		Months 6, 12, 24
Secondary	Safety and tolerability ((serious) adverse events (specifically: gastrointestinal AEs and cardiac AEs, serious infections), laboratory abnormalities, vital signs, electrocardiograms, physical examination).		Months 3, 6, 12, 24

External Links

•   Results for CAEB071B2201 from the Novartis Clinical Trials Website