ENESTg1: A Study of Nilotinib Versus Imatinib in GIST Patients

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00785785
• Collaborator: (none)

Study Details

Study Description

Brief Summary

This study will evaluate efficacy and safety of nilotinib versus imatinib in adult patients with unresectable or metastatic gastrointestinal stromal tumors (GIST).

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Stromal Tumor (GIST)	Drug: Nilotinib (AMN107); Drug: imatinib (STI571)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 644 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Open Label, Multi-center Phase III Study to Evaluate the Efficacy and Safety of Nilotinib Versus Imatinib in Adult Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors (GIST)
• Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nilotinib nilotinib 400 mg twice a day	Drug: Nilotinib (AMN107)
Active Comparator: Imatinib imatinib 400 mg once daily	Drug: imatinib (STI571); Other Names: Glivec/Gleevec

Outcome Measures

Primary Outcome Measures

1. Time to Progression Free Survival (PFS) [up to month 37]

   PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically confirmed diagnosis of GIST which is unresectable and/or metastatic and either:

• have not received any prior anti-neoplastic therapy other than adjuvant imatinib. Note: newly diagnosed patients may have received up to 14 days of treatment with imatinib for disease management while awaiting entry to the study or

• recurrent GIST after stopping adjuvant treatment with imatinib and no subsequent treatment with any other therapies.

1. At least one measurable site of disease on CT/MRI scan

2. Performance status ≤ 2 (capable of self-care but unable to carry out any work)

3. Normal organ, electrolyte and marrow function

Exclusion Criteria:

1. Any prior anti-neoplastic therapy with the exception of patients who have received adjuvant imatinib or patients with newly diagnosed metastatic/ unresectable GIST whose disease requires therapy while awaiting entry to the study.

2. Disease progression during adjuvant therapy with imatinib

3. History of active malignancy (other than GIST) within 10 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ.

4. Impaired cardiac function

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Hematology and Oncology Associates	Birmingham	Alabama	United States	35205
2	Northern Arizona Hematology/Oncology Associates, P.C. Dept. of No. AZ Hem-Onc	Flagstaff	Arizona	United States	86001
3	City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(4)	Duarte	California	United States	91010-3000
4	City of Hope National Medical Center Regulatory Document	Duarte	California	United States	91010-3000
5	University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (2)	La Jolla	California	United States	92093-0658
6	University of California at Los Angeles GI Oncology Program	Los Angeles	California	United States	90095
7	Stanford University Medical Center Stanford Cancer Center	Stanford	California	United States	94304
8	University of Colorado Dept. of Univ. of Colorado	Aurora	Colorado	United States	80045
9	Rocky Mountain Cancer Centers Dept. of Rocky Mountain Cancer	Greenwood Village	Colorado	United States
10	Washington Hospital Center Wash Hospital	Washington	District of Columbia	United States	20010
11	Ocala Oncology Center Dept. of Ocala Oncology Center	Ocala	Florida	United States	34474
12	Kootenai Medical Center Dept.ofKootenai Med.Ctr.	Coeur d'Alene	Idaho	United States	83814
13	Northwestern University Clinical Research Office (2)	Chicago	Illinois	United States	60611
14	Dana Farber Cancer Institute Centerfor Sarcoma&BoneOncology	Boston	Massachusetts	United States	02215
15	University of Michigan Comprehensive Cancer Center DeptofMichiganCancerCenter(6)	Ann Arbor	Michigan	United States	48109-0944
16	Minnesota Oncology Hematology, P.A. SC	Minneapolis	Minnesota	United States	55404
17	Mayo Clinic - Rochester Division of Hematology	Rochester	Minnesota	United States	55905
18	New York Oncology Hematology, P.C. NYOH Amsterdam	Troy	New York	United States	12180
19	New York Oncology Hematology, P.C. NYOH@AlbanyMedicalCenter(2)	Troy	New York	United States	12180
20	University of Pennsylvania Medical Center CAMN107G2301	Philadelphia	Pennsylvania	United States	19104-4283
21	Vanderbilt Univeristy Ingram Cancer Ctr.	Nashville	Tennessee	United States	37232
22	Texas Oncology, P.A. Tex Onc (2)	Bedford	Texas	United States	76022
23	Texas Oncology Wichita Falls	Dallas	Texas	United States	75246
24	University of Texas Southwestern Medical Center DeptofSimmons Cancer Center(3)	Dallas	Texas	United States	75390-8527
25	University of Texas/MD Anderson Cancer Center Dept. of MD Anderson (13)	Houston	Texas	United States	77030-4009
26	Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio(2)	San Antonio	Texas	United States	78229
27	Tyler Cancer Center Dept.ofTylerCancerCtr. (2)	Tyler	Texas	United States	75702
28	University of Utah / Huntsman Cancer Institute Dept.ofHuntsmanCancerInst.(3)	Salt Lake City	Utah	United States	84112
29	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1426ANZ
30	Novartis Investigative Site	Rosario	Santa Fe	Argentina	S2000PBH
31	Novartis Investigative Site	Buenos Aires		Argentina	C1264AAA
32	Novartis Investigative Site	Innsbruck	Tyrol	Austria	6020
33	Novartis Investigative Site	Graz		Austria	8036
34	Novartis Investigative Site	Leoben		Austria	A-8700
35	Novartis Investigative Site	Wels		Austria	4600
36	Novartis Investigative Site	Wien		Austria	A-1090
37	Novartis Investigative Site	Uberlândia	MG	Brazil	38408-150
38	Novartis Investigative Site	Florianopolis	SC	Brazil	88034-000
39	Novartis Investigative Site	Campinas	SP	Brazil	13083-970
40	Novartis Investigative Site	São Paulo	SP	Brazil	04023-900
41	Novartis Investigative Site	Sofia		Bulgaria	1784
42	Novartis Investigative Site	Varna		Bulgaria	9010
43	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 4E6
44	Novartis Investigative Site	Halifax	Nova Scotia	Canada	B3H 1V7
45	Novartis Investigative Site	Hamilton	Ontario	Canada	L8V 5C2
46	Novartis Investigative Site	Ottawa	Ontario	Canada	K1H 8L6
47	Novartis Investigative Site	Toronto	Ontario	Canada	M5G1X5
48	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
49	Novartis Investigative Site	Montreal	Quebec	Canada	H3A 1A1
50	Novartis Investigative Site	Quebec		Canada	G1R 2J6
51	Novartis Investigative Site	Beijing	Beijing	China	100730
52	Novartis Investigative Site	Nanjing	Jiangsu	China	210002
53	Novartis Investigative Site	Beijing		China	100036
54	Novartis Investigative Site	Guangzhou		China	510060
55	Novartis Investigative Site	Shanghai		China	200032
56	Novartis Investigative Site	Shanghai		China	200433
57	Novartis Investigative Site	Pereira		Colombia
58	Novartis Investigative Site	Olomouc		Czech Republic	775 20
59	Novartis Investigative Site	Herlev		Denmark	DK-2730
60	Novartis Investigative Site	Århus C		Denmark	DK-8000
61	Novartis Investigative Site	Alexandria		Egypt
62	Novartis Investigative Site	Cairo		Egypt
63	Novartis Investigative Site	Bordeaux		France	33076
64	Novartis Investigative Site	Chambray-lès-Tours		France	37170
65	Novartis Investigative Site	Lyon Cedex		France	69373
66	Novartis Investigative Site	Marseille Cedex 05		France	13385
67	Novartis Investigative Site	Paris Cedex 13		France	75651
68	Novartis Investigative Site	Saint-Herblain Cédex		France	44805
69	Novartis Investigative Site	Toulouse Cedex 4		France	31054
70	Novartis Investigative Site	Vandoeuvre les Nancy		France	54511
71	Novartis Investigative Site	Villejuif Cedex		France	94805
72	Novartis Investigative Site	Bad Saarow		Germany	15526
73	Novartis Investigative Site	Duesseldorf		Germany	40479
74	Novartis Investigative Site	Essen		Germany	45122
75	Novartis Investigative Site	Hannover		Germany	30625
76	Novartis Investigative Site	Mannheim		Germany	68167
77	Novartis Investigative Site	Muenchen		Germany	81377
78	Novartis Investigative Site	Weiden		Germany	92637
79	Novartis Investigative Site	Hong Kong SAR		Hong Kong
80	Novartis Investigative Site	Budapest		Hungary	1062
81	Novartis Investigative Site	Budapest		Hungary	1097
82	Novartis Investigative Site	Haifa		Israel	3525408
83	Novartis Investigative Site	Ramat Gan		Israel	5266202
84	Novartis Investigative Site	Bologna	BO	Italy	40138
85	Novartis Investigative Site	San Giovanni Rotondo	FG	Italy	71013
86	Novartis Investigative Site	Firenze	FI	Italy	50134
87	Novartis Investigative Site	Genova	GE	Italy	16132
88	Novartis Investigative Site	Milano	MI	Italy	20133
89	Novartis Investigative Site	Modena	MO	Italy	41100
90	Novartis Investigative Site	Palermo	PA	Italy	90127
91	Novartis Investigative Site	Aviano	PN	Italy	33081
92	Novartis Investigative Site	Candiolo	TO	Italy	10060
93	Novartis Investigative Site	Torino	TO	Italy	10153
94	Novartis Investigative Site	Nagoya	Aichi	Japan	464-8681
95	Novartis Investigative Site	Kashiwa	Chiba	Japan	277-8577
96	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	812-8582
97	Novartis Investigative Site	Sapporo-city	Hokkaido	Japan	060-8648
98	Novartis Investigative Site	Yokohama	Kanagawa	Japan	241-8515
99	Novartis Investigative Site	Kumamoto City	Kumamoto	Japan	860-8556
100	Novartis Investigative Site	Sendai-city	Miyagi	Japan	980-8574
101	Novartis Investigative Site	Niigata-city	Niigata	Japan	951-8520
102	Novartis Investigative Site	Kurashiki	Okayama	Japan	701-0192
103	Novartis Investigative Site	Suita-city	Osaka	Japan	565-0871
104	Novartis Investigative Site	Sunto-gun	Shizuoka	Japan	411-8777
105	Novartis Investigative Site	Chuo-ku	Tokyo	Japan	104-0045
106	Novartis Investigative Site	Gifu		Japan	501-1194
107	Novartis Investigative Site	Osaka		Japan	540-0006
108	Novartis Investigative Site	Toyama		Japan	930-0194
109	Novartis Investigative Site	Suwon	Gyeonggi-do	Korea, Republic of	443-380
110	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	05505
111	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06351
112	Novartis Investigative Site	México	Distrito Federal	Mexico	14080
113	Novartis Investigative Site	León	Guanajuato	Mexico	37000
114	Novartis Investigative Site	Chihuahua		Mexico	31000
115	Novartis Investigative Site	Leiden		Netherlands	2300 RC
116	Novartis Investigative Site	Oslo		Norway	NO-0310
117	Novartis Investigative Site	Kraków		Poland	31-501
118	Novartis Investigative Site	Warszawa		Poland	02-781
119	Novartis Investigative Site	Craiova	Dolj	Romania	200535
120	Novartis Investigative Site	Bucharest		Romania	022328
121	Novartis Investigative Site	Cluj-Napoca		Romania	3400
122	Novartis Investigative Site	Iasi		Romania	700106
123	Novartis Investigative Site	Kazan	Tatarstan Republic	Russian Federation	420029
124	Novartis Investigative Site	Ekaterinburg		Russian Federation	620036
125	Novartis Investigative Site	Moscow		Russian Federation	115478
126	Novartis Investigative Site	St. Petersburg		Russian Federation	198255
127	Novartis Investigative Site	Singapore		Singapore	119228
128	Novartis Investigative Site	Singapore		Singapore	169610
129	Novartis Investigative Site	Bratislava	Slovak Republic	Slovakia	83310
130	Novartis Investigative Site	Cape Town		South Africa	7500
131	Novartis Investigative Site	Johannesburg		South Africa	2199
132	Novartis Investigative Site	Pretoria		South Africa	0001
133	Novartis Investigative Site	Pretoria		South Africa	0002
134	Novartis Investigative Site	Pretoria		South Africa	0027
135	Novartis Investigative Site	Oviedo	Asturias	Spain	33006
136	Novartis Investigative Site	Sabadell	Barcelona	Spain	08208
137	Novartis Investigative Site	Barcelona		Spain	08041
138	Novartis Investigative Site	Madrid		Spain	28046
139	Novartis Investigative Site	Goteborg		Sweden	SE-413 45
140	Novartis Investigative Site	Linköping		Sweden	SE-581 85
141	Novartis Investigative Site	Lund		Sweden	SE-221 85
142	Novartis Investigative Site	Stockholm		Sweden	SE-171 76
143	Novartis Investigative Site	Umeå		Sweden	SE-901 85
144	Novartis Investigative Site	Uppsala		Sweden	SE-751 85
145	Novartis Investigative Site	Taipei	Taiwan, ROC	Taiwan	112
146	Novartis Investigative Site	Lin-Kou		Taiwan	33305
147	Novartis Investigative Site	Niaosong Township		Taiwan	83301
148	Novartis Investigative Site	Taipei		Taiwan	10002
149	Novartis Investigative Site	Bangkok		Thailand	10330
150	Novartis Investigative Site	Bangkok		Thailand	10700
151	Novartis Investigative Site	Khon Kaen		Thailand	40002
152	Novartis Investigative Site	Songkla		Thailand	90110
153	Novartis Investigative Site	Adana		Turkey	01330
154	Novartis Investigative Site	Ankara		Turkey	06100
155	Novartis Investigative Site	Ankara		Turkey	06500
156	Novartis Investigative Site	Balcova / Izmir		Turkey	35340
157	Novartis Investigative Site	Izmir		Turkey	35040
158	Novartis Investigative Site	Kartal		Turkey	34890
159	Novartis Investigative Site	Cambridge		United Kingdom	CB2 2QQ
160	Novartis Investigative Site	Glasgow		United Kingdom	G12 0YN
161	Novartis Investigative Site	London		United Kingdom	NW1 2BU
162	Novartis Investigative Site	London		United Kingdom	SW3 6JJ
163	Novartis Investigative Site	Manchester		United Kingdom	M20 4BX
164	Novartis Investigative Site	Newcastle-upon-Tyne		United Kingdom	NE7 7DN
165	Novartis Investigative Site	Caracas	Distrito Capital	Venezuela	1010

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00785785
• Other Study ID Numbers: CAMN107G2301; 2008-004758-34
• First Posted: Nov 5, 2008
• Last Update Posted: Jun 16, 2016
• Last Verified: May 1, 2016

• Keywords provided by Novartis Pharmaceuticals: Unresectable GIST; metastatic GIST; nilotinib; AMN107; imatinib; STI571
• Additional relevant MeSH terms: Gastrointestinal Stromal Tumors; Imatinib Mesylate

Study Results

Participant Flow

Arm/Group Title	Imatinib First, Then Nilotinib	Nilotinib First, Then Imatinib
Arm/Group Description	patients were on imatinib 400mg once daily in the core phase and then crossed over to nilotinib 400 mg twice a day in the extension phase	patients were on nilotinib 400 mg twice a day in the core phase and then crossed over to in the extension phase imatinib 400mg once daily
Period Title: Core Phase up to 36 Months
STARTED	324	320
COMPLETED	0	0
NOT COMPLETED	324	320
Period Title: Core Phase up to 36 Months
STARTED	39	125
COMPLETED	0	0
NOT COMPLETED	39	125

Baseline Characteristics

Arm/Group Title	Imatinib First, Then Nilotinib	Nilotinib First, Then Imatinib	Total
Arm/Group Description	patients were on imatinib 400mg once daily in the core phase and then crossed over to nilotinib 400 mg twice a day in the extension phase	patients were on nilotinib 400 mg twice a day in the core phase and then crossed over to in the extension phase imatinib 400mg once daily	Total of all reporting groups
Overall Participants	324	320	644
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.4 (12.91)	57.3 (12.63)	57.35 (12.77)
Sex: Female, Male (Count of Participants)
Female	145 44.8%	133 41.6%	278 43.2%
Male	179 55.2%	187 58.4%	366 56.8%

Outcome Measures

1. Primary Outcome

Title	Time to Progression Free Survival (PFS)
Description	PFS was defined as the time from the date of start of treatment to the date of the first documented progression or death due to any cause. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	up to month 37

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) consists of all randomized patients for the Core Phase.

Arm/Group Title	Nilotinib	Imatinib
Arm/Group Description	nilotinib 400 mg twice a day	imatinib 400 mg once daily
Measure Participants	324	320
Median (Full Range) [months]	25.9	29.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nilotinib, Imatinib
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0081
	Comments
	Method	Hazard Ratio
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.466
	Confidence Interval	(2-Sided) 95%; 1.104 to 1.945
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Nilotinib		Imatinib		Crossover Nilotinib		Crossover Imatinib
Arm/Group Description	Exposure to Nilotinib only		Exposure to Imatinib only		exposure to imatinib and then nilotinib		exposure to nilotinib and then imatinib
All Cause Mortality
	Nilotinib		Imatinib		Crossover Nilotinib		Crossover Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Nilotinib		Imatinib		Crossover Nilotinib		Crossover Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/321 (24.9%)		85/316 (26.9%)		15/39 (38.5%)		26/125 (20.8%)
Blood and lymphatic system disorders
Anaemia	6/321 (1.9%)		3/316 (0.9%)		2/39 (5.1%)		3/125 (2.4%)
Febrile neutropenia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Neutropenia	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Thrombocytopenia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Cardiac disorders
Acute myocardial infarction	2/321 (0.6%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Angina pectoris	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Angina unstable	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Arrhythmia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Atrial fibrillation	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Cardiac arrest	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Cardiac failure	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Cardiac failure congestive	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Cardio-respiratory arrest	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Mitral valve stenosis	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Myocardial infarction	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Palpitations	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Pericardial effusion	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Supraventricular tachycardia	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Congenital, familial and genetic disorders
Dermoid cyst	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Gastrointestinal disorders
Abdominal distension	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		1/125 (0.8%)
Abdominal hernia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Abdominal mass	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Abdominal pain	15/321 (4.7%)		12/316 (3.8%)		4/39 (10.3%)		3/125 (2.4%)
Abdominal pain upper	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Anal fissure	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Anal fistula	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Ascites	2/321 (0.6%)		1/316 (0.3%)		0/39 (0%)		2/125 (1.6%)
Colonic fistula	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		0/125 (0%)
Constipation	3/321 (0.9%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Diarrhoea	1/321 (0.3%)		4/316 (1.3%)		0/39 (0%)		2/125 (1.6%)
Faecaloma	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		1/125 (0.8%)
Gastric ulcer	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Gastric ulcer haemorrhage	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Gastritis	2/321 (0.6%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Gastritis haemorrhagic	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Gastrointestinal haemorrhage	5/321 (1.6%)		5/316 (1.6%)		1/39 (2.6%)		0/125 (0%)
Gastrointestinal obstruction	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Gastrooesophageal reflux disease	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Haematemesis	1/321 (0.3%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Haematochezia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Haemorrhoids	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Ileus	2/321 (0.6%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Intestinal obstruction	4/321 (1.2%)		2/316 (0.6%)		1/39 (2.6%)		3/125 (2.4%)
Intestinal perforation	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Intra-abdominal haemorrhage	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Jejunal perforation	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Large intestinal stenosis	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Mechanical ileus	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Nausea	2/321 (0.6%)		2/316 (0.6%)		0/39 (0%)		1/125 (0.8%)
Peptic ulcer	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Small intestinal haemorrhage	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		0/125 (0%)
Subileus	2/321 (0.6%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Upper gastrointestinal haemorrhage	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Vomiting	5/321 (1.6%)		3/316 (0.9%)		1/39 (2.6%)		4/125 (3.2%)
General disorders
Asthenia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Death	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Disease progression	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		1/125 (0.8%)
Face oedema	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Fatigue	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		1/125 (0.8%)
General physical health deterioration	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Generalised oedema	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Multi-organ failure	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		1/125 (0.8%)
Oedema mucosal	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Oedema peripheral	1/321 (0.3%)		3/316 (0.9%)		1/39 (2.6%)		0/125 (0%)
Pain	0/321 (0%)		0/316 (0%)		2/39 (5.1%)		1/125 (0.8%)
Performance status decreased	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Pyrexia	2/321 (0.6%)		6/316 (1.9%)		0/39 (0%)		3/125 (2.4%)
Hepatobiliary disorders
Bile duct obstruction	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Cholangitis	2/321 (0.6%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Hepatic failure	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Hepatic function abnormal	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Hepatic pain	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		0/125 (0%)
Hyperbilirubinaemia	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Jaundice	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Jaundice cholestatic	1/321 (0.3%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Portal hypertension	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Immune system disorders
Hypersensitivity	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Infections and infestations
Abdominal infection	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Abdominal wall abscess	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Appendicitis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Bacterial sepsis	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Bronchitis	0/321 (0%)		1/316 (0.3%)		1/39 (2.6%)		0/125 (0%)
Cellulitis	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Ear infection	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Eye infection	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Gastroenteritis	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Helicobacter gastritis	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Infection	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Infectious pleural effusion	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Lung infection	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Periodontitis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Peritonitis	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Pneumonia	3/321 (0.9%)		4/316 (1.3%)		1/39 (2.6%)		1/125 (0.8%)
Post procedural infection	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Postoperative wound infection	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		0/125 (0%)
Respiratory tract infection	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Sepsis	2/321 (0.6%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Septic shock	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Upper respiratory tract infection	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Urinary tract infection	4/321 (1.2%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Viral infection	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Fall	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Femur fracture	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Fracture	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Multiple fractures	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Overdose	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Post procedural bile leak	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Procedural pain	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Thermal burn	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Transfusion reaction	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Investigations
Alanine aminotransferase increased	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Aspartate aminotransferase increased	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Bilirubin conjugated increased	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Blood bilirubin increased	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Blood creatinine increased	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Blood potassium decreased	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Haemoglobin decreased	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Lipase increased	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Weight decreased	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Metabolism and nutrition disorders
Decreased appetite	4/321 (1.2%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Dehydration	0/321 (0%)		0/316 (0%)		0/39 (0%)		3/125 (2.4%)
Diabetes mellitus	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Fluid overload	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Hypoglycaemia	3/321 (0.9%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Hypokalaemia	1/321 (0.3%)		3/316 (0.9%)		1/39 (2.6%)		0/125 (0%)
Hypomagnesaemia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Hyponatraemia	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Hypophosphataemia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Hypovolaemia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Musculoskeletal and connective tissue disorders
Back pain	3/321 (0.9%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Fibromyalgia	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Joint swelling	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Osteoarthritis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Osteoporosis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Pain in extremity	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Tenosynovitis	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Bladder cancer	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Colon cancer	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Gastric cancer	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Gastrointestinal stromal tumour	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Hepatic neoplasm	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Hodgkin's disease	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Infected neoplasm	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Lip and/or oral cavity cancer	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Lung neoplasm malignant	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Metastases to liver	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Metastases to peritoneum	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Neoplasm	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Pancreatic carcinoma metastatic	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Small intestine carcinoma	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Thyroid cancer	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Tumour haemorrhage	3/321 (0.9%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Tumour necrosis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Tumour pain	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Tumour perforation	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Urinary tract neoplasm	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Nervous system disorders
Altered state of consciousness	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Cerebral haemorrhage	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Cerebral infarction	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Cerebral ischaemia	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Cerebrovascular accident	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Cognitive disorder	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Complex partial seizures	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Convulsion	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Dizziness	0/321 (0%)		0/316 (0%)		2/39 (5.1%)		0/125 (0%)
Epilepsy	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Haemorrhage intracranial	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Haemorrhagic stroke	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Headache	1/321 (0.3%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Hemiparesis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
IIIrd nerve paralysis	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Ischaemic stroke	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Loss of consciousness	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Migraine	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Myelitis transverse	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Peripheral motor neuropathy	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Peripheral sensory neuropathy	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Radiculopathy	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Sciatica	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Status epilepticus	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Syncope	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Psychiatric disorders
Confusional state	0/321 (0%)		2/316 (0.6%)		0/39 (0%)		0/125 (0%)
Mental status changes	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Renal and urinary disorders
Anuria	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Haematuria	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Pollakiuria	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Renal failure	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		1/125 (0.8%)
Renal failure acute	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Renal impairment	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Urinary tract obstruction	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Reproductive system and breast disorders
Scrotal oedema	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Chronic obstructive pulmonary disease	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Cough	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Dyspnoea	2/321 (0.6%)		1/316 (0.3%)		1/39 (2.6%)		0/125 (0%)
Interstitial lung disease	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Laryngeal oedema	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Pleural effusion	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Pneumothorax	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Pulmonary embolism	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Pulmonary fibrosis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Pulmonary infarction	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Pulmonary oedema	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Respiratory failure	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Respiratory tract haemorrhage	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Upper respiratory tract congestion	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Erythema multiforme	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Exfoliative rash	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Pityriasis rosea	0/321 (0%)		0/316 (0%)		0/39 (0%)		1/125 (0.8%)
Rash	0/321 (0%)		1/316 (0.3%)		1/39 (2.6%)		0/125 (0%)
Rash generalised	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Surgical and medical procedures
Cytoreductive surgery	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		0/125 (0%)
Gastrectomy	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Tumour excision	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Vascular disorders
Deep vein thrombosis	1/321 (0.3%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Femoral artery occlusion	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Hypotension	1/321 (0.3%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Peripheral arterial occlusive disease	2/321 (0.6%)		0/316 (0%)		0/39 (0%)		0/125 (0%)
Thrombosis	0/321 (0%)		0/316 (0%)		1/39 (2.6%)		0/125 (0%)
Vena cava thrombosis	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Venous thrombosis limb	0/321 (0%)		1/316 (0.3%)		0/39 (0%)		0/125 (0%)
Other (Not Including Serious) Adverse Events
	Nilotinib		Imatinib		Crossover Nilotinib		Crossover Imatinib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	291/321 (90.7%)		289/316 (91.5%)		28/39 (71.8%)		89/125 (71.2%)
Blood and lymphatic system disorders
Anaemia	38/321 (11.8%)		61/316 (19.3%)		7/39 (17.9%)		20/125 (16%)
Leukopenia	4/321 (1.2%)		35/316 (11.1%)		1/39 (2.6%)		10/125 (8%)
Neutropenia	4/321 (1.2%)		42/316 (13.3%)		1/39 (2.6%)		11/125 (8.8%)
Thrombocytopenia	2/321 (0.6%)		5/316 (1.6%)		2/39 (5.1%)		1/125 (0.8%)
Eye disorders
Eyelid oedema	5/321 (1.6%)		55/316 (17.4%)		0/39 (0%)		19/125 (15.2%)
Lacrimation increased	3/321 (0.9%)		21/316 (6.6%)		0/39 (0%)		3/125 (2.4%)
Periorbital oedema	2/321 (0.6%)		58/316 (18.4%)		0/39 (0%)		9/125 (7.2%)
Gastrointestinal disorders
Abdominal distension	17/321 (5.3%)		12/316 (3.8%)		1/39 (2.6%)		1/125 (0.8%)
Abdominal pain	63/321 (19.6%)		61/316 (19.3%)		6/39 (15.4%)		18/125 (14.4%)
Abdominal pain upper	38/321 (11.8%)		15/316 (4.7%)		1/39 (2.6%)		5/125 (4%)
Constipation	49/321 (15.3%)		24/316 (7.6%)		3/39 (7.7%)		3/125 (2.4%)
Diarrhoea	46/321 (14.3%)		106/316 (33.5%)		2/39 (5.1%)		17/125 (13.6%)
Nausea	73/321 (22.7%)		105/316 (33.2%)		12/39 (30.8%)		20/125 (16%)
Stomatitis	10/321 (3.1%)		14/316 (4.4%)		2/39 (5.1%)		1/125 (0.8%)
Vomiting	51/321 (15.9%)		65/316 (20.6%)		5/39 (12.8%)		10/125 (8%)
General disorders
Asthenia	27/321 (8.4%)		29/316 (9.2%)		0/39 (0%)		6/125 (4.8%)
Face oedema	5/321 (1.6%)		43/316 (13.6%)		0/39 (0%)		13/125 (10.4%)
Fatigue	66/321 (20.6%)		65/316 (20.6%)		7/39 (17.9%)		12/125 (9.6%)
Oedema peripheral	29/321 (9%)		68/316 (21.5%)		2/39 (5.1%)		17/125 (13.6%)
Pyrexia	23/321 (7.2%)		30/316 (9.5%)		3/39 (7.7%)		4/125 (3.2%)
Hepatobiliary disorders
Hyperbilirubinaemia	63/321 (19.6%)		11/316 (3.5%)		3/39 (7.7%)		3/125 (2.4%)
Infections and infestations
Nasopharyngitis	25/321 (7.8%)		19/316 (6%)		1/39 (2.6%)		1/125 (0.8%)
Upper respiratory tract infection	8/321 (2.5%)		17/316 (5.4%)		0/39 (0%)		1/125 (0.8%)
Investigations
Alanine aminotransferase increased	45/321 (14%)		18/316 (5.7%)		5/39 (12.8%)		3/125 (2.4%)
Amylase increased	8/321 (2.5%)		13/316 (4.1%)		2/39 (5.1%)		2/125 (1.6%)
Aspartate aminotransferase increased	23/321 (7.2%)		15/316 (4.7%)		2/39 (5.1%)		2/125 (1.6%)
Blood alkaline phosphatase increased	7/321 (2.2%)		3/316 (0.9%)		3/39 (7.7%)		2/125 (1.6%)
Blood bilirubin increased	32/321 (10%)		4/316 (1.3%)		2/39 (5.1%)		1/125 (0.8%)
Gamma-glutamyltransferase increased	9/321 (2.8%)		2/316 (0.6%)		4/39 (10.3%)		1/125 (0.8%)
Haemoglobin decreased	10/321 (3.1%)		20/316 (6.3%)		3/39 (7.7%)		5/125 (4%)
Lipase increased	27/321 (8.4%)		23/316 (7.3%)		1/39 (2.6%)		6/125 (4.8%)
Neutrophil count decreased	2/321 (0.6%)		24/316 (7.6%)		1/39 (2.6%)		7/125 (5.6%)
Weight decreased	27/321 (8.4%)		20/316 (6.3%)		3/39 (7.7%)		3/125 (2.4%)
White blood cell count decreased	3/321 (0.9%)		21/316 (6.6%)		0/39 (0%)		11/125 (8.8%)
Metabolism and nutrition disorders
Decreased appetite	40/321 (12.5%)		50/316 (15.8%)		5/39 (12.8%)		5/125 (4%)
Hyperglycaemia	15/321 (4.7%)		7/316 (2.2%)		2/39 (5.1%)		2/125 (1.6%)
Hyperuricaemia	2/321 (0.6%)		5/316 (1.6%)		2/39 (5.1%)		1/125 (0.8%)
Hypokalaemia	9/321 (2.8%)		19/316 (6%)		0/39 (0%)		8/125 (6.4%)
Hypophosphataemia	20/321 (6.2%)		53/316 (16.8%)		3/39 (7.7%)		10/125 (8%)
Musculoskeletal and connective tissue disorders
Arthralgia	20/321 (6.2%)		15/316 (4.7%)		2/39 (5.1%)		3/125 (2.4%)
Back pain	32/321 (10%)		18/316 (5.7%)		3/39 (7.7%)		3/125 (2.4%)
Muscle spasms	18/321 (5.6%)		47/316 (14.9%)		1/39 (2.6%)		2/125 (1.6%)
Myalgia	39/321 (12.1%)		17/316 (5.4%)		2/39 (5.1%)		2/125 (1.6%)
Pain in extremity	22/321 (6.9%)		16/316 (5.1%)		2/39 (5.1%)		3/125 (2.4%)
Nervous system disorders
Dizziness	22/321 (6.9%)		19/316 (6%)		2/39 (5.1%)		4/125 (3.2%)
Dysgeusia	10/321 (3.1%)		9/316 (2.8%)		2/39 (5.1%)		3/125 (2.4%)
Headache	54/321 (16.8%)		24/316 (7.6%)		5/39 (12.8%)		2/125 (1.6%)
Psychiatric disorders
Insomnia	21/321 (6.5%)		20/316 (6.3%)		1/39 (2.6%)		2/125 (1.6%)
Respiratory, thoracic and mediastinal disorders
Cough	28/321 (8.7%)		21/316 (6.6%)		1/39 (2.6%)		3/125 (2.4%)
Dyspnoea	17/321 (5.3%)		21/316 (6.6%)		2/39 (5.1%)		5/125 (4%)
Skin and subcutaneous tissue disorders
Alopecia	33/321 (10.3%)		13/316 (4.1%)		1/39 (2.6%)		3/125 (2.4%)
Dry skin	19/321 (5.9%)		21/316 (6.6%)		0/39 (0%)		3/125 (2.4%)
Pruritus	39/321 (12.1%)		25/316 (7.9%)		4/39 (10.3%)		2/125 (1.6%)
Rash	89/321 (27.7%)		46/316 (14.6%)		4/39 (10.3%)		12/125 (9.6%)

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.