Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01528345
• Collaborator: (none)
• Enrollment: 97
• Locations: 67
• Arms: 2
• Duration (Months): 36
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This trial is designed to enroll postmenopausal patients with locally advanced or metastatic, HER2- and HR+ breast cancer not amenable to curative treatment by surgery or radiotherapy, and whose disease has progressed on or after prior endocrine therapy.

Patients must undergo molecular pre-screening prior to entry.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer	Drug: Dovitinib; Drug: Fulvestrant; Drug: Dovitinib Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double Blind, Placebo Controlled, Phase II Trial Evaluating the Safety and Efficacy of Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer That Have Evidence of Disease Progression on or After Prior Endocrine Therapy
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fulvestrant + Dovitinib active Fulvestrant in combination with the study drug Dovitinib.	Drug: Dovitinib; Active Dovitinib (in tablet form) taken orally at a dose of 500 mg (i.e., 5 x 100mg tablets) on a 5 days on/2 days off dosing schedule; Other Names: TKI258 ; Drug: Fulvestrant; Fulvestrant (in solution) injected intramuscularly at a dose of 500 mg once on Week 1 Day 1, Week 3 Day 1 and Week 5 Day 1 and subsequently once every 4 weeks on Day 1 of the week.
Placebo Comparator: Fulvestrant + Dovitinib placebo Fulvestrant in combination with a placebo matching Dovitinib.	Drug: Fulvestrant; Fulvestrant (in solution) injected intramuscularly at a dose of 500 mg once on Week 1 Day 1, Week 3 Day 1 and Week 5 Day 1 and subsequently once every 4 weeks on Day 1 of the week.; Drug: Dovitinib Placebo; Dovitinib Placebo (in tablet form) taken orally at a dose of 500 mg (i.e., 5 x 100mg tablets) on a 5 days on/2 days off dosing schedule

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) Based on Local Investigator Assessment [Every 8 weeks assessed up to 34 months]

   PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause and was assessed based on RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.

Secondary Outcome Measures

1. Overall Response Rate (ORR) [Every 8 weeks assessed up to 34 months]

   ORR was defined as the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR) as per RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.

2. Duration of Response (DOR) [From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 months]

   DOR was defined as time from the date of the first documented response (CR or PR) to the date of the first documented or death due to disease. If a patient does not have a progression event, DOR will be censored on the date of the last adequate tumor assessment.

3. Overall Survival (OS) Using Kaplan- Meier Method [From date of randomization to date of death from any cause whichever comes first, assessed up to 34 months]

   OS was defined as the time from the date of randomization to the date of death from any cause. If a patient is not known to have died at the date of analysis cut-off, the OS will be censored at the last date of contact.

4. Number of Participants With Adverse Events as a Measure of Safety [Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)]

   The type, frequency and severity of adverse events, laboratory values, and Electrocardiograms (ECGs) experienced by patients will be assessed according to Common Terminology Criteria for Adverse Events. The study enrollment was terminated early due to challenges in enrolling patients with FGF amplified status. See safety section for safety details.

5. Time to Worsening of ECOG Performance Status [Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)]

   Eastern Cooperative Oncology Group (ECOG) Performance Status (scales and criteria used by doctors and researchers to assess how a patient's disease is progressing and assess how the disease affects the daily living abilities of the patient.)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Postmenopausal women with HER2-, HR+ locally advanced or metastatic breast cancer

• Progression on or after endocrine treatment

• Measureable disease as per RECIST

• ECOG 0, 1 or 2

Exclusion Criteria:

• Evidence of CNS or leptomeningeal metastases

• Previous treatment with fulvestrant

• Previous chemotherapy for locally advanced or metastatic breast cancer

• Cirrhosis or chronic active/persistent hepatitis

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ironwood Cancer and Research Centers SC	Chandler	Arizona	United States	85224
2	Highlands Oncology Group Dept of Highlands Oncology Grp	Fayetteville	Arkansas	United States	72703
3	City of Hope National Medical Center COH 3	Duarte	California	United States	91010-3000
4	University of California San Diego - Moores Cancer Center Moores UCSD Cancer Ctr. SC-1	La Jolla	California	United States	92093-0658
5	Cedars Sinai Medical Center Samuel Oschin Cancer Center	Los Angeles	California	United States	90048
6	H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC	Tampa	Florida	United States	33612
7	Oncology Specialists, SC Lutheran General Advanced Care	Park Ridge	Illinois	United States	60068-0736
8	Indiana University Health Goshen Center for Cancer SC	Goshen	Indiana	United States	46526
9	Nebraska Methodist Hospital Estabrook Cancer Center	Omaha	Nebraska	United States	68114
10	Saint Barnabas Medical Center CancerCenter of Saint Barnabas	Livingston	New Jersey	United States	07039
11	ProHealth Care	Lake Success	New York	United States	11042
12	New York Oncology Hematology, P.C. Dept. of New York Oncology. PC	Troy	New York	United States	12180
13	Duke University Medical Center Duke (SC)	Durham	North Carolina	United States	27710
14	Cancer Centers of the Carolinas Dept. of CC of the Carolinas	Greenville	South Carolina	United States	29605
15	Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)	San Antonio	Texas	United States	78229
16	Virginia Cancer Specialists, PC Dept.ofFairfax SC	Fairfax	Virginia	United States	22031
17	Medical Oncology Associates, PS	Spokane	Washington	United States	99208
18	Wenatchee Valley Medical Center Wenatchee Valley	Wenatchee	Washington	United States	98801
19	Novartis Investigative Site	Rio Negro	Viedma	Argentina	8500
20	Novartis Investigative Site	Buenos Aires		Argentina	C1050AAK
21	Novartis Investigative Site	Cordoba		Argentina	X5006IKK
22	Novartis Investigative Site	Tucuman		Argentina	T4000IAK
23	Novartis Investigative Site	Salzburg		Austria	5020
24	Novartis Investigative Site	Wien		Austria	1090
25	Novartis Investigative Site	Leuven		Belgium	3000
26	Novartis Investigative Site	Wilrijk		Belgium	2610
27	Novartis Investigative Site	Salvador	BA	Brazil	40170-110
28	Novartis Investigative Site	Londrina	PR	Brazil	86015-520
29	Novartis Investigative Site	Porto Alegre	RS	Brazil	90610-000
30	Novartis Investigative Site	Sao Jose do Rio Preto	SP	Brazil	15090-000
31	Novartis Investigative Site	São Paulo	SP	Brazil	01317-002
32	Novartis Investigative Site	Besançon cedex		France	25030
33	Novartis Investigative Site	Bordeaux		France	33076
34	Novartis Investigative Site	Lille Cedex		France	59020
35	Novartis Investigative Site	Saint-Herblain Cédex		France	44805
36	Novartis Investigative Site	Thonon-les-Bains Cedex		France	74203
37	Novartis Investigative Site	Villejuif Cedex		France	94805
38	Novartis Investigative Site	Budapest		Hungary	1134
39	Novartis Investigative Site	Budapest		Hungary	1145
40	Novartis Investigative Site	Budapest		Hungary	H-1083
41	Novartis Investigative Site	Debrecen		Hungary	4032
42	Novartis Investigative Site	Gyor		Hungary	H-9023
43	Novartis Investigative Site	Szeged		Hungary	H-6720
44	Novartis Investigative Site	Szolnok		Hungary	H-5000
45	Novartis Investigative Site	Macerata	MC	Italy	62100
46	Novartis Investigative Site	Parma	PR	Italy	43100
47	Novartis Investigative Site	Sondrio	SO	Italy	23100
48	Novartis Investigative Site	Maastricht		Netherlands	6229 HX
49	Novartis Investigative Site	Rotterdam		Netherlands	3075 EA
50	Novartis Investigative Site	Surquillo	Lima	Peru	34
51	Novartis Investigative Site	Poznan		Poland	60-569
52	Novartis Investigative Site	Rzeszow		Poland	35-021
53	Novartis Investigative Site	Warszawa		Poland	02-781
54	Novartis Investigative Site	Warszawa		Poland	03-291
55	Novartis Investigative Site	Warszawa		Poland	04-125
56	Novartis Investigative Site	Ryazan	Russia	Russian Federation	390011
57	Novartis Investigative Site	St. Petersburg		Russian Federation	197758
58	Novartis Investigative Site	Cape Town		South Africa	7500
59	Novartis Investigative Site	Parktown		South Africa	2193
60	Novartis Investigative Site	Port Elizabeth		South Africa	6045
61	Novartis Investigative Site	Toledo	Castilla la Mancha	Spain	45071
62	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
63	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46010
64	Novartis Investigative Site	Madrid		Spain	28007
65	Novartis Investigative Site	Niaosong Township		Taiwan	83301
66	Novartis Investigative Site	Taichung		Taiwan	407
67	Novartis Investigative Site	Taipei		Taiwan	10048

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: NCT01528345
• Other Study ID Numbers: CTKI258A2210; 2011-001230-42
• First Posted: Feb 8, 2012
• Last Update Posted: Jul 11, 2016
• Last Verified: May 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Breast Cancer; HER2-, HR+; post-menopausal; Locally advanced or metastatic Breast Cancer (HER2-, HR+)
• Additional relevant MeSH terms: Breast Neoplasms; Fulvestrant

Study Results

Participant Flow

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.
Period Title: Overall Study
STARTED	47	50
COMPLETED	0	0
NOT COMPLETED	47	50

Baseline Characteristics

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo	Total
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.	Total of all reporting groups
Overall Participants	47	50	97
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	63.5 (9.02)	61.7 (9.51)	62.6 (9.27)
Sex: Female, Male (Count of Participants)
Female	47 100%	50 100%	97 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Based on Local Investigator Assessment
Description	PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause and was assessed based on RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.
Time Frame	Every 8 weeks assessed up to 34 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they wereassigned at randomization.

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.
Measure Participants	47	50
All patients (n: 30, 34)	5.5	5.5
FGF amplified patients (n: 9, 9)	10.9	5.5
FGF non-amplified patients (n: 21, 25)	5.5	5.5

2. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	ORR was defined as the percentage of patients with a best overall response of Complete Response (CR) or Partial Response (PR) as per RECIST v1.1. Responses include: Complete Response: Disappearance of all non-nodal target lesions; Partial Response: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; Progressive Disease: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline; Stable Disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.
Time Frame	Every 8 weeks assessed up to 34 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they were assigned at randomization.

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.
Measure Participants	47	50
All patients	27.7 58.9%	10.0 20%
FGF amplified patients	20.0 42.6%	12.5 25%
FGF non-amplified patients	31.3 66.6%	8.8 17.6%

3. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as time from the date of the first documented response (CR or PR) to the date of the first documented or death due to disease. If a patient does not have a progression event, DOR will be censored on the date of the last adequate tumor assessment.
Time Frame	From date of first documented efficacy response (CR or PR) to time of documented progression (PD) whichever comes first, assessed up to 24 months

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed as the study was terminated before duration of response could be analyzed.

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.
Measure Participants	0	0

4. Secondary Outcome

Title	Overall Survival (OS) Using Kaplan- Meier Method
Description	OS was defined as the time from the date of randomization to the date of death from any cause. If a patient is not known to have died at the date of analysis cut-off, the OS will be censored at the last date of contact.
Time Frame	From date of randomization to date of death from any cause whichever comes first, assessed up to 34 months

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they were assigned at randomization.

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.
Measure Participants	47	50
Median (95% Confidence Interval) [Months]	NA	25.9

5. Secondary Outcome

Title	Number of Participants With Adverse Events as a Measure of Safety
Description	The type, frequency and severity of adverse events, laboratory values, and Electrocardiograms (ECGs) experienced by patients will be assessed according to Common Terminology Criteria for Adverse Events. The study enrollment was terminated early due to challenges in enrolling patients with FGF amplified status. See safety section for safety details.
Time Frame	Screening, Week 2, Week 4 and approximately every 4 weeks during treatment period (approximately 34 months)

Outcome Measure Data

Analysis Population Description

Safety Set: Consisted of all patients who received at least one dose of any compound of the study treatment (dovitinib +fulvestrant or placebo+fulvestrant). Patients were analyzed according to the actual study treatment received. Actual treatment received was defined as the treatment the patient received at the first day of study medication.

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.
Measure Participants	47	50
Number [Participants]	47 100%	50 100%

6. Secondary Outcome

Title	Time to Worsening of ECOG Performance Status
Description	Eastern Cooperative Oncology Group (ECOG) Performance Status (scales and criteria used by doctors and researchers to assess how a patient's disease is progressing and assess how the disease affects the daily living abilities of the patient.)
Time Frame	Screening, Every 4 weeks during treatment period, and every 8 weeks during follow-up (approximately 9-12 months)

Outcome Measure Data

Analysis Population Description

This outcome measure was not analyzed as the study was terminated before time to worsening ECOG performance could be analyzed.

Arm/Group Title	Fulvestrant + Dovitinib Active	Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.	Fulvestrant in combination with a placebo matching Dovitinib.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Fulvestrant + Dovitinib Active		Fulvestrant + Dovitinib Placebo
Arm/Group Description	Fulvestrant in combination with the study drug Dovitinib.		Fulvestrant in combination with a placebo matching Dovitinib.
All Cause Mortality
	Fulvestrant + Dovitinib Active		Fulvestrant + Dovitinib Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Fulvestrant + Dovitinib Active		Fulvestrant + Dovitinib Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/47 (29.8%)		10/50 (20%)
Blood and lymphatic system disorders
THROMBOCYTOPENIA	1/47 (2.1%)		0/50 (0%)
Cardiac disorders
PERICARDIAL EFFUSION	1/47 (2.1%)		0/50 (0%)
Gastrointestinal disorders
CONSTIPATION	0/47 (0%)		1/50 (2%)
DIARRHOEA	0/47 (0%)		1/50 (2%)
LUMBAR HERNIA	1/47 (2.1%)		0/50 (0%)
OESOPHAGEAL VARICES HAEMORRHAGE	1/47 (2.1%)		0/50 (0%)
PANCREATITIS	0/47 (0%)		1/50 (2%)
VARICES OESOPHAGEAL	1/47 (2.1%)		0/50 (0%)
General disorders
DEVICE BREAKAGE	0/47 (0%)		1/50 (2%)
GENERAL PHYSICAL HEALTH DETERIORATION	1/47 (2.1%)		0/50 (0%)
HYPERPYREXIA	0/47 (0%)		1/50 (2%)
NON-CARDIAC CHEST PAIN	0/47 (0%)		1/50 (2%)
Hepatobiliary disorders
BILE DUCT OBSTRUCTION	0/47 (0%)		1/50 (2%)
HYPERBILIRUBINAEMIA	1/47 (2.1%)		0/50 (0%)
Infections and infestations
INFECTION	1/47 (2.1%)		0/50 (0%)
PNEUMONIA	1/47 (2.1%)		0/50 (0%)
TOOTH ABSCESS	0/47 (0%)		1/50 (2%)
Injury, poisoning and procedural complications
FEMUR FRACTURE	0/47 (0%)		1/50 (2%)
Metabolism and nutrition disorders
DEHYDRATION	1/47 (2.1%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
ARTHRITIS	1/47 (2.1%)		0/50 (0%)
BONE PAIN	1/47 (2.1%)		0/50 (0%)
SPINAL PAIN	0/47 (0%)		1/50 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CERVIX CARCINOMA	1/47 (2.1%)		0/50 (0%)
MALIGNANT MELANOMA	0/47 (0%)		1/50 (2%)
Nervous system disorders
ISCHAEMIC CEREBRAL INFARCTION	1/47 (2.1%)		0/50 (0%)
Respiratory, thoracic and mediastinal disorders
LARYNGOSPASM	0/47 (0%)		1/50 (2%)
PLEURAL EFFUSION	1/47 (2.1%)		1/50 (2%)
PULMONARY EMBOLISM	3/47 (6.4%)		1/50 (2%)
Skin and subcutaneous tissue disorders
PIGMENTATION DISORDER	1/47 (2.1%)		0/50 (0%)
Vascular disorders
DEEP VEIN THROMBOSIS	2/47 (4.3%)		0/50 (0%)
HYPERTENSIVE CRISIS	0/47 (0%)		1/50 (2%)
HYPOTENSION	0/47 (0%)		1/50 (2%)
PERIPHERAL ARTERY THROMBOSIS	1/47 (2.1%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Fulvestrant + Dovitinib Active		Fulvestrant + Dovitinib Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/47 (100%)		45/50 (90%)
Blood and lymphatic system disorders
ANAEMIA	9/47 (19.1%)		4/50 (8%)
LEUKOPENIA	3/47 (6.4%)		0/50 (0%)
NEUTROPENIA	7/47 (14.9%)		0/50 (0%)
Ear and labyrinth disorders
EAR PAIN	5/47 (10.6%)		0/50 (0%)
VERTIGO	6/47 (12.8%)		0/50 (0%)
Eye disorders
DRY EYE	5/47 (10.6%)		0/50 (0%)
LACRIMATION INCREASED	6/47 (12.8%)		0/50 (0%)
VISION BLURRED	3/47 (6.4%)		0/50 (0%)
Gastrointestinal disorders
ABDOMINAL DISTENSION	4/47 (8.5%)		3/50 (6%)
ABDOMINAL PAIN	8/47 (17%)		5/50 (10%)
ABDOMINAL PAIN UPPER	10/47 (21.3%)		3/50 (6%)
CONSTIPATION	8/47 (17%)		5/50 (10%)
DIARRHOEA	37/47 (78.7%)		15/50 (30%)
DRY MOUTH	5/47 (10.6%)		1/50 (2%)
DYSPEPSIA	12/47 (25.5%)		0/50 (0%)
GASTRITIS	3/47 (6.4%)		0/50 (0%)
NAUSEA	34/47 (72.3%)		11/50 (22%)
STOMATITIS	10/47 (21.3%)		2/50 (4%)
VOMITING	27/47 (57.4%)		4/50 (8%)
General disorders
ASTHENIA	18/47 (38.3%)		11/50 (22%)
FATIGUE	16/47 (34%)		13/50 (26%)
INFLUENZA LIKE ILLNESS	3/47 (6.4%)		2/50 (4%)
MALAISE	4/47 (8.5%)		1/50 (2%)
OEDEMA PERIPHERAL	3/47 (6.4%)		3/50 (6%)
PAIN	4/47 (8.5%)		0/50 (0%)
PYREXIA	6/47 (12.8%)		5/50 (10%)
Infections and infestations
CONJUNCTIVITIS	3/47 (6.4%)		3/50 (6%)
NASOPHARYNGITIS	3/47 (6.4%)		1/50 (2%)
URINARY TRACT INFECTION	2/47 (4.3%)		4/50 (8%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	15/47 (31.9%)		5/50 (10%)
ASPARTATE AMINOTRANSFERASE INCREASED	10/47 (21.3%)		4/50 (8%)
BLOOD ALKALINE PHOSPHATASE INCREASED	11/47 (23.4%)		1/50 (2%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED	9/47 (19.1%)		4/50 (8%)
LIPASE INCREASED	3/47 (6.4%)		3/50 (6%)
WEIGHT DECREASED	7/47 (14.9%)		3/50 (6%)
WEIGHT INCREASED	1/47 (2.1%)		3/50 (6%)
Metabolism and nutrition disorders
DECREASED APPETITE	13/47 (27.7%)		8/50 (16%)
HYPERGLYCAEMIA	3/47 (6.4%)		1/50 (2%)
HYPERKALAEMIA	3/47 (6.4%)		2/50 (4%)
HYPERTRIGLYCERIDAEMIA	8/47 (17%)		1/50 (2%)
HYPOCALCAEMIA	3/47 (6.4%)		1/50 (2%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	7/47 (14.9%)		9/50 (18%)
BACK PAIN	7/47 (14.9%)		9/50 (18%)
BONE PAIN	3/47 (6.4%)		4/50 (8%)
MUSCLE SPASMS	3/47 (6.4%)		1/50 (2%)
MUSCULAR WEAKNESS	4/47 (8.5%)		0/50 (0%)
MUSCULOSKELETAL PAIN	4/47 (8.5%)		3/50 (6%)
MYALGIA	5/47 (10.6%)		1/50 (2%)
PAIN IN EXTREMITY	9/47 (19.1%)		3/50 (6%)
SPINAL PAIN	3/47 (6.4%)		1/50 (2%)
Nervous system disorders
AGEUSIA	3/47 (6.4%)		0/50 (0%)
DIZZINESS	4/47 (8.5%)		2/50 (4%)
DYSGEUSIA	15/47 (31.9%)		1/50 (2%)
HEADACHE	17/47 (36.2%)		3/50 (6%)
PARAESTHESIA	2/47 (4.3%)		3/50 (6%)
SYNCOPE	5/47 (10.6%)		0/50 (0%)
Psychiatric disorders
INSOMNIA	6/47 (12.8%)		4/50 (8%)
Respiratory, thoracic and mediastinal disorders
COUGH	7/47 (14.9%)		6/50 (12%)
DYSPNOEA	8/47 (17%)		6/50 (12%)
OROPHARYNGEAL PAIN	3/47 (6.4%)		0/50 (0%)
Skin and subcutaneous tissue disorders
ALOPECIA	4/47 (8.5%)		1/50 (2%)
DERMATITIS ACNEIFORM	3/47 (6.4%)		0/50 (0%)
DRY SKIN	9/47 (19.1%)		2/50 (4%)
PRURITUS	3/47 (6.4%)		2/50 (4%)
RASH	16/47 (34%)		3/50 (6%)
Vascular disorders
HOT FLUSH	4/47 (8.5%)		3/50 (6%)
HYPERTENSION	13/47 (27.7%)		4/50 (8%)

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.