JUMP: INC424 for Patients With Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01493414
• Collaborator: (none)
• Enrollment: 2,233
• Locations: 273
• Arm: 1
• Duration (Months): 65.4
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study was to collect additional safety of INC424 in patients with Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis, who either received prior treatment with commercially available agents or who have never received treatment.

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis	Drug: INC424	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2233 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter, Expanded Access Study of INC424 for Patients With Primary Myelofibrosis (PMF) or Post Polycythemia Myelofibrosis (PPV MF) or Post-essential Thrombocythemia Myelofibrosis (PET-MF).
• Study Start Date: Aug 16, 2011
• Actual Primary Completion Date: Jan 26, 2017
• Actual Study Completion Date: Jan 26, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INC424 5 - 25 mg twice a day (BID)	Drug: INC424; All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.; Other Names: Ruxolitinib

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years [Baseline up to approximately 5 years]

   An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-serious AE is any AE that does not meet the criteria above.

Secondary Outcome Measures

1. Percentage of Participants With at Least 50% Reduction in Spleen Length [Baseline up to approximately 5 years]

   Spleen length was assessed by manual palpation. Assessment of spleen response was repeated until early discontinuation of the study drug and also at study completion (28 days post end of treatment visit).

2. Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length [Baseline up to approximately 5 years]

   Overall response is analyzed using the spleen response, as assessed by the investigator and also by deriving the response using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. Participants with spleen length at baseline between 5 and 10 cm were reported as Responders if reporting non palpable spleen; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 100% from baseline in spleen length. Participants with spleen length at baseline more than 10 cm were reported as Responders with spleen reduction of 50% from baseline; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 50% from baseline in spleen length.

3. Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years [Baseline up to approximately 5 years]

   ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death.

4. Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48 [Baseline and Week 48]

   The FACT-Lym questionnaire consists of a total of 42 questions divided between five subscales (i.e., physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma subscale). Each subscale questionnaire rates each question on a 5-point scale from 0 = Not at all to 4 = Very much. These scores were summed to three total sum scores, namely FACT-Lym score, FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) and FACT-Lym total score. Total scores: FACT-Lym=0-60, FACT-TOI=0-116, FACT-G total=0-108, FACT-Lym Total= 0-168. Higher scores are reflective of better HRQoL.

5. Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status [Baseline up to approximately 5 years]

   Improvement was defined by the upper limit of the minimally important difference (MID). Patients with the best possible score at Baseline were excluded from this analysis because their HRQoL cannot be further improved. Responders and non-responders for each endpoint were defined based on change from baseline scores using pre specified cut-off points. Patients with an improved score compared to Baseline, for which the magnitude of the change was at least the cutoff value, were classified as responders; otherwise, as non-responders. The responder cutoff: ECOG cutoff=1, range=0 to 5, FACT-Lym cutoff=5.4, range 0-60, FACIT-Fatigue =5 and range=0-52.The median time to first improvement was estimated using the Kaplan Meier method and time to improvement event was determined based on upper bound of the MID. The time to improvement was calculated from the date of first study drug administration.

6. Medical Resource Utilization up to 5 Years [Baseline up to approximately 5 years.]

   Percentage of patients requiring medical resources (blood transfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) up to 5 years.

Eligibility Criteria

Criteria

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

Main Inclusion Criteria:

1. Patients must not be eligible for another ongoing INC424 clinical trial.

2. Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised International Standard Criteria, irrespective of JAK2 mutation status..

3. Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate risk level 1 (1 prognostic factor, no more) with an enlarged spleen (assessment to occur at the Screening Visit).

The prognostic factors, defined by the International Working Group are:

• Age > 65 years;

• Presence of constitutional symptoms (weight loss, fever, night sweats);

• Marked anemia (Hgb < 10g/dL)*;

• Leukocytosis (history of white blood cell (WBC) > 25 x109/L);

• Circulating blasts > 1%. * A hemoglobin value < 10 g/dL must be demonstrated during the Screening Visit for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have hemoglobin < 10 g/dL for the purpose of evaluation of risk factors.

1. Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.

2. Patients must have a peripheral blood blast count of < 10%.

3. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

4. Fedratinib pretreated patients with documented complete physical examination including full neurologic examination and cardiology assessment, thiamine level testing, and MRI of the brain if indicated based on signs or symptoms. Patients pretreated with fedratinib should have completed or be receiving thiamine supplementation according to the investigator's instructions.

Main Exclusion Criteria:

1. Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).

2. Patients with history of malignancy in past 3 years except for treated, early-stage squamous or basal cell carcinoma in situ.

3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).

4. Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol.

5. Patients with currently uncontrolled or unstable angina, rapid or paroxysmal atrial fibrillation or recent (approximately 6 months) myocardial infarction or acute coronary syndrome.

6. Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.

7. Patients with known active hepatitis A, B, C or who are HIV-positive.

8. Patients with inadequate bone marrow reserve at the Baseline visit as demonstrated by:

• Absolute neutrophil count (ANC) ≤ 1000/µL.

• Platelet count < 50,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.

1. Patients with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason.

2. In the case of ruxolitinib pretreated patients, ruxolitinib primary resistant patients defined as:

• No spleen reduction within the first 12 weeks after front line therapy with ruxolitinib.

AND

• No reduction in symptoms within the first 12 weeks after first-line treatment with ruxolitinib.

1. In the case of ruxolitinib pretreated patients, patients discontinuing ruxolitinib due to a Grade 4 Adverse event (AE) related or suspected to be related to ruxolitinib.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Alger		Algeria
2	Novartis Investigative Site	Caba	Buenos Aires	Argentina	1209
3	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1221ADC
4	Novartis Investigative Site	Paraná	Entre Rios	Argentina	E3100BBJ
5	Novartis Investigative Site	Buenos Aires		Argentina	C1114AAN
6	Novartis Investigative Site	Cordoba		Argentina	X5016KEH
7	Novartis Investigative Site	Corrientes		Argentina	W3410AVV
8	Novartis Investigative Site	Innsbruck	Tyrol	Austria	6020
9	Novartis Investigative Site	Graz		Austria	A-8036
10	Novartis Investigative Site	Linz		Austria	4010
11	Novartis Investigative Site	Linz		Austria	A-4010
12	Novartis Investigative Site	Salzburg		Austria	5020
13	Novartis Investigative Site	Wien		Austria	1140
14	Novartis Investigative Site	Wien		Austria	A-1090
15	Novartis Investigative Site	Arlon	Luxembourg	Belgium	1210
16	Novartis Investigative Site	Antwerpen		Belgium	2060
17	Novartis Investigative Site	Brugge		Belgium	8000
18	Novartis Investigative Site	Brussel		Belgium	1090
19	Novartis Investigative Site	Bruxelles		Belgium	1070
20	Novartis Investigative Site	Charleroi		Belgium	6000
21	Novartis Investigative Site	Edegem		Belgium	2650
22	Novartis Investigative Site	Gent		Belgium	9000
23	Novartis Investigative Site	Hasselt		Belgium	3500
24	Novartis Investigative Site	Kortrijk		Belgium	8500
25	Novartis Investigative Site	Leuven		Belgium	3000
26	Novartis Investigative Site	Liege		Belgium	4000
27	Novartis Investigative Site	Roeselare		Belgium	8800
28	Novartis Investigative Site	Wilrijk		Belgium	2610
29	Novartis Investigative Site	Yvoir		Belgium	5530
30	Novartis Investigative Site	Goiania	GO	Brazil	74605-050
31	Novartis Investigative Site	Belo Horizonte	MG	Brazil	30130-100
32	Novartis Investigative Site	Curitiba	PR	Brazil	80060-900
33	Novartis Investigative Site	Rio de Janeiro	RJ	Brazil	20.211-030
34	Novartis Investigative Site	Porto Alegre	RS	Brazil	90035-003
35	Novartis Investigative Site	Campinas	SP	Brazil	13083-970
36	Novartis Investigative Site	Ribeirao Preto	SP	Brazil	14048-900
37	Novartis Investigative Site	São Paulo	SP	Brazil	01224-000
38	Novartis Investigative Site	São Paulo	SP	Brazil	05651-901
39	Novartis Investigative Site	São Paulo	SP	Brazil	08270-070
40	Novartis Investigative Site	Edmonton	Alberta	Canada	T6G 1Z2
41	Novartis Investigative Site	Vancouver	British Columbia	Canada	V6Z1Y6
42	Novartis Investigative Site	Moncton	New Brunswick	Canada	E1C 6Z8
43	Novartis Investigative Site	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
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	M5G 2M9
48	Novartis Investigative Site	Windsor	Ontario	Canada	N8W 2X3
49	Novartis Investigative Site	Montreal	Quebec	Canada	H2W 1S6
50	Novartis Investigative Site	Québec	Quebec	Canada	G1J 1Z4
51	Novartis Investigative Site	Saskatoon	Saskatchewan	Canada	S7N 4H4
52	Novartis Investigative Site	Bogota	Cundinamarca	Colombia	111411
53	Novartis Investigative Site	Medellín		Colombia
54	Novartis Investigative Site	Brno	Czech Republic	Czechia	639 00
55	Novartis Investigative Site	Hradec Kralove	Czech Republic	Czechia	500 05
56	Novartis Investigative Site	Praha 2	Czech Republic	Czechia	128 20
57	Novartis Investigative Site	Olomouc		Czechia	775 20
58	Novartis Investigative Site	Mannheim	Baden-Württemberg	Germany	68305
59	Novartis Investigative Site	Aachen		Germany	52074
60	Novartis Investigative Site	Aschaffenburg		Germany	63739
61	Novartis Investigative Site	Bamberg		Germany	96049
62	Novartis Investigative Site	Berlin		Germany	13353
63	Novartis Investigative Site	Berlin		Germany	14195
64	Novartis Investigative Site	Bochum		Germany	44787
65	Novartis Investigative Site	Bonn		Germany	53113
66	Novartis Investigative Site	Bonn		Germany	53119
67	Novartis Investigative Site	Bottrop		Germany	46236
68	Novartis Investigative Site	Bremen		Germany	28177
69	Novartis Investigative Site	Chemnitz		Germany	09113
70	Novartis Investigative Site	Darmstadt		Germany	64283
71	Novartis Investigative Site	Dortmund		Germany	44263
72	Novartis Investigative Site	Dresden		Germany	01307
73	Novartis Investigative Site	Duisburg		Germany	47166
74	Novartis Investigative Site	Düsseldorf		Germany	40225
75	Novartis Investigative Site	Erlangen		Germany	91054
76	Novartis Investigative Site	Essen		Germany	45147
77	Novartis Investigative Site	Frankfurt, Oder		Germany	15236
78	Novartis Investigative Site	Frankfurt		Germany	60389
79	Novartis Investigative Site	Frankfurt		Germany	60590
80	Novartis Investigative Site	Freiburg		Germany	79106
81	Novartis Investigative Site	Friedrichshafen		Germany	88045
82	Novartis Investigative Site	Goslar		Germany	38642
83	Novartis Investigative Site	Greifswald		Germany	17475
84	Novartis Investigative Site	Göttingen		Germany	D-37075
85	Novartis Investigative Site	Halle		Germany	06110
86	Novartis Investigative Site	Hamburg		Germany	20099
87	Novartis Investigative Site	Hamburg		Germany	20246
88	Novartis Investigative Site	Hamm		Germany	59063
89	Novartis Investigative Site	Hannover		Germany	30625
90	Novartis Investigative Site	Hildesheim		Germany	31135
91	Novartis Investigative Site	Ingolstadt		Germany	85049
92	Novartis Investigative Site	Jena		Germany	07740
93	Novartis Investigative Site	Kiel		Germany	D-24116
94	Novartis Investigative Site	Koeln		Germany	50671
95	Novartis Investigative Site	Köln		Germany	50937
96	Novartis Investigative Site	Leer		Germany	26789
97	Novartis Investigative Site	Leipzig		Germany	04103
98	Novartis Investigative Site	Magdeburg		Germany	39120
99	Novartis Investigative Site	Mainz		Germany	55131
100	Novartis Investigative Site	Marburg		Germany	35037
101	Novartis Investigative Site	Marburg		Germany	35039
102	Novartis Investigative Site	Minden		Germany	32429
103	Novartis Investigative Site	Moers		Germany	47441
104	Novartis Investigative Site	Muenchen		Germany	80331
105	Novartis Investigative Site	Muenchen		Germany	81241
106	Novartis Investigative Site	München		Germany	81675
107	Novartis Investigative Site	Nuernberg		Germany	90403
108	Novartis Investigative Site	Oldenburg		Germany	26133
109	Novartis Investigative Site	Rostock		Germany	18057
110	Novartis Investigative Site	Stuttgart		Germany	70376
111	Novartis Investigative Site	Ulm		Germany	89081
112	Novartis Investigative Site	Wuerzburg		Germany	97080
113	Novartis Investigative Site	Athens	GR	Greece	115 27
114	Novartis Investigative Site	Athens	GR	Greece	GR-106 76
115	Novartis Investigative Site	Athens		Greece	GR 11527
116	Novartis Investigative Site	Patras		Greece	265 00
117	Novartis Investigative Site	Budapest		Hungary	H-1097
118	Novartis Investigative Site	Debrecen		Hungary	H-4032
119	Novartis Investigative Site	Kaposvár		Hungary	7400
120	Novartis Investigative Site	Szeged		Hungary	H-6720
121	Novartis Investigative Site	Szombathely		Hungary	9700
122	Novartis Investigative Site	Cork City	Cork	Ireland
123	Novartis Investigative Site	Afula		Israel	1834111
124	Novartis Investigative Site	Haifa		Israel	3339419
125	Novartis Investigative Site	Jerusalem		Israel	9112001
126	Novartis Investigative Site	Petach Tikva		Israel	49100
127	Novartis Investigative Site	Ramat Gan		Israel	5266202
128	Novartis Investigative Site	Tel-Aviv		Israel	6423906
129	Novartis Investigative Site	Alessandria	AL	Italy	15100
130	Novartis Investigative Site	Ancona	AN	Italy	60126
131	Novartis Investigative Site	Avellino	AV	Italy	83100
132	Novartis Investigative Site	Bari	BA	Italy	70124
133	Novartis Investigative Site	Bergamo	BG	Italy	24128
134	Novartis Investigative Site	Bologna	BO	Italy	40138
135	Novartis Investigative Site	Brescia	BS	Italy	25123
136	Novartis Investigative Site	Cagliari	CA	Italy	09100
137	Novartis Investigative Site	Cagliari	CA	Italy	09126
138	Novartis Investigative Site	Catania	CT	Italy	95100
139	Novartis Investigative Site	Catania	CT	Italy	95124
140	Novartis Investigative Site	Catanzaro	CZ	Italy	88100
141	Novartis Investigative Site	Cona	FE	Italy	44100
142	Novartis Investigative Site	San Giovanni Rotondo	FG	Italy	71013
143	Novartis Investigative Site	Firenze	FI	Italy	50134
144	Novartis Investigative Site	Genova	GE	Italy	16132
145	Novartis Investigative Site	Lecce	LE	Italy	73100
146	Novartis Investigative Site	Monza	MB	Italy	20900
147	Novartis Investigative Site	Milano	MI	Italy	20122
148	Novartis Investigative Site	Milano	MI	Italy	20133
149	Novartis Investigative Site	Milano	MI	Italy	20162
150	Novartis Investigative Site	Modena	MO	Italy	41100
151	Novartis Investigative Site	Palermo	PA	Italy	90146
152	Novartis Investigative Site	Padova	PD	Italy	35128
153	Novartis Investigative Site	Pescara	PE	Italy	65124
154	Novartis Investigative Site	Pisa	PI	Italy	56126
155	Novartis Investigative Site	Pesaro	PU	Italy	61100
156	Novartis Investigative Site	Pavia	PV	Italy	27100
157	Novartis Investigative Site	Rionero in Vulture	PZ	Italy	85028
158	Novartis Investigative Site	Ravenna	RA	Italy	48100
159	Novartis Investigative Site	Reggio Calabria	RC	Italy	89124
160	Novartis Investigative Site	Reggio Emilia	RE	Italy	42123
161	Novartis Investigative Site	Roma	RM	Italy	00128
162	Novartis Investigative Site	Roma	RM	Italy	00133
163	Novartis Investigative Site	Roma	RM	Italy	00144
164	Novartis Investigative Site	Roma	RM	Italy	00152
165	Novartis Investigative Site	Roma	RM	Italy	00161
166	Novartis Investigative Site	Roma	RM	Italy	00168
167	Novartis Investigative Site	Roma	RM	Italy	00185
168	Novartis Investigative Site	Pagani	SA	Italy	84016
169	Novartis Investigative Site	Siena	SI	Italy	53100
170	Novartis Investigative Site	Taranto	TA	Italy	74100
171	Novartis Investigative Site	Orbassano	TO	Italy	10043
172	Novartis Investigative Site	Torino	TO	Italy	10126
173	Novartis Investigative Site	Terni	TR	Italy	05100
174	Novartis Investigative Site	Treviso	TV	Italy	31100
175	Novartis Investigative Site	Udine	UD	Italy	33100
176	Novartis Investigative Site	Varese	VA	Italy	21100
177	Novartis Investigative Site	Venezia	VE	Italy	30174
178	Novartis Investigative Site	Vicenza	VI	Italy	36100
179	Novartis Investigative Site	Verona	VR	Italy	37126
180	Novartis Investigative Site	Ronciglione	VT	Italy	01100
181	Novartis Investigative Site	Napoli		Italy	80131
182	Novartis Investigative Site	Napoli		Italy	80132
183	Novartis Investigative Site	Napoli		Italy	80136
184	Novartis Investigative Site	Novara		Italy	28100
185	Novartis Investigative Site	Pavia		Italy	27100
186	Novartis Investigative Site	Perugia		Italy	06129
187	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	06726
188	Novartis Investigative Site	Guadalajara	Jalisco	Mexico	44280
189	Novartis Investigative Site	Monterrey	Nuevo León	Mexico	64020
190	Novartis Investigative Site	Hermosillo	Sonora	Mexico	83000
191	Novartis Investigative Site	Puebla		Mexico	72000
192	Novartis Investigative Site	Marrakech		Morocco
193	Novartis Investigative Site	Gdansk		Poland	80-958
194	Novartis Investigative Site	Katowice		Poland	40-027
195	Novartis Investigative Site	Krakow		Poland	31-503
196	Novartis Investigative Site	Opole		Poland	45-372
197	Novartis Investigative Site	Torun		Poland	87-100
198	Novartis Investigative Site	Warszawa		Poland	02-776
199	Novartis Investigative Site	Coimbra		Portugal	3000-075
200	Novartis Investigative Site	Faro		Portugal	8000-386
201	Novartis Investigative Site	Lisboa		Portugal	1749-035
202	Novartis Investigative Site	Porto		Portugal	4099-001
203	Novartis Investigative Site	Vila Real		Portugal	5000 - 508
204	Novartis Investigative Site	Irkutsk		Russian Federation	664079
205	Novartis Investigative Site	Moscow		Russian Federation	125167
206	Novartis Investigative Site	Nizhnii Novgorod		Russian Federation	603126
207	Novartis Investigative Site	Novosibirsk		Russian Federation	630051
208	Novartis Investigative Site	Rostov-on-Don		Russian Federation	344022
209	Novartis Investigative Site	St Petersburg		Russian Federation	191024
210	Novartis Investigative Site	St Petersburg		Russian Federation	197341
211	Novartis Investigative Site	Jeddah		Saudi Arabia	21423
212	Novartis Investigative Site	Riyadh		Saudi Arabia	11426
213	Novartis Investigative Site	Bratislava		Slovakia	85107
214	Novartis Investigative Site	Soweto	Gauteng	South Africa	2013
215	Novartis Investigative Site	Cape Town	Western Province	South Africa	7801
216	Novartis Investigative Site	Johannesburg		South Africa	2196
217	Novartis Investigative Site	Pretoria		South Africa	0001
218	Novartis Investigative Site	Pretoria		South Africa	0027
219	Novartis Investigative Site	Ferrol	A Coruna	Spain	15405
220	Novartis Investigative Site	Granada	Andalucia	Spain	18014
221	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
222	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
223	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
224	Novartis Investigative Site	Cadiz	Andalucía	Spain	11009
225	Novartis Investigative Site	Jaen	Andalucía	Spain	23007
226	Novartis Investigative Site	Oviedo	Asturias	Spain	33006
227	Novartis Investigative Site	Sabadell	Barcelona	Spain	08208
228	Novartis Investigative Site	Santander	Cantabria	Spain	39008
229	Novartis Investigative Site	Toledo	Castilla La Mancha	Spain	45071
230	Novartis Investigative Site	Burgos	Castilla Y Leon	Spain	09005
231	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007
232	Novartis Investigative Site	Valladolid	Castilla Y Leon	Spain	47012
233	Novartis Investigative Site	Badalona	Catalunya	Spain	08916
234	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
235	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
236	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
237	Novartis Investigative Site	Girona	Catalunya	Spain	17007
238	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya	Spain	08907
239	Novartis Investigative Site	Tarragona	Catalunya	Spain	43005
240	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03010
241	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46010
242	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46026
243	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
244	Novartis Investigative Site	Palma De Mallorca	Islas Baleares	Spain	07120
245	Novartis Investigative Site	Las Palmas de Gran Canaria	Las Palmas De G.C	Spain	35010
246	Novartis Investigative Site	Alcala de Henares	Madrid	Spain	28805
247	Novartis Investigative Site	Majadahonda	Madrid	Spain	28222
248	Novartis Investigative Site	Pozuelo de Alarcón	Madrid	Spain	28223
249	Novartis Investigative Site	San Sebastian de los Reyes	Madrid	Spain	28702
250	Novartis Investigative Site	El Palmar	Murcia	Spain	30120
251	Novartis Investigative Site	Pamplona	Navarra	Spain	31008
252	Novartis Investigative Site	Bilbao	Pais Vasco	Spain	48013
253	Novartis Investigative Site	San Sebastian	Pais Vasco	Spain	20080
254	Novartis Investigative Site	Logrono	Rioja	Spain	26006
255	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife	Spain	38320
256	Novartis Investigative Site	Baracaldo	Vizcaya	Spain	48903
257	Novartis Investigative Site	Barcelona		Spain	08041
258	Novartis Investigative Site	Las Palmas de Gran Canaria		Spain	35016
259	Novartis Investigative Site	Madrid		Spain	28006
260	Novartis Investigative Site	Madrid		Spain	28034
261	Novartis Investigative Site	Madrid		Spain	28040
262	Novartis Investigative Site	Madrid		Spain	28041
263	Novartis Investigative Site	Madrid		Spain	28046
264	Novartis Investigative Site	Zaragoza		Spain	50009
265	Novartis Investigative Site	Zaragoza		Spain	50015
266	Novartis Investigative Site	Bangkok		Thailand	10330
267	Novartis Investigative Site	Bangkok		Thailand	10400
268	Novartis Investigative Site	Bangkok		Thailand	10700
269	Novartis Investigative Site	Chiang Mai		Thailand	50200
270	Novartis Investigative Site	Sfax	Tunisie	Tunisia	3029
271	Novartis Investigative Site	Sousse		Tunisia	4000
272	Novartis Investigative Site	Tunis		Tunisia	1008
273	Novartis Investigative Site	Tunis		Tunisia

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Statistical Analysis Plan - Apr 26, 2017
• Study Protocol - Mar 21, 2016

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01493414
• Other Study ID Numbers: CINC424A2401; 2010-024473-39
• First Posted: Dec 16, 2011
• Last Update Posted: Apr 26, 2019
• Last Verified: Oct 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Myelofibrosis; Primary myelofibrosis; PMF; Post polycythemia myelofibrosis; PPV MF; Post-essential thrombocythemia myelofibrosis; PET-MF; INC424; Ruxolitinib
• Additional relevant MeSH terms: Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential

Study Results

Participant Flow

Recruitment Details	This was an expanded access study intended to provide an access path to ruxolitinib for patients with Myelofibrosis (MF) and to allow for collection of additional safety and efficacy data for ruxolitinib.

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Period Title: Overall Study
STARTED	2233
COMPLETED	1283
NOT COMPLETED	950

Baseline Characteristics

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Overall Participants	2233
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.6 (10.50)
Sex: Female, Male (Count of Participants)
Female	1016 45.5%
Male	1217 54.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 0.3%
Asian	23 1%
Native Hawaiian or Other Pacific Islander	1 0%
Black or African American	20 0.9%
White	2087 93.5%
More than one race	96 4.3%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
Hispanic/Latino	509 22.8%
Chinese	1 0%
Indian (Indian subcontinent)	1 0%
Japanese	0 0%
Mixed Ethnicity	15 0.7%
Others	1707 76.4%
ECOG score (Count of Participants)
0	1061 47.5%
1	960 43%
2	197 8.8%
3	1 0%
4	0 0%
Missing	14 0.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years
Description	An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-serious AE is any AE that does not meet the criteria above.
Time Frame	Baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description

Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment.

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Measure Participants	2233
Adverse Events	2153 96.4%
Serious adverse events	830 37.2%

2. Secondary Outcome

Title	Percentage of Participants With at Least 50% Reduction in Spleen Length
Description	Spleen length was assessed by manual palpation. Assessment of spleen response was repeated until early discontinuation of the study drug and also at study completion (28 days post end of treatment visit).
Time Frame	Baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description

Full analysis set includes all patients who received at least one administration of study drug.

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Measure Participants	2049
Number (95% Confidence Interval) [percentage of participants]	71.7 3.2%

3. Secondary Outcome

Title	Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length
Description	Overall response is analyzed using the spleen response, as assessed by the investigator and also by deriving the response using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. Participants with spleen length at baseline between 5 and 10 cm were reported as Responders if reporting non palpable spleen; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 100% from baseline in spleen length. Participants with spleen length at baseline more than 10 cm were reported as Responders with spleen reduction of 50% from baseline; Stable disease does not meet criteria for response or disease progression and Progressive disease with an increase of 50% from baseline in spleen length.
Time Frame	Baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description

Full analysis set includes all patients who received at least one administration of study drug and were observed from baseline in to the study follow-up period.

Arm/Group Title	INC424 - Responders	INC424 - Stable Disease	INC424 - Progressive Disease	INC424 - Missing
Arm/Group Description	Responders with spleen length between 5 and 10 cm=non palpable spleen. Responders with spleen length more than 10 cm=Spleen reduction of 50% from baseline. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	Participants with Stable Disease with spleen length between 5 and 10 cm=does not meet criteria for response or disease progression. Participants with Stable Disease with spleen length more than 10 cm=does not meet criteria for response or disease progression. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	Participants with Progressive Disease with spleen length between 5 and 10 cm=increase of 100% from baseline in spleen length. Participants with Progressive Disease with spleen length more than 10 cm=increase of 50% from baseline in spleen length. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.	Missing values. 5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Measure Participants	2178	2178	2178	2178
Spleen length at baseline-Less than 5 cm	NA NaN	NA NaN	NA NaN	NA NaN
Spleen length at baseline-Between 5 and 10 cm	421 18.9%	334 NaN	1 NaN	9 NaN
Spleen length at baseline-More than 10 cm	742 33.2%	463 NaN	0 NaN	19 NaN

4. Secondary Outcome

Title	Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years
Description	ECOG Performance Score has 5 grades. 0 = Fully active, able to carry out all pre-disease activities; 1 = Restricted in strenuous activity but ambulatory and able to carry out work of light or sedentary nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities. Active about 50% of waking hours; 3 = Capable of limited self-care, confined to bed/chair more than 50% of waking hours; 4 = Completely disabled; cannot carry on self-care. Totally confined to bed/chair. 5 = Death.
Time Frame	Baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description

Full analysis set includes all patients who received at least one administration of study drug.

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Measure Participants	2233
Worst value post-baseline: Grade 0	598 26.8%
Worst value post-baseline: Grade 1	377 16.9%
Worst value post-baseline: Grade 2	62 2.8%
Worst value post-baseline: Grade 3	12 0.5%
Worst value post-baseline: Grade 4	7 0.3%
Worst value post-baseline: Grade 5	0 0%
Worst value post-baseline: Missing	5 0.2%
Worst value post-baseline: Grade 0	89 4%
Worst value post-baseline: Grade 1	629 28.2%
Worst value post-baseline: Grade 2	187 8.4%
Worst value post-baseline: Grade 3	26 1.2%
Worst value post-baseline: Grade 4	12 0.5%
Worst value post-baseline: Grade 5	1 0%
Worst value post-baseline: Missing	16 0.7%
Worst value post-baseline: Grade 0	3 0.1%
Worst value post-baseline: Grade 1	43 1.9%
Worst value post-baseline: Grade 2	111 5%
Worst value post-baseline: Grade 3	20 0.9%
Worst value post-baseline: Grade 4	12 0.5%
Worst value post-baseline: Grade 5	1 0%
Worst value post-baseline: Missing	7 0.3%
Worst value post-baseline: Grade 0	0 0%
Worst value post-baseline: Grade 1	0 0%
Worst value post-baseline: Grade 2	0 0%
Worst value post-baseline: Grade 3	1 0%
Worst value post-baseline: Grade 4	0 0%
Worst value post-baseline: Grade 5	0 0%
Worst value post-baseline: Missing	0 0%
Worst value post-baseline: Grade 0	0 0%
Worst value post-baseline: Grade 1	0 0%
Worst value post-baseline: Grade 2	0 0%
Worst value post-baseline: Grade 3	0 0%
Worst value post-baseline: Grade 4	0 0%
Worst value post-baseline: Grade 5	0 0%
Worst value post-baseline: Missing	0 0%
Worst value post-baseline: Grade 0	1 0%
Worst value post-baseline: Grade 1	8 0.4%
Worst value post-baseline: Grade 2	4 0.2%
Worst value post-baseline: Grade 3	1 0%
Worst value post-baseline: Grade 4	0 0%
Worst value post-baseline: Grade 5	0 0%
Worst value post-baseline: Missing	0 0%

5. Secondary Outcome

Title	Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48
Description	The FACT-Lym questionnaire consists of a total of 42 questions divided between five subscales (i.e., physical well-being, social/family well-being, emotional well-being, functional well-being and lymphoma subscale). Each subscale questionnaire rates each question on a 5-point scale from 0 = Not at all to 4 = Very much. These scores were summed to three total sum scores, namely FACT-Lym score, FACT-Lym Trial Outcome Index (TOI), FACT-General (FACT-G) and FACT-Lym total score. Total scores: FACT-Lym=0-60, FACT-TOI=0-116, FACT-G total=0-108, FACT-Lym Total= 0-168. Higher scores are reflective of better HRQoL.
Time Frame	Baseline and Week 48

Outcome Measure Data

Analysis Population Description

Full analysis set includes all patients who received at least one administration of study drug.

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Measure Participants	2233
FACT-Lymphoma Baseline	42.3 (10.20)
FACT-Lymphoma Week 48	47.9 (8.47)
FACT-Lymphoma TOI Baseline	77.9 (18.99)
FACT-Lymphoma TOI Week 48	86.8 (16.42)
FACT-Lymphoma total score Baseline	113.9 (24.01)
FACT-Lymphoma total score Week 48	123.3 (22.34)
FACT-G Baseline	71.6 (15.98)
FACT-G Week 48	75.5 (15.59)

6. Secondary Outcome

Title	Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status
Description	Improvement was defined by the upper limit of the minimally important difference (MID). Patients with the best possible score at Baseline were excluded from this analysis because their HRQoL cannot be further improved. Responders and non-responders for each endpoint were defined based on change from baseline scores using pre specified cut-off points. Patients with an improved score compared to Baseline, for which the magnitude of the change was at least the cutoff value, were classified as responders; otherwise, as non-responders. The responder cutoff: ECOG cutoff=1, range=0 to 5, FACT-Lym cutoff=5.4, range 0-60, FACIT-Fatigue =5 and range=0-52.The median time to first improvement was estimated using the Kaplan Meier method and time to improvement event was determined based on upper bound of the MID. The time to improvement was calculated from the date of first study drug administration.
Time Frame	Baseline up to approximately 5 years

Outcome Measure Data

Analysis Population Description

Full analysis set includes all patients who received at least one administration of study drug.

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Measure Participants	2233
FACT-Lym Total score median time to improvement	10.9
FACIT - Fatigue score median time to improvement	4.6
ECOG score median time to improvement	63.1

7. Secondary Outcome

Title	Medical Resource Utilization up to 5 Years
Description	Percentage of patients requiring medical resources (blood transfusions, hospitalization, emergency room visits, general practitioners or specialists consultations, urgent care or splenic irradiation) up to 5 years.
Time Frame	Baseline up to approximately 5 years.

Outcome Measure Data

Analysis Population Description

Full analysis set includes all patients who received at least one administration of study drug.

Arm/Group Title	INC424
Arm/Group Description	5 - 25 mg twice a day (BID) INC424: All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.
Measure Participants	2233
End of Study - Dependency	129 5.8%
End of Study - Independency	29 1.3%
End of Study - Dependency	480 21.5%
End of Study - Independency	1595 71.4%

Adverse Events

Time Frame	Adverse Events (AEs) were collected up to 24-months after last patient first visit (LPFV), approximately 5 years .
Adverse Event Reporting Description	Safety set includes all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. Adverse events occurring more than 28 days after the discontinuation of study treatment are not summarized.
Arm/Group Title	INC424
Arm/Group Description	All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 25 mg twice a day. No INC424 dose will exceed 20 mg BID orally.
All Cause Mortality
	INC424
	Affected / at Risk (%)	# Events
Total	205/2233 (9.2%)
Serious Adverse Events
	INC424
	Affected / at Risk (%)	# Events
Total	830/2233 (37.2%)
Blood and lymphatic system disorders
Agranulocytosis	1/2233 (0%)
Anaemia	94/2233 (4.2%)
Autoimmune haemolytic anaemia	1/2233 (0%)
Bone marrow oedema	1/2233 (0%)
Coagulopathy	1/2233 (0%)
Disseminated intravascular coagulation	1/2233 (0%)
Febrile neutropenia	8/2233 (0.4%)
Haemolytic anaemia	2/2233 (0.1%)
Histiocytosis haematophagic	1/2233 (0%)
Hypercoagulation	1/2233 (0%)
Leukocytosis	8/2233 (0.4%)
Leukostasis syndrome	1/2233 (0%)
Lymphadenopathy	1/2233 (0%)
Lymphocytosis	1/2233 (0%)
Monoclonal B-cell lymphocytosis	1/2233 (0%)
Neutropenia	10/2233 (0.4%)
Pancytopenia	3/2233 (0.1%)
Polycythaemia	1/2233 (0%)
Splenic haematoma	3/2233 (0.1%)
Splenic infarction	4/2233 (0.2%)
Splenomegaly	8/2233 (0.4%)
Spontaneous haematoma	1/2233 (0%)
Thrombocytopenia	24/2233 (1.1%)
Thrombocytosis	1/2233 (0%)
Cardiac disorders
Acute coronary syndrome	2/2233 (0.1%)
Acute myocardial infarction	9/2233 (0.4%)
Angina pectoris	8/2233 (0.4%)
Aortic valve incompetence	1/2233 (0%)
Atrial fibrillation	21/2233 (0.9%)
Atrioventricular block	1/2233 (0%)
Atrioventricular block first degree	1/2233 (0%)
Bradycardia	4/2233 (0.2%)
Cardiac arrest	16/2233 (0.7%)
Cardiac disorder	3/2233 (0.1%)
Cardiac failure	43/2233 (1.9%)
Cardiac failure acute	5/2233 (0.2%)
Cardiac failure chronic	1/2233 (0%)
Cardiac failure congestive	7/2233 (0.3%)
Cardiac tamponade	2/2233 (0.1%)
Cardio-respiratory arrest	9/2233 (0.4%)
Cardiogenic shock	5/2233 (0.2%)
Cardiopulmonary failure	1/2233 (0%)
Conduction disorder	1/2233 (0%)
Congestive cardiomyopathy	1/2233 (0%)
Cor pulmonale	1/2233 (0%)
Coronary artery disease	5/2233 (0.2%)
Coronary artery stenosis	1/2233 (0%)
Hypertensive heart disease	1/2233 (0%)
Intracardiac thrombus	1/2233 (0%)
Left ventricular dysfunction	1/2233 (0%)
Left ventricular failure	1/2233 (0%)
Left ventricular hypertrophy	1/2233 (0%)
Mitral valve incompetence	2/2233 (0.1%)
Myocardial infarction	5/2233 (0.2%)
Myocardial ischaemia	2/2233 (0.1%)
Palpitations	1/2233 (0%)
Pericardial effusion	3/2233 (0.1%)
Pericardial haemorrhage	1/2233 (0%)
Pericarditis	1/2233 (0%)
Right ventricular dysfunction	1/2233 (0%)
Right ventricular failure	2/2233 (0.1%)
Sinus node dysfunction	1/2233 (0%)
Sinus tachycardia	1/2233 (0%)
Stress cardiomyopathy	2/2233 (0.1%)
Supraventricular tachycardia	3/2233 (0.1%)
Tachyarrhythmia	1/2233 (0%)
Tachycardia	1/2233 (0%)
Tricuspid valve incompetence	1/2233 (0%)
Ventricular dysfunction	1/2233 (0%)
Ventricular hypokinesia	1/2233 (0%)
Congenital, familial and genetic disorders
Hydrocele	2/2233 (0.1%)
Ear and labyrinth disorders
Hypoacusis	2/2233 (0.1%)
Vertigo	5/2233 (0.2%)
Endocrine disorders
Adrenal insufficiency	1/2233 (0%)
Eye disorders
Cataract	3/2233 (0.1%)
Corneal oedema	1/2233 (0%)
Diplopia	1/2233 (0%)
Macular degeneration	1/2233 (0%)
Optic ischaemic neuropathy	1/2233 (0%)
Uveitis	1/2233 (0%)
Gastrointestinal disorders
Abdominal hernia	1/2233 (0%)
Abdominal mass	1/2233 (0%)
Abdominal pain	28/2233 (1.3%)
Abdominal pain lower	1/2233 (0%)
Abdominal pain upper	5/2233 (0.2%)
Abdominal tenderness	1/2233 (0%)
Abdominal wall haematoma	1/2233 (0%)
Anal fissure	2/2233 (0.1%)
Anal prolapse	1/2233 (0%)
Anal ulcer	1/2233 (0%)
Ascites	14/2233 (0.6%)
Barrett's oesophagus	1/2233 (0%)
Colitis	3/2233 (0.1%)
Constipation	2/2233 (0.1%)
Diarrhoea	17/2233 (0.8%)
Diarrhoea haemorrhagic	1/2233 (0%)
Diverticular perforation	2/2233 (0.1%)
Diverticulum intestinal haemorrhagic	1/2233 (0%)
Enteritis	1/2233 (0%)
Enterovesical fistula	1/2233 (0%)
Faecaloma	1/2233 (0%)
Femoral hernia	1/2233 (0%)
Gastric haemorrhage	4/2233 (0.2%)
Gastric stenosis	1/2233 (0%)
Gastric ulcer	1/2233 (0%)
Gastric varices haemorrhage	1/2233 (0%)
Gastritis	1/2233 (0%)
Gastrointestinal haemorrhage	21/2233 (0.9%)
Haematemesis	2/2233 (0.1%)
Haematochezia	2/2233 (0.1%)
Haemorrhoids	1/2233 (0%)
Ileus	1/2233 (0%)
Ileus paralytic	3/2233 (0.1%)
Inguinal hernia	5/2233 (0.2%)
Inguinal hernia strangulated	1/2233 (0%)
Intestinal haemorrhage	2/2233 (0.1%)
Intestinal infarction	1/2233 (0%)
Intestinal obstruction	2/2233 (0.1%)
Intestinal perforation	1/2233 (0%)
Mallory-Weiss syndrome	1/2233 (0%)
Melaena	4/2233 (0.2%)
Mesenteric haemorrhage	1/2233 (0%)
Mesenteric vein thrombosis	2/2233 (0.1%)
Mouth haemorrhage	1/2233 (0%)
Nausea	5/2233 (0.2%)
Oesophageal haemorrhage	2/2233 (0.1%)
Oesophageal rupture	1/2233 (0%)
Oesophageal varices haemorrhage	10/2233 (0.4%)
Pancreatitis	2/2233 (0.1%)
Peritoneal haemorrhage	2/2233 (0.1%)
Pneumoperitoneum	1/2233 (0%)
Rectal haemorrhage	3/2233 (0.1%)
Rectal polyp	1/2233 (0%)
Retroperitoneal haematoma	2/2233 (0.1%)
Retroperitoneal haemorrhage	1/2233 (0%)
Small intestinal obstruction	1/2233 (0%)
Small intestinal stenosis	1/2233 (0%)
Splenic artery aneurysm	1/2233 (0%)
Subileus	3/2233 (0.1%)
Tooth loss	1/2233 (0%)
Toothache	1/2233 (0%)
Upper gastrointestinal haemorrhage	5/2233 (0.2%)
Varices oesophageal	5/2233 (0.2%)
Vomiting	16/2233 (0.7%)
General disorders
Asthenia	14/2233 (0.6%)
Chest pain	8/2233 (0.4%)
Death	12/2233 (0.5%)
Disease progression	4/2233 (0.2%)
Drug withdrawal syndrome	2/2233 (0.1%)
Face oedema	1/2233 (0%)
Fatigue	11/2233 (0.5%)
Gait disturbance	1/2233 (0%)
General physical health deterioration	19/2233 (0.9%)
Generalised oedema	5/2233 (0.2%)
Hernia	1/2233 (0%)
Hyperpyrexia	2/2233 (0.1%)
Malaise	1/2233 (0%)
Multiple organ dysfunction syndrome	11/2233 (0.5%)
Nodule	1/2233 (0%)
Non-cardiac chest pain	1/2233 (0%)
Oedema peripheral	10/2233 (0.4%)
Pain	1/2233 (0%)
Peripheral swelling	1/2233 (0%)
Polyp	1/2233 (0%)
Pseudocyst	1/2233 (0%)
Pyrexia	79/2233 (3.5%)
Sudden death	2/2233 (0.1%)
Hepatobiliary disorders
Bile duct stone	2/2233 (0.1%)
Biliary colic	1/2233 (0%)
Cholangitis chronic	1/2233 (0%)
Cholecystitis	3/2233 (0.1%)
Cholecystitis acute	3/2233 (0.1%)
Cholelithiasis	5/2233 (0.2%)
Hepatic failure	1/2233 (0%)
Hepatitis	1/2233 (0%)
Hepatorenal syndrome	1/2233 (0%)
Hepatotoxicity	1/2233 (0%)
Hyperbilirubinaemia	1/2233 (0%)
Jaundice	1/2233 (0%)
Portal hypertension	3/2233 (0.1%)
Portal vein thrombosis	5/2233 (0.2%)
Immune system disorders
Cytokine release syndrome	1/2233 (0%)
Hypersensitivity	1/2233 (0%)
Immunosuppression	1/2233 (0%)
Infections and infestations
Actinomycosis	1/2233 (0%)
Anal abscess	1/2233 (0%)
Appendicitis	5/2233 (0.2%)
Arthritis bacterial	2/2233 (0.1%)
Aspergillus infection	1/2233 (0%)
Atypical pneumonia	1/2233 (0%)
Bacterial infection	2/2233 (0.1%)
Biliary sepsis	1/2233 (0%)
Bone tuberculosis	1/2233 (0%)
Bronchitis	9/2233 (0.4%)
Bronchitis bacterial	1/2233 (0%)
Bronchopulmonary aspergillosis	2/2233 (0.1%)
Campylobacter infection	1/2233 (0%)
Cellulitis	8/2233 (0.4%)
Cerebral toxoplasmosis	1/2233 (0%)
Community acquired infection	1/2233 (0%)
Corneal abscess	1/2233 (0%)
Cystitis	1/2233 (0%)
Dengue fever	1/2233 (0%)
Dermo-hypodermitis	1/2233 (0%)
Device related infection	2/2233 (0.1%)
Device related sepsis	1/2233 (0%)
Diverticulitis	2/2233 (0.1%)
Endocarditis	2/2233 (0.1%)
Enterococcal infection	1/2233 (0%)
Enterococcal sepsis	1/2233 (0%)
Epididymitis	1/2233 (0%)
Erysipelas	3/2233 (0.1%)
Escherichia infection	2/2233 (0.1%)
Escherichia sepsis	6/2233 (0.3%)
Escherichia urinary tract infection	1/2233 (0%)
Gangrene	2/2233 (0.1%)
Gastroenteritis	11/2233 (0.5%)
Gastroenteritis norovirus	1/2233 (0%)
Gastroenteritis salmonella	1/2233 (0%)
Gastroenteritis viral	2/2233 (0.1%)
Gastrointestinal infection	3/2233 (0.1%)
Genital herpes	1/2233 (0%)
H1N1 influenza	1/2233 (0%)
Hepatic echinococciasis	1/2233 (0%)
Hepatitis B	1/2233 (0%)
Hepatitis E	1/2233 (0%)
Hepatitis infectious	1/2233 (0%)
Herpes simplex	1/2233 (0%)
Herpes simplex pneumonia	1/2233 (0%)
Herpes zoster	5/2233 (0.2%)
Herpes zoster infection neurological	1/2233 (0%)
Infection	3/2233 (0.1%)
Infectious pleural effusion	1/2233 (0%)
Influenza	5/2233 (0.2%)
Klebsiella infection	2/2233 (0.1%)
Localised infection	1/2233 (0%)
Lower respiratory tract infection	3/2233 (0.1%)
Lung abscess	1/2233 (0%)
Lung infection	11/2233 (0.5%)
Lymph node tuberculosis	3/2233 (0.1%)
Meningitis	1/2233 (0%)
Mycobacterial infection	1/2233 (0%)
Neurocryptococcosis	1/2233 (0%)
Ophthalmic herpes zoster	1/2233 (0%)
Oral candidiasis	2/2233 (0.1%)
Pelvic inflammatory disease	1/2233 (0%)
Perirectal abscess	1/2233 (0%)
Peritoneal tuberculosis	2/2233 (0.1%)
Peritonitis	4/2233 (0.2%)
Peritonitis bacterial	2/2233 (0.1%)
Pharyngitis	2/2233 (0.1%)
Pneumococcal infection	1/2233 (0%)
Pneumocystis jirovecii infection	1/2233 (0%)
Pneumonia	123/2233 (5.5%)
Pneumonia bacterial	2/2233 (0.1%)
Pneumonia pneumococcal	1/2233 (0%)
Pseudomonal sepsis	1/2233 (0%)
Psoas abscess	1/2233 (0%)
Pulmonary sepsis	2/2233 (0.1%)
Pulmonary tuberculosis	2/2233 (0.1%)
Pulpitis dental	1/2233 (0%)
Pyelonephritis	1/2233 (0%)
Q fever	1/2233 (0%)
Respiratory syncytial virus infection	1/2233 (0%)
Respiratory tract infection	19/2233 (0.9%)
Sepsis	31/2233 (1.4%)
Septic shock	21/2233 (0.9%)
Sinusitis	2/2233 (0.1%)
Skin infection	6/2233 (0.3%)
Soft tissue infection	1/2233 (0%)
Staphylococcal infection	3/2233 (0.1%)
Staphylococcal sepsis	1/2233 (0%)
Streptococcal sepsis	1/2233 (0%)
Subcutaneous abscess	1/2233 (0%)
Tooth abscess	1/2233 (0%)
Tracheitis	1/2233 (0%)
Tracheobronchitis	1/2233 (0%)
Tuberculosis	5/2233 (0.2%)
Tubo-ovarian abscess	1/2233 (0%)
Upper respiratory tract infection	3/2233 (0.1%)
Urinary tract infection	23/2233 (1%)
Urinary tract infection bacterial	1/2233 (0%)
Urosepsis	8/2233 (0.4%)
Vestibular neuronitis	1/2233 (0%)
Viral infection	1/2233 (0%)
Injury, poisoning and procedural complications
Anastomotic leak	1/2233 (0%)
Ankle fracture	2/2233 (0.1%)
Arterial injury	1/2233 (0%)
Brain contusion	1/2233 (0%)
Craniocerebral injury	1/2233 (0%)
Crush injury	1/2233 (0%)
Face injury	2/2233 (0.1%)
Facial bones fracture	1/2233 (0%)
Fall	6/2233 (0.3%)
Femoral neck fracture	1/2233 (0%)
Femur fracture	6/2233 (0.3%)
Foot fracture	2/2233 (0.1%)
Fractured sacrum	1/2233 (0%)
Head injury	4/2233 (0.2%)
Heart injury	1/2233 (0%)
Hip fracture	1/2233 (0%)
Humerus fracture	2/2233 (0.1%)
Joint injury	1/2233 (0%)
Limb injury	1/2233 (0%)
Lower limb fracture	1/2233 (0%)
Lumbar vertebral fracture	2/2233 (0.1%)
Meniscus injury	2/2233 (0.1%)
Overdose	1/2233 (0%)
Patella fracture	1/2233 (0%)
Post procedural haemorrhage	4/2233 (0.2%)
Rib fracture	2/2233 (0.1%)
Road traffic accident	1/2233 (0%)
Spinal compression fracture	1/2233 (0%)
Spinal fracture	2/2233 (0.1%)
Splenic injury	1/2233 (0%)
Splenic rupture	7/2233 (0.3%)
Subarachnoid haemorrhage	1/2233 (0%)
Subdural haemorrhage	1/2233 (0%)
Tendon rupture	1/2233 (0%)
Thoracic vertebral fracture	1/2233 (0%)
Transfusion reaction	1/2233 (0%)
Traumatic fracture	1/2233 (0%)
Traumatic haemorrhage	1/2233 (0%)
Upper limb fracture	1/2233 (0%)
Wound dehiscence	1/2233 (0%)
Investigations
Blast cell count increased	3/2233 (0.1%)
Blood alkaline phosphatase increased	1/2233 (0%)
Blood lactate dehydrogenase increased	2/2233 (0.1%)
Body temperature increased	1/2233 (0%)
C-reactive protein increased	2/2233 (0.1%)
Cardioactive drug level increased	1/2233 (0%)
Ejection fraction decreased	1/2233 (0%)
Electrocardiogram QT prolonged	1/2233 (0%)
Electrocardiogram T wave abnormal	1/2233 (0%)
Electrocardiogram T wave amplitude increased	1/2233 (0%)
Epstein-Barr virus antigen positive	1/2233 (0%)
Gamma-glutamyltransferase increased	1/2233 (0%)
General physical condition abnormal	4/2233 (0.2%)
Haemoglobin decreased	2/2233 (0.1%)
Heart rate irregular	1/2233 (0%)
Hepatic enzyme increased	1/2233 (0%)
Lipase increased	1/2233 (0%)
Myeloblast count increased	1/2233 (0%)
Platelet count decreased	1/2233 (0%)
Portal vein pressure increased	1/2233 (0%)
Sensory level abnormal	1/2233 (0%)
Transaminases increased	1/2233 (0%)
Troponin I increased	1/2233 (0%)
White blood cell count increased	1/2233 (0%)
Metabolism and nutrition disorders
Cachexia	3/2233 (0.1%)
Decreased appetite	1/2233 (0%)
Dehydration	8/2233 (0.4%)
Diabetes mellitus	3/2233 (0.1%)
Diabetic metabolic decompensation	1/2233 (0%)
Electrolyte imbalance	1/2233 (0%)
Fluid retention	1/2233 (0%)
Gout	3/2233 (0.1%)
Hypercalcaemia	1/2233 (0%)
Hyperkalaemia	8/2233 (0.4%)
Hyperlactacidaemia	1/2233 (0%)
Hyperuricaemia	1/2233 (0%)
Hypocalcaemia	2/2233 (0.1%)
Hypoglycaemia	3/2233 (0.1%)
Hypokalaemia	1/2233 (0%)
Hyponatraemia	3/2233 (0.1%)
Hypophosphataemia	1/2233 (0%)
Hypovolaemia	1/2233 (0%)
Metabolic acidosis	3/2233 (0.1%)
Tumour lysis syndrome	4/2233 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/2233 (0.1%)
Arthritis	2/2233 (0.1%)
Arthropathy	1/2233 (0%)
Back pain	8/2233 (0.4%)
Bone pain	11/2233 (0.5%)
Chondrocalcinosis pyrophosphate	1/2233 (0%)
Compartment syndrome	1/2233 (0%)
Crystal arthropathy	1/2233 (0%)
Flank pain	1/2233 (0%)
Gouty arthritis	1/2233 (0%)
Haemarthrosis	1/2233 (0%)
Intervertebral disc protrusion	1/2233 (0%)
Meniscal degeneration	1/2233 (0%)
Muscle haemorrhage	1/2233 (0%)
Muscle tightness	1/2233 (0%)
Muscular weakness	2/2233 (0.1%)
Musculoskeletal chest pain	1/2233 (0%)
Musculoskeletal pain	1/2233 (0%)
Myalgia	1/2233 (0%)
Neck pain	2/2233 (0.1%)
Osteoarthritis	1/2233 (0%)
Osteolysis	2/2233 (0.1%)
Osteonecrosis	1/2233 (0%)
Osteoporotic fracture	1/2233 (0%)
Pain in extremity	4/2233 (0.2%)
Rotator cuff syndrome	1/2233 (0%)
Soft tissue necrosis	1/2233 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon	1/2233 (0%)
Acute leukaemia	13/2233 (0.6%)
Acute myeloid leukaemia	18/2233 (0.8%)
Adenocarcinoma pancreas	1/2233 (0%)
B-cell lymphoma	1/2233 (0%)
Basal cell carcinoma	10/2233 (0.4%)
Bladder transitional cell carcinoma	1/2233 (0%)
Blast cell crisis	1/2233 (0%)
Chloroma	1/2233 (0%)
Cholangiocarcinoma	1/2233 (0%)
Chronic lymphocytic leukaemia	2/2233 (0.1%)
Chronic myeloid leukaemia	1/2233 (0%)
Chronic myeloid leukaemia transformation	2/2233 (0.1%)
Chronic myelomonocytic leukaemia	1/2233 (0%)
Intestinal adenocarcinoma	1/2233 (0%)
Leukaemia	7/2233 (0.3%)
Lung neoplasm malignant	4/2233 (0.2%)
Lymphangioma	1/2233 (0%)
Malignant melanoma	1/2233 (0%)
Metastases to liver	1/2233 (0%)
Metastases to lung	1/2233 (0%)
Monoclonal gammopathy	1/2233 (0%)
Myelofibrosis	5/2233 (0.2%)
Myeloid metaplasia	2/2233 (0.1%)
Neoplasm	2/2233 (0.1%)
Neoplasm skin	3/2233 (0.1%)
Neuroendocrine carcinoma	1/2233 (0%)
Neuroendocrine tumour	1/2233 (0%)
Non-Hodgkin's lymphoma	2/2233 (0.1%)
Pelvic neoplasm	1/2233 (0%)
Prostate cancer	4/2233 (0.2%)
Rectal adenocarcinoma	1/2233 (0%)
Second primary malignancy	1/2233 (0%)
Squamous cell carcinoma	9/2233 (0.4%)
Squamous cell carcinoma of skin	6/2233 (0.3%)
Squamous cell carcinoma of the vagina	1/2233 (0%)
Transitional cell carcinoma	1/2233 (0%)
Tumour thrombosis	1/2233 (0%)
Uterine leiomyoma	1/2233 (0%)
Nervous system disorders
Basilar artery aneurysm	1/2233 (0%)
Central nervous system haemorrhage	1/2233 (0%)
Central nervous system lesion	1/2233 (0%)
Cerebral haemorrhage	2/2233 (0.1%)
Cerebral ischaemia	1/2233 (0%)
Cerebrovascular accident	4/2233 (0.2%)
Coma	1/2233 (0%)
Cranial nerve paralysis	1/2233 (0%)
Dizziness	5/2233 (0.2%)
Drop attacks	1/2233 (0%)
Dysarthria	1/2233 (0%)
Embolic stroke	1/2233 (0%)
Encephalopathy	1/2233 (0%)
Extrapyramidal disorder	1/2233 (0%)
Generalised tonic-clonic seizure	1/2233 (0%)
Haemorrhagic stroke	2/2233 (0.1%)
Headache	3/2233 (0.1%)
Hepatic encephalopathy	1/2233 (0%)
Hydrocephalus	1/2233 (0%)
Hyperaesthesia	1/2233 (0%)
Ischaemic stroke	1/2233 (0%)
Loss of consciousness	1/2233 (0%)
Muscle contractions involuntary	1/2233 (0%)
Myoclonus	1/2233 (0%)
Neuralgia	1/2233 (0%)
Neurological decompensation	1/2233 (0%)
Neuropathy peripheral	3/2233 (0.1%)
Osmotic demyelination syndrome	1/2233 (0%)
Paraesthesia	1/2233 (0%)
Parkinson's disease	1/2233 (0%)
Posterior reversible encephalopathy syndrome	1/2233 (0%)
Presyncope	1/2233 (0%)
Pyramidal tract syndrome	1/2233 (0%)
Sciatica	1/2233 (0%)
Seizure	3/2233 (0.1%)
Somnolence	1/2233 (0%)
Speech disorder	1/2233 (0%)
Syncope	11/2233 (0.5%)
Transient ischaemic attack	5/2233 (0.2%)
Product Issues
Device leakage	1/2233 (0%)
Psychiatric disorders
Anxiety	1/2233 (0%)
Anxiety disorder	1/2233 (0%)
Confusional state	3/2233 (0.1%)
Delirium	1/2233 (0%)
Depression	1/2233 (0%)
Disorientation	2/2233 (0.1%)
Renal and urinary disorders
Acute kidney injury	19/2233 (0.9%)
Acute prerenal failure	1/2233 (0%)
Anuria	1/2233 (0%)
Calculus bladder	2/2233 (0.1%)
Chronic kidney disease	6/2233 (0.3%)
Dysuria	1/2233 (0%)
Haematuria	2/2233 (0.1%)
Hydronephrosis	1/2233 (0%)
Nephrolithiasis	6/2233 (0.3%)
Nephropathy	1/2233 (0%)
Nephrotic syndrome	1/2233 (0%)
Renal colic	3/2233 (0.1%)
Renal failure	12/2233 (0.5%)
Renal impairment	2/2233 (0.1%)
Renal infarct	1/2233 (0%)
Tubulointerstitial nephritis	1/2233 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/2233 (0%)
Cervical dysplasia	1/2233 (0%)
Menometrorrhagia	1/2233 (0%)
Ovarian cyst	1/2233 (0%)
Postmenopausal haemorrhage	1/2233 (0%)
Prostatitis	2/2233 (0.1%)
Testicular pain	1/2233 (0%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	4/2233 (0.2%)
Acute respiratory distress syndrome	7/2233 (0.3%)
Acute respiratory failure	7/2233 (0.3%)
Alveolitis	1/2233 (0%)
Asthma	1/2233 (0%)
Bronchospasm	3/2233 (0.1%)
Chronic obstructive pulmonary disease	3/2233 (0.1%)
Chronic respiratory failure	1/2233 (0%)
Cough	6/2233 (0.3%)
Dyspnoea	36/2233 (1.6%)
Emphysema	1/2233 (0%)
Epistaxis	10/2233 (0.4%)
Haemoptysis	4/2233 (0.2%)
Haemothorax	1/2233 (0%)
Hydrothorax	1/2233 (0%)
Interstitial lung disease	3/2233 (0.1%)
Lung infiltration	2/2233 (0.1%)
Oropharyngeal pain	1/2233 (0%)
Pleural effusion	13/2233 (0.6%)
Pneumonia aspiration	1/2233 (0%)
Pneumonitis	5/2233 (0.2%)
Pneumothorax	1/2233 (0%)
Productive cough	1/2233 (0%)
Pulmonary embolism	18/2233 (0.8%)
Pulmonary haemorrhage	1/2233 (0%)
Pulmonary hypertension	8/2233 (0.4%)
Pulmonary oedema	5/2233 (0.2%)
Respiratory distress	2/2233 (0.1%)
Respiratory failure	26/2233 (1.2%)
Thoracic haemorrhage	1/2233 (0%)
Skin and subcutaneous tissue disorders
Dermal cyst	1/2233 (0%)
Dermatitis	1/2233 (0%)
Erythema nodosum	1/2233 (0%)
Hyperhidrosis	1/2233 (0%)
Panniculitis	1/2233 (0%)
Pruritus	2/2233 (0.1%)
Skin lesion	1/2233 (0%)
Skin mass	1/2233 (0%)
Skin ulcer	2/2233 (0.1%)
Surgical and medical procedures
Stem cell transplant	1/2233 (0%)
Vascular disorders
Aortic aneurysm	2/2233 (0.1%)
Aortic rupture	1/2233 (0%)
Aortic stenosis	1/2233 (0%)
Arterial disorder	2/2233 (0.1%)
Arterial haemorrhage	1/2233 (0%)
Circulatory collapse	2/2233 (0.1%)
Deep vein thrombosis	10/2233 (0.4%)
Embolism	1/2233 (0%)
Haematoma	9/2233 (0.4%)
Hyperaemia	1/2233 (0%)
Hypertension	3/2233 (0.1%)
Hypertensive crisis	1/2233 (0%)
Hypotension	7/2233 (0.3%)
Pallor	1/2233 (0%)
Peripheral artery occlusion	1/2233 (0%)
Peripheral artery stenosis	1/2233 (0%)
Peripheral ischaemia	3/2233 (0.1%)
Phlebitis	1/2233 (0%)
Shock	1/2233 (0%)
Thrombophlebitis superficial	1/2233 (0%)
Venous thrombosis	1/2233 (0%)
Other (Not Including Serious) Adverse Events
	INC424
	Affected / at Risk (%)	# Events
Total	2008/2233 (89.9%)
Blood and lymphatic system disorders
Anaemia	1300/2233 (58.2%)
Neutropenia	146/2233 (6.5%)
Thrombocytopenia	990/2233 (44.3%)
Gastrointestinal disorders
Abdominal pain	149/2233 (6.7%)
Constipation	121/2233 (5.4%)
Diarrhoea	267/2233 (12%)
Nausea	128/2233 (5.7%)
General disorders
Asthenia	331/2233 (14.8%)
Fatigue	215/2233 (9.6%)
Oedema peripheral	182/2233 (8.2%)
Pyrexia	310/2233 (13.9%)
Infections and infestations
Herpes zoster	112/2233 (5%)
Nasopharyngitis	115/2233 (5.2%)
Urinary tract infection	114/2233 (5.1%)
Investigations
Alanine aminotransferase increased	134/2233 (6%)
Platelet count decreased	198/2233 (8.9%)
Weight increased	140/2233 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	176/2233 (7.9%)
Back pain	115/2233 (5.2%)
Pain in extremity	147/2233 (6.6%)
Nervous system disorders
Headache	191/2233 (8.6%)
Respiratory, thoracic and mediastinal disorders
Cough	186/2233 (8.3%)
Dyspnoea	155/2233 (6.9%)
Skin and subcutaneous tissue disorders
Pruritus	131/2233 (5.9%)

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