CERTES02: Everolimus in a Cyclosporine Microemulsion-free Regimen Compared to a Low-dose Cyclosporine Microemulsion Regimen, in de Novo Kidney Transplant Patients

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00154284
• Collaborator: (none)
• Enrollment: 114
• Arms: 2
• Duration (Months): 36

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of everolimus in combination with basiliximab, and steroids with and without cyclosporine microemulsion in de novo kidney transplant recipients.

Condition or Disease	Intervention/Treatment	Phase
Organ Transplantation, Renal Transplantation	Drug: Everolimus (Certican); Drug: Cyclosporine (Neoral); Drug: Steroid; Drug: Basiliximab (Simulect)	Phase 3

Detailed Description

This is a combined analysis using 81 patients randomized and treated in CRAD001A2419 (NCT00154284) with 33 randomized and treated in CRAD001A2423 (NCT00170807). This approach is reflected in the protocol amendments for each study, and the one clinical study report for both.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 12 Month, Multicenter, Randomized, Parallel, Open-label Study, to Evaluate Renal Function and Efficacy of Everolimus With Basiliximab and Cyclosporine Microemulsion Discontinuation at 3 Month Post-transplant Versus Minimization, in de Novo Kidney Transplant Recipients
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Everolimus (Certican) with Cyclosporine (Neoral) Continuation Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Drug: Everolimus (Certican); Other Names: Certican ; Drug: Cyclosporine (Neoral); Other Names: Neoral ; Drug: Steroid; Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.; Other Names: Prednisone ; Drug: Basiliximab (Simulect); Other Names: Simulect
Experimental: Everolimus (Certican) with Cyclosporine (Neoral) Withdrawal Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Drug: Everolimus (Certican); Other Names: Certican ; Drug: Cyclosporine (Neoral); Other Names: Neoral ; Drug: Steroid; Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.; Other Names: Prednisone ; Drug: Basiliximab (Simulect); Other Names: Simulect

Outcome Measures

Primary Outcome Measures

1. Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula) [At Month 3 and Month 12]

   Nankivell's formula for calculated GFR is shown below: GFR [mL/min] = 6.7/C + W/4 - UREA/2 - 100/H2+ 35 (25 for females). Where W is body weight at specific visit [kg], H is height at specific visit [m], C is the serum concentration of creatinine [mmol/L], and UREA is the serum concentration of urea [mmol/L]. UREA was calculated from blood urea nitrogen (BUN) lab data by: UREA = 2.1441*BUN. If a GFR value from Nankivell formula was less than 10 [mL/min], then the value was assigned as 10 [mL/min].

Secondary Outcome Measures

1. Number of Participants With Biopsy-proven Acute Rejection (BPAR) Episodes, Graft Loss, Death or Loss to Follow-up [Month 12]

   Renal biopsies were collected for all cases of suspected acute rejection. For these cases, regardless of initiation of anti-rejection treatment, a graft core biopsy had been performed within 48 hours. These biopsies were listed on the Kidney Allograft Biopsy eCRF and the results used for patient management for BPAR. Graft loss was defined as the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis as well as re-transplant. BPAR, graft loss, death, or loss to follow-up was analyzed by means of frequency tables.

2. Serum Creatinine at Month 6 and 12 [6 month and 12 months]

   serum creatinine summarized by mean and standard deviation

3. Calculated Creatinine Clearance at 6 Month and 12 Month [6 month and 12 months]

   Creatinine clearance calculated by Cockcroft-Gault formula and summarized by mean, and standard deviation. Cockcroft-Gault formula to calculate Creatinine Clearance (CrCl[mL/min]) is shown below: CrCl[mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit [kg], C is the serum concentration of creatinine [mg/dL], R = 1 if the patient is male and = 0.85 if female.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Recipients of a first renal transplant from a primary cadaveric or non-HLA identical living related donor.

• Renal cold ischemic time < 36 hours.

• Age of donor < 65 years.

Exclusion Criteria:

• Patients who have received an investigational drug within 4 weeks of baseline period.

• Patients who are recipients of multiple organ transplants, including any organ other than kidney.

• Recipients of non-heart beating donor organs.

Other protocol-defined exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Novartis

Investigators

• Study Director: Novartis, Novartis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00154284
• Other Study ID Numbers: CRAD001A2419; CRAD001A2423; NCT00170807
• First Posted: Sep 12, 2005
• Last Update Posted: Aug 9, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by , ,: Renal transplantation,; everolimus,; immunosuppressants,; basiliximab,; cyclosporine microemulsion discontinuation, cyclosporine microemulsion minimization
• Additional relevant MeSH terms: Cyclosporine; Prednisone; Everolimus; Cyclosporins; Basiliximab

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from Spain from July 2005 to July 2008. As per protocol amendment, data were analyzed together with data from study CRAD001A2423 (NCT00154284) and CRAD001A2423 (NCT00170807).

Arm/Group Title	Everolimus (Certican) With Cyclosporine (Neoral) Continuation	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal
Arm/Group Description	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Period Title: Overall Study
STARTED	59	55
Intent to Treat (ITT) Population	57	53
COMPLETED	52	42
NOT COMPLETED	7	13

Baseline Characteristics

Arm/Group Title	Everolimus (Certican) With Cyclosporine (Neoral) Continuation	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal	Total
Arm/Group Description	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Total of all reporting groups
Overall Participants	59	55	114
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.7 (11.62)	41.5 (12.27)	43.6 (12.07)
Sex: Female, Male (Count of Participants)
Female	18 30.5%	20 36.4%	38 33.3%
Male	41 69.5%	35 63.6%	76 66.7%

Outcome Measures

1. Primary Outcome

Title	Renal Function Measured by Calculated Glomerular Filtration Rate (GFR Calculated According to the Nankivell Formula)
Description	Nankivell's formula for calculated GFR is shown below: GFR [mL/min] = 6.7/C + W/4 - UREA/2 - 100/H2+ 35 (25 for females). Where W is body weight at specific visit [kg], H is height at specific visit [m], C is the serum concentration of creatinine [mmol/L], and UREA is the serum concentration of urea [mmol/L]. UREA was calculated from blood urea nitrogen (BUN) lab data by: UREA = 2.1441*BUN. If a GFR value from Nankivell formula was less than 10 [mL/min], then the value was assigned as 10 [mL/min].
Time Frame	At Month 3 and Month 12

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population.

Arm/Group Title	Everolimus (Certican) With Cyclosporine (Neoral) Continuation	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal
Arm/Group Description	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Measure Participants	57	53
GFR at 3 months (Pre-randomization)	68.5 (19.92)	69.2 (18.40)
GFR at 12 months	63.6 (14.61)	68.3 (15.13)

2. Secondary Outcome

Title	Number of Participants With Biopsy-proven Acute Rejection (BPAR) Episodes, Graft Loss, Death or Loss to Follow-up
Description	Renal biopsies were collected for all cases of suspected acute rejection. For these cases, regardless of initiation of anti-rejection treatment, a graft core biopsy had been performed within 48 hours. These biopsies were listed on the Kidney Allograft Biopsy eCRF and the results used for patient management for BPAR. Graft loss was defined as the allograft was presumed to be lost on the day the patient started dialysis and was not able to subsequently be removed from dialysis as well as re-transplant. BPAR, graft loss, death, or loss to follow-up was analyzed by means of frequency tables.
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population.

Arm/Group Title	Everolimus (Certican) With Cyclosporine (Neoral) Continuation	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal
Arm/Group Description	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Measure Participants	57	53
Biopsy-proven Acute Rejection (BPAR)	10 16.9%	10 18.2%
Graft Loss	0 0%	0 0%
Death	0 0%	0 0%
Loss to Follow-up	0 0%	0 0%

3. Secondary Outcome

Title	Serum Creatinine at Month 6 and 12
Description	serum creatinine summarized by mean and standard deviation
Time Frame	6 month and 12 months

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population.

Arm/Group Title	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal	Everolimus (Certican) With Cyclosporine (Neoral) Continuation
Arm/Group Description	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Measure Participants	53	57
6 Month	120.1 (31.22)	139.1 (47.03)
12 Month	123.0 (40.28)	135.6 (40.61)

4. Secondary Outcome

Title	Calculated Creatinine Clearance at 6 Month and 12 Month
Description	Creatinine clearance calculated by Cockcroft-Gault formula and summarized by mean, and standard deviation. Cockcroft-Gault formula to calculate Creatinine Clearance (CrCl[mL/min]) is shown below: CrCl[mL/min] = (140 - A) * W / (72 * C) * R. Where A is age at sample date [years], W is body weight at specific visit [kg], C is the serum concentration of creatinine [mg/dL], R = 1 if the patient is male and = 0.85 if female.
Time Frame	6 month and 12 months

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) population.

Arm/Group Title	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal	Everolimus (Certican) With Cyclosporine (Neoral) Continuation
Arm/Group Description	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
Measure Participants	53	57
6 Month	72.9 (19.34)	63.6 (19.65)
12 Month	72.3 (20.50)	65.6 (19.24)

Adverse Events

Arm/Group Title	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal		Everolimus (Certican) With Cyclosporine (Neoral) Continuation
Arm/Group Description	Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. Therefore, patients were randomized to cyclosporine withdrawal over a period of 1 month (±1 week) in study A2419 (NCT00154284) and over 3 months (±1 week) in study A2423 (NCT00170807). After randomization, final target trough range for everolimus was 8 - 12 ng/mL. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.		Patients were treated with everolimus and cyclosporine for 3 months post-transplantation. Everolimus (Certican) was administered orally, in two divided doses (b.i.d), and at the same time as Cyclosporine (Neoral). Everolimus (Certican) dose was adjusted in order to maintain a trough level between 3 and 8 ng/mL until randomization. After randomization the target trough range remained at 3 - 8 ng/mL in the cyclosporine (Neoral) continuation groups for a period of 9 months. Each patient was administered i.v. prednisone (or equivalent) pre- or intra-operatively according to center practice.
All Cause Mortality
	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal		Everolimus (Certican) With Cyclosporine (Neoral) Continuation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal		Everolimus (Certican) With Cyclosporine (Neoral) Continuation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/55 (29.1%)		14/59 (23.7%)
Cardiac disorders
Acute myocardial infarction	0/55 (0%)		1/59 (1.7%)
Gastrointestinal disorders
Diarrhoea	1/55 (1.8%)		1/59 (1.7%)
Stomatitis	1/55 (1.8%)		0/59 (0%)
Vomiting	1/55 (1.8%)		0/59 (0%)
General disorders
Pyrexia	1/55 (1.8%)		1/59 (1.7%)
Immune system disorders
Transplant rejection	0/55 (0%)		2/59 (3.4%)
Infections and infestations
Abdominal wall infection	1/55 (1.8%)		0/59 (0%)
Anal abscess	1/55 (1.8%)		0/59 (0%)
Appendiceal abscess	1/55 (1.8%)		0/59 (0%)
Appendicitis	1/55 (1.8%)		0/59 (0%)
Bronchitis	0/55 (0%)		1/59 (1.7%)
Enterocolitis infectious	1/55 (1.8%)		0/59 (0%)
Febrile infection	0/55 (0%)		1/59 (1.7%)
Gastroenteritis	2/55 (3.6%)		2/59 (3.4%)
Pneumonia	1/55 (1.8%)		1/59 (1.7%)
Pneumonia bacterial	1/55 (1.8%)		0/59 (0%)
Renal cyst infection	0/55 (0%)		1/59 (1.7%)
Sepsis	1/55 (1.8%)		2/59 (3.4%)
Soft tissue infection	1/55 (1.8%)		0/59 (0%)
Urinary tract infection	0/55 (0%)		3/59 (5.1%)
Injury, poisoning and procedural complications
Complications of transplanted kidney	1/55 (1.8%)		1/59 (1.7%)
Foot fracture	1/55 (1.8%)		0/59 (0%)
Renal lymphocele	0/55 (0%)		1/59 (1.7%)
Wound dehiscence	1/55 (1.8%)		0/59 (0%)
Investigations
Blood creatinine increased	1/55 (1.8%)		0/59 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	1/55 (1.8%)		0/59 (0%)
Hypovolaemia	1/55 (1.8%)		0/59 (0%)
Renal and urinary disorders
Calculus urinary	0/55 (0%)		1/59 (1.7%)
Haematuria	1/55 (1.8%)		0/59 (0%)
Hydronephrosis	0/55 (0%)		1/59 (1.7%)
Renal failure acute	3/55 (5.5%)		0/59 (0%)
Renal impairment	0/55 (0%)		2/59 (3.4%)
Reproductive system and breast disorders
Uterine haemorrhage	1/55 (1.8%)		0/59 (0%)
Vascular disorders
Haemorrhage	1/55 (1.8%)		0/59 (0%)
Lymphocele	1/55 (1.8%)		2/59 (3.4%)
Other (Not Including Serious) Adverse Events
	Everolimus (Certican) With Cyclosporine (Neoral) Withdrawal		Everolimus (Certican) With Cyclosporine (Neoral) Continuation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/55 (69.1%)		35/59 (59.3%)
Blood and lymphatic system disorders
Anaemia	5/55 (9.1%)		8/59 (13.6%)
Polycythaemia	3/55 (5.5%)		1/59 (1.7%)
Gastrointestinal disorders
Diarrhoea	3/55 (5.5%)		5/59 (8.5%)
General disorders
Oedema	6/55 (10.9%)		4/59 (6.8%)
Oedema peripheral	6/55 (10.9%)		4/59 (6.8%)
Pyrexia	4/55 (7.3%)		5/59 (8.5%)
Infections and infestations
Bronchitis	1/55 (1.8%)		3/59 (5.1%)
Gastroenteritis	3/55 (5.5%)		0/59 (0%)
Nasopharyngitis	7/55 (12.7%)		1/59 (1.7%)
Urinary tract infection	5/55 (9.1%)		9/59 (15.3%)
Metabolism and nutrition disorders
Dyslipidaemia	4/55 (7.3%)		2/59 (3.4%)
Hypercholesterolaemia	2/55 (3.6%)		6/59 (10.2%)
Hypertriglyceridaemia	2/55 (3.6%)		3/59 (5.1%)
Musculoskeletal and connective tissue disorders
Myalgia	0/55 (0%)		3/59 (5.1%)
Renal and urinary disorders
Proteinuria	4/55 (7.3%)		1/59 (1.7%)
Renal impairment	4/55 (7.3%)		4/59 (6.8%)
Skin and subcutaneous tissue disorders
Acne	4/55 (7.3%)		0/59 (0%)

Limitations/Caveats

This is a combined analysis using 81 patients randomized and treated in CRAD001A2419 with 33 randomized and treated in CRAD001A2423. This approach is reflected in the protocol amendments for each study, and the one clinical study report for both.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.