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Trial record 1 of 1 for:    D4200L00007
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Vandetanib Gemcitabine Or Placebo Plus Gemcitabine Or Vandetanib Monotherapy In Advanced Biliary Tract Cancer (VANGOGH)

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ClinicalTrials.gov Identifier: NCT00753675
Recruitment Status : Completed
First Posted : September 16, 2008
Results First Posted : November 28, 2013
Last Update Posted : October 10, 2016
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Biliary Tract Cancer
Gallbladder Cancer
Cancer Of The Extrahepatic Bile Duct
Ampullary Carcinoma
Interventions Drug: ZD6474, Vandetanib
Drug: Gemcitabine
Drug: Placebo matching ZD6474
Enrollment 174
Recruitment Details 180 subjects were screened at 19 sites and 174 were randomized
Pre-assignment Details  
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Hide Arm/Group Description Vandetanib 300 mg as a once daily oral dose, from Day 1 Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy) Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
Period Title: Overall Study
Started 59 59 56
Completed 0 0 0
Not Completed 59 59 56
Reason Not Completed
other reason             11             12             13
Death             1             2             4
Adverse Event             11             9             4
Objective progression of disease             35             35             35
Withdrawal by Subject             0             1             0
Lost to Follow-up             1             0             0
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine Total
Hide Arm/Group Description Vandetanib 300 mg as a once daily oral dose, from Day 1 Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy) Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy). Total of all reporting groups
Overall Number of Baseline Participants 59 58 56 173
Hide Baseline Analysis Population Description
Patient screened 180 Patient Randomized 174 (1 never treated) Sceening failures 6 Patient Treated 173 (ITT=165 ; 8 excluded from ITT due to missing postbaseline assesment)
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 59 participants 58 participants 56 participants 173 participants
62.39  (10.108) 64.41  (9.455) 63.95  (8.764) 63.57  (9.456)
[1]
Measure Description: Safety Population
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants 58 participants 56 participants 173 participants
Female
34
  57.6%
27
  46.6%
31
  55.4%
92
  53.2%
Male
25
  42.4%
31
  53.4%
25
  44.6%
81
  46.8%
[1]
Measure Description: Safety Population
1.Primary Outcome
Title Progression Free Survival
Hide Description Progression was defined as Time from the date of first dose of study medication to progression of disease, or death (it also includes patients who are lost to follow-up or have withdrawn consent) and evaluated with RECIST criteria as an increase of at least 20% in the sum of longest diameter (LD) of target lesion(s) taking as reference the smallest sum of LD since the treatment started or any new lesion(s).
Time Frame up to 1032 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Hide Arm/Group Description:
Vandetanib 300 mg as a once daily oral dose, from Day 1
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
Overall Number of Participants Analyzed 56 57 52
Median (95% Confidence Interval)
Unit of Measure: days
105
(72 to 155)
114
(91 to 193)
148
(72 to 225)
2.Secondary Outcome
Title Objective Tumor Response Rate (CR+PR),
Hide Description Objective Tumor Response Rate was defined as complete response (CR) + partial response (PR) evaluated by RECIST. CR was defined as disappearance of all target lesions. PR was defined as at least 30% decrease in the sum of longest diameters (LD) of target lesion(s) taking as reference the baseline sum of LD
Time Frame up to 1032 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Hide Arm/Group Description:
Vandetanib 300 mg as a once daily oral dose, from Day 1
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
Overall Number of Participants Analyzed 56 57 52
Measure Type: Number
Unit of Measure: Participants
Objective Response = NO 54 46 45
Objective Response = YES 2 11 7
3.Secondary Outcome
Title Disease Control Rate (CR+PR+SD)
Hide Description DCR is the sum of patients with a best overall CR, PR or SD (>=8 weeks) by the patient in the analysis
Time Frame up to 1032 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Hide Arm/Group Description:
Vandetanib 300 mg as a once daily oral dose, from Day 1
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
Overall Number of Participants Analyzed 56 57 52
Measure Type: Number
Unit of Measure: Partecipants
Disease control rate = NO 42 40 32
Disease control rate = YES 14 17 20
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR is defined from the date of first documentation of response until date of PD or death
Time Frame up to 1032 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (best response of CR or PR only)
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Hide Arm/Group Description:
Vandetanib 300 mg as a once daily oral dose, from Day 1
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
Overall Number of Participants Analyzed 2 11 7
Median (95% Confidence Interval)
Unit of Measure: Days
277
(267 to 286)
179
(85 to 369)
127
(85 to 152)
5.Secondary Outcome
Title Overall Survival
Hide Description OS is defined from the date of randomization to death
Time Frame up to 1032 days
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Hide Arm/Group Description:
Vandetanib 300 mg as a once daily oral dose, from Day 1
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy)
Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
Overall Number of Participants Analyzed 56 57 52
Median (95% Confidence Interval)
Unit of Measure: Days
228
(190 to 364)
284
(213 to 359)
307
(254 to 523)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Hide Arm/Group Description Vandetanib 300 mg as a once daily oral dose, from Day 1 Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to plus Vandetanib 100 mg orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy) Gemcitabine administered intravenously at 1000 mg/m2 over 30 minutes on Days 1 and 8 of each 21-day cycle up to 6 cycles plus Vandetanib 100 mg Matching Placebo orally once-daily, from Day 1 (after 6 cycles, in the absence of disease progression or unacceptable toxicity, Investigators remain at liberty to continue Gemcitabine plus Vandetanib / Placebo or to continue Vandetanib / Placebo monotherapy).
All-Cause Mortality
Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   16/59 (27.12%)      15/58 (25.86%)      12/56 (21.43%)    
Blood and lymphatic system disorders       
Disseminated Intravascular  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Pancytopenia  3  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Thrombocytopenia  3  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Cardiac disorders       
Acute Myocardial Infarction  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Cardiac Failure Acute  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Torsade de Pointes  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Gastrointestinal disorders       
Abdominal Pain   0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Ascites  1  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Duodenal Obstruction  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Intestinal Obstruction  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Nausea  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Vomiting  1  3/59 (5.08%)  3 0/58 (0.00%)  0 2/56 (3.57%)  2
General disorders       
Asthenia  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Condition Aggravated  2  0/59 (0.00%)  0 1/58 (1.72%)  1 1/56 (1.79%)  1
Fatigue  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
General Physical Health Deterioration  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Pyrexia  2  3/59 (5.08%)  3 0/58 (0.00%)  0 2/56 (3.57%)  2
Hepatobiliary disorders       
Acute Hepatic Failure  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Cholangites  2  1/59 (1.69%)  1 1/58 (1.72%)  1 1/56 (1.79%)  1
Hepatic Failure  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Hyperbilirubineamia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Jaundice  2  0/59 (0.00%)  0 2/58 (3.45%)  2 2/56 (3.57%)  2
Infections and infestations       
Pneumonia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Investigations       
Blood Bilirubin  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Blood Bilirubin increased  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Electrocardiogram Repolarisation Abnormaly  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Metabolism and nutrition disorders       
Cachexia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Dehydration  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Metabolic Acidosis  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Musculoskeletal and connective tissue disorders       
Back Pain  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Nervous system disorders       
Epilepsy  2  2/59 (3.39%)  2 0/0  0 0/0  0
Renal and urinary disorders       
Oliguria  2  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Renal Failure  2  0/59 (0.00%)  0 2/58 (3.45%)  2 1/56 (1.79%)  1
Renal Failure Acute  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  2  1/59 (1.69%)  1 2/58 (3.45%)  2 0/56 (0.00%)  0
Pleural Effusion  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Pulmonary embolism  2  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Pulmonary Hypertension  2  0/59 (0.00%)  0 2/58 (3.45%)  2 0/56 (0.00%)  0
Vascular disorders       
Hypertension  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Hypotension  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
2
Term from vocabulary, MeDRA 15.0
3
Term from vocabulary, MeDra
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Arm A Vandetanib 300 mg Arm B Vandetanib 100mg + Gemcitab ARM C Placebo+ Gemcitabine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   57/59 (96.61%)      53/58 (91.38%)      50/56 (89.29%)    
Blood and lymphatic system disorders       
Anemia  1  1/59 (1.69%)  4 10/58 (17.24%)  20 7/56 (12.50%)  18
Anemia macrocytic  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Autoimmune thrombocytopenia  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Dessemintaed Intracascula Coagulation  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Hyperbilirubineamia  2  0/59 (0.00%)  0 1/58 (1.72%)  2 0/56 (0.00%)  0
Iron deficency anemia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Leukcytosis  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Leukopenia  2  0/59 (0.00%)  0 3/58 (5.17%)  6 6/56 (10.71%)  17
Pancytopenia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Platelet production decreased  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Thrombocytopenia  2  2/59 (3.39%)  2 5/58 (8.62%)  7 2/56 (3.57%)  2
Thrombocytosis  1  0/59 (0.00%)  0 1/58 (1.72%)  1 1/56 (1.79%)  1
White blood cell disorder  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Neutropenia  2  0/59 (0.00%)  0 7/58 (12.07%)  15 10/56 (17.86%)  28
Cardiac disorders       
Acute Myocardial Infarction  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Arrhytmia  2  1/59 (1.69%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Atrial Fibrillation  2  1/59 (1.69%)  1 1/58 (1.72%)  2 1/56 (1.79%)  1
Bundle branch block  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Bundle Branch block right  2  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Cardiac Failure  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Cardiac Failure Acute  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Extrasystoles  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Oedema peripheral  2  0/59 (0.00%)  0 2/58 (3.45%)  2 0/56 (0.00%)  0
Sinus tachycardia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Tachycardia  2  2/59 (3.39%)  2 1/58 (1.72%)  1 0/56 (0.00%)  0
Torsade de pointes  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Ear and labyrinth disorders       
Vertigo  2  2/59 (3.39%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Endocrine disorders       
Diabete Mellitus  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Hyperglycamia  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Eye disorders       
Conjunctival hemorrhage  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Eye pruritus  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Ocular icterus  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Periorbital Oedema  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Gastrointestinal disorders       
Abdominal Distension  1  1/59 (1.69%)  1 0/58 (0.00%)  0 2/56 (3.57%)  3
Abdominal mass  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Abdominal pain  2  15/59 (25.42%)  16 8/58 (13.79%)  9 14/56 (25.00%)  17
Abdominal Pain upper  2  3/59 (5.08%)  3 6/58 (10.34%)  6 6/56 (10.71%)  6
Aborectal discomfort  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Ascites  2  4/59 (6.78%)  4 2/58 (3.45%)  2 2/56 (3.57%)  3
Constipation  2  2/59 (3.39%)  2 3/58 (5.17%)  3 9/56 (16.07%)  9
Diarrhoea  2  15/59 (25.42%)  32 6/58 (10.34%)  13 8/56 (14.29%)  10
Dry mouth  2  2/59 (3.39%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Duodenal obstruction  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Dysgeusia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Dyspepsia  2  1/59 (1.69%)  1 1/58 (1.72%)  1 2/56 (3.57%)  4
Dyshagia  2  1/59 (1.69%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Gastrointestinal toxicity  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Gastroesophageal reflux disease  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Gingivitis  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Haemorrhoids  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Hiccups  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Intestinal Obstruction  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Nausea  2  5/59 (8.47%)  6 6/58 (10.34%)  7 17/56 (30.36%)  29
Oral Mucosal erythema  2  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Pelvic Pain  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
proctalgia  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Proctitis  2  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Stomatitis  2  1/59 (1.69%)  1 1/58 (1.72%)  1 3/56 (5.36%)  3
Vomiting  2  8/59 (13.56%)  11 5/58 (8.62%)  7 9/56 (16.07%)  21
General disorders       
Asthenia  1 [1]  7/59 (11.86%)  7 14/58 (24.14%)  17 15/56 (26.79%)  20
Chest Pain  2  3/59 (5.08%)  3 2/58 (3.45%)  2 1/56 (1.79%)  2
Chills  1  1/59 (1.69%)  1 1/58 (1.72%)  2 0/56 (0.00%)  0
Condition aggravated  2  0/59 (0.00%)  0 2/58 (3.45%)  2 2/56 (3.57%)  2
Fatigue  2  8/59 (13.56%)  9 7/58 (12.07%)  9 8/56 (14.29%)  11
General physical health deterioration  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Gravitational oedema  2  2/59 (3.39%)  2 1/58 (1.72%)  1 1/56 (1.79%)  1
Hyperhidrosis  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Hyperpyrexia  2  2/59 (3.39%)  2 0/58 (0.00%)  0 2/56 (3.57%)  2
Malaise  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Mucosal Inflammation  2  4/59 (6.78%)  4 4/58 (6.90%)  6 0/56 (0.00%)  0
Multi organ failure  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Oedema  2  0/59 (0.00%)  0 0/58 (0.00%)  0 3/56 (5.36%)  3
Oedema Peripheral  2  2/59 (3.39%)  2 3/58 (5.17%)  9 1/56 (1.79%)  3
Pain  1  2/59 (3.39%)  2 3/58 (5.17%)  4 1/56 (1.79%)  2
Pyrexia  1  8/59 (13.56%)  10 14/58 (24.14%)  22 14/56 (25.00%)  22
Hepatobiliary disorders       
Acute Hepatic Failure  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Ascites  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Bile Duct Obstruction  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Cholangites  1  3/59 (5.08%)  3 2/58 (3.45%)  3 3/56 (5.36%)  3
Hepatic Failure  1  0/59 (0.00%)  0 1/58 (1.72%)  1 1/56 (1.79%)  1
Hyperbilirubinaemia  1  4/59 (6.78%)  10 5/58 (8.62%)  10 3/56 (5.36%)  3
Hypertrasaminasaemia  1  2/59 (3.39%)  3 2/58 (3.45%)  2 2/56 (3.57%)  2
Hypoalbuminaemia  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Jaundice  1  2/59 (3.39%)  3 3/58 (5.17%)  3 3/56 (5.36%)  3
Liver injury  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Hepatic pain  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Immune system disorders       
Dermatitis allergic  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Seasonal allergy  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Contrast media allergy  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Infections and infestations       
Bacterial Rhinitis  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Cystis escherichia  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Folliculitis  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Hepatobiliary infection  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Influenza  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Nasopharyngitis  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Oral Herpes  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Pneumonia  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Skin Infection  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Tooth abcess  1  0/59 (0.00%)  0 0/58 (0.00%)  0 2/56 (3.57%)  3
Urinary tract infection  1  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Viral infection  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Injury, poisoning and procedural complications       
Spinal Fracture  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Investigations       
Alanine aminotransferase  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Alanine aminotransferase increased  1  1/59 (1.69%)  1 2/58 (3.45%)  2 1/56 (1.79%)  1
Aspartate aminotranferase  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Asparteate amonotranferase increased  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Blood alkaline phosphatase  1  2/59 (3.39%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Blood Bilirubin  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Blood Bilirubin increased  1  3/59 (5.08%)  5 1/58 (1.72%)  1 0/56 (0.00%)  0
Blood creatine  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Blood creatinine increased  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Blood glucose decreased  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Blood lactate dehdrogenase increased  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Blood potassium increased  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Blood urea increased  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Electrocardiogram QT prolonged  1  2/59 (3.39%)  2 2/58 (3.45%)  2 1/56 (1.79%)  1
Electrocardiogram T wave inversion  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Electrocardiogram abnormal  1  2/59 (3.39%)  3 0/58 (0.00%)  0 0/56 (0.00%)  0
Electrocardiogram repolarisation abnormaly  1  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Gamma -glumayltransferase  1  2/59 (3.39%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Gamma-glutamyltransferase increased  1  0/59 (0.00%)  0 1/58 (1.72%)  2 3/56 (5.36%)  5
International normalised ratio increased  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Platelet count decreased  1  0/59 (0.00%)  0 3/58 (5.17%)  3 0/56 (0.00%)  0
Platelet count increased  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Transaminase increased  1  1/59 (1.69%)  2 1/58 (1.72%)  2 0/56 (0.00%)  0
Weight decreased  1  2/59 (3.39%)  2 1/58 (1.72%)  1 0/56 (0.00%)  0
Urine colour abnormal  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Metabolism and nutrition disorders       
Cachexia  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Decreased appetite  1  5/59 (8.47%)  5 8/58 (13.79%)  10 4/56 (7.14%)  4
Deydratation  1  2/59 (3.39%)  2 1/58 (1.72%)  1 0/56 (0.00%)  0
Hyperbilirubinaemia  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Hypercalcemia  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Hypercreatininaemia  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Hyperglycaemia  1  0/59 (0.00%)  0 2/58 (3.45%)  2 1/56 (1.79%)  1
Hypoalbuminaemia  1  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Hypocalcaemia  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Hypoglycaemia  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Metabolic Acidosis  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Hypokalaemia  1  0/59 (0.00%)  0 2/58 (3.45%)  2 0/56 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/59 (1.69%)  1 1/58 (1.72%)  1 5/56 (8.93%)  5
Back pain  1  2/59 (3.39%)  2 1/58 (1.72%)  1 3/56 (5.36%)  3
Bone Pain  1  0/59 (0.00%)  0 0/58 (0.00%)  0 2/56 (3.57%)  2
Hypercreatinaemia  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Intervertebral disc degeneration  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Musculoskeletal chest pain  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Musculoskeletal pain  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Myalgia  1  1/59 (1.69%)  1 1/58 (1.72%)  1 2/56 (3.57%)  2
Neck Pain  1  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Pain in the extremity  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Spinal Compression Fracture  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Metastic Neoplasm  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Metastic Pain  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Tumor associated fever  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Nervous system disorders       
Agitated Depression  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Clonus  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Convulsion  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Dizziness  1  1/59 (1.69%)  1 2/58 (3.45%)  2 0/56 (0.00%)  0
Dysarthria  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Dysgeusia  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Epilepsy  1  2/59 (3.39%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Head Discomfort  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Headache  1  1/59 (1.69%)  1 0/58 (0.00%)  0 5/56 (8.93%)  5
Hypogeusia  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Insomnia  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Loss of consciousness  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Neuralgia  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Neuropathy peripheral  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Paraesthesia  1  1/59 (1.69%)  3 0/58 (0.00%)  0 1/56 (1.79%)  1
Peripheral sensory neuropathy  1  0/59 (0.00%)  0 2/58 (3.45%)  3 0/56 (0.00%)  0
Somnolence  1  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Syncope  1  2/59 (3.39%)  3 0/58 (0.00%)  0 0/56 (0.00%)  0
Tremor  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Psychiatric disorders       
Anxiety  1  1/59 (1.69%)  1 1/58 (1.72%)  1 0/56 (0.00%)  0
Depression  2  1/59 (1.69%)  2 2/58 (3.45%)  3 2/56 (3.57%)  2
Insomnia  2  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Panic disorder  2  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Sleep disorder due to general medical condition , insomnia type  2  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Renal and urinary disorders       
Bladder hypertrophy  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Dysuria  2  0/59 (0.00%)  0 3/58 (5.17%)  5 0/56 (0.00%)  0
Haematuria  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Hypercreatininaemia  2  0/59 (0.00%)  0 1/58 (1.72%)  1 1/56 (1.79%)  1
Oliguria  2  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Proteinuria  2  1/59 (1.69%)  1 3/58 (5.17%)  3 1/56 (1.79%)  5
Renal failure  2  2/59 (3.39%)  2 3/58 (5.17%)  4 1/56 (1.79%)  1
Renal failure acute  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Strangury  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Urinary incontinence  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Urinary Tract Infection  2  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/59 (1.69%)  1 1/58 (1.72%)  1 2/56 (3.57%)  2
Dysphonia  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Dysponea  1  3/59 (5.08%)  3 3/58 (5.17%)  3 4/56 (7.14%)  4
Dysponea exertional  1  1/59 (1.69%)  1 2/58 (3.45%)  2 0/56 (0.00%)  0
Epistaxis  1  0/59 (0.00%)  0 1/58 (1.72%)  1 1/56 (1.79%)  1
Pulmonary embolism  1  1/59 (1.69%)  1 1/58 (1.72%)  1 1/56 (1.79%)  1
Pulmonary hypertension  1  0/59 (0.00%)  0 2/58 (3.45%)  2 0/56 (0.00%)  0
Skin and subcutaneous tissue disorders       
Acne  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Angioedema  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Dermatitis  1  2/59 (3.39%)  8 3/58 (5.17%)  4 0/56 (0.00%)  0
Dermatitis allergic  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Drug Eruption  1  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Dry Skin  1  2/59 (3.39%)  2 0/58 (0.00%)  0 2/56 (3.57%)  2
Erythema  1  5/59 (8.47%)  13 4/58 (6.90%)  4 4/56 (7.14%)  5
Exfoliative rash  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Face Oedema  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Folliculitis  1  3/59 (5.08%)  4 1/58 (1.72%)  1 1/56 (1.79%)  1
Onycholysis  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Palmar-plantar erythrodysaesthesia syndrome  1  2/59 (3.39%)  2 1/58 (1.72%)  1 0/56 (0.00%)  0
Pruritus  1  1/59 (1.69%)  1 2/58 (3.45%)  2 4/56 (7.14%)  5
Pruritus generalised  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  2
Rash  1  15/59 (25.42%)  21 5/58 (8.62%)  5 3/56 (5.36%)  3
Rash erythematous  1  2/59 (3.39%)  2 0/58 (0.00%)  0 0/56 (0.00%)  0
Rash maculo-papular  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Skin Toxicity  1  2/59 (3.39%)  6 3/58 (5.17%)  3 1/56 (1.79%)  1
Vascular disorders       
Deep Vein thrombosis  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Diastolic hypotension  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Epistaxis  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Essential hypertension  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Haemorrhoids  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  1
Hypertension  1  14/59 (23.73%)  17 9/58 (15.52%)  10 4/56 (7.14%)  6
Hypertensive crisis  1  1/59 (1.69%)  1 0/58 (0.00%)  0 1/56 (1.79%)  1
Hypotension  1  2/59 (3.39%)  2 1/58 (1.72%)  1 1/56 (1.79%)  1
Phlebitis  1  0/59 (0.00%)  0 0/58 (0.00%)  0 1/56 (1.79%)  2
Pulmonary embolism  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Systolic hypertension  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Venous insufficiency  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Venous thrombosis  1  0/59 (0.00%)  0 1/58 (1.72%)  1 0/56 (0.00%)  0
Venous thrombosis limb  1  1/59 (1.69%)  1 0/58 (0.00%)  0 0/56 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.0
2
Term from vocabulary, MeDRA 15.0
[1]
General disorders and administration site conditions
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.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00753675     History of Changes
Other Study ID Numbers: D4200L00007
EUDRACT n° 2007-003056-12
First Submitted: September 15, 2008
First Posted: September 16, 2008
Results First Submitted: September 27, 2013
Results First Posted: November 28, 2013
Last Update Posted: October 10, 2016