RECORD-4: Everolimus as Second-line Therapy in Metastatic Renal Cell Carcinoma

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01491672
• Collaborator: (none)
• Enrollment: 134
• Locations: 17
• Arm: 1
• Duration (Months): 42
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate everolimus as second-line therapy in patients with metastatic renal cell carcinoma. Each patient will be enrolled and stratified in one of three cohorts based upon their first-line therapy: 1) prior cytokines, 2) prior sunitinib, or 3) prior anti-VEGF therapy other than sunitinib.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Renal Cell Carcinoma	Drug: RAD001	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 134 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter Phase II Study to Examine the Efficacy and Safety of Everolimus as Second-line Therapy in the Treatment of Patients With Metastatic Renal Cell Carcinoma
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAD001 Participants, received RAD001 10 mg orally once daily.	Drug: RAD001; Study drug was supplied as 5 mg tablets in blister packs.; Other Names: Everolimus

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) - All Participants [20 months]

   PFS during second-line treatment was defined as the time from the date of enrollment to the date of the first documented disease progression or death due to any cause. The primary analysis of PFS was based on a local radiology review of CT scans and MRI collected until the participant experienced disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.

Secondary Outcome Measures

1. Duration of PFS for Each First-line Treatment Cohort [20 months]

   Duration of PFS during second-line treatment was defined as the time from the date of enrollment to the date of the first documented disease progression or death due to any cause. Participants' assessment was based on the local radiological data according to the RECIST 1.0 Criteria.

2. Overall Survival (OS) [28 months]

   OS was defined as the time from date of enrollment to date of death due to any cause.

3. Clinical Benefit Rate (CBR) [20 months]

   CBR was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) or stable disease based on the local radiological data according to the RECIST 1.0 criteria.

4. Objective Response Rate (ORR) [20 months]

   ORR was defined as the proportion of participants with best overall response of CR or PR based on the local radiological data according to the RECIST 1.0 Criteria

5. Duration of Response (DoR) [20 months]

   DoR was defined as the time from the first occurrence of PR or CR (as per local radiological review) until the date of the first documented disease progression or death due to underlying cancer.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Age ≥ 18 years old.

2. Patients with advanced renal cell carcinoma of a histological or cytological confirmation of clear cell (or with a component of clear cell) renal carcinoma that have previously progressed on or were intolerant to first-line therapy with sunitinib, sorafenib, pazopanib, axitinib, bevacizumab, or cytokine therapy.

3. Patients must have had prior nephrectomy (partial or total).

4. Patients with at least one measurable lesion at baseline as per the RECIST 1.0 criteria. If skin lesions are reported as target lesions, they should be documented (at baseline and at every physical exam) using color photography and a measuring device (such as a caliper) in clear focus to allow the size of the lesion(s) to be determined from the photograph.

5. Patients with a Karnofsky Performance Status ≥ 70%.

6. Adequate bone marrow function as shown by:

7. ANC ≥ 1.5 x 109/L,

8. Platelets ≥ 100 x 109/L,

9. Hemoglobin >9 g/dL

10. Adequate liver function as shown by:

11. Serum bilirubin ≤ 1.5 x ULN,

12. ALT and AST ≤ 2.5 x ULN. Patients with known liver metastases may enroll if their AST and ALT ≤ 5 x ULN,

13. INR < 1.3 (INR < 3 in patients treated with anticoagulants)

14. Adequate renal function: serum creatinine ≤ 2.0 x ULN.

15. Fasting serum cholesterol ≤300 mg/dl OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN.

16. Written informed consent obtained before any trial related activity and according to local guidelines.

Exclusion Criteria:

1. Patients with brain metastases.

2. Patients within 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal or intrapelvic), open biopsy, or significant traumatic injury to avoid wound healing complications.

Minor procedures and percutaneous biopsies or placement of vascular access device require 7 days prior to study entry.

1. Patients in anticipation of the need for major surgical procedure during the course of the study.

2. Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed up to 2 weeks prior to study treatment start).

3. Patients with a serious non-healing wound, ulcer, or bone fracture.

4. Patients with a history of seizure(s) not controlled with standard medical therapy.

5. Patients who have received more than one prior treatment regimen for metastatic renalcell carcinoma

6. Patients who have received adjuvant therapy for RCC

7. Patients who have previously received systemic mTOR inhibitors (eg, sirolimus, temsirolimus, everolimus)

8. Patients with a known hypersensitivity to everolimus or other rapamycins (eg, sirolimus, temsirolimus) or to its excipients.

9. History or clinical evidence of central nervous system (CNS) metastases.

10. Clinically significant gastrointestinal abnormalities including, but not limited to:

11. Malabsorption syndrome:

12. Major resection of the stomach or small bowel that could affect the absorption of study drug

13. Active peptic ulcer disease

14. Inflammatory bowel disease:

1. Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation ii. History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.

1. Patients with a known history of HIV seropositivity. Screening for HIV infection at baseline is not required.

2. Active bleeding diathesis

3. Uncontrolled diabetes mellitus as defined by fasting serum glucose > 2.0 x ULN.

4. Patients who have any severe and/or uncontrolled medical conditions such as:

5. unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction

≤ 6 months prior to enrollment, serious uncontrolled cardiac arrhythmia,

1. active or uncontrolled severe infection,

2. history of invasive fungal infections,

3. severe hepatic impairment (Child-Pugh class C),

4. severely impaired lung function

5. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA) ≤ 6 months before start of study treatment.

6. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.

7. Patients who have a history of another primary malignancy and off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix or breast, and localized cancer of the bladder (T1) and prostate (T1 - T2).

8. Female patients who are pregnant or nursing (lactating).

9. Adults of reproductive potential who are not using effective birth control methods.

Adequate contraceptives must be used throughout the trial and for 8 weeks after last study drug administration in female patients. Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to first administration of study drug.

1. Patients who are using other investigational agents or who had received investigational drugs ≤ 2 weeks prior to study treatment start. This should not include sunitinib, sorafenib, axitinib, pazopanib and cytokines.

2. Patients unwilling or unable to comply with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	NY	New York	United States	90033
2	Novartis Investigative Site	Rio Negro	Viedma	Argentina	8500
3	Novartis Investigative Site	Tucuman		Argentina	T4000
4	Novartis Investigative Site	Florianopolis	SC	Brazil	88034-000
5	Novartis Investigative Site	Barretos	SP	Brazil	14784-400
6	Novartis Investigative Site	São Paulo	SP	Brazil	01246-000
7	Novartis Investigative Site	São Paulo	SP	Brazil	01509-900
8	Novartis Investigative Site	Sofia		Bulgaria	1784
9	Novartis Investigative Site	Beijing	Beijing	China	100730
10	Novartis Investigative Site	Hangzhou	Zhejiang	China	310003
11	Novartis Investigative Site	Beijing		China	100021
12	Novartis Investigative Site	Guangzhou		China	510060
13	Novartis Investigative Site	Shanghai		China	200032
14	Novartis Investigative Site	Leningrad Region	Russia	Russian Federation	188663
15	Novartis Investigative Site	Moscow	Russia	Russian Federation	125284
16	Novartis Investigative Site	Nizhny Novgorod	Russia	Russian Federation	603001
17	Novartis Investigative Site	Obninsk	Russia	Russian Federation	249036

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01491672
• Other Study ID Numbers: CRAD001L2404; 2010-020447-13
• First Posted: Dec 14, 2011
• Last Update Posted: Jun 6, 2016
• Last Verified: Jun 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Metastatic Renal Cell Carcinoma; Second Line; Everolimus; RAD001
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Everolimus

Study Results

Participant Flow

Recruitment Details	This was an open-label study where all eligible participants were enrolled into one of 3 cohorts based upon prior first-line therapy.

Arm/Group Title	Prior Sunitinib	Other Prior Vascular Endothelial Growth Factor (VEGF)	Prior Cytokines
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.	Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.	Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
Period Title: Overall Study
STARTED	58	62	14
Safety Set	58	61	14
COMPLETED	2	2	3
NOT COMPLETED	56	60	11

Baseline Characteristics

Arm/Group Title	Prior Sunitinib	Other Prior Vascular Endothelial Growth Factor (VEGF)	Prior Cytokines	Total
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.	Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.	Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.	Total of all reporting groups
Overall Participants	58	62	14	134
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.0 (12.06)	56.5 (11.14)	60.3 (10.59)	56.7 (11.48)
Sex: Female, Male (Count of Participants)
Female	15 25.9%	22 35.5%	6 42.9%	43 32.1%
Male	43 74.1%	40 64.5%	8 57.1%	91 67.9%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS) - All Participants
Description	PFS during second-line treatment was defined as the time from the date of enrollment to the date of the first documented disease progression or death due to any cause. The primary analysis of PFS was based on a local radiology review of CT scans and MRI collected until the participant experienced disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) was used. It included all enrolled participants.

Arm/Group Title	All Participants
Arm/Group Description	All participants received RAD001 10 mg daily.
Measure Participants	134
Median (95% Confidence Interval) [months]	7.4

2. Secondary Outcome

Title	Duration of PFS for Each First-line Treatment Cohort
Description	Duration of PFS during second-line treatment was defined as the time from the date of enrollment to the date of the first documented disease progression or death due to any cause. Participants' assessment was based on the local radiological data according to the RECIST 1.0 Criteria.
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

The FAS was used. It included all enrolled participants.

Arm/Group Title	Prior Sunitinib	Other Prior Vascular Endothelial Growth Factor (VEGF)	Prior Cytokines
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.	Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.	Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
Measure Participants	58	62	14
Median (95% Confidence Interval) [months]	5.6	7.8	12.9

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from date of enrollment to date of death due to any cause.
Time Frame	28 months

Outcome Measure Data

Analysis Population Description

The FAS was used. It included all enrolled participants.

Arm/Group Title	Prior Sunitinib	Other Prior Vascular Endothelial Growth Factor (VEGF)	Prior Cytokines	All Participants
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.	Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.	Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.	All participants received RAD001 10 mg daily.
Measure Participants	58	62	14	134
Median (95% Confidence Interval) [months]	23.8	17.2	NA	23.8

4. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
Description	CBR was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) or stable disease based on the local radiological data according to the RECIST 1.0 criteria.
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

The FAS was used. It included all enrolled participants.

Arm/Group Title	Prior Sunitinib	Other Prior Vascular Endothelial Growth Factor (VEGF)	Prior Cytokines	All Participants
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.	Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.	Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.	All participants received RAD001 10 mg daily.
Measure Participants	58	62	14	134
Number [Participants]	41 70.7%	48 77.4%	11 78.6%	100 74.6%

5. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	ORR was defined as the proportion of participants with best overall response of CR or PR based on the local radiological data according to the RECIST 1.0 Criteria
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

The FAS was used. It included all enrolled participants.

Arm/Group Title	Prior Sunitinib	Other Prior Vascular Endothelial Growth Factor (VEGF)	Prior Cytokines	All Participants
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.	Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.	Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.	All participants received RAD001 10 mg daily.
Measure Participants	58	62	14	134
Number [Participants]	4 6.9%	3 4.8%	3 21.4%	10 7.5%

6. Secondary Outcome

Title	Duration of Response (DoR)
Description	DoR was defined as the time from the first occurrence of PR or CR (as per local radiological review) until the date of the first documented disease progression or death due to underlying cancer.
Time Frame	20 months

Outcome Measure Data

Analysis Population Description

The FAS was considered for this analysis. The FAS included all enrolled participants. Only participants who achieved a CR or PR were analyzed. Therefore, actual n=4,3,3,10.

Arm/Group Title	Prior Sunitinib	Other Prior Vascular Endothelial Growth Factor (VEGF)	Prior Cytokines	All Participants
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.	Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.	Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.	All participants received RAD001 10 mg daily.
Measure Participants	58	62	14	134
Median (95% Confidence Interval) [months]	10.8	7.4	9.2	9.2

Adverse Events

Arm/Group Title	Prior Sunitinib		Other Prior Anti VEGF		Prior Cytokines
Arm/Group Description	Participants, who received prior sunitinib therapy, received RAD001 10 mg orally once daily.		Participants, who received prior anti-VEGF other than sunitinib, received RAD001 10 mg orally once daily.		Participants, who received prior cytokine therapy, received RAD001 10 mg orally once daily.
All Cause Mortality
	Prior Sunitinib		Other Prior Anti VEGF		Prior Cytokines
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Prior Sunitinib		Other Prior Anti VEGF		Prior Cytokines
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/58 (22.4%)		16/61 (26.2%)		3/14 (21.4%)
Blood and lymphatic system disorders
Anaemia	0/58 (0%)		2/61 (3.3%)		0/14 (0%)
Cardiac disorders
Cardiac failure	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Cardiac failure congestive	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Gastrointestinal disorders
Abdominal pain	2/58 (3.4%)		0/61 (0%)		0/14 (0%)
Constipation	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Gastritis	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Gastrointestinal haemorrhage	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
General disorders
Multi-organ failure	1/58 (1.7%)		2/61 (3.3%)		0/14 (0%)
Sudden death	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Infections and infestations
Anal abscess	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Appendicitis	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Cellulitis	2/58 (3.4%)		0/61 (0%)		0/14 (0%)
Lobar pneumonia	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Necrotising fasciitis	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Perirectal abscess	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Pneumonia	2/58 (3.4%)		0/61 (0%)		0/14 (0%)
Sepsis	2/58 (3.4%)		1/61 (1.6%)		0/14 (0%)
Injury, poisoning and procedural complications
Concussion	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Femur fracture	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Laceration	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Lower limb fracture	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Lumbar vertebral fracture	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Wound complication	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Investigations
X-ray with contrast upper gastrointestinal tract abnormal	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/58 (1.7%)		1/61 (1.6%)		0/14 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Pathological fracture	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Renal neoplasm	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Nervous system disorders
Cerebral haemorrhage	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Hypertensive encephalopathy	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Seizure	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Psychiatric disorders
Disorientation	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Renal and urinary disorders
Acute kidney injury	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/58 (1.7%)		1/61 (1.6%)		0/14 (0%)
Hydrothorax	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Interstitial lung disease	1/58 (1.7%)		2/61 (3.3%)		0/14 (0%)
Pleural effusion	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Pleural fibrosis	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Pulmonary embolism	1/58 (1.7%)		0/61 (0%)		0/14 (0%)
Respiratory failure	1/58 (1.7%)		3/61 (4.9%)		0/14 (0%)
Vascular disorders
Hypertension	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Thrombosis	0/58 (0%)		1/61 (1.6%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Prior Sunitinib		Other Prior Anti VEGF		Prior Cytokines
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/58 (48.3%)		33/61 (54.1%)		12/14 (85.7%)
Blood and lymphatic system disorders
Anaemia	8/58 (13.8%)		8/61 (13.1%)		4/14 (28.6%)
Iron deficiency anaemia	0/58 (0%)		1/61 (1.6%)		1/14 (7.1%)
Gastrointestinal disorders
Diarrhoea	5/58 (8.6%)		1/61 (1.6%)		0/14 (0%)
Mouth ulceration	2/58 (3.4%)		2/61 (3.3%)		1/14 (7.1%)
Stomatitis	5/58 (8.6%)		8/61 (13.1%)		5/14 (35.7%)
General disorders
Fatigue	0/58 (0%)		2/61 (3.3%)		1/14 (7.1%)
General physical health deterioration	3/58 (5.2%)		1/61 (1.6%)		0/14 (0%)
Pyrexia	2/58 (3.4%)		5/61 (8.2%)		1/14 (7.1%)
Infections and infestations
Localised infection	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Tonsillitis	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Upper respiratory tract infection	3/58 (5.2%)		1/61 (1.6%)		0/14 (0%)
Investigations
Alanine aminotransferase increased	2/58 (3.4%)		0/61 (0%)		1/14 (7.1%)
Blood creatinine increased	1/58 (1.7%)		1/61 (1.6%)		1/14 (7.1%)
Blood pressure increased	0/58 (0%)		1/61 (1.6%)		1/14 (7.1%)
Blood uric acid increased	0/58 (0%)		1/61 (1.6%)		1/14 (7.1%)
Hepatitis B DNA increased	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Lymphocyte count decreased	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Weight decreased	2/58 (3.4%)		0/61 (0%)		1/14 (7.1%)
Metabolism and nutrition disorders
Diabetes mellitus	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Hypercholesterolaemia	3/58 (5.2%)		3/61 (4.9%)		2/14 (14.3%)
Hyperglycaemia	3/58 (5.2%)		5/61 (8.2%)		1/14 (7.1%)
Hypertriglyceridaemia	3/58 (5.2%)		4/61 (6.6%)		2/14 (14.3%)
Renal and urinary disorders
Proteinuria	4/58 (6.9%)		0/61 (0%)		0/14 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	2/58 (3.4%)		4/61 (6.6%)		0/14 (0%)
Oropharyngeal pain	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Pneumonitis	1/58 (1.7%)		4/61 (6.6%)		1/14 (7.1%)
Pneumothorax	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Dry skin	0/58 (0%)		0/61 (0%)		1/14 (7.1%)
Vascular disorders
Hypertension	2/58 (3.4%)		1/61 (1.6%)		1/14 (7.1%)

Limitations/Caveats

[Not Specified]

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 or disclosure of trial results in their entirety.