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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01128335

Collaborator

(none)

200

Enrollment

Locations

Arms

Duration (Months)

5.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Transplantation	Drug: MMF(1000mg bid) + tacrolimus + standard of care medications Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications Drug: sotrastaurin (300 mg bid) + tacrolimus + standard of care medications	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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 Start Date :

Apr 1, 2010

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 MMF(1000mg bid) + tacrolimus + standard of care medications	Drug: MMF(1000mg bid) + tacrolimus + standard of care medications MMF(1000mg bid) + tacrolimus + standard of care medications
Experimental: Arm 2 sotrastaurin (200mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications sotrastaurin (200mg bid) + tacrolimus + standard of care medications
Experimental: Arm 3 sotrastaurin (200mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (200mg bid) + tacrolimus + standard of care medications sotrastaurin (200mg bid) + tacrolimus + standard of care medications
Experimental: Arm 4 sotrastaurin (300 mg bid) + tacrolimus + standard of care medications	Drug: sotrastaurin (300 mg bid) + tacrolimus + standard of care medications sotrastaurin (300 mg bid) + tacrolimus + standard of care medications

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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]
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]
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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Los Angeles	California	United States	90095
2	Novartis Investigative Site	San Francisco	California	United States	94143
3	Novartis Investigative Site	Detroit	Michigan	United States	48202-2689
4	Novartis Investigative Site	Minneapolis	Minnesota	United States	55455
5	Novartis Investigative Site	Rochester	Minnesota	United States	55905
6	Novartis Investigative Site	Cincinnati	Ohio	United States	45219
7	Novartis Investigative Site	Dallas	Texas	United States	75246
8	Novartis Investigative Site	Houston	Texas	United States	77030
9	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1118AAT
10	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1181ACH
11	Novartis Investigative Site	San Martin	Buenos Aires	Argentina	C1107BEA
12	Novartis Investigative Site	Innsbruck		Austria	A-6020
13	Novartis Investigative Site	Wien		Austria	A-1090
14	Novartis Investigative Site	Gent		Belgium	9000
15	Novartis Investigative Site	Leuven		Belgium	3000
16	Novartis Investigative Site	London	Ontario	Canada	N6A 4G5
17	Novartis Investigative Site	Praha 4	Czech Republic	Czechia	140 21
18	Novartis Investigative Site	Brno		Czechia	656 91
19	Novartis Investigative Site	HUS		Finland	00029
20	Novartis Investigative Site	Bordeaux Cedex		France	33076
21	Novartis Investigative Site	Chambray les Tours		France	37044
22	Novartis Investigative Site	Creteil		France	94000
23	Novartis Investigative Site	Paris		France	75012
24	Novartis Investigative Site	Strasbourg		France	67098
25	Novartis Investigative Site	Villejuif		France	94805
26	Novartis Investigative Site	Berlin		Germany	13353
27	Novartis Investigative Site	Essen		Germany	45147
28	Novartis Investigative Site	Hamburg		Germany	20246
29	Novartis Investigative Site	Hannover		Germany	30625
30	Novartis Investigative Site	Heidelberg		Germany	69120
31	Novartis Investigative Site	Regensburg		Germany	93053
32	Novartis Investigative Site	Milano	MI	Italy	20162
33	Novartis Investigative Site	Padova	PD	Italy	35128
34	Novartis Investigative Site	Pisa	PI	Italy	56124
35	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
36	Novartis Investigative Site	L'Hospitalet de Llobregat	Cataluña	Spain	08907
37	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46026
38	Novartis Investigative Site	La Coruna	Galicia	Spain	15006
39	Novartis Investigative Site	Zurich		Switzerland	8091