Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 43 of 78 for:    vismodegib

A Study of Vismodegib in Patients With Relapsed/Refractory Acute Myelogenous Leukemia and Relapsed Refractory High-Risk Myelodysplastic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01880437
Recruitment Status : Terminated
First Posted : June 19, 2013
Results First Posted : December 15, 2015
Last Update Posted : December 15, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Myelodysplastic Syndromes, Myelogenous Leukemia, Acute
Interventions Drug: cytarabine
Drug: vismodegib
Enrollment 38
Recruitment Details A total of 47 participants were screened; of which,7 participants failed screening and 2 participants were erroneously entered but did not receive study drug.A total of 38 participants were enrolled and treated. It was planned to enroll 2 cohorts; Cohort 1 (vismodegib) and Cohort 2 (vismodegib + cytarabine).
Pre-assignment Details Based on lower-than-expected efficacy observed in interim data review, study was terminated prior to initiation of Cohort 2. Results are reported as per subgroups of Cohort 1: “Poor Risk Cytogenetics”, “FLT-3 Mutation Positive”, “Neither Poor Risk Cytogenetics Nor FLT-3”, unless otherwise specified.
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Hide Arm/Group Description Participants with relapsed/refractory acute myeloid leukemia (AML) or relapsed/refractory high-risk myelodysplastic syndrome (MDS) falling under 'poor risk cytogenetics' subgroup received oral 150 milligrams (mg) dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent. Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent. Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Period Title: Overall Study
Started 15 4 19
Completed 0 0 0
Not Completed 15 4 19
Reason Not Completed
Death             12             4             17
Study terminated by Sponsor             3             0             2
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3 Total
Hide Arm/Group Description Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent. Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent. Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent. Total of all reporting groups
Overall Number of Baseline Participants 15 4 19 38
Hide Baseline Analysis Population Description
Included all enrolled participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 4 participants 19 participants 38 participants
61.5  (20.7) 54.5  (5.9) 66.2  (14.7) 63.1  (16.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 4 participants 19 participants 38 participants
Female
6
  40.0%
2
  50.0%
9
  47.4%
17
  44.7%
Male
9
  60.0%
2
  50.0%
10
  52.6%
21
  55.3%
1.Primary Outcome
Title Percentage of Participants With a Complete Response (CR) or CR With Incomplete Blood Count Recovery (CRi) or Morphologic Leukemia Free State (MLFS) or Partial Response (PR) at Week 8
Hide Description CR was defined as achieved if the neutrophils count was greater than (>) 1000 cells per microliter (µL), platelets count >100000/µL, bone marrow blasts percentage (%) less than (<) 5, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of extra medullary disease (EMD). CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils >1000 cells/µL or Not applicable [NA] or platelets count >100000/µL or NA), bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
As the primary efficacy time-point (Week 8) was not reached for all participants due to study termination based on interim data analysis, the analysis of this outcome measure could not be performed, as per planned analysis.
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT3
Hide Arm/Group Description:
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
2.Secondary Outcome
Title Percentage of Participants With CR, CRi, MLFS or PR at Anytime During Study Treatment
Hide Description CR was defined as achieved if the neutrophils count >1000 cells/µL, platelets count >100000/µL, bone marrow blasts <5%, no Auer rods (clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts), no transfusion requirements and no signs of EMD. CRi was defined if either of the cell (neutrophil or platelet) lineage was not recovered (neutrophils > 1000 cells/µL or NA or platelets count >100000/µL or NA, bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. MLFS (neutrophil and platelet criteria were NA) was defined as bone marrow blasts <5% with no Auer rods and confirmed by flow cytometry with no signs of EMD. PR was defined as neutrophils count >1000 cells/µL, platelets count >100000/µL, and >50% decrease from baseline to a range of 5-25% of bone marrow blasts or blasts <5% with Auer rods. The 95% confidence intervals (CI) were constructed using Blyth-Still-Cassella method.
Time Frame Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis population included all enrolled participants. Here “number of participants analyzed” included participants who were evaluable for tumor response at anytime during the study.
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT3
Hide Arm/Group Description:
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Overall Number of Participants Analyzed 13 4 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
CR
0
(0.00 to 22.51)
0
(0.00 to 52.71)
0
(0.00 to 19.75)
CRi
0
(0.00 to 22.51)
0
(0.00 to 52.71)
6.3
(0.32 to 29.88)
MLFS
0
(0.00 to 22.51)
0
(0.00 to 52.71)
0
(0.00 to 19.75)
PR
0
(0.00 to 22.51)
0
(0.00 to 52.71)
6.3
(0.32 to 29.88)
3.Secondary Outcome
Title Duration of Overall Response (DOR)
Hide Description DOR is defined as the time from the first occurrence of a documented overall response to the time of relapse, as determined by the investigator using International Working Group (IWG) criteria (Participants not falling under any of the response criteria [CR or CRi or MLFS or PR] described under outcome measure 1 were considered as non-responders) or death from any cause during the study (defined as death within 30 days after the last dose of study drug).
Time Frame Up to 30 days of last dose of study drug (maximum treatment duration = 225 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy population including participants who were considered as responders.
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT3
Hide Arm/Group Description:
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Overall Number of Participants Analyzed 0 0 2
Median (95% Confidence Interval)
Unit of Measure: weeks
DOR of participants with CRi (n=0,0,1)
13 [1] 
(NA to NA)
DOR of participants with PR (n=0,0,1)
6.1 [1] 
(NA to NA)
[1]
The 95% CI was not estimable as only 1 participant was evaluable.
4.Secondary Outcome
Title Median Overall Survival (OS) Time
Hide Description OS was defined as the time from start of study drug to death from any cause. OS was estimated using Kaplan-Meier analysis. Participants alive at the last date known to be alive were censored for the analysis.
Time Frame Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis population.
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Hide Arm/Group Description:
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Overall Number of Participants Analyzed 15 4 19
Median (95% Confidence Interval)
Unit of Measure: months
3.38
(2.37 to 4.83)
1.43
(0.33 to 3.94)
3.65
(1.94 to 5.36)
5.Secondary Outcome
Title Percentage of Participants With an Event of Death During the Study
Hide Description [Not Specified]
Time Frame Up to death or 30 days of last dose of study drug (maximum treatment duration = 225 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Efficacy analysis population.
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Hide Arm/Group Description:
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Overall Number of Participants Analyzed 15 4 19
Measure Type: Number
Unit of Measure: percentage of participants
80.0 100.0 89.5
6.Secondary Outcome
Title Pharmacokinetics (PK): Steady-state Plasma Concentration of Vismodegib
Hide Description PK data was planned to be reported only if the results of Cohort 2 are available.
Time Frame Predose on Days 8, 29 and 57
Hide Outcome Measure Data
Hide Analysis Population Description
As the study was terminated prior to Cohort 2 enrollment, PK analysis could not be performed, as planned.
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Hide Arm/Group Description:
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Area Under the Concentration-time Curve (AUC) of Cytarabine
Hide Description PK data was planned to be reported only if the results of Cohort 2 are available.
Time Frame Predose, 0.25, 0.5, 1, 3, 6 hours post-dose on Days 1, 8 and 29
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were enrolled as the study was terminated prior to the initiation of Cohort 2.
Arm/Group Title Planned Cohort 2
Hide Arm/Group Description:
Participants in Cohort 2 were planned to receive low-dose subcutaneous injections of cytarabine in combination with continuous daily vismodegib (150 mg orally).
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame From screening until study completion or early termination visit (Up to 14 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Hide Arm/Group Description Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'poor risk cytogenetics' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent. Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling under 'FLT-3 mutation positive' subgroup received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent. Participants with relapsed/refractory AML or relapsed/refractory high-risk MDS falling neither under 'poor risk cytogenetics' nor 'FLT-3 mutation positive' subgroup were included in this group and received oral 150 mg dose of vismodegib capsule once daily until disease progression, intolerable toxicity most probably attributable to vismodegib, or participant withdrawal of consent.
All-Cause Mortality
Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/15 (66.67%)   3/4 (75.00%)   13/19 (68.42%) 
Blood and lymphatic system disorders       
Febrile neutropenia * 1  2/15 (13.33%)  1/4 (25.00%)  4/19 (21.05%) 
Thrombocytopenia * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Cardiac disorders       
Pericardial effusion * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  2/15 (13.33%)  0/4 (0.00%)  0/19 (0.00%) 
Haemorrhoids * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Lower gastrointestinal haemorrhage * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Nausea * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Oesophageal pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
General disorders       
Fatigue * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Mucosal inflammation * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Multi-organ failure * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Pyrexia * 1  0/15 (0.00%)  1/4 (25.00%)  6/19 (31.58%) 
Immune system disorders       
Graft versus host disease * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Infections and infestations       
Appendicitis * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Atypical pneumonia * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Bacteraemia * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Cellulitis * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Hepatic infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Infection * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Lung infection * 1  3/15 (20.00%)  0/4 (0.00%)  1/19 (5.26%) 
Pneumonia * 1  1/15 (6.67%)  0/4 (0.00%)  3/19 (15.79%) 
Sepsis * 1  0/15 (0.00%)  1/4 (25.00%)  1/19 (5.26%) 
Urinary tract infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Vaginal abscess * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Injury, poisoning and procedural complications       
Fall * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Subdural haematoma * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Wrist fracture * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Nervous system disorders       
Haemorrhage intracranial * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Status epilepticus * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Renal and urinary disorders       
Haematuria * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Renal failure acute * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Urinary retention * 1  2/15 (13.33%)  0/4 (0.00%)  0/19 (0.00%) 
Urinary tract pain * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Surgical and medical procedures       
Central venous catheterisation * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Vascular disorders       
Hypotension * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Poor Risk Cytogenetics FLT-3 Mutation Positive Neither Poor Risk Cytogenetics Nor FLT-3
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/15 (86.67%)   4/4 (100.00%)   19/19 (100.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  2/15 (13.33%)  1/4 (25.00%)  4/19 (21.05%) 
Febrile neutropenia * 1  1/15 (6.67%)  1/4 (25.00%)  0/19 (0.00%) 
Haemoglobinaemia * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Leukocytosis * 1  0/15 (0.00%)  2/4 (50.00%)  2/19 (10.53%) 
Leukopenia * 1  0/15 (0.00%)  0/4 (0.00%)  3/19 (15.79%) 
Neutropenia * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Thrombocytopenia * 1  2/15 (13.33%)  0/4 (0.00%)  3/19 (15.79%) 
Cardiac disorders       
Angina pectoris * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Pericardial effusion * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Sinus tachycardia * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Tachycardia * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Ear and labyrinth disorders       
Cerumen impaction * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Hearing impaired * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Hypoacusis * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Eye disorders       
Eye haemorrhage * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Eye pruritus * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Ocular hyperaemia * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Scleral discolouration * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  4/15 (26.67%)  0/4 (0.00%)  1/19 (5.26%) 
Abdominal pain upper * 1  0/15 (0.00%)  1/4 (25.00%)  2/19 (10.53%) 
Anal fissure * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Aphthous stomatitis * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Breath odour * 1  0/15 (0.00%)  1/4 (25.00%)  0/19 (0.00%) 
Cheilitis * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Constipation * 1  4/15 (26.67%)  0/4 (0.00%)  2/19 (10.53%) 
Dental caries * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Diarrhoea * 1  1/15 (6.67%)  0/4 (0.00%)  6/19 (31.58%) 
Dry mouth * 1  0/15 (0.00%)  1/4 (25.00%)  0/19 (0.00%) 
Dyspepsia * 1  0/15 (0.00%)  1/4 (25.00%)  0/19 (0.00%) 
Faecal incontinence * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Gingival bleeding * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Haematochezia * 1  0/15 (0.00%)  1/4 (25.00%)  1/19 (5.26%) 
Haemorrhoids * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Melaena * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Nausea * 1  4/15 (26.67%)  0/4 (0.00%)  10/19 (52.63%) 
Oesophageal pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Oesophagitis * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Oral pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Rectal haemorrhage * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Salivary hypersecretion * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Stomatitis * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Toothache * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Vomiting * 1  2/15 (13.33%)  1/4 (25.00%)  4/19 (21.05%) 
General disorders       
Asthenia * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Catheter site pain * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Chest discomfort * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Chest pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Chills * 1  1/15 (6.67%)  1/4 (25.00%)  2/19 (10.53%) 
Early satiety * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Fatigue * 1  1/15 (6.67%)  2/4 (50.00%)  5/19 (26.32%) 
Feeling cold * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Localised oedema * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Malaise * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Mucosal dryness * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Mucosal inflammation * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Multi-organ failure * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Non-cardiac chest pain * 1  2/15 (13.33%)  0/4 (0.00%)  0/19 (0.00%) 
Oedema * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Oedema peripheral * 1  4/15 (26.67%)  0/4 (0.00%)  4/19 (21.05%) 
Pain * 1  1/15 (6.67%)  0/4 (0.00%)  3/19 (15.79%) 
Peripheral swelling * 1  2/15 (13.33%)  0/4 (0.00%)  1/19 (5.26%) 
Pyrexia * 1  3/15 (20.00%)  3/4 (75.00%)  5/19 (26.32%) 
Infections and infestations       
Candida infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Catheter site infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Cellulitis * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Clostridium difficile infection * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Enterococcal infection * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Erysipelas * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Escherichia bacteraemia * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Herpes simplex * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Influenza * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Liver abscess * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Localised infection * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Mucosal infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Oral candidiasis * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Oral fungal infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Oral herpes * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Post procedural infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Rhinitis * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Staphylococcal infection * 1  0/15 (0.00%)  1/4 (25.00%)  1/19 (5.26%) 
Tooth infection * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Upper respiratory tract infection * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Injury, poisoning and procedural complications       
Allergic transfusion reaction * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Contusion * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Fall * 1  1/15 (6.67%)  0/4 (0.00%)  2/19 (10.53%) 
Laceration * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Ligament sprain * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Procedural pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Scratch * 1  0/15 (0.00%)  1/4 (25.00%)  0/19 (0.00%) 
Skin abrasion * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Investigations       
Alanine aminotransferase increased * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Aspartate aminotransferase increased * 1  1/15 (6.67%)  0/4 (0.00%)  2/19 (10.53%) 
Blood bilirubin increased * 1  2/15 (13.33%)  0/4 (0.00%)  0/19 (0.00%) 
Blood creatinine increased * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
C-reactive protein increased * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Cardiac murmur * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Liver function test abnormal * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Neutrophil count decreased * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Platelet count decreased * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Weight decreased * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  4/15 (26.67%)  1/4 (25.00%)  4/19 (21.05%) 
Dehydration * 1  3/15 (20.00%)  0/4 (0.00%)  2/19 (10.53%) 
Electrolyte imbalance * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Failure to thrive * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Hyperglycaemia * 1  2/15 (13.33%)  1/4 (25.00%)  1/19 (5.26%) 
Hyperkalaemia * 1  1/15 (6.67%)  1/4 (25.00%)  1/19 (5.26%) 
Hypoalbuminaemia * 1  2/15 (13.33%)  0/4 (0.00%)  0/19 (0.00%) 
Hypokalaemia * 1  1/15 (6.67%)  1/4 (25.00%)  6/19 (31.58%) 
Hypomagnesaemia * 1  3/15 (20.00%)  0/4 (0.00%)  3/19 (15.79%) 
Hyponatraemia * 1  2/15 (13.33%)  1/4 (25.00%)  2/19 (10.53%) 
Hypophosphataemia * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Vitamin B12 deficiency * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  2/15 (13.33%)  0/4 (0.00%)  2/19 (10.53%) 
Back pain * 1  2/15 (13.33%)  1/4 (25.00%)  1/19 (5.26%) 
Bone pain * 1  2/15 (13.33%)  0/4 (0.00%)  1/19 (5.26%) 
Flank pain * 1  0/15 (0.00%)  1/4 (25.00%)  0/19 (0.00%) 
Groin pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Joint swelling * 1  2/15 (13.33%)  0/4 (0.00%)  0/19 (0.00%) 
Muscle spasms * 1  3/15 (20.00%)  1/4 (25.00%)  5/19 (26.32%) 
Muscular weakness * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Musculoskeletal pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Myalgia * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Neck pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Pain in extremity * 1  2/15 (13.33%)  0/4 (0.00%)  3/19 (15.79%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acrochordon * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Chloroma * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Renal cell carcinoma * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Nervous system disorders       
Dizziness * 1  2/15 (13.33%)  0/4 (0.00%)  6/19 (31.58%) 
Dysgeusia * 1  4/15 (26.67%)  1/4 (25.00%)  7/19 (36.84%) 
Headache * 1  2/15 (13.33%)  1/4 (25.00%)  1/19 (5.26%) 
Hyperaesthesia * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Neuropathy peripheral * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Orthostatic intolerance * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Radicular pain * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Restless legs syndrome * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Sinus headache * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Somnolence * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Psychiatric disorders       
Depression * 1  0/15 (0.00%)  0/4 (0.00%)  2/19 (10.53%) 
Disorientation * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Insomnia * 1  1/15 (6.67%)  0/4 (0.00%)  2/19 (10.53%) 
Mental status changes * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Restlessness * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Sleep disorder * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Renal and urinary disorders       
Haematuria * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Pollakiuria * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Urinary incontinence * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Reproductive system and breast disorders       
Vaginal haemorrhage * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Vulval ulceration * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Vulvovaginal pain * 1  1/15 (6.67%)  0/4 (0.00%)  1/19 (5.26%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  1/15 (6.67%)  0/4 (0.00%)  3/19 (15.79%) 
Dysphonia * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Dyspnoea * 1  3/15 (20.00%)  0/4 (0.00%)  3/19 (15.79%) 
Dyspnoea exertional * 1  0/15 (0.00%)  1/4 (25.00%)  2/19 (10.53%) 
Epistaxis * 1  1/15 (6.67%)  0/4 (0.00%)  8/19 (42.11%) 
Hypoxia * 1  3/15 (20.00%)  1/4 (25.00%)  1/19 (5.26%) 
Nasal congestion * 1  0/15 (0.00%)  1/4 (25.00%)  1/19 (5.26%) 
Oropharyngeal pain * 1  0/15 (0.00%)  1/4 (25.00%)  3/19 (15.79%) 
Pleural effusion * 1  1/15 (6.67%)  0/4 (0.00%)  2/19 (10.53%) 
Productive cough * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Pulmonary oedema * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Respiratory failure * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Rhinorrhoea * 1  1/15 (6.67%)  1/4 (25.00%)  2/19 (10.53%) 
Sleep apnoea syndrome * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Snoring * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Wheezing * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  1/15 (6.67%)  0/4 (0.00%)  2/19 (10.53%) 
Decubitus ulcer * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Dermatitis acneiform * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Drug eruption * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Dry skin * 1  2/15 (13.33%)  1/4 (25.00%)  1/19 (5.26%) 
Ecchymosis * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Erythema * 1  0/15 (0.00%)  1/4 (25.00%)  1/19 (5.26%) 
Night sweats * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Petechiae * 1  1/15 (6.67%)  1/4 (25.00%)  1/19 (5.26%) 
Pruritus * 1  1/15 (6.67%)  0/4 (0.00%)  2/19 (10.53%) 
Rash * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Urticaria * 1  0/15 (0.00%)  0/4 (0.00%)  1/19 (5.26%) 
Vascular disorders       
Flushing * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Haematoma * 1  0/15 (0.00%)  0/4 (0.00%)  3/19 (15.79%) 
Hypertension * 1  1/15 (6.67%)  0/4 (0.00%)  2/19 (10.53%) 
Hypotension * 1  1/15 (6.67%)  0/4 (0.00%)  4/19 (21.05%) 
Subclavian vein thrombosis * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
Vasculitis * 1  1/15 (6.67%)  0/4 (0.00%)  0/19 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.1)
This study was prematurely terminated because of lower-than-expected efficacy observed in interim data analyses.
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-LaRoche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01880437     History of Changes
Other Study ID Numbers: GO28852
2013-001570-14 ( EudraCT Number )
First Submitted: June 11, 2013
First Posted: June 19, 2013
Results First Submitted: November 11, 2015
Results First Posted: December 15, 2015
Last Update Posted: December 15, 2015