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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01064791
• Collaborator: (none)
• Enrollment: 298
• Locations: 44
• Arms: 4
• Duration (Months): 32
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.2

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 renal transplantation.

Condition or Disease	Intervention/Treatment	Phase
Renal Transplantation	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	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 298 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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 Start Date: Dec 1, 2009
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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]

2. 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]

3. 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]

4. Evaluate safety and tolerability (adverse events, serious adverse events, laboratory abnormalities, vital signs, electrocardiograms, physical examination). [Months 6, 12, 24, and 36]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35233
2	Novartis Investigative Site	Aurora	Colorado	United States	80045
3	Novartis Investigative Site	Ann Arbor	Michigan	United States	48109
4	Novartis Investigative Site	Detroit	Michigan	United States	48202-2689
5	Novartis Investigative Site	Cincinnati	Ohio	United States	45219
6	Novartis Investigative Site	Cincinnati	Ohio	United States	45267-0585
7	Novartis Investigative Site	Madison	Wisconsin	United States	53792
8	Novartis Investigative Site	Cordoba		Argentina	X5016KEH
9	Novartis Investigative Site	Cordoba		Argentina	X5022CPU
10	Novartis Investigative Site	Corrientes		Argentina	W3400
11	Novartis Investigative Site	Camperdown	New South Wales	Australia	2050
12	Novartis Investigative Site	Woolloongabba	Queensland	Australia	4102
13	Novartis Investigative Site	Adelaide	South Australia	Australia	5000
14	Novartis Investigative Site	Melbourne	Victoria	Australia	3050
15	Novartis Investigative Site	Bruxelles		Belgium	1070
16	Novartis Investigative Site	Bruxelles		Belgium	1200
17	Novartis Investigative Site	Leuven		Belgium	3000
18	Novartis Investigative Site	Porto Alegre	RS	Brazil	90035-903
19	Novartis Investigative Site	São Paulo	SP	Brazil	04023-900
20	Novartis Investigative Site	Vancouver	British Columbia	Canada	V6Z 1Y6
21	Novartis Investigative Site	Cali		Colombia
22	Novartis Investigative Site	Aarhus		Denmark	8000 C
23	Novartis Investigative Site	Berlin		Germany	10098
24	Novartis Investigative Site	Berlin		Germany	13353
25	Novartis Investigative Site	Essen		Germany	45147
26	Novartis Investigative Site	Hamburg		Germany	20246
27	Novartis Investigative Site	Hannover		Germany	30625
28	Novartis Investigative Site	Heidelberg		Germany	69120
29	Novartis Investigative Site	Koeln		Germany	51109
30	Novartis Investigative Site	Regensburg		Germany	93053
31	Novartis Investigative Site	Budapest		Hungary	1082
32	Novartis Investigative Site	Szeged		Hungary	6720
33	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	120-752
34	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	138-736
35	Novartis Investigative Site	Rotterdam		Netherlands	3015 CE
36	Novartis Investigative Site	Coimbra		Portugal	3000-075
37	Novartis Investigative Site	Lisbon		Portugal	1069-166
38	Novartis Investigative Site	Porto		Portugal	4099-001
39	Novartis Investigative Site	Göteborg		Sweden	SE-413 45
40	Novartis Investigative Site	Stockholm		Sweden	141 86
41	Novartis Investigative Site	Uppsala		Sweden	751 85
42	Novartis Investigative Site	Glasgow		United Kingdom	G11 6NT
43	Novartis Investigative Site	Leicester		United Kingdom	LE5 4PW
44	Novartis Investigative Site	Manchester		United Kingdom	M13 9WL

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
• Study Director: Novartis Pharmceuticals, Novartis Pharmceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Novartis Results on CAEB071A2214 from the Novartis Clinical Trials Website

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01064791
• Other Study ID Numbers: CAEB071A2214; 2009-015456-14
• First Posted: Feb 8, 2010
• Last Update Posted: Dec 22, 2020
• Last Verified: Nov 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Renal transplantation
• Additional relevant MeSH terms: Mycophenolic Acid; Tacrolimus

Study Results

No Results Posted as of Dec 22, 2020