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Study of PF-05212384 (Also Known as PKI-587)Administered Intravenously To Subjects With Solid Tumors (B2151001)

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: NCT00940498
Recruitment Status : Completed
First Posted : July 16, 2009
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neoplasms
Intervention Drug: PF-05212384 (also known as PKI-587)
Enrollment 78
Recruitment Details  
Pre-assignment Details The study was conducted in two parts: Part 1 to determine the maximum tolerated dose (MTD) and Part 2 to confirm the MTD. As per the sponsor’s decision, data was reported for the combined population of Part 1 and Part 2 which was considered more informative.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description PF-05212384 10 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study. PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Period Title: Overall Study
Started 4 4 4 4 43 7 8 4
Completed 1 3 1 2 34 6 7 3
Not Completed 3 1 3 2 9 1 1 1
Reason Not Completed
Death             2             0             0             1             5             0             1             0
Lost to Follow-up             1             1             2             0             1             0             0             1
Disease Progression             0             0             1             1             0             1             0             0
Physician Decision             0             0             0             0             2             0             0             0
Not treated due to disease related pain             0             0             0             0             1             0             0             0
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg Total
Hide Arm/Group Description PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study. PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. Total of all reporting groups
Overall Number of Baseline Participants 4 4 4 4 42 7 8 4 77
Hide Baseline Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study medication.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 4 participants 42 participants 7 participants 8 participants 4 participants 77 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
 100.0%
3
  75.0%
4
 100.0%
4
 100.0%
34
  81.0%
4
  57.1%
7
  87.5%
4
 100.0%
64
  83.1%
>=65 years
0
   0.0%
1
  25.0%
0
   0.0%
0
   0.0%
8
  19.0%
3
  42.9%
1
  12.5%
0
   0.0%
13
  16.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 4 participants 4 participants 42 participants 7 participants 8 participants 4 participants 77 participants
Female
1
  25.0%
3
  75.0%
1
  25.0%
2
  50.0%
20
  47.6%
5
  71.4%
4
  50.0%
4
 100.0%
40
  51.9%
Male
3
  75.0%
1
  25.0%
3
  75.0%
2
  50.0%
22
  52.4%
2
  28.6%
4
  50.0%
0
   0.0%
37
  48.1%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.
Time Frame Baseline up to Cycle 14 (each cycle is 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study medication.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 4 4 42 7 8 4
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
4
 100.0%
4
 100.0%
4
 100.0%
4
 100.0%
42
 100.0%
7
 100.0%
8
 100.0%
4
 100.0%
SAEs
2
  50.0%
1
  25.0%
1
  25.0%
1
  25.0%
16
  38.1%
0
   0.0%
5
  62.5%
2
  50.0%
2.Primary Outcome
Title Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)
Hide Description Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs included both serious and non-serious adverse events.
Time Frame Baseline up to Cycle 14 (each cycle is 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study medication.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 4 4 42 7 8 4
Measure Type: Count of Participants
Unit of Measure: Participants
AEs
3
  75.0%
3
  75.0%
4
 100.0%
4
 100.0%
40
  95.2%
7
 100.0%
8
 100.0%
4
 100.0%
SAEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.4%
0
   0.0%
0
   0.0%
2
  50.0%
3.Primary Outcome
Title Number of Participants With Laboratory Abnormalities
Hide Description Criteria for laboratory test abnormality: hematology (hemoglobin [less than {<} 0.8*lower limit of normal {LLN}], platelets [<0.5*LLN or greater than {>} 1.75*upper limit of normal {ULN}], white blood cells [<0.6*LLN or >1.5*ULN], lymphocytes [<0.8*LLN or >1.2*ULN], total neutrophils [<0.8*LLN or >1.2*ULN], basophils, eosinophils, monocytes [>1.2*ULN]); coagulation [partial thromboplastin time, prothrombin (PT), PT international ratio [>1.1*ULN]); liver function (total bilirubin [>1.5*ULN], aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase [>0.3*ULN], total protein, albumin [<0.8*LLN or >1.2*ULN]).
Time Frame Baseline up to Cycle 14 (each cycle is 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study medication.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 4 4 42 7 8 4
Measure Type: Count of Participants
Unit of Measure: Participants
4
 100.0%
3
  75.0%
4
 100.0%
3
  75.0%
41
  97.6%
7
 100.0%
7
  87.5%
4
 100.0%
4.Primary Outcome
Title Number of Participants With Dose Limiting Toxicities (DLTs)
Hide Description DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: Grade 3 nonhematologic AE (including nausea, vomiting, or diarrhea despite optimal therapy; or greater than or equal to [>=] grade 3 asthenia >2 days; or fasting serum glucose >250 milligrams per deciliter (mg/dL) despite optimal therapy); >=Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia lasting more than 7 days; Febrile neutropenia; other Grade 4 hematologic AE; delay of treatment >2 consecutive weeks due to toxicity. Grades were based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Time Frame Baseline up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
DLT evaluable analysis set included all enrolled participants who started treatment and did not have had a major treatment deviation in the first cycle of treatment.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 3 4 3 4 40 7 8 4
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   5.0%
5
  71.4%
3
  37.5%
2
  50.0%
5.Primary Outcome
Title Recommended Phase-2 Dose (RP2D)
Hide Description RP2D of PF-05212384 was determined based on the safety profile including laboratory and clinical assessments and pharmacodynamics findings.
Time Frame Baseline up to Cycle 14 (each cycle is 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis population included all participants who received at least 1 dose of study medication.
Arm/Group Title PF-05212384 : All Participants
Hide Arm/Group Description:
All participants who received PF-05212384 10 mg or 21 mg or 43 mg or 89 mg or 154 mg or 222 mg or 266 mg or 319 mg, intravenous infusion, once weekly in each 28 day cycle until progression of disease, uncontrollable toxicity, or a decision by the participant or investigator to discontinue.
Overall Number of Participants Analyzed 77
Measure Type: Number
Unit of Measure: mg
154
6.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of PF-05212384: Single and Multiple Dose
Hide Description [Not Specified]
Time Frame Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 4 4 42 7 8 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per milliliter (ng/mL)
Cycle 1 Number Analyzed 4 participants 4 participants 4 participants 4 participants 42 participants 7 participants 8 participants 3 participants
714.1
(33%)
1674
(10%)
3317
(10%)
6508
(106%)
9988
(28%)
14730
(54%)
14240
(29%)
27090
(26%)
Cycle 2 Number Analyzed 3 participants 3 participants 4 participants 4 participants 31 participants 4 participants 7 participants 2 participants
542.8
(28%)
1482
(24%)
2601
(33%)
4250
(43%)
8594
(64%)
15660
(86%)
10840
(46%)
NA [1] 
(NA%)
[1]
Results were not summarized if evaluable participants were less than 3, considered as insufficient values by investigator to calculate a reliable estimation.
7.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05212384: Single Dose
Hide Description Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (Clast).
Time Frame Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 3 4 42 7 8 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram*hour per milliliter(ng*hr/mL)
1149
(35%)
2367
(24%)
5741
(14%)
13090
(77%)
15780
(28%)
26550
(30%)
28180
(36%)
46760
(2%)
8.Secondary Outcome
Title Plasma Decay Half-Life (t1/2) of PF-05212384: Single and Multiple Dose
Hide Description Plasma decay half-life is the time measured for the plasma concentration of drug to decrease by one half.
Time Frame Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 4 4 42 7 8 3
Mean (Standard Deviation)
Unit of Measure: hours (hr)
Cycle 1 Number Analyzed 4 participants 4 participants 3 participants 4 participants 39 participants 6 participants 7 participants 3 participants
15.14  (6.1475) 17.34  (9.8683) 40.73  (7.7822) 35.95  (9.1267) 35.84  (6.2454) 33.33  (4.8144) 37.51  (4.8516) 38.53  (4.5457)
Cycle 2 Number Analyzed 0 participants 1 participants 2 participants 3 participants 23 participants 4 participants 6 participants 1 participants
NA [1]   (NA) NA [1]   (NA) 37.10  (4.4238) 35.97  (5.3197) 34.03  (6.6385) 36.38  (5.1188) NA [1]   (NA)
[1]
Results were not summarized if evaluable participants were less than 3, considered as insufficient values by investigator to calculate a reliable estimation.
9.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-05212384: Single Dose
Hide Description AUCinf= Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - inf).
Time Frame Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 3 4 39 6 7 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
1238
(32%)
2485
(23%)
5881
(14%)
13280
(78%)
16250
(28%)
27210
(33%)
28280
(39%)
47460
(2%)
10.Secondary Outcome
Title Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05212384: Single and Multiple Dose
Hide Description Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 168 hours (1 Week). For Cycle 2, the last PK sample for parameter calculations was on 120 hours after the Day 1 dose, however AUCtau was extrapolated to 168 hours using t1/2.
Time Frame Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 3 4 42 7 8 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*hr/mL
Cycle 1 Number Analyzed 4 participants 4 participants 3 participants 4 participants 42 participants 7 participants 8 participants 3 participants
1256
(29%)
2604
(22%)
5753
(13%)
13100
(78%)
15810
(28%)
26740
(30%)
28220
(36%)
46730
(2%)
Cycle 2 Number Analyzed 3 participants 2 participants 3 participants 3 participants 23 participants 4 participants 6 participants 1 participants
2991
(26%)
NA [1] 
(NA%)
15820
(29%)
25010
(49%)
47130
(54%)
79380
(64%)
61910
(42%)
NA [1] 
(NA%)
[1]
Results were not summarized if evaluable participants were less than 3, considered as insufficient values by investigator to calculate a reliable estimation.
11.Secondary Outcome
Title Number of Participants With Maximum Increase From Baseline in Corrected QT Interval
Hide Description Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia’s formula (QTcF = QT divided by cube root of RR) and by Bazette’s formula (QTcB = QT divided by square root of RR). Number of Participants with maximum increase from baseline in QTcB and QTcF of < 30 msec, between <=30 to <60 msec and >=60 were reported.
Time Frame Baseline up to Cycle 14 (each cycle is 28 days)
Hide Outcome Measure Data
Hide Analysis Population Description
The QTc analysis set included all enrolled participants who had at least one ECG assessment after receiving PF-05212384
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 4 3 42 7 8 4
Measure Type: Count of Participants
Unit of Measure: Participants
QTcB: Change <30
3
  75.0%
3
  75.0%
3
  75.0%
3
 100.0%
26
  61.9%
6
  85.7%
4
  50.0%
4
 100.0%
QTcB: <= 30 and <60
1
  25.0%
1
  25.0%
1
  25.0%
0
   0.0%
13
  31.0%
1
  14.3%
3
  37.5%
0
   0.0%
QTcB: Change >=60
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3
   7.1%
0
   0.0%
1
  12.5%
0
   0.0%
QTcF: Change <30
3
  75.0%
3
  75.0%
4
 100.0%
3
 100.0%
34
  81.0%
6
  85.7%
6
  75.0%
4
 100.0%
QTcF: <= 30 and <60
1
  25.0%
1
  25.0%
0
   0.0%
0
   0.0%
7
  16.7%
1
  14.3%
2
  25.0%
0
   0.0%
QTcF: Change >=60
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.4%
0
   0.0%
0
   0.0%
0
   0.0%
12.Secondary Outcome
Title Change From Baseline in Serum Glucose at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment
Hide Description [Not Specified]
Time Frame Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Serum biomarker analysis set included all enrolled participants who started treatment and had baseline and on-treatment serum biomarker samples successfully analyzed for at least 1 biomarker.
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 4 4 4 41 7 7 4
Mean (Standard Deviation)
Unit of Measure: milligram per deciliter (mg/dL)
Baseline Number Analyzed 4 participants 4 participants 4 participants 4 participants 38 participants 5 participants 4 participants 3 participants
100.3  (14.15) 103.1  (14.55) 87.0  (6.22) 91.1  (7.40) 95.6  (13.48) 96.7  (10.85) 88.4  (18.14) 93.3  (3.06)
Change at Cycle 1 Day 2 Number Analyzed 4 participants 2 participants 3 participants 3 participants 40 participants 7 participants 7 participants 4 participants
12.5  (29.59) -4.0  (7.07) 0.3  (10.60) 13.5  (4.08) 13.7  (21.49) 21.1  (24.97) 65.5  (41.41) 54.5  (94.71)
Change at Cycle 2 Day 1 Number Analyzed 3 participants 4 participants 4 participants 4 participants 33 participants 5 participants 6 participants 2 participants
1.0  (18.36) 28.4  (26.90) 11.5  (7.59) 3.0  (9.56) 2.8  (15.74) 5.0  (6.67) 12.9  (14.45) 9.5  (3.54)
Change at Cycle 3 Day 1 Number Analyzed 1 participants 1 participants 1 participants 2 participants 14 participants 2 participants 5 participants 2 participants
19.0 [1]   (NA) 19.0 [1]   (NA) 2.0 [1]   (NA) 9.3  (4.68) 10.4  (29.02) 16.0  (15.56) 26.9  (33.77) -11.0  (1.41)
Change at Cycle 4 Day 1 Number Analyzed 1 participants 1 participants 1 participants 2 participants 8 participants 1 participants 4 participants 2 participants
-1.0 [1]   (NA) 7.0 [1]   (NA) 0.0 [1]   (NA) 3.6  (7.64) 2.0  (10.81) 26.0 [1]   (NA) 41.6  (45.85) 6.5  (0.71)
Change at Cycle 5 Day 1 Number Analyzed 1 participants 1 participants 0 participants 2 participants 5 participants 1 participants 4 participants 2 participants
-9.0 [1]   (NA) 8.0 [1]   (NA) 8.2  (8.78) -3.8  (9.39) -3.0 [1]   (NA) 29.7  (33.08) -7.0  (2.83)
Change at Cycle 6 Day 1 Number Analyzed 1 participants 1 participants 0 participants 2 participants 3 participants 1 participants 4 participants 2 participants
-7.0 [1]   (NA) 2.0 [1]   (NA) 1.0  (1.41) -10.0  (8.66) 14.0 [1]   (NA) 29.1  (28.17) 5.0  (5.66)
Change at Cycle 7 Day 1 Number Analyzed 1 participants 1 participants 0 participants 1 participants 2 participants 0 participants 4 participants 1 participants
-9.0 [1]   (NA) 10.0 [1]   (NA) 8.0 [1]   (NA) -5.0  (2.83) 48.7  (50.13) 7.0 [1]   (NA)
Change at Cycle 8 Day 1 Number Analyzed 1 participants 1 participants 0 participants 1 participants 2 participants 0 participants 3 participants 1 participants
-12.0 [1]   (NA) 6.0 [1]   (NA) 11.0 [1]   (NA) 1.5  (21.92) 39.0  (32.70) -3.0 [1]   (NA)
Change at Cycle 9 Day 1 Number Analyzed 1 participants 1 participants 0 participants 1 participants 0 participants 0 participants 3 participants 1 participants
-7.0 [1]   (NA) 9.0 [1]   (NA) 5.0 [1]   (NA) 65.0  (42.66) 1.0 [1]   (NA)
Change at Cycle 10 Day 1 Number Analyzed 1 participants 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants
-2.0 [1]   (NA) 15.0 [1]   (NA) 11.0 [1]   (NA)
Change at Cycle 11 Day 1 Number Analyzed 1 participants 1 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
-8.0 [1]   (NA) -15.0 [1]   (NA) 39.6 [1]   (NA)
Change at Cycle 12 Day 1 Number Analyzed 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
-9.0 [1]   (NA) 28.8 [1]   (NA)
Change at Cycle 13 Day 1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
-1.8 [1]   (NA)
Change at Cycle 14 Day 1 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
36.0 [1]   (NA)
Change at EOT Number Analyzed 3 participants 3 participants 4 participants 3 participants 29 participants 6 participants 7 participants 2 participants
10.7  (34.12) 7.2  (12.64) 23.3  (31.48) 16.1  (15.07) 7.4  (21.08) -6.7  (13.52) 27.5  (32.75) 42.0  (72.12)
[1]
Standard deviation was not estimable since only one participant was evaluable.
13.Secondary Outcome
Title Change From Baseline in Serum Insulin at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment
Hide Description [Not Specified]
Time Frame Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Serum biomarker analysis set. Here, ‘N’ (number of participants analyzed) signifies those participants who were evaluable for this outcome measure (OM).
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description:
PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 4 1 3 2 37 6 7 4
Mean (Standard Deviation)
Unit of Measure: microunits per milliliter (mcU/mL)
Baseline ( n=4,1,3,2,35,4,4,3) Number Analyzed 4 participants 1 participants 3 participants 2 participants 35 participants 4 participants 4 participants 3 participants
23.8  (22.90) 10.2 [1]   (NA) 8.6  (4.40) 5.3  (1.84) 13.1  (9.34) 18.2  (14.14) 5.9  (7.86) 11.4  (7.00)
Change at Cycle 1 Day 2 (n =4,1,3,2,37,6,7,4) Number Analyzed 4 participants 1 participants 3 participants 2 participants 37 participants 6 participants 7 participants 4 participants
4.0  (33.56) 2.5 [1]   (NA) 2.9  (6.81) 4.7  (2.90) 22.8  (25.68) 40.9  (47.05) 57.5  (41.66) 110.3  (117.23)
Change at Cycle 2 Day 1 (n =0,0,0,2,27,5,3,1) Number Analyzed 0 participants 0 participants 0 participants 2 participants 27 participants 5 participants 3 participants 1 participants
5.4  (3.54) 1.3  (8.66) 2.6  (7.88) 7.3  (10.31) -2.9 [1]   (NA)
Change at Cycle 3 Day 1 (n =0,1,1,1,14,1,3,1) Number Analyzed 0 participants 1 participants 1 participants 1 participants 14 participants 1 participants 3 participants 1 participants
1.4 [1]   (NA) 2.1 [1]   (NA) 0.9 [1]   (NA) -0.7  (11.66) 4.2 [1]   (NA) 2.1  (4.38) 18.0 [1]   (NA)
Change at Cycle 4 Day 1 (n =0,0,1,1,8,0,3,2) Number Analyzed 0 participants 0 participants 1 participants 1 participants 8 participants 0 participants 3 participants 2 participants
3.1 [1]   (NA) 3.0 [1]   (NA) 2.9  (6.35) 4.2  (2.54) 0.6  (3.32)
Change at Cycle 5 Day 1 (n =0,1,0,1,5,0,3,1) Number Analyzed 0 participants 1 participants 0 participants 1 participants 5 participants 0 participants 3 participants 1 participants
-0.7 [1]   (NA) 0.1 [1]   (NA) 2.3  (5.24) 3.3  (1.86) -3.0 [1]   (NA)
Change at C6D1 (n=0,1,0,1,3,0,2,2) Number Analyzed 0 participants 1 participants 0 participants 1 participants 3 participants 0 participants 2 participants 2 participants
-1.2 [1]   (NA) 3.1 [1]   (NA) 0.9  (5.14) 0.8  (0.07) 0.3  (0.42)
Change at Cycle 7 Day 1 (n=0,1,0,1,2,0,3,1) Number Analyzed 0 participants 1 participants 0 participants 1 participants 2 participants 0 participants 3 participants 1 participants
0.9 [1]   (NA) 0.2 [1]   (NA) 2.1  (0.85) 6.9  (8.31) 5.0 [1]   (NA)
Change at Cycle 8 Day 1 (n =0,1,0,1,2,0,3,1) Number Analyzed 0 participants 1 participants 0 participants 1 participants 2 participants 0 participants 3 participants 1 participants
-1.9 [1]   (NA) 3.1 [1]   (NA) 4.5  (4.17) -0.9  (2.71) -1.4 [1]   (NA)
Change at Cycle 9 Day 1 ( n=0,1,0,1,0,0,2,1) Number Analyzed 0 participants 1 participants 0 participants 1 participants 0 participants 0 participants 2 participants 1 participants
5.0 [1]   (NA) 0.9 [1]   (NA) 1.8  (4.60) -1.7 [1]   (NA)
Change at Cycle 10 Day 1 (n =1,1,0,0,0,0,0,1) Number Analyzed 1 participants 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants
-18.3 [1]   (NA) 3.4 [1]   (NA) 5.8 [1]   (NA)
Change at Cycle 11 Day 1 (n =1,1,0,0,0,0,1,0) Number Analyzed 1 participants 1 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
-32.2 [1]   (NA) 0.1 [1]   (NA) 38.6 [1]   (NA)
Change at Cycle 12 Day 1 (n =1,0,0,0,0,0,0,0) Number Analyzed 1 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants
-4.3 [1]   (NA)
Change at Cycle 13 D 1 (n =0,0,0,0,0,0,1,0) Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
22.0 [1]   (NA)
Change at Cycle 14 Day 1 (n =0,0,0,0,0,0,1,0) Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
107.0 [1]   (NA)
Change at EOT (n =1,0,1,1,21,4,6,1) Number Analyzed 1 participants 0 participants 1 participants 1 participants 21 participants 4 participants 6 participants 1 participants
19.1 [1]   (NA) 0.0 [1]   (NA) 0.8 [1]   (NA) 1.7  (8.59) -4.8  (9.04) 19.6  (21.67) -4.3 [1]   (NA)
[1]
Standard deviation was not estimable since only one participant was evaluable.
14.Secondary Outcome
Title Change From Baseline in Serum C-peptide at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment
Hide Description [Not Specified]
Time Frame Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)
Hide Outcome Measure Data
Hide Analysis Population Description
Serum biomarker analysis set. Here, N= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for reporting arms: PF-05212384 10 mg, 21 mg, 43 mg, 89 mg, and 319 mg, as pre specified in protocol Amendment 5.
Arm/Group Title Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg
Hide Arm/Group Description:
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 35 5 3
Mean (Standard Deviation)
Unit of Measure: ng/mL
Baseline Number Analyzed 35 participants 5 participants 3 participants
3.0  (1.82) 3.0  (1.19) 4.6  (1.92)
Change at Cycle 1 Day 2 Number Analyzed 34 participants 5 participants 2 participants
3.6  (2.23) 6.2  (4.23) 5.0  (5.37)
Change at Cycle 2 Day 1 Number Analyzed 26 participants 4 participants 2 participants
0.4  (1.36) 1.0  (1.30) -1.1  (2.23)
Change at Cycle 3 Day 1 Number Analyzed 12 participants 1 participants 2 participants
0.5  (1.15) 2.5 [1]   (NA) -1.8  (3.11)
Change at Cycle 4 Day 1 Number Analyzed 7 participants 0 participants 2 participants
0.9  (1.45) 0.1  (1.56)
Change at Cycle 5 Day 1 Number Analyzed 4 participants 0 participants 2 participants
0.4  (0.86) -1.2  (2.87)
Change at Cycle 6 Day 1 Number Analyzed 2 participants 0 participants 2 participants
-0.0  (0.54) -0.3  (1.60)
Change at Cycle 7 Day 1 Number Analyzed 2 participants 0 participants 2 participants
0.1  (0.36) 1.9  (1.20)
Change at Cycle 8 Day 1 Number Analyzed 2 participants 0 participants 2 participants
0.3  (0.14) -0.9  (3.75)
Change at Cycle 9 Day 1 Number Analyzed 0 participants 0 participants 1 participants
2.9 [1]   (NA)
Change at Cycle 10 Day 1 Number Analyzed 0 participants 0 participants 0 participants
Change at Cycle 11 Day 1 Number Analyzed 0 participants 0 participants 0 participants
Change at Cycle 12 Day 1 Number Analyzed 0 participants 0 participants 0 participants
Change at Cycle 13 Day 1 Number Analyzed 0 participants 0 participants 0 participants
Change at Cycle 14 Day 1 Number Analyzed 0 participants 0 participants 0 participants
Change at EOT Number Analyzed 24 participants 5 participants 2 participants
1.1  (1.82) -0.1  (0.80) 5.3  (1.68)
[1]
Standard deviation was not estimable since only one participant was evaluable.
15.Secondary Outcome
Title Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 1
Hide Description Analysis of hair follicles was conducted using a Reverse Phase Microarrays (RPMA) assay. Phosphoprotein biomarkers measured were pAkt S473, pAkt T308, pStat3 (Y705), Ki-67, and pPRAS40 (T246).
Time Frame Baseline, 2, 3 and 72 hours (H) postdose on Day 1 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Hair follicle analysis set. Here, N= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for reporting arms: PF-05212384 10 mg, 21 mg, 43 mg, 89 mg, and 319 mg, as pre specified in protocol Amendment 5.
Arm/Group Title Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg
Hide Arm/Group Description:
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
Overall Number of Participants Analyzed 20 4 1
Mean (Standard Deviation)
Unit of Measure: normalized fluorescence units (NFU)
Baseline: pAkt S473 Number Analyzed 19 participants 4 participants 0 participants
12.2  (4.58) 17.2  (5.26)
Baseline: pAkt T308 Number Analyzed 20 participants 3 participants 0 participants
44.3  (19.41) 36.2  (15.95)
Baseline: pStat3 (Y705) Number Analyzed 17 participants 2 participants 0 participants
172.3  (47.26) 224.2  (117.43)
Baseline: Ki-67 Number Analyzed 19 participants 3 participants 1 participants
82.1  (21.79) 128.1  (30.80) 145.7 [1]   (NA)
Baseline: pPRAS40 (T246) Number Analyzed 19 participants 3 participants 0 participants
111.7  (31.75) 99.6  (30.11)
Change at C1D1 2H:pAkt S473 Number Analyzed 18 participants 3 participants 0 participants
-1.7  (3.59) 6.8  (5.77)
Change at C1D1 2H:pAkt T308 Number Analyzed 18 participants 1 participants 0 participants
2.3  (17.06) -4.6 [1]   (NA)
Change at C1D1 2H:pStat3 (Y705) Number Analyzed 15 participants 1 participants 0 participants
-6.2  (34.78) 126.3 [1]   (NA)
Change at C1D1 2H:Ki-67 Number Analyzed 15 participants 1 participants 1 participants
1.0  (29.41) 34.7 [1]   (NA) -36.2 [1]   (NA)
Change at C1D1 2H:pPRAS40-T246 Number Analyzed 15 participants 3 participants 0 participants
-27.4  (22.59) 42.0  (26.01)
Change at C1D1 3hr: pAkt S473 Number Analyzed 15 participants 4 participants 0 participants
-0.9  (2.93) 0.2  (9.26)
Change at C1D1 3hr: pAkt T308 Number Analyzed 16 participants 3 participants 0 participants
0.4  (14.25) 6.9  (18.50)
Change at C1D1 3H: pStat3 (Y705) Number Analyzed 11 participants 1 participants 0 participants
-11.7  (54.88) -142.2 [1]   (NA)
Change at C1D1 3hr: Ki-67 Number Analyzed 13 participants 2 participants 0 participants
-8.5  (23.59) 25.2  (15.68)
Change at C1D1 3H:pPRAS40-T246 Number Analyzed 12 participants 3 participants 0 participants
-27.8  (27.11) 49.8  (56.37)
Change at C1D4 72H:pAkt S473 Number Analyzed 12 participants 3 participants 0 participants
-0.9  (3.69) 1.7  (9.45)
Change at C1D4 72H:pAkt-T308 Number Analyzed 13 participants 3 participants 0 participants
9.4  (38.19) 11.8  (15.16)
Change at C1D4 72H: pStat3 (Y705) Number Analyzed 9 participants 1 participants 0 participants
1.9  (35.99) 239.8 [1]   (NA)
Change at C1D4 72hr: Ki-67 Number Analyzed 9 participants 3 participants 0 participants
5.7  (38.59) 13.5  (57.80)
Change atC1D4-72H:pPRAS40 T246 Number Analyzed 13 participants 2 participants 0 participants
-2.1  (31.55) 35.6  (77.10)
[1]
Standard deviation was not estimable since only one participant was evaluable.
16.Secondary Outcome
Title Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 22
Hide Description Tumor biopsies were taken from participants of reporting arm PF-05212384 154 mg dose level at baseline and at Cycle 1/Day 22. Biopsies were fixed in optimal cutting temperature compound and analyzed via RPMA. The biomarkers tested were phosphorylated versions of the proteins: AKT S473, AKT T308, FKHR T24 / FKHR1 T32, and STAT3. This outcome measure was planned to be analyzed only for the reporting arm Part 1 and 2: PF-05212384 154 mg, as pre-specified in protocol.
Time Frame Baseline, Day 22 of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
Tumor biopsy analysis set=all enrolled participants who had treatment &had baseline,on-treatment tumor tissue successfully analyzed for at least 1 biomarker.N=participants evaluable for this OM. This OM was planned to analyzed only in reporting arm- Part 1 and 2:PF-05212384 154 mg.
Arm/Group Title Part 1 and 2: PF-05212384 154 mg
Hide Arm/Group Description:
PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study.
Overall Number of Participants Analyzed 8
Mean (Standard Deviation)
Unit of Measure: normalized to cytokeratin (NFC)
Baseline: AKT S473 Number Analyzed 8 participants
34.3  (26.82)
Baseline: AKT T308 Number Analyzed 7 participants
38.5  (25.80)
Baseline: FKHR T24 / FKHR1 T32 Number Analyzed 8 participants
145.1  (113.99)
Baseline: STAT3 Number Analyzed 7 participants
231.4  (219.22)
Change at C1D22: AKT S473 Number Analyzed 8 participants
-12.3  (36.88)
Change at C1D22: AKT T308 Number Analyzed 7 participants
-5.8  (25.42)
Change at C1D22: FKHR T24 / FKHR1 T32 Number Analyzed 8 participants
-27.0  (82.92)
Change at C1D22: STAT3 Number Analyzed 7 participants
-45.6  (139.67)
17.Secondary Outcome
Title Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue
Hide Description Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were PIK3CA and phosphatase and tensin homolog (PTEN) by immunohistochemistry.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Baseline tumor tissue biomarker analysis set: All enrolled patients who start treatment and had baseline tumor tissues successfully analyzed for at least one of the biomarkers. Here, ‘N’ (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title PF-05212384 : All Participants
Hide Arm/Group Description:
PF-05212384-10,21,43,89,154,222,266,319 milligram (mg) intravenous infusion over approximately 30 minutes once weekly in each 28 day cycle until progression of disease, uncontrollable toxicity, or a decision by the patient or investigator to discontinue.
Overall Number of Participants Analyzed 70
Measure Type: Count of Participants
Unit of Measure: Participants
PTEN Mutation: Present NA [1] 
PTEN Mutation: Absent NA [1] 
PTEN Deletion: Present
28
  40.0%
PTEN Deletion: Absent
28
  40.0%
PTEN Amplification: Present NA [2] 
PTEN Amplification: Absent NA [2] 
PIK3CA Mutation: Present
4
   5.7%
PIK3CA Mutation: Absent
27
  38.6%
PIK3CA Deletion: Present NA [3] 
PIK3CA Deletion: Absent NA [3] 
PIK3CA Amplification: Present
2
   2.9%
PIK3CA Amplification: Absent
56
  80.0%
[1]
Data for mutation was not collected based on sponsors decision since it was not a biologically relevant parameter for PTEN.
[2]
Data for amplification was not collected based on sponsors decision since it was not a biologically relevant parameter for PTEN.
[3]
Data for deletion was not collected based on sponsors decision since it was not a biologically relevant parameter for PIK3CA.
18.Secondary Outcome
Title Percentage of Participants With Objective Response (OR)
Hide Description Objective response was defined as having complete response (CR) or Partial Response (PR) assessed by RECIST 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). Percentage of participants with objective response were reported.
Time Frame Baseline until disease progression or death due to any cause (up to Cycle 14 [each cycle 28 days])
Hide Outcome Measure Data
Hide Analysis Population Description
Response-evaluable population included participants who received at least 1 dose of study drug, had an adequate baseline tumor assessment and at least 1 post baseline disease assessment for analyses of response.
Arm/Group Title PF-05212384 : All Participants
Hide Arm/Group Description:
Entire study population treated with PF-05212384-10,21,43,89,154,222,266,319 mg intravenous infusion over approximately 30 minutes once weekly in each 28 day cycle until progression of disease, uncontrollable toxicity, or a decision by the participant or investigator to discontinue.
Overall Number of Participants Analyzed 77
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
2.6
(0.3 to 9.1)
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
 
Arm/Group Title Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Hide Arm/Group Description PF-05212384 10 milligram (mg), intravenous (IV) infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 21 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 43 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 89 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384 154 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) and Part 2 (MTD confirmation) of the study. PF-05212384 222 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384-266 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study. PF-05212384-319 mg IV infusion, once weekly in each 28-day cycle until progression of disease, uncontrollable toxicity or a decision by the participant or investigator to discontinue during Part 1 (MTD estimation) of the study.
All-Cause Mortality
Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/4 (50.00%)   1/4 (25.00%)   1/4 (25.00%)   1/4 (25.00%)   16/42 (38.10%)   0/7 (0.00%)   5/8 (62.50%)   2/4 (50.00%) 
Blood and lymphatic system disorders                 
Anaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Gastrointestinal disorders                 
Abdominal pain * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Colonic obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Diarrhoea * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Dysphagia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Gastrointestinal obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Intestinal obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Nausea * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Rectal haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Vomiting * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
General disorders                 
Disease progression * 1  2/4 (50.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Mucosal inflammation * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Pyrexia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hepatobiliary disorders                 
Bile duct obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hyperbilirubinaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Infections and infestations                 
Gastrointestinal infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Lung infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Pneumonia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Respiratory tract infection * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Septic shock * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Injury, poisoning and procedural complications                 
Hepatic haematoma * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Humerus fracture * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Tracheal obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Investigations                 
Electrocardiogram T wave inversion * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Back pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Gastrointestinal stromal tumour * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Nervous system disorders                 
Convulsion * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Vocal cord paralysis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Respiratory, thoracic and mediastinal disorders                 
Dyspnoea * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Pleural effusion * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Pulmonary embolism * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Respiratory failure * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Vascular disorders                 
Aortic disorder * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Part 1: PF-05212384 10 mg Part 1: PF-05212384 21 mg Part 1: PF-05212384 43 mg Part 1: PF-05212384 89 mg Part 1 and 2: PF-05212384 154 mg Part 1: PF-05212384 222 mg Part 1: PF-05212384 266 mg Part 1: PF-05212384 319 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   4/4 (100.00%)   4/4 (100.00%)   4/4 (100.00%)   42/42 (100.00%)   7/7 (100.00%)   8/8 (100.00%)   4/4 (100.00%) 
Blood and lymphatic system disorders                 
Anaemia * 1  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  1/4 (25.00%)  6/42 (14.29%)  1/7 (14.29%)  2/8 (25.00%)  2/4 (50.00%) 
Hypochromic anaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Leukocytosis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Leukopenia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Lymphopenia * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  4/42 (9.52%)  0/7 (0.00%)  0/8 (0.00%)  2/4 (50.00%) 
Neutropenia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Thrombocytopenia * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Cardiac disorders                 
Atrial fibrillation * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Sinus tachycardia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Tachycardia * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Ear and labyrinth disorders                 
Cerumen impaction * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hearing impaired * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Tinnitus * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Eye disorders                 
Blepharitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Cataract * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Conjunctivitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Diplopia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Eyelid oedema * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Vision blurred * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Gastrointestinal disorders                 
Abdominal discomfort * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Abdominal distension * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Abdominal pain * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  6/42 (14.29%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Abdominal pain lower * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Abdominal pain upper * 1  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  3/7 (42.86%)  2/8 (25.00%)  0/4 (0.00%) 
Anal pruritus * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Ascites * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Constipation * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  13/42 (30.95%)  2/7 (28.57%)  2/8 (25.00%)  0/4 (0.00%) 
Diarrhoea * 1  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%)  9/42 (21.43%)  2/7 (28.57%)  2/8 (25.00%)  2/4 (50.00%) 
Dry mouth * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  4/42 (9.52%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Dyspepsia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  2/8 (25.00%)  1/4 (25.00%) 
Dysphagia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Flatulence * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Gastric varices * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Gastrointestinal haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  1/8 (12.50%)  0/4 (0.00%) 
Gastrointestinal hypomotility * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Gastrooesophageal reflux disease * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Gingival inflammation * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Glossitis * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Haematochezia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Haemorrhoids * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Hypoaesthesia oral * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Intestinal obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Mouth haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Mouth ulceration * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Nausea * 1  3/4 (75.00%)  2/4 (50.00%)  2/4 (50.00%)  1/4 (25.00%)  22/42 (52.38%)  3/7 (42.86%)  6/8 (75.00%)  3/4 (75.00%) 
Odynophagia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Oral discomfort * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Oral dysaesthesia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Oral mucosal erythema * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Oral pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  1/42 (2.38%)  1/7 (14.29%)  0/8 (0.00%)  1/4 (25.00%) 
Painful defaecation * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Paraesthesia oral * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  2/7 (28.57%)  0/8 (0.00%)  2/4 (50.00%) 
Perianal erythema * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Proctalgia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Proctitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Rectal discharge * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Rectal haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Rectal ulcer * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Stomatitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  5/42 (11.90%)  2/7 (28.57%)  2/8 (25.00%)  1/4 (25.00%) 
Tongue coated * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Tooth loss * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Upper gastrointestinal haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Varices oesophageal * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Vomiting * 1  3/4 (75.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  15/42 (35.71%)  2/7 (28.57%)  5/8 (62.50%)  1/4 (25.00%) 
General disorders                 
Asthenia * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  14/42 (33.33%)  1/7 (14.29%)  4/8 (50.00%)  0/4 (0.00%) 
Catheter site pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Catheter site rash * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Chest pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  3/42 (7.14%)  1/7 (14.29%)  1/8 (12.50%)  0/4 (0.00%) 
Chills * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  4/42 (9.52%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Early satiety * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Face oedema * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Facial pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Fatigue * 1  3/4 (75.00%)  2/4 (50.00%)  2/4 (50.00%)  0/4 (0.00%)  10/42 (23.81%)  3/7 (42.86%)  3/8 (37.50%)  2/4 (50.00%) 
Feeling jittery * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Influenza like illness * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Infusion site reaction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Injection site reaction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Localised oedema * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Malaise * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Mucosal inflammation * 1  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  19/42 (45.24%)  5/7 (71.43%)  6/8 (75.00%)  3/4 (75.00%) 
Oedema peripheral * 1  2/4 (50.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  1/8 (12.50%)  1/4 (25.00%) 
Pain * 1  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Performance status decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Pyrexia * 1  0/4 (0.00%)  2/4 (50.00%)  0/4 (0.00%)  1/4 (25.00%)  11/42 (26.19%)  1/7 (14.29%)  2/8 (25.00%)  1/4 (25.00%) 
Sensation of foreign body * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Thirst * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Hepatobiliary disorders                 
Bile duct obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hepatic failure * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hepatic function abnormal * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hepatic pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hyperbilirubinaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Immune system disorders                 
Hypersensitivity * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Infections and infestations                 
Candidiasis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Cystitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Device related infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Diverticulitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  1/8 (12.50%)  0/4 (0.00%) 
Enterocolitis infectious * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Folliculitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Fungal infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Gastroenteritis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Herpes zoster * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Laryngitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Lip infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Localised infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Lower respiratory tract infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Nasopharyngitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Oral candidiasis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Oral herpes * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Pharyngitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Respiratory tract infection * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%)  2/42 (4.76%)  0/7 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Rhinitis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Sputum purulent * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Tinea pedis * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Upper respiratory tract infection * 1  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Urinary tract infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Vaginal infection * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Injury, poisoning and procedural complications                 
Ear injury * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Fall * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Investigations                 
Activated partial thromboplastin time prolonged * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Alanine aminotransferase increased * 1  2/4 (50.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  9/42 (21.43%)  2/7 (28.57%)  0/8 (0.00%)  0/4 (0.00%) 
Amylase increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Aspartate aminotransferase increased * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  10/42 (23.81%)  2/7 (28.57%)  0/8 (0.00%)  0/4 (0.00%) 
Blood albumin decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood alkaline phosphatase increased * 1  3/4 (75.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  6/42 (14.29%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood bilirubin increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood calcium decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood cholesterol increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood creatinine increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Blood magnesium decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood potassium decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Blood sodium decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Breath sounds abnormal * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Electrocardiogram QT prolonged * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Gamma-glutamyltransferase increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Glycosylated haemoglobin increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Haemoglobin decreased * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  4/42 (9.52%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Heart rate increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
International normalised ratio increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Liver palpable subcostal * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Pancreatic enzymes increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Platelet count decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Transaminases increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Weight decreased * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Metabolism and nutrition disorders                 
Acidosis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Cachexia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Decreased appetite * 1  2/4 (50.00%)  1/4 (25.00%)  2/4 (50.00%)  1/4 (25.00%)  16/42 (38.10%)  3/7 (42.86%)  2/8 (25.00%)  2/4 (50.00%) 
Dehydration * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Fluid overload * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Glucose tolerance impaired * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Gout * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hyperamylasaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hypercalcaemia * 1  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hyperchloraemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Hypercholesterolaemia * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  4/42 (9.52%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Hyperglycaemia * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  12/42 (28.57%)  1/7 (14.29%)  4/8 (50.00%)  3/4 (75.00%) 
Hyperkalaemia * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Hyperlipasaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hyperlipidaemia * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hypernatraemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Hypertriglyceridaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  4/42 (9.52%)  0/7 (0.00%)  1/8 (12.50%)  1/4 (25.00%) 
Hypoalbuminaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hypocalcaemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Hypokalaemia * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  1/8 (12.50%)  1/4 (25.00%) 
Hypomagnesaemia * 1  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  2/7 (28.57%)  1/8 (12.50%)  1/4 (25.00%) 
Hyponatraemia * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  4/42 (9.52%)  0/7 (0.00%)  1/8 (12.50%)  1/4 (25.00%) 
Hypophagia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Hypophosphataemia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  2/8 (25.00%)  1/4 (25.00%) 
Back pain * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  2/4 (50.00%)  9/42 (21.43%)  0/7 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Bone pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Flank pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Inguinal mass * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Intervertebral disc protrusion * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Joint stiffness * 1  1/4 (25.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Joint swelling * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Muscle spasms * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Muscular weakness * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Musculoskeletal chest pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Musculoskeletal pain * 1  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Musculoskeletal stiffness * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Myalgia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  4/42 (9.52%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Pain in extremity * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  4/42 (9.52%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Pain in jaw * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Metastases to bone * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Tumour haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Tumour pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Nervous system disorders                 
Aphasia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Brain oedema * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Convulsion * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Dizziness * 1  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  1/8 (12.50%)  1/4 (25.00%) 
Dizziness postural * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Dysaesthesia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Dysgeusia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  8/42 (19.05%)  2/7 (28.57%)  0/8 (0.00%)  1/4 (25.00%) 
Headache * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  4/42 (9.52%)  1/7 (14.29%)  1/8 (12.50%)  0/4 (0.00%) 
Hemianopia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Hypersomnia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Hypoaesthesia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Intracranial pressure increased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Motor dysfunction * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Neuralgia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Neuropathy peripheral * 1  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Paraesthesia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Presyncope * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Somnolence * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Psychiatric disorders                 
Anxiety * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Confusional state * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Insomnia * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  6/42 (14.29%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Libido decreased * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Nervousness * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Renal and urinary disorders                 
Dysuria * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  2/42 (4.76%)  1/7 (14.29%)  2/8 (25.00%)  0/4 (0.00%) 
Haematuria * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Nephrolithiasis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Oliguria * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Polyuria * 1  0/4 (0.00%)  1/4 (25.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Proteinuria * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  2/4 (50.00%) 
Renal vein thrombosis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/4 (25.00%) 
Urinary incontinence * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Reproductive system and breast disorders                 
Pelvic pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Scrotal swelling * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Testicular pain * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  0/4 (0.00%) 
Vaginal discharge * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/42 (2.38%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Vaginal haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  1/8 (12.50%)  1/4 (25.00%) 
Respiratory, thoracic and mediastinal disorders                 
Bronchospasm * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/42 (0.00%)  0/7 (0.00%)  2/8 (25.00%)  0/4 (0.00%) 
Cough * 1  1/4 (25.00%)  2/4 (50.00%)  0/4 (0.00%)  0/4 (0.00%)  9/42 (21.43%)  2/7 (28.57%)  4/8 (50.00%)  0/4 (0.00%) 
Dysphonia * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  1/4 (25.00%)  3/42 (7.14%)  1/7 (14.29%)  0/8 (0.00%)  0/4 (0.00%) 
Dyspnoea * 1  0/4 (0.00%)  1/4 (25.00%)  1/4 (25.00%)  0/4 (0.00%)  5/42 (11.90%)  3/7 (42.86%)  3/8 (37.50%)  1/4 (25.00%) 
Dyspnoea exertional * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)  3/42 (7.14%)  0/7 (0.00%)  0/8 (0.00%)  0/4 (0.00%) 
Epistaxis * 1  0/4 (0.00%)  0/4 (0.00%)  0/4 (0.00%)