Clinical trial NCT01064791: Efficacy, Safety, Tolerability, and Pharmacokinetics of Sotrastaurin Combined With Tacrolimus vs. a Mycophenolic Acid-tacrolimus Regimen in Renal Transplant Patients
Official title: A Partially Blinded, Prospective, Randomized Multicenter Study Evaluating Efficacy, Safety and Tolerability of Oral Sotrastaurin Plus Standard or Reduced Exposure Tacrolimus vs. Mycophenolic Acid Plus Tacrolimus in de Novo Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Transplantation
Keywords: Renal transplantation
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-02-08
Enrollment: 298
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 renal transplantation.


Eligibility criteria: Inclusion criteria:

* Recipients of a first or second kidney transplant from a deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor.
* Recipients of a kidney with a cold ischemia time \< 30 hours.
* Recipients of a kidney from a donor 10 - 65 years old.

Exclusion criteria:

* Multi-organ transplant recipients.
* Recipients of an organ from an non-heart beating donor.
* Patients receiving a second kidney allograft if the first allograft was
* Functional for less than three years
* Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) at screening and cannot discontinue this treatment.

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Demonstrate that at least one of the sotrastaurin + tacrolimus treatment arms is non-inferior to the active control regimen with respect to composite efficacy failure (treated BPAR of grade IA or higher, graft loss, death or lost to follow up).
timeFrame: Month 6
Secondary outcomes:
measure: Evaluate renal allograft function post-transplantation (estimated GFR by MDRD equation; estimated creatinine clearance by Cockroft-Gault formula; serum creatinine)
timeFrame: Months 6, 12, 24, and 36
measure: Demonstrate that at least one of the sotrastaurin + tacrolimus treatment arms is non-inferior to the active control regimen with respect to composite efficacy failure (treated BPAR of grade IA or higher, graft loss, death or lost to follow up).
timeFrame: Months 12, 24, and 36
measure: Evaluate individual components of the composite efficacy endpoint (treated BPAR, severity of acute rejections by Banff 2007 diagnostic category).
timeFrame: Months 6, 12, 24, and 36
measure: Evaluate safety and tolerability (adverse events, serious adverse events, laboratory abnormalities, vital signs, electrocardiograms, physical examination).
timeFrame: Months 6, 12, 24, and 36
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Ann Arbor
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Detroit
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Corrientes
country: Argentina
facility: Novartis Investigative Site
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Woolloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Cali
country: Colombia
facility: Novartis Investigative Site
city: Aarhus
country: Denmark
facility: Novartis Investigative Site
city: Berlin
country: Germany
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: Koeln
country: Germany
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisbon
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Göteborg
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis Pharmceuticals
name: Novartis Pharmceuticals
role: STUDY_DIRECTOR
References:
citation: Russ GR, Tedesco-Silva H, Kuypers DR, Cohney S, Langer RM, Witzke O, Eris J, Sommerer C, von Zur-Muhlen B, Woodle ES, Gill J, Ng J, Klupp J, Chodoff L, Budde K. Efficacy of sotrastaurin plus tacrolimus after de novo kidney transplantation: randomized, phase II trial results. Am J Transplant. 2013 Jul;13(7):1746-56. doi: 10.1111/ajt.12251. Epub 2013 May 13.