Efficacy, Safety, Tolerability, and Pharmacokinetics of Sotrastaurin Combined With Tacrolimus vs. a Mycophenolic Acid-tacrolimus Regimen in Renal Transplant Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Transplantation
• Intervention / Treatment: Drug: sotrastaurin (Dose 1) + tacrolimus + standard of care medications; Drug: sotrastaurin (Dose 2) + tacrolimus + standard of care medications; Drug: sotrastaurin (Dose 3) + tacrolimus + standard of care medications; Drug: mycophenolic acid + tacrolimus + standard of care medications

• Study Type: Interventional
• Enrollment (Actual): 298
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, X5016KEH
    • Novartis Investigative Site
  • Cordoba, Argentina, X5022CPU
    • Novartis Investigative Site
  • Corrientes, Argentina, W3400
    • Novartis Investigative Site
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Novartis Investigative Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Novartis Investigative Site
• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-903
      • Novartis Investigative Site
  • SP
    • São Paulo, SP, Brazil, 04023-900
      • Novartis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Novartis Investigative Site
• Colombia
  • Cali, Colombia
    • Novartis Investigative Site
• Denmark
  • Aarhus, Denmark, 8000 C
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10098
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 20246
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Koeln, Germany, 51109
    • Novartis Investigative Site
  • Regensburg, Germany, 93053
    • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1082
    • Novartis Investigative Site
  • Szeged, Hungary, 6720
    • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 120-752
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 138-736
      • Novartis Investigative Site
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Novartis Investigative Site
• Portugal
  • Coimbra, Portugal, 3000-075
    • Novartis Investigative Site
  • Lisbon, Portugal, 1069-166
    • Novartis Investigative Site
  • Porto, Portugal, 4099-001
    • Novartis Investigative Site
• Sweden
  • Göteborg, Sweden, SE-413 45
    • Novartis Investigative Site
  • Stockholm, Sweden, 141 86
    • Novartis Investigative Site
  • Uppsala, Sweden, 751 85
    • Novartis Investigative Site
• United Kingdom
  • Glasgow, United Kingdom, G11 6NT
    • Novartis Investigative Site
  • Leicester, United Kingdom, LE5 4PW
    • Novartis Investigative Site
  • Manchester, United Kingdom, M13 9WL
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Novartis Investigative Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novartis Investigative Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Novartis Investigative Site
    • Detroit, Michigan, United States, 48202-2689
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Novartis Investigative Site
    • Cincinnati, Ohio, United States, 45267-0585
      • Novartis Investigative Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; sotrastaurin (100mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (Dose 1) + tacrolimus + standard of care medications; sotrastaurin (100mg bid) + tacrolimus + standard of care medications
Experimental: Arm 2; sotrastaurin (200mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (Dose 2) + tacrolimus + standard of care medications; sotrastaurin (200mg bid) + tacrolimus + standard of care medications
Experimental: Arm 3; sotrastaurin (300mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (Dose 3) + tacrolimus + standard of care medications; sotrastaurin (300mg bid) + tacrolimus + standard of care medications
Active Comparator: Arm 4; mycophenolic acid (720mg bid) + tacrolimus + standard of care medications	Drug: mycophenolic acid + tacrolimus + standard of care medications; mycophenolic acid (720mg bid) + tacrolimus + standard of care medications

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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).	Month 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Evaluate renal allograft function post-transplantation (estimated GFR by MDRD equation; estimated creatinine clearance by Cockroft-Gault formula; serum creatinine)	Months 6, 12, 24, and 36
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).	Months 12, 24, and 36
Evaluate individual components of the composite efficacy endpoint (treated BPAR, severity of acute rejections by Banff 2007 diagnostic category).	Months 6, 12, 24, and 36
Evaluate safety and tolerability (adverse events, serious adverse events, laboratory abnormalities, vital signs, electrocardiograms, physical examination).	Months 6, 12, 24, and 36

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

• Novartis Results on CAEB071A2214 from the Novartis Clinical Trials Website

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: February 2, 2010
• First Submitted That Met QC Criteria: February 5, 2010
• First Posted (Estimate): February 8, 2010

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 15, 2020
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Renal transplantation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Tacrolimus; Mycophenolic Acid
• Other Study ID Numbers: CAEB071A2214; 2009-015456-14 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No