Clinical trial NCT01128335: Efficacy, Safety, Tolerability, Pharmacokinetics of Sotrastaurin-tacrolimus vs. Mycophenolic Acid-tacrolimus in de Novo Liver Transplant Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Transplantation
Keywords: Liver transplantation
HCV-negative recipient
deceased donor
sotrastaurin
oran transplantation
tacrolimus
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-05-21
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: Month 6
Secondary outcomes:
measure: Evaluate renal allograft function post-transplantation (estimated GFR by MDRD equation; estimated creatinine clearance by Cockcroft-Gault formula; serum creatinine).
timeFrame: Months 3, 6, 12, and 24
measure: 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.
timeFrame: Months 12, 24
measure: Occurrence of rejection requiring T-cell depleting antibody, occurrence of treated biopsy-proven acute rejections of Banff grade ≥ 1 that is steroid-resistant
timeFrame: Months 6, 12, 24
measure: Safety and tolerability ((serious) adverse events (specifically: gastrointestinal AEs and cardiac AEs, serious infections), laboratory abnormalities, vital signs, electrocardiograms, physical examination).
timeFrame: Months 3, 6, 12, 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Novartis Investigative Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Minneapolis
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Rochester
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Martin
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Innsbruck
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: HUS
country: Finland
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Chambray les Tours
country: France
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Villejuif
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Pisa
country: Italy
facility: Novartis Investigative Site
state: PI
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: L'Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Zurich
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmceuticals
role: STUDY_DIRECTOR
References:
citation: Pascher A, De Simone P, Pratschke J, Salame 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. doi: 10.1111/ajt.13175. Epub 2015 Feb 12.