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A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma

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ClinicalTrials.gov Identifier: NCT01264380
Recruitment Status : Completed
First Posted : December 21, 2010
Results First Posted : December 17, 2015
Last Update Posted : November 2, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Melanoma
Intervention Drug: RO5185426
Enrollment 16
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vemurafenib (RO5185426): Fasted Then Fed Vemurafenib (RO5185426): Fed Then Fasted Vemurafenib (RO5185426)
Hide Arm/Group Description Single oral dose of vemurafenib tablet at 960 milligrams (mg) on Day 1 was administered to participants in fasted condition (Period A [Day 1 to Day 10]) followed by single oral dose of vemurafenib tablet at 960 mg on Day 1 in fed condition (Period B [Day 11 to Day 20]). A washout period of 10 days was maintained between Period A and B. Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition (Period A [Day 1 to Day 10]) followed by single oral dose of vemurafenib tablet at 960 mg on Day 1 in fasted condition Period B [Day 11 to Day 20]). A washout period of 10 days was maintained between Period A and B. Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).
Period Title: Period A
Started 8 8 0
Completed 8 8 0
Not Completed 0 0 0
Period Title: Period B
Started 8 8 0
Completed 8 8 0
Not Completed 0 0 0
Period Title: Period C
Started 0 0 16
Completed 0 0 2
Not Completed 0 0 14
Reason Not Completed
Disease Progression             0             0             4
Death             0             0             2
Follow-up for survival status             0             0             6
Withdrawal by Subject             0             0             1
Adverse Event             0             0             1
Arm/Group Title All Participants
Hide Arm/Group Description Included all participants who received single oral dose of vemurafenib tablet at 960 mg in fasted condition first and fed condition first in Period A and Period B and twice daily dose of vemurafenib tablet at 960 mg in Period C.
Overall Number of Baseline Participants 16
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of vemurafenib.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants
60.6  (10.31)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants
Female
6
  37.5%
Male
10
  62.5%
1.Primary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States
Hide Description Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.
Time Frame Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population included participants who received both single doses of vemurafenib in Periods A and B without protocol violation and provided adequate PK assessments to calculate important PK parameters. Here “number of participants analyzed”=participants who were evaluable for this outcome measure.
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed
Hide Arm/Group Description:
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).
Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: micrograms*hour per milliliter (µg*h/mL)
115  (110) 351  (189)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vemurafenib (RO5185426): Fasted, Vemurafenib (RO5185426): Fed
Comments The point estimate and 90 percent (%) confidence interval (CI) of vemurafenib plasma AUC geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Geometric Mean
Estimated Value 4.64
Confidence Interval (2-Sided) 90%
2.83 to 7.60
Estimation Comments [Not Specified]
2.Primary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States
Hide Description PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Time Frame Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population. Here “number of participants analyzed”=participants who were evaluable for this outcome measure.
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed
Hide Arm/Group Description:
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).
Overall Number of Participants Analyzed 15 14
Mean (Standard Deviation)
Unit of Measure: µg*h/mL
94.3  (81.8) 320  (158)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vemurafenib (RO5185426): Fasted, Vemurafenib (RO5185426): Fed
Comments The point estimate and 90% CI of vemurafenib plasma AUC geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Geometric Mean
Estimated Value 5.05
Confidence Interval (2-Sided) 90%
2.99 to 8.55
Estimation Comments [Not Specified]
3.Primary Outcome
Title Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States
Hide Description PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Time Frame Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population.
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed
Hide Arm/Group Description:
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: µg/mL
3.48  (2.02) 7.38  (1.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vemurafenib (RO5185426): Fasted, Vemurafenib (RO5185426): Fed
Comments The point estimate and 90% CI of vemurafenib plasma Cmax geometric means ratios of the Fed to Fasted conditions following an oral administration of a single dose of 960 mg vemurafenib were analyzed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Geometric Mean
Estimated Value 2.45
Confidence Interval (2-Sided) 90%
1.81 to 3.32
Estimation Comments [Not Specified]
4.Primary Outcome
Title Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States
Hide Description Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Time Frame Pre-dose on Periods A and B
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population.
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed
Hide Arm/Group Description:
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).
Overall Number of Participants Analyzed 16 16
Mean (Standard Deviation)
Unit of Measure: µg/mL
NA [1]   (NA) NA [1]   (NA)
[1]
Since the study was a single-dose study, Cmin was not reached.
5.Primary Outcome
Title Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States
Hide Description PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Time Frame Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population.
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed
Hide Arm/Group Description:
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).
Overall Number of Participants Analyzed 16 16
Median (Full Range)
Unit of Measure: hour
4
(2 to 12.58)
7.51
(5 to 16)
6.Primary Outcome
Title Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States
Hide Description T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Time Frame Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population. Here “number of participants analyzed”=participants who were evaluable for this outcome measure.
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed
Hide Arm/Group Description:
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).
Overall Number of Participants Analyzed 16 15
Mean (Standard Deviation)
Unit of Measure: hour
24.6  (17.2) 26.0  (17.1)
7.Primary Outcome
Title Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States
Hide Description Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants.
Time Frame Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis population. Here "number of participants analyzed"=participants who were evaluable for this outcome measure.
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed
Hide Arm/Group Description:
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B).
Single oral dose of vemurafenib tablet at 960 mg on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B).
Overall Number of Participants Analyzed 15 14
Mean (Standard Deviation)
Unit of Measure: 1/h
0.04  (0.03) 0.04  (0.02)
8.Secondary Outcome
Title Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)
Hide Description BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included participants with measurable disease who received at least 1 dose of vemurafenib. Here “number of participants analyzed”=participants who were evaluable for this outcome measure.
Arm/Group Title Vemurafenib (RO5185426)
Hide Arm/Group Description:
Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
64.3
(35.1 to 87.2)
9.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.
Time Frame From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124)
Hide Outcome Measure Data
Hide Analysis Population Description
Data for OS was not collected as there was a change in planned analysis, not to collect the data.
Arm/Group Title Vemurafenib (RO5185426)
Hide Arm/Group Description:
Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Baseline up to 28 days after last dose (Week 114)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed Vemurafenib (RO5185426)
Hide Arm/Group Description Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fasted condition, in any intervention periods (Period A or B). Single oral dose of vemurafenib tablet at 960 milligram (mg) on Day 1 was administered to participants in fed condition, in any intervention periods (Period A or B). Participants received vemurafenib tablet at 960 mg orally twice daily in 21-day cycles starting from Day 21 until disease progression, unacceptable toxicity, or consent withdrawal (Period C).
All-Cause Mortality
Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed Vemurafenib (RO5185426)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed Vemurafenib (RO5185426)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/16 (0.00%)   9/16 (56.25%) 
Cardiac disorders       
Coronary artery disease * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Gastrointestinal disorders       
Mesenteric vein thrombosis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Infections and infestations       
Cellulitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Investigations       
Transaminases increased * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Squamous cell carcinoma of skin * 1  0/16 (0.00%)  0/16 (0.00%)  5/16 (31.25%) 
Keratoacanthoma * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Basal cell carcinoma * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Nervous system disorders       
Haemorrhage intracranial * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vemurafenib (RO5185426): Fasted Vemurafenib (RO5185426): Fed Vemurafenib (RO5185426)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/16 (18.75%)   5/16 (31.25%)   16/16 (100.00%) 
Blood and lymphatic system disorders       
Haemorrhagic diathesis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Cardiac disorders       
Sinus bradycardia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Tachycardia * 1  0/16 (0.00%)  1/16 (6.25%)  2/16 (12.50%) 
Eye disorders       
Blepharitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Cataract * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Conjunctival hyperaemia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Diplopia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Dry eye * 1  0/16 (0.00%)  0/16 (0.00%)  6/16 (37.50%) 
Eye irritation * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Eye pain * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Lacrimation increased * 1  0/16 (0.00%)  1/16 (6.25%)  1/16 (6.25%) 
Ocular hyperaemia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Ocular rosacea * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Photophobia * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Vision blurred * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Vitreous floaters * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Gastrointestinal disorders       
Abdominal distention * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Cheilitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Abdominal pain * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Constipation * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Diarrhoea * 1  0/16 (0.00%)  1/16 (6.25%)  6/16 (37.50%) 
Dyspepsia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Gingival pain * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Hiatus hernia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Lip swelling * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Nausea * 1  0/16 (0.00%)  0/16 (0.00%)  5/16 (31.25%) 
Oral disorder * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Stomatitis * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Toothache * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Vomiting * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
General disorders       
Chest discomfort * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Chills * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Fatigue * 1  1/16 (6.25%)  1/16 (6.25%)  10/16 (62.50%) 
Influenza like illness * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Oedema peripheral * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Pyrexia * 1  1/16 (6.25%)  0/16 (0.00%)  2/16 (12.50%) 
Hepatobiliary disorders       
Cholelithiasis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Infections and infestations       
Bronchitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Chronic sinusitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Conjunctivitis infective * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Gastroenteritis viral * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Nasopharyngitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Onychomycosis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Oral candidiasis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Pneumonia pseudomonas aeruginosa * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Sinusitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Upper respiratory tract infection * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Urinary tract infection * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Injury, poisoning and procedural complications       
Contusion * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Incision site pain * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Investigations       
Aspartate aminotransferase increased * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Blood alkaline phosphatase increased * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Blood creatinine increased * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Breath sounds abnormal * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Gamma-glutamyltransferase increased * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Neutrophil count increased * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  0/16 (0.00%)  0/16 (0.00%)  5/16 (31.25%) 
Dehydration * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Hypercalcaemia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Hypercholesterolaemia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Hyperglycaemia * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Hyperlipidaemia * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Hypoglycaemia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Hypokalaemia * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Hypomagnesaemia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  0/16 (0.00%)  0/16 (0.00%)  10/16 (62.50%) 
Back pain * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Joint effusion * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Muscular weakness * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Musculoskeletal pain * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Myalgia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Neck pain * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Pain in extremity * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Sensation of heaviness * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Dysplastic naevus * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Haemangioma * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Keratoacanthoma * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Lipoma * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Melanocytic naevus * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Metastatic pain * 1  0/16 (0.00%)  1/16 (6.25%)  0/16 (0.00%) 
Pyogenic granuloma * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Seborrhoeic keratosis * 1  0/16 (0.00%)  0/16 (0.00%)  6/16 (37.50%) 
Skin papilloma * 1  0/16 (0.00%)  0/16 (0.00%)  6/16 (37.50%) 
Tumour pain * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Nervous system disorders       
Aphasia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Cerebrovascular accident * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Dizziness * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Dysgeusia * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Headache * 1  1/16 (6.25%)  0/16 (0.00%)  5/16 (31.25%) 
Paraesthesia * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Psychiatric disorders       
Agitation * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Anxiety * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Claustrophobia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Depression * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Insomnia * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Mental status changes * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Renal and urinary disorders       
Haematuria * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Proteinuria * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Reproductive system and breast disorders       
Gynaecomastia * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Ovarian cyst * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Dyspnoea * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Nasal congestion * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Oropharyngeal pain * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Pleural effusion * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Respiratory disorder * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Rhinitis allergic * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Dyspnoea Paroxysmal Nocturna * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Skin and subcutaneous tissue disorders       
Acne Conglobata * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Actinic keratosis * 1  0/16 (0.00%)  0/16 (0.00%)  6/16 (37.50%) 
Alopecia * 1  0/16 (0.00%)  0/16 (0.00%)  6/16 (37.50%) 
Dermal cyst * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Dermatitis acneiform * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Dry skin * 1  0/16 (0.00%)  0/16 (0.00%)  5/16 (31.25%) 
Eczema * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Erythema * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Erythema nodosum * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Granuloma skin * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Hair texture abnormal * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Hyperkeratosis * 1  0/16 (0.00%)  0/16 (0.00%)  12/16 (75.00%) 
Neurodermatitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Night sweats * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Palmar−plantar erythrodysaesthesia syndrome * 1  0/16 (0.00%)  0/16 (0.00%)  6/16 (37.50%) 
Panniculitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Photosensitivity reaction * 1  0/16 (0.00%)  0/16 (0.00%)  7/16 (43.75%) 
Pruritus * 1  1/16 (6.25%)  0/16 (0.00%)  1/16 (6.25%) 
Pruritus generalised * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Purpura * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Rash * 1  0/16 (0.00%)  0/16 (0.00%)  4/16 (25.00%) 
Rash erythematous * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
Rash maculo-papular * 1  0/16 (0.00%)  0/16 (0.00%)  6/16 (37.50%) 
Rash papular * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Skin hypertrophy * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Skin lesion * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Skin mass * 1  0/16 (0.00%)  0/16 (0.00%)  2/16 (12.50%) 
Vascular disorders       
Hypertension * 1  0/16 (0.00%)  0/16 (0.00%)  3/16 (18.75%) 
Hypotension * 1  1/16 (6.25%)  1/16 (6.25%)  1/16 (6.25%) 
Vasculitis * 1  0/16 (0.00%)  0/16 (0.00%)  1/16 (6.25%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Results for OS was not reported due to change in planned analysis.
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 Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor’s intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01264380     History of Changes
Other Study ID Numbers: NP25396
First Submitted: December 20, 2010
First Posted: December 21, 2010
Results First Submitted: July 29, 2015
Results First Posted: December 17, 2015
Last Update Posted: November 2, 2016