Paclitaxel With / Without GW572016 (Lapatinib) As First Line Therapy For Women With Advanced Or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00075270
First received: January 7, 2004
Last updated: February 13, 2014
Last verified: December 2013
Results First Received: March 14, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Neoplasms, Breast
Interventions: Drug: Paclitaxel
Drug: GW572016 (Lapatinib)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 580 participants were enrolled and randomized to treatment; however one participant withdrew from the study before taking any medication. Thus, only 579 participants were included in the Intent-to-Treat Population (comprised of all randomized participants who had received at least one dose of randomized therapy [lapatinib or placebo]).

Reporting Groups
  Description
Lapatinib With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.

Participant Flow:   Overall Study
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
STARTED     291     288  
Missing     26 [1]   13 [1]
COMPLETED     5     4  
NOT COMPLETED     286     284  
Withdrawal by Subject                 28                 21  
Lost to Follow-up                 25                 28  
Protocol Violation                 0                 2  
Death                 198                 215  
Other/Unknown                 9                 5  
Missing                 26                 13  
[1] These participants have no completion status information recorded on the case report forms.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Lapatinib With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Total Total of all reporting groups

Baseline Measures
    Lapatinib With Paclitaxel     Placebo With Paclitaxel     Total  
Number of Participants  
[units: participants]
  291     288     579  
Age  
[units: Years]
Mean ± Standard Deviation
  51.3  ± 10.45     52.4  ± 10.98     51.8  ± 10.72  
Gender  
[units: Participants]
     
Female     291     288     579  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
White     190     182     372  
Black     10     10     20  
Asian     30     35     65  
American Hispanic     54     53     107  
Unknown     7     8     15  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Progression as Evaluated by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

2.  Primary:   Time to Progression as Evaluated by the Independent Review Committee (IRC)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

3.  Secondary:   Number of Participants With Tumor Response as Evaluated by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

4.  Secondary:   Number of Participants With Tumor Response as Evaluated by the Independent Review Committee   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

5.  Secondary:   Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

6.  Secondary:   Number of Participants With a Response of CR or PR by the Indicated Study Week   [ Time Frame: Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72 ]

7.  Secondary:   Duration of Response (DOR)   [ Time Frame: From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks) ]

8.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

9.  Secondary:   Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)   [ Time Frame: Randomization until the date of disease progression or death (average of 26 weeks) ]

10.  Secondary:   Overall Survival   [ Time Frame: Randomization until the date of death due to any cause (average of 24 months) ]

11.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

12.  Secondary:   Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

13.  Secondary:   Change From Baseline in Trial Outcome Index (TOI) Questionnaire Scores   [ Time Frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal ]

14.  Secondary:   Number of Participants With the Indicated ErbB2 Status at Baseline   [ Time Frame: Baseline ]

15.  Secondary:   ErbB2 Ratio   [ Time Frame: Baseline ]

16.  Secondary:   Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening   [ Time Frame: Screening (Day -1) ]

17.  Secondary:   Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results   [ Time Frame: Baseline ]

18.  Secondary:   Serum ErbB1 Concentration   [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

19.  Secondary:   Serum ErbB2 Concentration   [ Time Frame: Screening (Day-1) and Withdrawal (up to Study Week 129) ]

20.  Secondary:   Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4   [ Time Frame: Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks) ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame Serious adverse events (SAEs) and adverse events were collected from the first dose of randomized therapy until 30 days after the last dose of randomized therapy (average of 26 weeks).
Additional Description SAEs and AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of investigational product (based on the actual treatment received if this differed from that to which the participant was randomized). Two participants randomized to the placebo group actually received lapatinib.

Frequency Threshold
Threshold above which other adverse events are reported   0%  

Reporting Groups
  Description
Lapatinib With Paclitaxel Participants received lapatinib 1500 milligrams (mg) orally once daily (OD) with paclitaxel 175 mg/meters squared (m^2) intravenously (IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.
Placebo With Paclitaxel Participants received matching placebo orally OD with paclitaxel (175 mg/m^2 IV) over the course of 3 hours, every 3 weeks. The treatment group was stratified by sites of metastatic disease and stage of disease. Participants were treated until disease progression, unacceptable toxicity, or consent withdrawal.

Other Adverse Events
    Lapatinib With Paclitaxel     Placebo With Paclitaxel  
Total, other (not including serious) adverse events      
# participants affected / at risk     287/293     278/286  
Blood and lymphatic system disorders      
Neutropenia † 1    
# participants affected / at risk     76/293 (25.94%)     58/286 (20.28%)  
Anemia † 1    
# participants affected / at risk     32/293 (10.92%)     35/286 (12.24%)  
Leukopenia † 1    
# participants affected / at risk     26/293 (8.87%)     25/286 (8.74%)  
Febrile neutropenia † 1    
# participants affected / at risk     12/293 (4.10%)     4/286 (1.40%)  
Leukocytosis † 1    
# participants affected / at risk     2/293 (0.68%)     5/286 (1.75%)  
Thrombocytopenia † 1    
# participants affected / at risk     2/293 (0.68%)     4/286 (1.40%)  
Lymphopenia † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Lymph node pain † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Thrombocytosis † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Disseminated intravascular coagulation † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Eosinophilia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hyperchromasia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Monocytosis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pancytopenia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Ear and labyrinth disorders      
Vertigo † 1    
# participants affected / at risk     4/293 (1.37%)     7/286 (2.45%)  
Tinnitus † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Deafness † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Ear pain † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypoacusis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Endocrine disorders      
Cushingoid † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypothyroidism † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Gastrointestinal disorders      
Diarrhea † 1    
# participants affected / at risk     171/293 (58.36%)     73/286 (25.52%)  
Nausea † 1    
# participants affected / at risk     100/293 (34.13%)     85/286 (29.72%)  
Vomiting † 1    
# participants affected / at risk     74/293 (25.26%)     48/286 (16.78%)  
Constipation † 1    
# participants affected / at risk     35/293 (11.95%)     48/286 (16.78%)  
Dyspepsia † 1    
# participants affected / at risk     38/293 (12.97%)     13/286 (4.55%)  
Abdominal pain † 1    
# participants affected / at risk     33/293 (11.26%)     17/286 (5.94%)  
Stomatitis † 1    
# participants affected / at risk     21/293 (7.17%)     13/286 (4.55%)  
Abdominal pain upper † 1    
# participants affected / at risk     12/293 (4.10%)     16/286 (5.59%)  
Abdominal distension † 1    
# participants affected / at risk     14/293 (4.78%)     9/286 (3.15%)  
Dry mouth † 1    
# participants affected / at risk     9/293 (3.07%)     5/286 (1.75%)  
Hemorrhoids † 1    
# participants affected / at risk     6/293 (2.05%)     4/286 (1.40%)  
Flatulence † 1    
# participants affected / at risk     5/293 (1.71%)     3/286 (1.05%)  
Gastroesophageal reflux disease † 1    
# participants affected / at risk     4/293 (1.37%)     4/286 (1.40%)  
Dysphagia † 1    
# participants affected / at risk     5/293 (1.71%)     2/286 (0.70%)  
Cheilitis † 1    
# participants affected / at risk     3/293 (1.02%)     3/286 (1.05%)  
Epigastric discomfort † 1    
# participants affected / at risk     2/293 (0.68%)     4/286 (1.40%)  
Mouth ulceration † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Esophagitis † 1    
# participants affected / at risk     4/293 (1.37%)     1/286 (0.35%)  
Abdominal discomfort † 1    
# participants affected / at risk     2/293 (0.68%)     3/286 (1.05%)  
Colitis † 1    
# participants affected / at risk     3/293 (1.02%)     1/286 (0.35%)  
Gastritis † 1    
# participants affected / at risk     2/293 (0.68%)     2/286 (0.70%)  
Retching † 1    
# participants affected / at risk     1/293 (0.34%)     3/286 (1.05%)  
Toothache † 1    
# participants affected / at risk     3/293 (1.02%)     1/286 (0.35%)  
Abdominal pain lower † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Anal hemorrhage † 1    
# participants affected / at risk     3/293 (1.02%)     0/286 (0.00%)  
Rectal hemorrhage † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Abdominal tenderness † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Apthous stomatitis † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Ascites † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Gingival pain † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Gingivitis † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Hematochezia † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Oral discomfort † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Oral pain † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Proctalgia † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Abdominal rigidity † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Anorectal discomfort † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Anal fissure † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Anal ulcer † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Diabetic gastropathy † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Fecaloma † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Gastric disorder † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Gastrointestinal pain † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Gastrointestinal toxicity † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Gingival bleeding † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Gingival pain † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Glossodynia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hemorrhoidal hemorrhage † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hiatus hernia † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hyperchlorhydria † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypoaesthesia oral † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Ileus † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Impaired gastric emptying † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Intestinal ischemia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Lip dry † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Lip edema † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Loose tooth † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Melena † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Odynophagia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Esophageal discomfort † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pancreatitis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Parasthesia oral † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Reflux gastritis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Subileus † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Tongue pigmentation † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Tongue ulceration † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
General disorders      
Fatigue † 1    
# participants affected / at risk     65/293 (22.18%)     61/286 (21.33%)  
Asthenia † 1    
# participants affected / at risk     62/293 (21.16%)     36/286 (12.59%)  
Pyrexia † 1    
# participants affected / at risk     32/293 (10.92%)     33/286 (11.54%)  
Mucosal inflammation † 1    
# participants affected / at risk     38/293 (12.97%)     9/286 (3.15%)  
Edema perpheral † 1    
# participants affected / at risk     18/293 (6.14%)     19/286 (6.64%)  
Pain † 1    
# participants affected / at risk     19/293 (6.48%)     16/286 (5.59%)  
Chest pain † 1    
# participants affected / at risk     19/293 (6.48%)     14/286 (4.90%)  
Chills † 1    
# participants affected / at risk     6/293 (2.05%)     8/286 (2.80%)  
Malaise † 1    
# participants affected / at risk     6/293 (2.05%)     7/286 (2.45%)  
Chest discomfort † 1    
# participants affected / at risk     6/293 (2.05%)     4/286 (1.40%)  
Axillary pain † 1    
# participants affected / at risk     4/293 (1.37%)     4/286 (1.40%)  
Influenza like illness † 1    
# participants affected / at risk     4/293 (1.37%)     5/286 (1.75%)  
Face edema † 1    
# participants affected / at risk     4/293 (1.37%)     2/286 (0.70%)  
Edema † 1    
# participants affected / at risk     3/293 (1.02%)     3/286 (1.05%)  
Catheter site pain † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Inflammation † 1    
# participants affected / at risk     3/293 (1.02%)     0/286 (0.00%)  
Adverse drug reaction † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Discomfort † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Injection site reaction † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Irritability † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Breakthrough pain † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Catheter site inflammation † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Catheter site related reaction † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Death † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Early satiety † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Extravasation † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Facial pain † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Granuloma † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Implant site scar † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Infusion site extravasation † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Infusion site edema † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Infusion site pain † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Local swelling † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Localized edema † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Performance status decreased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Vessel puncture site pain † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Thirst † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Vessel puncture site reaction † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Generalized edema † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Injection site pain † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hepatobiliary disorders      
Hyperbilirubinemia † 1    
# participants affected / at risk     6/293 (2.05%)     4/286 (1.40%)  
Jaundice † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Cholecystitis † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Hepatotoxicity † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Cholecystitis chronic † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Cholelithiasis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Jaundice cholestatic † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Immune system disorders      
Hypersensitivity † 1    
# participants affected / at risk     11/293 (3.75%)     3/286 (1.05%)  
Drug hypersensitivity † 1    
# participants affected / at risk     3/293 (1.02%)     1/286 (0.35%)  
Anaphylactic reaction † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Anaphylactic shock † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Multiple allergies † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Contrast media allergy † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Infections and infestations      
Nasopharyngitis † 1    
# participants affected / at risk     17/293 (5.80%)     7/286 (2.45%)  
Upper respiratory tract infection † 1    
# participants affected / at risk     8/293 (2.73%)     15/286 (5.24%)  
Urinary tract infection † 1    
# participants affected / at risk     15/293 (5.12%)     8/286 (2.80%)  
Influenza † 1    
# participants affected / at risk     5/293 (1.71%)     9/286 (3.15%)  
Pharyngitis † 1    
# participants affected / at risk     9/293 (3.07%)     3/286 (1.05%)  
Cellulitis † 1    
# participants affected / at risk     4/293 (1.37%)     5/286 (1.75%)  
Rhinitis † 1    
# participants affected / at risk     7/293 (2.39%)     2/286 (0.70%)  
Pneumonia † 1    
# participants affected / at risk     4/293 (1.37%)     4/286 (1.40%)  
Bronchitis † 1    
# participants affected / at risk     5/293 (1.71%)     4/286 (1.40%)  
Infection † 1    
# participants affected / at risk     6/293 (2.05%)     1/286 (0.35%)  
Respiratory tract infection † 1    
# participants affected / at risk     5/293 (1.71%)     2/286 (0.70%)  
Cystitis † 1    
# participants affected / at risk     2/293 (0.68%)     4/286 (1.40%)  
Herpes simplex † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Herpes zoster † 1    
# participants affected / at risk     3/293 (1.02%)     3/286 (1.05%)  
Oral candidiasis † 1    
# participants affected / at risk     4/293 (1.37%)     2/286 (0.70%)  
Device related infection † 1    
# participants affected / at risk     2/293 (0.68%)     3/286 (1.05%)  
Folliculitis † 1    
# participants affected / at risk     3/293 (1.02%)     2/286 (0.70%)  
Oral herpes † 1    
# participants affected / at risk     5/293 (1.71%)     0/286 (0.00%)  
Acarodermatitis † 1    
# participants affected / at risk     4/293 (1.37%)     0/286 (0.00%)  
Fungal infection † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Laryngitis † 1    
# participants affected / at risk     1/293 (0.34%)     3/286 (1.05%)  
Lung infection † 1    
# participants affected / at risk     1/293 (0.34%)     3/286 (1.05%)  
Paronychia † 1    
# participants affected / at risk     5/293 (1.71%)     0/286 (0.00%)  
Breast infection † 1    
# participants affected / at risk     0/293 (0.00%)     3/286 (1.05%)  
Fungal infection † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Lower respiratory tract infection † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Nail infection † 1    
# participants affected / at risk     3/293 (1.02%)     0/286 (0.00%)  
Sepsis † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Sinusitis † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Tonsillitis † 1    
# participants affected / at risk     3/293 (1.02%)     0/286 (0.00%)  
Candidiasis † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Catheter site infection † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Gastroenteritis † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Kidney infection † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Lymphangitis † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Otiits externa † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Otitis media chronic † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Respiratory tract infection viral † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Septic shock † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Skin infection † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Staphylococcal infection † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Viral infection † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Vulvovaginal mycotic infection † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Breast abscess † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Bronchopneumonia † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Catheter site cellulitis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Clostridial infection † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Clostridium difficile colitis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Enterocolitis infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Epstein-Barr virus infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Erysipelas † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Furuncle † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Gallbladder abscess † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Gastrointestinal fungal infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Fungal skin infection † 1    
# participants affected / at risk     0/293 (0.00%)     3/286 (1.05%)  
Genital candidiasis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Klebsiella infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Localized infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Omphalitis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Oral fungal infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pneumonia primary atypical † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Postoperative wound infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pyelonephritis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Subcutaneous abscess † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Tooth abscess † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Tuberculosis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Urosepsis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Vaginal infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Viral rash † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Viral upper respiratory tract infection † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Injury, poisoning and procedural complications      
Upper limb fracture † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Wound secretion † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     27/293 (9.22%)     23/286 (8.04%)  
Aspartete aminotransferase increased † 1    
# participants affected / at risk     22/293 (7.51%)     20/286 (6.99%)  
Blood alkaline phosphatase increased † 1    
# participants affected / at risk     19/293 (6.48%)     19/286 (6.64%)  
Weight decreased † 1    
# participants affected / at risk     17/293 (5.80%)     14/286 (4.90%)  
Ejection fraction decreased † 1    
# participants affected / at risk     6/293 (2.05%)     6/286 (2.10%)  
Hemoglobin decreased † 1    
# participants affected / at risk     8/293 (2.73%)     4/286 (1.40%)  
Blood urea increased † 1    
# participants affected / at risk     2/293 (0.68%)     3/286 (1.05%)  
Weight increased † 1    
# participants affected / at risk     1/293 (0.34%)     9/286 (3.15%)  
Neutrophil count decreased † 1    
# participants affected / at risk     5/293 (1.71%)     3/286 (1.05%)  
White blood cell count decreased † 1    
# participants affected / at risk     5/293 (1.71%)     1/286 (0.35%)  
Body temperature increased † 1    
# participants affected / at risk     2/293 (0.68%)     3/286 (1.05%)  
Gamma-glutamyltransferase increased † 1    
# participants affected / at risk     3/293 (1.02%)     2/286 (0.70%)  
Blood albumin decreased † 1    
# participants affected / at risk     3/293 (1.02%)     1/286 (0.35%)  
Blood creatinine increased † 1    
# participants affected / at risk     2/293 (0.68%)     2/286 (0.70%)  
Blood lactate dehydogenase increased † 1    
# participants affected / at risk     2/293 (0.68%)     2/286 (0.70%)  
Blood bilirubin increased † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Blood potassium decreased † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Blood glucose increased † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Blood uric acid increased † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
International normalized ratio increased † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Activated partial thromboplastin time prolonged † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Blood bilirubin decreased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Blood calcium decreased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Blood homocysteine increased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Blood pressure increased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Blood sodium increased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Blood urine present † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hemoglobin † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Heart rate irregular † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Platelet count decreased † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Prothrombin level decreased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Prothrombin time prolonged † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
White blood cell count increased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Metabolism and nutrition disorders      
Decreased appetite † 1    
# participants affected / at risk     50/293 (17.06%)     32/286 (11.19%)  
Hypercalcemia † 1    
# participants affected / at risk     7/293 (2.39%)     8/286 (2.80%)  
Hyperglycemia † 1    
# participants affected / at risk     7/293 (2.39%)     8/286 (2.80%)  
Dehydration † 1    
# participants affected / at risk     12/293 (4.10%)     2/286 (0.70%)  
Hypokalemia † 1    
# participants affected / at risk     12/293 (4.10%)     2/286 (0.70%)  
Hyperuricemia † 1    
# participants affected / at risk     5/293 (1.71%)     7/286 (2.45%)  
Hyponatremia † 1    
# participants affected / at risk     4/293 (1.37%)     2/286 (0.70%)  
Hyperkalemia † 1    
# participants affected / at risk     3/293 (1.02%)     3/286 (1.05%)  
Hypoalbuminemia † 1    
# participants affected / at risk     3/293 (1.02%)     2/286 (0.70%)  
Hypocalcemia † 1    
# participants affected / at risk     3/293 (1.02%)     2/286 (0.70%)  
Hypernatremia † 1    
# participants affected / at risk     2/293 (0.68%)     3/286 (1.05%)  
Hypoglycemia † 1    
# participants affected / at risk     2/293 (0.68%)     2/286 (0.70%)  
Hypercholesterolemia † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Diabetes mellitus † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Fluid overload † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hyperchloremia † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hyperphagia † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hyperproteinemia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypomagnesemia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypophosphatemia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypoproteinemia † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hypovolemia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Tumor lysis syndrome † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Tetany † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Musculoskeletal and connective tissue disorders      
Myalgia † 1    
# participants affected / at risk     94/293 (32.08%)     74/286 (25.87%)  
Arthralgia † 1    
# participants affected / at risk     70/293 (23.89%)     58/286 (20.28%)  
Pain in extremity † 1    
# participants affected / at risk     50/293 (17.06%)     50/286 (17.48%)  
Bone pain † 1    
# participants affected / at risk     34/293 (11.60%)     32/286 (11.19%)  
Back pain † 1    
# participants affected / at risk     26/293 (8.87%)     29/286 (10.14%)  
Musculoskeletal pain † 1    
# participants affected / at risk     23/293 (7.85%)     27/286 (9.44%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     3/293 (1.02%)     12/286 (4.20%)  
Muscular weakness † 1    
# participants affected / at risk     8/293 (2.73%)     4/286 (1.40%)  
Neck pain † 1    
# participants affected / at risk     6/293 (2.05%)     4/286 (1.40%)  
Muscle spasms † 1    
# participants affected / at risk     4/293 (1.37%)     5/286 (1.75%)  
Groin pain † 1    
# participants affected / at risk     2/293 (0.68%)     2/286 (0.70%)  
Musculoskeletal discomfort † 1    
# participants affected / at risk     2/293 (0.68%)     2/286 (0.70%)  
Musculoskeletal stiffness † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Arthritis † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Flank pain † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Pain in jaw † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Pathological fracture † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Intervertebral disc disorder † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Joint effusion † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Joint swelling † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Myopathy † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Myositis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Nodule on extremity † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Osteoporosis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Sensation of heaviness † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Tumor pain † 1    
# participants affected / at risk     2/293 (0.68%)     5/286 (1.75%)  
Breast cancer † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hemangioma † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Metastases to central nervous system † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Metastases to liver † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pyogenic granuloma † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Salivary gland adenoma † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Squamous cell carcinoma † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Tumor hemorrhage † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Uterine leiomyoma † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Nervous system disorders      
Peripheral sensory neuropathy † 1    
# participants affected / at risk     48/293 (16.38%)     54/286 (18.88%)  
Paraesthesia † 1    
# participants affected / at risk     43/293 (14.68%)     42/286 (14.69%)  
Headache † 1    
# participants affected / at risk     32/293 (10.92%)     30/286 (10.49%)  
Neuropathy peripheral † 1    
# participants affected / at risk     54/293 (18.43%)     32/286 (11.19%)  
Dysgeusia † 1    
# participants affected / at risk     12/293 (4.10%)     11/286 (3.85%)  
Dizziness † 1    
# participants affected / at risk     13/293 (4.44%)     9/286 (3.15%)  
Hypoaesthesia † 1    
# participants affected / at risk     11/293 (3.75%)     10/286 (3.50%)  
Polyneuropathy † 1    
# participants affected / at risk     9/293 (3.07%)     3/286 (1.05%)  
Peripheral motor neuropathy † 1    
# participants affected / at risk     8/293 (2.73%)     4/286 (1.40%)  
Neuralgia † 1    
# participants affected / at risk     3/293 (1.02%)     4/286 (1.40%)  
Memory impairment † 1    
# participants affected / at risk     3/293 (1.02%)     3/286 (1.05%)  
Syncope † 1    
# participants affected / at risk     3/293 (1.02%)     2/286 (0.70%)  
Convulsion † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Neurotoxicity † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Somnolence † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Tremor † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Cerebral infarction † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Disturbance in attention † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Hemiplegia † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Migraine † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Restless legs syndrome † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Sinus headache † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Aphasia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Aphonia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Brain edema † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Carpal tunnel syndrome † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Cerebrovascular disorder † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Coma hepatic † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Convulsions local † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Depressed level of consiousness † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Dysaesthesia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Epilepsy † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Facial palsy † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hyperaesthesia † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hypersomnia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hyporeflexia † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Intracranial pressure increased † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Lethargy † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Loss of consciousness † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Lumbar radiculopathy † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Mental impairment † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Motor dysfunction † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Neuritis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Paraparesis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Parosmia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Peripheral sensorimotor neurophathy † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Sciatica † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Sensory loss † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Psychiatric disorders      
Insomnia † 1    
# participants affected / at risk     34/293 (11.60%)     29/286 (10.14%)  
Anxiety † 1    
# participants affected / at risk     13/293 (4.44%)     13/286 (4.55%)  
Depression † 1    
# participants affected / at risk     10/293 (3.41%)     13/286 (4.55%)  
Depressed mood † 1    
# participants affected / at risk     4/293 (1.37%)     4/286 (1.40%)  
Confusional state † 1    
# participants affected / at risk     2/293 (0.68%)     3/286 (1.05%)  
Restlessness † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Hallucination † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Mood altered † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Eating disorder † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Emotional distress † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Mental status changes † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Nervousness † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Panic attack † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Personality change † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Personality disorder † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Psychotic disorder † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Suicidal ideation † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Renal and urinary disorders      
Dysuria † 1    
# participants affected / at risk     6/293 (2.05%)     2/286 (0.70%)  
Hematuria † 1    
# participants affected / at risk     3/293 (1.02%)     0/286 (0.00%)  
Urinary incontinence † 1    
# participants affected / at risk     1/293 (0.34%)     3/286 (1.05%)  
Hydronephrosis † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Polyuria † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Enuresis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Micturition disorder † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pollakiuria † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Renal colic † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Renal failure acute † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Urinary retention † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Respiratory, thoracic and mediastinal disorders      
Cough † 1    
# participants affected / at risk     33/293 (11.26%)     42/286 (14.69%)  
Dyspnoea † 1    
# participants affected / at risk     29/293 (9.90%)     28/286 (9.79%)  
Oropharyngeal pain † 1    
# participants affected / at risk     12/293 (4.10%)     10/286 (3.50%)  
Epistaxis † 1    
# participants affected / at risk     13/293 (4.44%)     4/286 (1.40%)  
Dysphonia † 1    
# participants affected / at risk     8/293 (2.73%)     6/286 (2.10%)  
Productive cough † 1    
# participants affected / at risk     5/293 (1.71%)     2/286 (0.70%)  
Dyspnoea exertional † 1    
# participants affected / at risk     3/293 (1.02%)     1/286 (0.35%)  
Rhinitis allergic † 1    
# participants affected / at risk     2/293 (0.68%)     2/286 (0.70%)  
Hemoptysis † 1    
# participants affected / at risk     0/293 (0.00%)     3/286 (1.05%)  
Nasal congestion † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Nasal dryness † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Wheezing † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Asthma † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Bronchospasm † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Hypoxia † 1    
# participants affected / at risk     0/293 (0.00%)     3/286 (1.05%)  
Increased upper airway secretion † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Nasal inflammation † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Pharyngeal erythema † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Pleural effusion † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Pulmonary embolism † 1    
# participants affected / at risk     2/293 (0.68%)     0/286 (0.00%)  
Pleuritic pain † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Atelectasis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Bronchostenosis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hemothorax † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Lung infiltration † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Nasal discomfort † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Nasal ulcer † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Pain respiration † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pleural fibrosis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pneumonitis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Pulmonary hemorrhage † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Pulmonary edema † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Rales † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Respiratory disorder † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Rhinorrhoea † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Sinus congestion † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Sputum discoloured † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Upper airway obstruction † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Skin and subcutaneous tissue disorders      
Alopecia † 1    
# participants affected / at risk     153/293 (52.22%)     183/286 (63.99%)  
Rash † 1    
# participants affected / at risk     145/293 (49.49%)     66/286 (23.08%)  
Pruritus † 1    
# participants affected / at risk     46/293 (15.70%)     37/286 (12.94%)  
Dry skin † 1    
# participants affected / at risk     13/293 (4.44%)     8/286 (2.80%)  
Nail disorder † 1    
# participants affected / at risk     8/293 (2.73%)     5/286 (1.75%)  
Pain of skin † 1    
# participants affected / at risk     4/293 (1.37%)     4/286 (1.40%)  
Skin hyperpigmentation † 1    
# participants affected / at risk     7/293 (2.39%)     1/286 (0.35%)  
Hyperhidrosis † 1    
# participants affected / at risk     3/293 (1.02%)     3/286 (1.05%)  
Rash generalized † 1    
# participants affected / at risk     3/293 (1.02%)     2/286 (0.70%)  
Palmar-plantar erythrodysaesthesia syndrome † 1    
# participants affected / at risk     5/293 (1.71%)     1/286 (0.35%)  
Urticaria † 1    
# participants affected / at risk     2/293 (0.68%)     3/286 (1.05%)  
Ecchymosis † 1    
# participants affected / at risk     1/293 (0.34%)     2/286 (0.70%)  
Rash erythematous † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Dermatitis allergic † 1    
# participants affected / at risk     2/293 (0.68%)     1/286 (0.35%)  
Nail discoloration † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Night sweats † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Pruritus generalized † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Skin exfoliation † 1    
# participants affected / at risk     0/293 (0.00%)     2/286 (0.70%)  
Skin fissures † 1    
# participants affected / at risk     1/293 (0.34%)     1/286 (0.35%)  
Blister † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Butterfly rash † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Cold sweat † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Erythema multiforme † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hemorrhage subcutaneous † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Hair growth abnormal † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hirsutism † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypertrichosis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Hypoaesthesia facial † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Ingrowing nail † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Intertrigo † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Madarosis † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Onychalgia † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Onycholysis † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Periorbital edema † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Rosacea † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Skin chapped † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Skin discomfort † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Skin disorder † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Skin lesion † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Swelling face † 1    
# participants affected / at risk     1/293 (0.34%)     0/286 (0.00%)  
Social circumstances      
Immobile † 1    
# participants affected / at risk     0/293 (0.00%)     1/286 (0.35%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications:
Publications automatically indexed to this study:

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00075270     History of Changes
Obsolete Identifiers: NCT00085046
Other Study ID Numbers: EGF30001
Study First Received: January 7, 2004
Results First Received: March 14, 2013
Last Updated: February 13, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration