Clinical Trial Results:
A Double-blind, Randomised, Parallel Group, Phase III Study to Demonstrate Equivalent Efficacy and Comparable Safety of CT-P6 and Herceptin, Both in Combination with Paclitaxel, in Patients with Metastatic Breast Cancer

Trial information Top of page
Trial identification
Sponsor protocol code	CT-P6 3.1
Additional study identifiers
ISRCTN number	-
US NCT number	NCT01084876
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	Celltrion, Inc.
Sponsor organisation address	23, Academy-ro, Yeonsu-gu, Incheon, Korea, Republic of, 22014
Public contact	Celltrion, Inc., Celltrion, Inc., 82 850 5000, contact@celltrion.com
Scientific contact	Celltrion, Inc., Celltrion, Inc., 82 850 5000, contact@celltrion.com
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Interim
Date of interim/final analysis	31 Aug 2016
Is this the analysis of the primary completion data?	Yes
Primary completion date	08 Jul 2012
Global end of trial reached?	No
General information about the trial
Main objective of the trial	The primary objective of this study is to demonstrate equivalence of CT-P6 and Herceptin, both given in combination with paclitaxel, in terms of efficacy determined by overall response rate (ORR).
Protection of trial subjects	The study was conducted according to the protocol and in compliance with Good Clinical Practice (GCP) and other applicable regulatory requirements.
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	15 Jun 2010
Long term follow-up planned	Yes
Long term follow-up rationale	Safety
Long term follow-up duration	40 Months
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Belarus: 16
Country: Number of subjects enrolled	Bulgaria: 20
Country: Number of subjects enrolled	Georgia: 21
Country: Number of subjects enrolled	Hong Kong: 2
Country: Number of subjects enrolled	India: 66
Country: Number of subjects enrolled	Korea, Republic of: 63
Country: Number of subjects enrolled	Latvia: 13
Country: Number of subjects enrolled	Malaysia: 5
Country: Number of subjects enrolled	Philippines: 32
Country: Number of subjects enrolled	Poland: 8
Country: Number of subjects enrolled	Romania: 13
Country: Number of subjects enrolled	Russian Federation: 86
Country: Number of subjects enrolled	Serbia: 9
Country: Number of subjects enrolled	Singapore: 1
Country: Number of subjects enrolled	Thailand: 7
Country: Number of subjects enrolled	Turkey: 6
Country: Number of subjects enrolled	Ukraine: 107
Worldwide total number of subjects	475
EEA total number of subjects	54
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	419
From 65 to 84 years	56
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Patients were enrolled at 84 sites across Bulgaria, Poland, Romania, Ukraine, Russia, Georgia, Belarus, India, Turkey, Hong Kong, Singapore, Thailand, Malaysia, and the Philippines.
Pre-assignment
Screening details	This study included females 18 years of age or older with Her-2 positive metastatic breast cancer who had not been treated in the first line metastatic setting.
Period 1
Period 1 title	Primary endpoint (8 cycle treatment) (overall period)
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Monitor, Data analyst, Carer
Arms
Are arms mutually exclusive	Yes
Arm title	CT-P6
Arm description	-
Arm type	Experimental
Investigational medicinal product name	CT-P6
Investigational medicinal product code
Other name
Pharmaceutical forms	Powder for infusion
Routes of administration	Intravenous use
Dosage and administration details	Initial dose of 8 mg/kg, then at a dose of 6 mg/kg every three weeks
Arm title	Herceptin
Arm description	-
Arm type	Active comparator
Investigational medicinal product name	Herceptin
Investigational medicinal product code
Other name
Pharmaceutical forms	Powder for infusion
Routes of administration	Intravenous use
Dosage and administration details	Initial dose of 8 mg/kg, then at a dose of 6 mg/kg every three weeks
Number of subjects in period 1 CT-P6 Herceptin Started 244 231 Completed 185 193 Not completed 59 38      Adverse event, serious fatal 2 2      Consent withdrawn by subject 4 -      Physician decision 2 -      Disease progression 41 21      Adverse event, non-fatal 8 6      Other 2 9

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	CT-P6
Reporting group description	-
Reporting group title	Herceptin
Reporting group description	-
Reporting group values CT-P6 Herceptin Total Number of subjects 244 231 475 Age categorical Units: Subjects     Adults (18-64 years) 210 209 419     From 65-84 years 34 22 56     85 years and over 0 0 0 Age continuous Units: years     median (full range (min-max)) 54.0 (31 to 75) 53.0 (25 to 78) - Gender categorical Units: Subjects     Female 244 231 475     Male 0 0 0
Subject analysis sets
Subject analysis set title	Full Analysis Set (FAS)
Subject analysis set type	Full analysis
Subject analysis set description	All randomised patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication
Subject analysis sets values Full Analysis Set (FAS) Number of subjects 475 Age categorical Units: Subjects     Adults (18-64 years) 419     From 65-84 years 56     85 years and over 0 Age continuous Units: years     median (full range (min-max)) 54.0 (25 to 78) Gender categorical Units: Subjects     Female 475     Male 0

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	CT-P6
Reporting group description	-
Reporting group title	Herceptin
Reporting group description	-
Subject analysis set title	Full Analysis Set (FAS)
Subject analysis set type	Full analysis
Subject analysis set description	All randomised patients who received any study drug and had at least one post-baseline assessment, with the exception of the patients who violated against Herceptin indication

End points Top of page

Primary: Overall Response Rate at 6 Months Top of page
End point title	Overall Response Rate at 6 Months
End point description
End point type	Primary
End point timeframe	6 months
End point values CT-P6 Herceptin Number of subjects analysed 244 [1] 231 [2] Units: Number of patients with CR or PR     ORR (CR or PR) 138 143
Notes [1] - Full Analysis Set (FAS) [2] - Full Analysis Set (FAS)
Statistical analysis title	ORR at 6 month
Comparison groups	Herceptin v CT-P6
Number of subjects included in analysis	475
Analysis specification	Pre-specified
Analysis type	equivalence [3]
Method
Parameter type	Risk difference (RD)
Point estimate	-0.0535
Confidence interval
level	95%
sides	2-sided
lower limit	-0.143
upper limit	0.036
Notes [3] - Equivalence margin (-0.15, 0.15)

Primary: Overall Response Rate at 6 Months Top of page

Adverse events Top of page
Adverse events information
Timeframe for reporting adverse events	2 years
Assessment type	Systematic
Dictionary used for adverse event reporting
Dictionary name	MedDRA
Dictionary version	13
Reporting groups
Reporting group title	CT-P6
Reporting group description	-
Reporting group title	Herceptin
Reporting group description	-
Serious adverse events CT-P6 Herceptin Total subjects affected by serious adverse events      subjects affected / exposed 34 / 244 (13.93%) 37 / 231 (16.02%)      number of deaths (all causes) 117 121      number of deaths resulting from adverse events 8 8 Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 Malignant pleural effusion      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Metastases to central nervous system      subjects affected / exposed 0 / 244 (0.00%) 3 / 231 (1.30%)      occurrences causally related to treatment / all 0 / 0 0 / 3      deaths causally related to treatment / all 0 / 0 0 / 2 Vascular disorders Hypertension      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Surgical and medical procedures Biliary drainage      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Cataract operation      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Extended radical mastectomy      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Mastectomy      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 General disorders and administration site conditions Death      subjects affected / exposed 0 / 244 (0.00%) 2 / 231 (0.87%)      occurrences causally related to treatment / all 0 / 0 0 / 2      deaths causally related to treatment / all 0 / 0 0 / 2 Disease progression      subjects affected / exposed 4 / 244 (1.64%) 6 / 231 (2.60%)      occurrences causally related to treatment / all 0 / 4 0 / 6      deaths causally related to treatment / all 0 / 4 0 / 3 Inflammation      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Infusion related reaction      subjects affected / exposed 2 / 244 (0.82%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 2 / 2 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Pyrexia      subjects affected / exposed 2 / 244 (0.82%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 1 / 2 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Immune system disorders Hypersensitivity      subjects affected / exposed 2 / 244 (0.82%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 1 / 3 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Reproductive system and breast disorders Metrorrhagia      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Vulval ulceration      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Respiratory, thoracic and mediastinal disorders Dyspnoea      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Interstitial lung disease      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Pleural effusion      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Respiratory failure      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 Investigations Hepatic enzyme increased      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Injury, poisoning and procedural complications Concussion      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Femur fracture      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Radius fracture      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Cardiac disorders Cardiac arrest      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 Cardiac failure acute      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 1 / 1      deaths causally related to treatment / all 0 / 0 1 / 1 Cardiac failure congestive      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Left ventricular dysfunction      subjects affected / exposed 2 / 244 (0.82%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 3 / 3 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Nervous system disorders Brain oedema      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Cerebrovascular accident      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 1 0 / 0 Neuropathy peripheral      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 1 / 244 (0.41%) 2 / 231 (0.87%)      occurrences causally related to treatment / all 1 / 1 1 / 2      deaths causally related to treatment / all 0 / 0 0 / 0 Febrile neutropenia      subjects affected / exposed 5 / 244 (2.05%) 4 / 231 (1.73%)      occurrences causally related to treatment / all 2 / 5 1 / 4      deaths causally related to treatment / all 0 / 0 0 / 0 Neutropenia      subjects affected / exposed 2 / 244 (0.82%) 6 / 231 (2.60%)      occurrences causally related to treatment / all 0 / 2 1 / 6      deaths causally related to treatment / all 0 / 0 0 / 0 Thrombocytopenia      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Colitis      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Diarrhoea      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Nausea      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Vomiting      subjects affected / exposed 1 / 244 (0.41%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 1 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Hepatobiliary disorders Cholangitis      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 2      deaths causally related to treatment / all 0 / 0 0 / 0 Skin and subcutaneous tissue disorders Leukocytoclastic vasculitis      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 1 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Musculoskeletal and connective tissue disorders Back pain      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Infections and infestations Acute tonsillitis      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Bacteraemia      subjects affected / exposed 2 / 244 (0.82%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 2 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Gangrene      subjects affected / exposed 1 / 244 (0.41%) 0 / 231 (0.00%)      occurrences causally related to treatment / all 0 / 1 0 / 0      deaths causally related to treatment / all 0 / 0 0 / 0 Gastroenteritis      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Herpes zoster      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Malaria      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Neutropenic infection      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Pneumonia      subjects affected / exposed 2 / 244 (0.82%) 3 / 231 (1.30%)      occurrences causally related to treatment / all 1 / 2 0 / 3      deaths causally related to treatment / all 0 / 0 0 / 0 Urinary tract infection      subjects affected / exposed 1 / 244 (0.41%) 2 / 231 (0.87%)      occurrences causally related to treatment / all 0 / 1 0 / 2      deaths causally related to treatment / all 0 / 0 0 / 0 Metabolism and nutrition disorders Hypercalcaemia      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0 Hypoglycaemia      subjects affected / exposed 0 / 244 (0.00%) 1 / 231 (0.43%)      occurrences causally related to treatment / all 0 / 0 0 / 1      deaths causally related to treatment / all 0 / 0 0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events CT-P6 Herceptin Total subjects affected by non serious adverse events      subjects affected / exposed 226 / 244 (92.62%) 214 / 231 (92.64%) Investigations Alanine aminotransferase increased      subjects affected / exposed 23 / 244 (9.43%) 24 / 231 (10.39%)      occurrences all number 51 50 Aspartate aminotransferase increased      subjects affected / exposed 17 / 244 (6.97%) 15 / 231 (6.49%)      occurrences all number 28 24 Blood alkaline phosphatase increased      subjects affected / exposed 13 / 244 (5.33%) 10 / 231 (4.33%)      occurrences all number 18 18 Gamma-glutamyltransferase increased      subjects affected / exposed 18 / 244 (7.38%) 12 / 231 (5.19%)      occurrences all number 39 27 Vascular disorders Hypertension      subjects affected / exposed 10 / 244 (4.10%) 14 / 231 (6.06%)      occurrences all number 12 19 Nervous system disorders Dizziness      subjects affected / exposed 17 / 244 (6.97%) 24 / 231 (10.39%)      occurrences all number 24 35 Headache      subjects affected / exposed 21 / 244 (8.61%) 33 / 231 (14.29%)      occurrences all number 26 46 Neuropathy peripheral      subjects affected / exposed 65 / 244 (26.64%) 57 / 231 (24.68%)      occurrences all number 147 130 Paraesthesia      subjects affected / exposed 15 / 244 (6.15%) 9 / 231 (3.90%)      occurrences all number 16 18 Peripheral sensory neuropathy      subjects affected / exposed 50 / 244 (20.49%) 54 / 231 (23.38%)      occurrences all number 125 85 Blood and lymphatic system disorders Anaemia      subjects affected / exposed 31 / 244 (12.70%) 38 / 231 (16.45%)      occurrences all number 58 67 Leukopenia      subjects affected / exposed 28 / 244 (11.48%) 50 / 231 (21.65%)      occurrences all number 40 85 Neutropenia      subjects affected / exposed 68 / 244 (27.87%) 76 / 231 (32.90%)      occurrences all number 126 152 General disorders and administration site conditions Asthenia      subjects affected / exposed 49 / 244 (20.08%) 34 / 231 (14.72%)      occurrences all number 108 52 Chills      subjects affected / exposed 10 / 244 (4.10%) 19 / 231 (8.23%)      occurrences all number 15 20 Fatigue      subjects affected / exposed 30 / 244 (12.30%) 34 / 231 (14.72%)      occurrences all number 78 62 Oedema peripheral      subjects affected / exposed 10 / 244 (4.10%) 13 / 231 (5.63%)      occurrences all number 13 18 Pain      subjects affected / exposed 11 / 244 (4.51%) 16 / 231 (6.93%)      occurrences all number 17 31 Pyrexia      subjects affected / exposed 23 / 244 (9.43%) 28 / 231 (12.12%)      occurrences all number 40 42 Gastrointestinal disorders Abdominal pain      subjects affected / exposed 14 / 244 (5.74%) 13 / 231 (5.63%)      occurrences all number 20 14 Constipation      subjects affected / exposed 10 / 244 (4.10%) 18 / 231 (7.79%)      occurrences all number 14 22 Diarrhoea      subjects affected / exposed 34 / 244 (13.93%) 44 / 231 (19.05%)      occurrences all number 52 74 Nausea      subjects affected / exposed 41 / 244 (16.80%) 40 / 231 (17.32%)      occurrences all number 129 74 Stomatitis      subjects affected / exposed 14 / 244 (5.74%) 16 / 231 (6.93%)      occurrences all number 25 19 Vomiting      subjects affected / exposed 23 / 244 (9.43%) 27 / 231 (11.69%)      occurrences all number 34 37 Respiratory, thoracic and mediastinal disorders Cough      subjects affected / exposed 25 / 244 (10.25%) 22 / 231 (9.52%)      occurrences all number 34 31 Dyspnoea      subjects affected / exposed 13 / 244 (5.33%) 10 / 231 (4.33%)      occurrences all number 19 13 Skin and subcutaneous tissue disorders Alopecia      subjects affected / exposed 122 / 244 (50.00%) 127 / 231 (54.98%)      occurrences all number 153 151 Pruritus      subjects affected / exposed 10 / 244 (4.10%) 18 / 231 (7.79%)      occurrences all number 14 24 Rash      subjects affected / exposed 19 / 244 (7.79%) 15 / 231 (6.49%)      occurrences all number 27 38 Psychiatric disorders Insomnia      subjects affected / exposed 11 / 244 (4.51%) 16 / 231 (6.93%)      occurrences all number 18 19 Musculoskeletal and connective tissue disorders Arthralgia      subjects affected / exposed 22 / 244 (9.02%) 33 / 231 (14.29%)      occurrences all number 82 123 Back pain      subjects affected / exposed 15 / 244 (6.15%) 20 / 231 (8.66%)      occurrences all number 20 30 Bone pain      subjects affected / exposed 24 / 244 (9.84%) 17 / 231 (7.36%)      occurrences all number 63 30 Musculoskeletal pain      subjects affected / exposed 9 / 244 (3.69%) 13 / 231 (5.63%)      occurrences all number 10 21 Myalgia      subjects affected / exposed 47 / 244 (19.26%) 53 / 231 (22.94%)      occurrences all number 173 167 Pain in extremity      subjects affected / exposed 23 / 244 (9.43%) 31 / 231 (13.42%)      occurrences all number 36 49 Infections and infestations Upper respiratory tract infection      subjects affected / exposed 8 / 244 (3.28%) 13 / 231 (5.63%)      occurrences all number 11 17 Metabolism and nutrition disorders Decreased appetite      subjects affected / exposed 19 / 244 (7.79%) 16 / 231 (6.93%)      occurrences all number 37 30 Hypercholesterolaemia      subjects affected / exposed 8 / 244 (3.28%) 14 / 231 (6.06%)      occurrences all number 23 24 Hyperglycaemia      subjects affected / exposed 10 / 244 (4.10%) 15 / 231 (6.49%)      occurrences all number 31 36

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? Yes
Date	Amendment
19 May 2010	Amendments in the eligibility crieria and procedures
03 Jul 2013	The blinded study drug information was opened
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
The study is planned to analyze the data from both phase I/IIa and III and data collected from phase III are not analyzed separately.

More information Top of page