Trial Outcomes & Findings for Asian Phase I Study Of PF-03446962 (NCT NCT01337050)

NCT ID: NCT01337050

Last Updated: 2015-10-28

Results Overview

The MTD was defined as the highest dose of PF-03446962 associated with the occurrence of Dose Limiting Toxicities (DLTs) in at most 1 of 6 participants with the next higher dose having at least 2/3 or 2/6 participants experiencing DLTs (that is (i.e.) Maximum Administrated Dose). DLT is defined if the participants meets the following criteria during the first 6 weeks of treatment, possibly attributable to PF-03446962. Neutropenia grade 4 (less than \[\< \])500/cubic millimeter \[mm\^ 3\]) lasting for greater than equal to (\>=) 8 days; Febrile Neutropenia \>= Grade 3; Neutropenic Infection \>= Grade 3; Grade 4 thrombocytopenia (\<25,000/mm\^3); Grade 3 thrombocytopenia (\<50,000/mm\^3) with active bleeding; Grade 3 or higher non-hematological toxicity.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 36 participants
• Primary outcome timeframe: Baseline up to Week 6
• Results posted on: 2015-10-28

Participant Flow

Participant milestones

Measure	PF-03446962 4.5 mg/kg PF-03446962 4.5 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Overall Study STARTED	4	13	19
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	4	13	19

Reasons for withdrawal

Measure	PF-03446962 4.5 mg/kg PF-03446962 4.5 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Overall Study Death	0	0	4
Overall Study Other	4	6	8
Overall Study Participants refused further follow-up	0	7	7

Baseline Characteristics

Asian Phase I Study Of PF-03446962

Baseline characteristics by cohort

Measure	PF-03446962 4.5 mg/kg n=4 Participants PF-03446962 4.5 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	Total n=36 Participants Total of all reporting groups
Age, Continuous	59.0 years STANDARD_DEVIATION 10.9 • n=5 Participants	56.5 years STANDARD_DEVIATION 12.4 • n=7 Participants	57.7 years STANDARD_DEVIATION 13.1 • n=5 Participants	57.4 years STANDARD_DEVIATION 12.3 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants	25 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 6

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

The MTD was defined as the highest dose of PF-03446962 associated with the occurrence of Dose Limiting Toxicities (DLTs) in at most 1 of 6 participants with the next higher dose having at least 2/3 or 2/6 participants experiencing DLTs (that is (i.e.) Maximum Administrated Dose). DLT is defined if the participants meets the following criteria during the first 6 weeks of treatment, possibly attributable to PF-03446962. Neutropenia grade 4 (less than [< ])500/cubic millimeter [mm^ 3]) lasting for greater than equal to (>=) 8 days; Febrile Neutropenia >= Grade 3; Neutropenic Infection >= Grade 3; Grade 4 thrombocytopenia (<25,000/mm^3); Grade 3 thrombocytopenia (<50,000/mm^3) with active bleeding; Grade 3 or higher non-hematological toxicity.

Outcome measures

Measure	PF-03446962 n=12 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Maximum Tolerated Dose (MTD)	10.0 mg/kg	—	—

PRIMARY outcome

Timeframe: Baseline up to 28 days after last dose of study medication

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

RP2D was determined by a comprehensive assessments based on all the safety data, efficacy data, pharmacokinetics profile and biomarker data using blood and tumor samples.

Outcome measures

Measure	PF-03446962 n=36 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Recommended Phase-2 Dose (RP2D)	7.0 mg/kg	—	—

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

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 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious adverse events (non-SAEs).

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	3 participants	13 participants	19 participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; Grade 1 (Mild Adverse Event), Grade 2 (Moderate Adverse Event), Grade 3 (Severe Adverse Event), Grade 4 (Life- Threatening or Disabling Adverse Event), Grade 5 (Death Related to Adverse Event).

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity Grade 1	0 participants	4 participants	5 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity Grade 2	1 participants	3 participants	6 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity Grade 3	2 participants	4 participants	8 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity Grade 4	0 participants	1 participants	0 participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity Grade 5	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

An 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. AEs included both SAEs and non-serious adverse events (non-SAEs). Relatedness to study drug was assessed based on investigator's discretion.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	3 participants	9 participants	14 participants
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline up to 28 days after last dose

Population: Safety analysis set included all participants who received at least 1 dose of study medication.

Laboratory abnormalities were segregated into hematology, chemistry, coagulation and urinalysis test. It had been graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) into Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Life-threatening). Participants with abnormality of any of these grades are reported.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Number of Participants With Laboratory Abnormalities Anemia	2 participants	10 participants	13 participants
Number of Participants With Laboratory Abnormalities Hemoglobin increased	1 participants	1 participants	1 participants
Number of Participants With Laboratory Abnormalities Lymphocyte count increased	0 participants	2 participants	2 participants
Number of Participants With Laboratory Abnormalities Lymphopenia	2 participants	1 participants	5 participants
Number of Participants With Laboratory Abnormalities Neutrophils (absolute)	0 participants	1 participants	1 participants
Number of Participants With Laboratory Abnormalities Platelets	0 participants	5 participants	11 participants
Number of Participants With Laboratory Abnormalities White Blood Cells (WBC)	1 participants	2 participants	1 participants
Number of Participants With Laboratory Abnormalities Alanine aminotransferase (ALT)	2 participants	5 participants	9 participants
Number of Participants With Laboratory Abnormalities Alkaline phosphatase	2 participants	7 participants	13 participants
Number of Participants With Laboratory Abnormalities Amylase	1 participants	3 participants	5 participants
Number of Participants With Laboratory Abnormalities Aspartate aminotransferase (AST)	1 participants	8 participants	13 participants
Number of Participants With Laboratory Abnormalities Total bilirubin	0 participants	4 participants	4 participants
Number of Participants With Laboratory Abnormalities Creatinine	4 participants	13 participants	18 participants
Number of Participants With Laboratory Abnormalities Hypercalcemia	0 participants	1 participants	2 participants
Number of Participants With Laboratory Abnormalities Hyperglycemia	4 participants	13 participants	17 participants
Number of Participants With Laboratory Abnormalities Hyperkalemia	1 participants	2 participants	4 participants
Number of Participants With Laboratory Abnormalities Hypernatremia	0 participants	0 participants	0 participants
Number of Participants With Laboratory Abnormalities Hypoalbuminemia	3 participants	6 participants	10 participants
Number of Participants With Laboratory Abnormalities Hypocalcemia	2 participants	5 participants	5 participants
Number of Participants With Laboratory Abnormalities Hyponatremia	3 participants	4 participants	7 participants
Number of Participants With Laboratory Abnormalities Hypophosphatemia	1 participants	3 participants	5 participants
Number of Participants With Laboratory Abnormalities Lipase	0 participants	7 participants	2 participants
Number of Participants With Laboratory Abnormalities Prothrombin time (PT)	1 participants	4 participants	7 participants
Number of Participants With Laboratory Abnormalities PT International Normalized Ratio(INR)	1 participants	2 participants	3 participants
Number of Participants With Laboratory Abnormalities Urine protein	4 participants	10 participants	11 participants
Number of Participants With Laboratory Abnormalities Hypoglycemia	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: Pharmacokinetic (PK) parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Maximum Observed Serum Concentration (Cmax)	89420 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 47	121100 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 34	169000 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 28

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Outcome measures

Measure	PF-03446962 n=3 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=12 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=14 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Minimum Observed Serum Trough Concentration (Cmin)	6689 ng/mL Geometric Coefficient of Variation 47	14680 ng/mL Geometric Coefficient of Variation 22	22940 ng/mL Geometric Coefficient of Variation 27

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Time to Reach Maximum Observed Plasma Concentration (Tmax)	1.74 hours (hr) Full Range 47 • Interval 0.983 to 8.0	2.00 hours (hr) Full Range 22 • Interval 0.9 to 8.02	1.50 hours (hr) Full Range 27 • Interval 0.95 to 8.07

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

AUC (0-28)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-28).

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=12 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=14 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Area Under the Curve From Time Zero to 28 Days [AUC (0-28)]	12360000 nanogram*hour per milliliter (ng*hr/mL) Geometric Coefficient of Variation 36	21980000 nanogram*hour per milliliter (ng*hr/mL) Geometric Coefficient of Variation 14	30360000 nanogram*hour per milliliter (ng*hr/mL) Geometric Coefficient of Variation 22

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) for drug.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	12050000 ng*hr/mL Geometric Coefficient of Variation 39	20500000 ng*hr/mL Geometric Coefficient of Variation 30	26070000 ng*hr/mL Geometric Coefficient of Variation 62

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=7 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=2 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Systemic Clearance (CL)	0.01880 liter per hour (L/hr) Geometric Coefficient of Variation 31	0.01482 liter per hour (L/hr) Geometric Coefficient of Variation 20	NA liter per hour (L/hr) Geometric Coefficient of Variation NA Data was not reported if less than 3 participants data was available, as planned.

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=7 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=2 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Volume of Distribution (Vd)	7.535 liter (L) Geometric Coefficient of Variation 23	6.556 liter (L) Geometric Coefficient of Variation 23	NA liter (L) Geometric Coefficient of Variation NA Data was not analyzed if less than 3 participants were evaluable for the measure, as per planned analysis.

SECONDARY outcome

Timeframe: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=7 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=2 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Plasma Decay Half-Life (t1/2)	14.58 days Standard Deviation 2.2081	14.16 days Standard Deviation 1.7822	NA days Standard Deviation NA Data was not analyzed if less than 3 participants were evaluable for the measure, as per planned analysis.

SECONDARY outcome

Timeframe: Baseline, Day 1, 0 hour (H), 6 H Cycle 1 Day 1, Day 22 of Cycle 1, Day 1 Cycle 2, Day 1 Cycle 3 and end of treatment (up to cycle 30)

Population: Biomarker analysis population included all enrolled and treated participants with baseline and on-treatment biomarker sample analyzed. Here "n"= participants who were evaluable for specified biomarker at given time point for each arm, respectively.

Soluble proteins related to Activin Receptor-Like Kinase 1 (ALK-1) signaling and angiogenesis signaling including Vascular adhesion molecule (VAM), Monocyte chemotactic protein 1 (MCP-1), Angiopoietin 2, Tear intercellular adhesive molecule 1 (ICAM-1), Soluble intracellular adhesion molecule 1 (SIAM-1), Soluble vascular adhesion molecule 1 (SVAM-1), Vascular endothelial growth factor A (VEGF-A), Vascular endothelial growth factor C (VEGF-C), Vascular endothelial growth factor D (VEGF-D), Soluble vascular endothelial growth factor- Receptor 1 (REC 1) (SVEGF-REC 1), Soluble vascular endothelial growth factor- REC 2 (SVEGF-REC 2), Soluble vascular endothelial growth factor- REC 3 (SVEGF-REC 3), Bone morphogenetic protein-9 (BMP-9), Endoglin, Transforming growth factor- beta 1 (TGF- Beta 1), Placental growth factor (PGF) was evaluated.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Soluble Proteins Level Endoglin: End of Treatment (n=4,7,11)	21756.8 picogram per milliliter (pg/mL) Standard Deviation 5825.18	31653.3 picogram per milliliter (pg/mL) Standard Deviation 9829.63	33159.2 picogram per milliliter (pg/mL) Standard Deviation 10674.69
Soluble Proteins Level Angioprotein-2: Cycle3/Day1 (n=2,8,5)	309.1 picogram per milliliter (pg/mL) Standard Deviation 48.30	510.8 picogram per milliliter (pg/mL) Standard Deviation 256.27	416.4 picogram per milliliter (pg/mL) Standard Deviation 514.40
Soluble Proteins Level Angioprotein-2: End of Treatment (n=4,7,11)	288.6 picogram per milliliter (pg/mL) Standard Deviation 154.63	666.1 picogram per milliliter (pg/mL) Standard Deviation 510.48	1147.2 picogram per milliliter (pg/mL) Standard Deviation 1452.48
Soluble Proteins Level ICAM-1: Baseline (n=0,1,10)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	1277073.8 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	931954.7 picogram per milliliter (pg/mL) Standard Deviation 1058110.51
Soluble Proteins Level ICAM-1: Cycle1/Day1 0H (n=0,1,10)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	878849.0 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	844534.8 picogram per milliliter (pg/mL) Standard Deviation 802742.55
Soluble Proteins Level ICAM-1: Cycle1/Day1 6H (n=0,1,10,)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	806572.4 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	915166.4 picogram per milliliter (pg/mL) Standard Deviation 923611.09
Soluble Proteins Level ICAM-1: Cycle1/Day22(n=0,0,10)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	1226089.9 picogram per milliliter (pg/mL) Standard Deviation 1128415.32
Soluble Proteins Level ICAM-1: Cycle2/Day1 (n=0,0,8)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	827621.8 picogram per milliliter (pg/mL) Standard Deviation 367125.98
Soluble Proteins Level VAM: Baseline (n=0,1,10)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	5769662.5 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	4529407.4 picogram per milliliter (pg/mL) Standard Deviation 2147607.09
Soluble Proteins Level VAM: Cycle1/Day1 0H(n=0,1,10)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	5013301.1 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	4834240.9 picogram per milliliter (pg/mL) Standard Deviation 4649500.22
Soluble Proteins Level VAM: Cycle1/Day1 6H (n=0,1,10)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	6403610.0 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	5787177.6 picogram per milliliter (pg/mL) Standard Deviation 4880400.90
Soluble Proteins Level VAM: Cycle1/Day22 (n=0,0,10)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	6388997.9 picogram per milliliter (pg/mL) Standard Deviation 3326806.56
Soluble Proteins Level VAM: Cycle2/Day1 (n=0,0,8)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	8156950.3 picogram per milliliter (pg/mL) Standard Deviation 8059603.45
Soluble Proteins Level VAM: Cycle3/Day1 (n=0,1,3)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	3539105.4 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	6601473.2 picogram per milliliter (pg/mL) Standard Deviation 3524102.00
Soluble Proteins Level VAM: End of Treatment (n=0,3,5)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	10329091.1 picogram per milliliter (pg/mL) Standard Deviation 1748797.03	5648426.5 picogram per milliliter (pg/mL) Standard Deviation 1095588.29
Soluble Proteins Level MCP-1: Baseline (n=4,13,19)	1049.6 picogram per milliliter (pg/mL) Standard Deviation 202.58	934.8 picogram per milliliter (pg/mL) Standard Deviation 444.61	1016.7 picogram per milliliter (pg/mL) Standard Deviation 341.58
Soluble Proteins Level MCP-1: Cycle1/Day1 0H (n=4,13,19)	916.9 picogram per milliliter (pg/mL) Standard Deviation 79.30	911.2 picogram per milliliter (pg/mL) Standard Deviation 233.53	867.9 picogram per milliliter (pg/mL) Standard Deviation 345.20
Soluble Proteins Level MCP-1: Cycle1/Day1 6H (n=4,13,19)	1246.8 picogram per milliliter (pg/mL) Standard Deviation 453.48	1774.5 picogram per milliliter (pg/mL) Standard Deviation 1150.89	2283.8 picogram per milliliter (pg/mL) Standard Deviation 1462.53
Soluble Proteins Level MCP-1: Cycle1/Day22 (n=4,12,16)	932.2 picogram per milliliter (pg/mL) Standard Deviation 241.45	870.5 picogram per milliliter (pg/mL) Standard Deviation 233.82	1201.5 picogram per milliliter (pg/mL) Standard Deviation 654.63
Soluble Proteins Level MCP-1: Cycle2/Day1 (n=3,12,14)	1202.9 picogram per milliliter (pg/mL) Standard Deviation 208.51	864.1 picogram per milliliter (pg/mL) Standard Deviation 188.86	1154.6 picogram per milliliter (pg/mL) Standard Deviation 741.31
Soluble Proteins Level MCP-1: Cycle3/Day1 (n=2,8,5)	857.5 picogram per milliliter (pg/mL) Standard Deviation 95.32	916.8 picogram per milliliter (pg/mL) Standard Deviation 288.98	797.8 picogram per milliliter (pg/mL) Standard Deviation 403.62
Soluble Proteins Level MCP-1: End of Treatment (n=4,7,11)	811.3 picogram per milliliter (pg/mL) Standard Deviation 185.47	1066.0 picogram per milliliter (pg/mL) Standard Deviation 451.04	1144.0 picogram per milliliter (pg/mL) Standard Deviation 547.92
Soluble Proteins Level Angioprotein-2: Baseline (n=4,13,19)	358.7 picogram per milliliter (pg/mL) Standard Deviation 183.72	490.5 picogram per milliliter (pg/mL) Standard Deviation 300.64	730.1 picogram per milliliter (pg/mL) Standard Deviation 800.18
Soluble Proteins Level Angioprotein-2: Cycle1/Day1 0H (n=4,13,19)	369.9 picogram per milliliter (pg/mL) Standard Deviation 167.24	439.2 picogram per milliliter (pg/mL) Standard Deviation 190.70	654.3 picogram per milliliter (pg/mL) Standard Deviation 686.73
Soluble Proteins Level Angioprotein-2: Cycle1/Day1 6H (n=4,13,19)	282.1 picogram per milliliter (pg/mL) Standard Deviation 130.38	416.0 picogram per milliliter (pg/mL) Standard Deviation 239.46	792.7 picogram per milliliter (pg/mL) Standard Deviation 813.77
Soluble Proteins Level Angioprotein-2: Cycle1/Day22 (n=4,12,16)	406.8 picogram per milliliter (pg/mL) Standard Deviation 234.83	503.4 picogram per milliliter (pg/mL) Standard Deviation 242.67	1282.8 picogram per milliliter (pg/mL) Standard Deviation 1901.84
Soluble Proteins Level Angioprotein-2: Cycle2/Day1 (n=3,12,14)	269.5 picogram per milliliter (pg/mL) Standard Deviation 122.91	513.6 picogram per milliliter (pg/mL) Standard Deviation 280.22	752.2 picogram per milliliter (pg/mL) Standard Deviation 568.44
Soluble Proteins Level SVEGF-REC 1: Cycle2/Day1 (n=3,12,14)	447.4 picogram per milliliter (pg/mL) Standard Deviation 467.46	222.5 picogram per milliliter (pg/mL) Standard Deviation 142.78	261.0 picogram per milliliter (pg/mL) Standard Deviation 115.68
Soluble Proteins Level SVEGF-REC 1: Cycle3/Day1 (n=2,8,5)	103.8 picogram per milliliter (pg/mL) Standard Deviation 29.27	155.5 picogram per milliliter (pg/mL) Standard Deviation 80.26	192.5 picogram per milliliter (pg/mL) Standard Deviation 82.80
Soluble Proteins Level ICAM-1: Cycle3/Day1 (n=0,1,3)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	479439.4 picogram per milliliter (pg/mL) Standard Deviation NA Standard deviation could not be calculated because only 1 participant was evaluable.	542607.5 picogram per milliliter (pg/mL) Standard Deviation 150328.01
Soluble Proteins Level ICAM-1: End of Treatment (n=0,3,5)	NA picogram per milliliter (pg/mL) Standard Deviation NA Data was not available as no participant was evaluable.	1271075.6 picogram per milliliter (pg/mL) Standard Deviation 515605.73	1651061.8 picogram per milliliter (pg/mL) Standard Deviation 2042387.17
Soluble Proteins Level SIAM-1: Baseline (n=4,12,9)	701303.4 picogram per milliliter (pg/mL) Standard Deviation 294804.13	466302.8 picogram per milliliter (pg/mL) Standard Deviation 309842.34	525958.2 picogram per milliliter (pg/mL) Standard Deviation 113283.77
Soluble Proteins Level SIAM-1: Cycle1/Day1 0H (n=4,12,9)	623840.0 picogram per milliliter (pg/mL) Standard Deviation 181192.64	504021.3 picogram per milliliter (pg/mL) Standard Deviation 256755.23	532390.8 picogram per milliliter (pg/mL) Standard Deviation 180640.87
Soluble Proteins Level SIAM-1: Cycle1/Day1 6H (n=4,12,9)	604163.5 picogram per milliliter (pg/mL) Standard Deviation 214935.46	411628.1 picogram per milliliter (pg/mL) Standard Deviation 261009.28	569359.0 picogram per milliliter (pg/mL) Standard Deviation 201989.70
Soluble Proteins Level SIAM-1: Cycle1/Day22 (n=4,12,6)	668593.1 picogram per milliliter (pg/mL) Standard Deviation 184915.57	501742.8 picogram per milliliter (pg/mL) Standard Deviation 320205.39	622325.0 picogram per milliliter (pg/mL) Standard Deviation 238791.57
Soluble Proteins Level SIAM-1: Cycle2/Day1 (n=3,12,6)	552736.5 picogram per milliliter (pg/mL) Standard Deviation 184915.57	501742.8 picogram per milliliter (pg/mL) Standard Deviation 320205.39	622325.0 picogram per milliliter (pg/mL) Standard Deviation 238791.57
Soluble Proteins Level SIAM-1: Cycle3/Day1 (n=2,7,2)	638075.4 picogram per milliliter (pg/mL) Standard Deviation 127112.48	598448.3 picogram per milliliter (pg/mL) Standard Deviation 317579.77	438595.7 picogram per milliliter (pg/mL) Standard Deviation 166268.03
Soluble Proteins Level SIAM-1: End of Treatment (n=4,4,6)	628177.9 picogram per milliliter (pg/mL) Standard Deviation 163803.34	464669.7 picogram per milliliter (pg/mL) Standard Deviation 174245.04	719398.7 picogram per milliliter (pg/mL) Standard Deviation 231843.95
Soluble Proteins Level SVAM-1: Baseline (n=4,12,9)	2135238.6 picogram per milliliter (pg/mL) Standard Deviation 849420.75	3651583.3 picogram per milliliter (pg/mL) Standard Deviation 2216213.70	2551024.9 picogram per milliliter (pg/mL) Standard Deviation 595975.01
Soluble Proteins Level SVAM-1: Cycle1/Day1 0H (n=4,12,9)	2061387.9 picogram per milliliter (pg/mL) Standard Deviation 858687.41	3583328.2 picogram per milliliter (pg/mL) Standard Deviation 1998977.25	2620267.2 picogram per milliliter (pg/mL) Standard Deviation 1001526.82
Soluble Proteins Level SVAM-1: Cycle1/Day1 6H (n=4,12,9)	2034173.6 picogram per milliliter (pg/mL) Standard Deviation 756983.20	3576192.6 picogram per milliliter (pg/mL) Standard Deviation 2751678.60	3071682.9 picogram per milliliter (pg/mL) Standard Deviation 1447507.40
Soluble Proteins Level SVAM-1: Cycle1/Day22 (n=4,12,6)	2665272.7 picogram per milliliter (pg/mL) Standard Deviation 1159532.95	4276947.7 picogram per milliliter (pg/mL) Standard Deviation 2862681.78	3653830.7 picogram per milliliter (pg/mL) Standard Deviation 1746452.25
Soluble Proteins Level SVAM-1: Cycle2/Day1 (n=3,12,6)	1892498.5 picogram per milliliter (pg/mL) Standard Deviation 68777.63	4628918.3 picogram per milliliter (pg/mL) Standard Deviation 3257637.40	3574717.1 picogram per milliliter (pg/mL) Standard Deviation 1661302.68
Soluble Proteins Level SVAM-1: Cycle3/Day1 (n=2,7,2)	2117070.8 picogram per milliliter (pg/mL) Standard Deviation 747786.71	4755433.2 picogram per milliliter (pg/mL) Standard Deviation 2598745.99	2349177.5 picogram per milliliter (pg/mL) Standard Deviation 638957.67
Soluble Proteins Level BMP-9: Cycle2/Day1 (n=3,12,14)	8.1 picogram per milliliter (pg/mL) Standard Deviation 5.01	61.5 picogram per milliliter (pg/mL) Standard Deviation 158.39	24.7 picogram per milliliter (pg/mL) Standard Deviation 12.58
Soluble Proteins Level SVAM-1: End of Treatment (n=4,4,6)	3802384.0 picogram per milliliter (pg/mL) Standard Deviation 2865638.01	3318897.7 picogram per milliliter (pg/mL) Standard Deviation 1948986.96	3748602.8 picogram per milliliter (pg/mL) Standard Deviation 1332529.49
Soluble Proteins Level VEGF-A: Baseline (n=4,13,19)	429.4 picogram per milliliter (pg/mL) Standard Deviation 208.76	889.8 picogram per milliliter (pg/mL) Standard Deviation 1475.25	463.4 picogram per milliliter (pg/mL) Standard Deviation 425.39
Soluble Proteins Level VEGF-A: Cycle1/Day1 0H (n=4,13,19)	455.4 picogram per milliliter (pg/mL) Standard Deviation 175.23	595.3 picogram per milliliter (pg/mL) Standard Deviation 628.14	410.3 picogram per milliliter (pg/mL) Standard Deviation 419.93
Soluble Proteins Level VEGF-A: Cycle1/Day1 6H (n=4,13,19)	438.6 picogram per milliliter (pg/mL) Standard Deviation 210.06	631.9 picogram per milliliter (pg/mL) Standard Deviation 644.09	460.5 picogram per milliliter (pg/mL) Standard Deviation 344.90
Soluble Proteins Level VEGF-A: Cycle1/Day22 (n=4,12,16)	703.7 picogram per milliliter (pg/mL) Standard Deviation 416.74	462.8 picogram per milliliter (pg/mL) Standard Deviation 381.85	529.1 picogram per milliliter (pg/mL) Standard Deviation 511.82
Soluble Proteins Level VEGF-A: Cycle2/Day1 (n=3,12,14)	941.0 picogram per milliliter (pg/mL) Standard Deviation 415.59	508.0 picogram per milliliter (pg/mL) Standard Deviation 406.78	524.7 picogram per milliliter (pg/mL) Standard Deviation 541.09
Soluble Proteins Level VEGF-A: Cycle3/Day1 (n=2,8,5)	904.2 picogram per milliliter (pg/mL) Standard Deviation 1051.75	355.7 picogram per milliliter (pg/mL) Standard Deviation 259.00	373.5 picogram per milliliter (pg/mL) Standard Deviation 124.19
Soluble Proteins Level VEGF-A: End of Treatment (n=4,7,11)	632.2 picogram per milliliter (pg/mL) Standard Deviation 676.85	491.6 picogram per milliliter (pg/mL) Standard Deviation 329.84	556.7 picogram per milliliter (pg/mL) Standard Deviation 740.20
Soluble Proteins Level VEGF-C: Baseline (n=4,13,19)	110.6 picogram per milliliter (pg/mL) Standard Deviation 64.88	112.0 picogram per milliliter (pg/mL) Standard Deviation 91.80	139.9 picogram per milliliter (pg/mL) Standard Deviation 92.74
Soluble Proteins Level VEGF-C: Cycle1/Day1 0H (n=4,13,19)	104.2 picogram per milliliter (pg/mL) Standard Deviation 62.45	98.2 picogram per milliliter (pg/mL) Standard Deviation 101.48	95.6 picogram per milliliter (pg/mL) Standard Deviation 81.09
Soluble Proteins Level VEGF-C: Cycle1/Day1 6H (n=4,13,19)	81.8 picogram per milliliter (pg/mL) Standard Deviation 52.85	79.3 picogram per milliliter (pg/mL) Standard Deviation 64.75	104.2 picogram per milliliter (pg/mL) Standard Deviation 91.99
Soluble Proteins Level VEGF-C: Cycle1/Day22 (n=4,12,16)	115.0 picogram per milliliter (pg/mL) Standard Deviation 67.41	94.2 picogram per milliliter (pg/mL) Standard Deviation 90.41	105.1 picogram per milliliter (pg/mL) Standard Deviation 92.55
Soluble Proteins Level VEGF-C: Cycle2/Day1 (n=3,12,14)	91.6 picogram per milliliter (pg/mL) Standard Deviation 61.06	93.0 picogram per milliliter (pg/mL) Standard Deviation 106.58	93.7 picogram per milliliter (pg/mL) Standard Deviation 96.83
Soluble Proteins Level VEGF-C: Cycle3/Day1 (n=2,8,5)	31.3 picogram per milliliter (pg/mL) Standard Deviation 0.00	82.2 picogram per milliliter (pg/mL) Standard Deviation 124.89	128.3 picogram per milliliter (pg/mL) Standard Deviation 116.64
Soluble Proteins Level VEGF-C: End of Treatment (n=4,7,11)	70.9 picogram per milliliter (pg/mL) Standard Deviation 60.02	93.3 picogram per milliliter (pg/mL) Standard Deviation 111.24	64.7 picogram per milliliter (pg/mL) Standard Deviation 68.37
Soluble Proteins Level VEGF-D: Baseline (n=4,13,19)	988.6 picogram per milliliter (pg/mL) Standard Deviation 208.49	1349.5 picogram per milliliter (pg/mL) Standard Deviation 1133.71	1176.4 picogram per milliliter (pg/mL) Standard Deviation 361.43
Soluble Proteins Level VEGF-D: Cycle1/Day1 0H (n=4,13,19)	941.6 picogram per milliliter (pg/mL) Standard Deviation 114.91	1323.1 picogram per milliliter (pg/mL) Standard Deviation 962.53	1059.7 picogram per milliliter (pg/mL) Standard Deviation 365.10
Soluble Proteins Level VEGF-D: Cycle1/Day1 6H (n=4,13,19)	881.9 picogram per milliliter (pg/mL) Standard Deviation 89.36	1341.9 picogram per milliliter (pg/mL) Standard Deviation 1154.09	1160.3 picogram per milliliter (pg/mL) Standard Deviation 389.49
Soluble Proteins Level VEGF-D: Cycle1/Day22 (n=4,12,16)	853.9 picogram per milliliter (pg/mL) Standard Deviation 176.92	1327.6 picogram per milliliter (pg/mL) Standard Deviation 984.57	1365.8 picogram per milliliter (pg/mL) Standard Deviation 431.90
Soluble Proteins Level VEGF-D: Cycle2/Day1 (n=3,12,14)	836.2 picogram per milliliter (pg/mL) Standard Deviation 161.42	1430.0 picogram per milliliter (pg/mL) Standard Deviation 1203.55	1315.8 picogram per milliliter (pg/mL) Standard Deviation 527.01
Soluble Proteins Level VEGF-D: Cycle3/Day1 (n=2,8,5)	995.7 picogram per milliliter (pg/mL) Standard Deviation 263.82	1445.3 picogram per milliliter (pg/mL) Standard Deviation 1403.28	995.2 picogram per milliliter (pg/mL) Standard Deviation 443.14
Soluble Proteins Level VEGF-D: End of Treatment (n=4,7,11)	809.4 picogram per milliliter (pg/mL) Standard Deviation 176.66	1494.1 picogram per milliliter (pg/mL) Standard Deviation 1000.50	1420.1 picogram per milliliter (pg/mL) Standard Deviation 402.57
Soluble Proteins Level SVEGF-REC 1: End of Treatment (n=4,7,11)	113.7 picogram per milliliter (pg/mL) Standard Deviation 33.47	234.2 picogram per milliliter (pg/mL) Standard Deviation 172.30	276.8 picogram per milliliter (pg/mL) Standard Deviation 227.19
Soluble Proteins Level SVEGF-REC 2: Baseline (n=4,13,19)	7436.6 picogram per milliliter (pg/mL) Standard Deviation 1857.86	6888.7 picogram per milliliter (pg/mL) Standard Deviation 2231.62	8440.8 picogram per milliliter (pg/mL) Standard Deviation 2437.27
Soluble Proteins Level SVEGF-REC 2: Cycle1/Day1 0H (n=4,13,19)	7914.2 picogram per milliliter (pg/mL) Standard Deviation 2988.27	7026.7 picogram per milliliter (pg/mL) Standard Deviation 2025.46	7741.2 picogram per milliliter (pg/mL) Standard Deviation 2133.30
Soluble Proteins Level SVEGF-REC 2: Cycle1/Day1 6H (n=4,13,19)	7870.7 picogram per milliliter (pg/mL) Standard Deviation 3373.09	6586.3 picogram per milliliter (pg/mL) Standard Deviation 2081.36	8378.4 picogram per milliliter (pg/mL) Standard Deviation 1904.55
Soluble Proteins Level SVEGF-REC 2: Cycle1/Day22 (n=4,12,16)	7235.8 picogram per milliliter (pg/mL) Standard Deviation 2807.65	7069.1 picogram per milliliter (pg/mL) Standard Deviation 2453.67	8493.1 picogram per milliliter (pg/mL) Standard Deviation 1844.69
Soluble Proteins Level SVEGF-REC 2: Cycle2/Day1 (n=3,12,14)	7597.3 picogram per milliliter (pg/mL) Standard Deviation 3168.18	7245.4 picogram per milliliter (pg/mL) Standard Deviation 2560.56	7965.4 picogram per milliliter (pg/mL) Standard Deviation 2421.06
Soluble Proteins Level SVEGF-REC 2: Cycle3/Day1 (n=2,8,5)	8516.8 picogram per milliliter (pg/mL) Standard Deviation 3960.15	6827.8 picogram per milliliter (pg/mL) Standard Deviation 2613.39	8193.9 picogram per milliliter (pg/mL) Standard Deviation 2074.23
Soluble Proteins Level SVEGF-REC 2: End of Treatment (n=4,7,11)	6714.4 picogram per milliliter (pg/mL) Standard Deviation 2171.59	6908.6 picogram per milliliter (pg/mL) Standard Deviation 2872.56	8963.3 picogram per milliliter (pg/mL) Standard Deviation 1366.42
Soluble Proteins Level SVEGF-REC 3: Baseline (n=4,13,19)	456712.6 picogram per milliliter (pg/mL) Standard Deviation 63869.92	332957.5 picogram per milliliter (pg/mL) Standard Deviation 114561.87	434940.1 picogram per milliliter (pg/mL) Standard Deviation 109510.31
Soluble Proteins Level SVEGF-REC 3: Cycle1/Day1 0H (n=4,13,19)	406786.4 picogram per milliliter (pg/mL) Standard Deviation 11524.53	355960.5 picogram per milliliter (pg/mL) Standard Deviation 132035.48	407148.7 picogram per milliliter (pg/mL) Standard Deviation 92393.49
Soluble Proteins Level SVEGF-REC 3: Cycle1/Day1 6H (n=4,13,19)	395896.6 picogram per milliliter (pg/mL) Standard Deviation 61076.24	336962.5 picogram per milliliter (pg/mL) Standard Deviation 141091.61	416266.6 picogram per milliliter (pg/mL) Standard Deviation 90886.33
Soluble Proteins Level SVEGF-REC 3: Cycle1/Day22 (n=4,12,16)	374514.7 picogram per milliliter (pg/mL) Standard Deviation 33518.13	310883.6 picogram per milliliter (pg/mL) Standard Deviation 87289.24	454274.1 picogram per milliliter (pg/mL) Standard Deviation 141305.28
Soluble Proteins Level SVEGF-REC 3: Cycle2/Day1 (n=3,12,14)	405961.9 picogram per milliliter (pg/mL) Standard Deviation 34525.64	317659.8 picogram per milliliter (pg/mL) Standard Deviation 79198.45	450339.2 picogram per milliliter (pg/mL) Standard Deviation 162644.43
Soluble Proteins Level SVEGF-REC 3: Cycle3/Day1 (n=2,8,5)	421505.5 picogram per milliliter (pg/mL) Standard Deviation 23124.80	289021.4 picogram per milliliter (pg/mL) Standard Deviation 73419.94	311026.0 picogram per milliliter (pg/mL) Standard Deviation 93213.81
Soluble Proteins Level SVEGF-REC 3: End of Treatment (n=4,7,11)	345569.6 picogram per milliliter (pg/mL) Standard Deviation 19964.62	307319.1 picogram per milliliter (pg/mL) Standard Deviation 99790.00	434549.1 picogram per milliliter (pg/mL) Standard Deviation 95476.81
Soluble Proteins Level BMP-9: Baseline (n=4,13,19)	8.3 picogram per milliliter (pg/mL) Standard Deviation 4.77	64.5 picogram per milliliter (pg/mL) Standard Deviation 155.34	24.8 picogram per milliliter (pg/mL) Standard Deviation 18.39
Soluble Proteins Level BMP-9: Cycle1/Day1 0H (n=4,13,19)	7.4 picogram per milliliter (pg/mL) Standard Deviation 5.00	47.3 picogram per milliliter (pg/mL) Standard Deviation 114.00	22.0 picogram per milliliter (pg/mL) Standard Deviation 12.61
Soluble Proteins Level BMP-9: Cycle3/Day1 (n=2,8,5)	16.5 picogram per milliliter (pg/mL) Standard Deviation 16.33	84.8 picogram per milliliter (pg/mL) Standard Deviation 194.91	25.2 picogram per milliliter (pg/mL) Standard Deviation 10.90
Soluble Proteins Level BMP-9: End of Treatment (n=4,7,11)	11.2 picogram per milliliter (pg/mL) Standard Deviation 6.09	123.3 picogram per milliliter (pg/mL) Standard Deviation 259.17	47.0 picogram per milliliter (pg/mL) Standard Deviation 70.74
Soluble Proteins Level Endoglin: Baseline (n=4,13,19)	22292.9 picogram per milliliter (pg/mL) Standard Deviation 7065.67	26312.5 picogram per milliliter (pg/mL) Standard Deviation 8345.99	31096.0 picogram per milliliter (pg/mL) Standard Deviation 7553.99
Soluble Proteins Level Endoglin: Cycle1/Day1 0H (n=4,13,19)	21148.2 picogram per milliliter (pg/mL) Standard Deviation 4493.48	26514.1 picogram per milliliter (pg/mL) Standard Deviation 4171.10	29437.1 picogram per milliliter (pg/mL) Standard Deviation 8796.80
Soluble Proteins Level Endoglin: Cycle1/Day1 6H (n=4,13,19)	20252.9 picogram per milliliter (pg/mL) Standard Deviation 3093.23	24385.0 picogram per milliliter (pg/mL) Standard Deviation 7947.74	29898.7 picogram per milliliter (pg/mL) Standard Deviation 7743.02
Soluble Proteins Level Endoglin: Cycle1/Day22 (n=4,12,16)	20304.6 picogram per milliliter (pg/mL) Standard Deviation 3085.27	28106.4 picogram per milliliter (pg/mL) Standard Deviation 6786.70	39570.2 picogram per milliliter (pg/mL) Standard Deviation 11857.18
Soluble Proteins Level Endoglin: Cycle2/Day1 (n=3,12,14)	18974.4 picogram per milliliter (pg/mL) Standard Deviation 2212.35	29533.7 picogram per milliliter (pg/mL) Standard Deviation 8065.27	35585.1 picogram per milliliter (pg/mL) Standard Deviation 8558.35
Soluble Proteins Level Endoglin: Cycle3/Day1 (n=2,8,5)	20441.2 picogram per milliliter (pg/mL) Standard Deviation 5168.88	28063.4 picogram per milliliter (pg/mL) Standard Deviation 6794.28	33439.4 picogram per milliliter (pg/mL) Standard Deviation 7464.88
Soluble Proteins Level TGF-Beta1: Baseline (n=4,13,19)	439154.4 picogram per milliliter (pg/mL) Standard Deviation 194384.01	288057.2 picogram per milliliter (pg/mL) Standard Deviation 95964.14	264779.6 picogram per milliliter (pg/mL) Standard Deviation 245081.23
Soluble Proteins Level TGF-Beta1: Cycle1/Day1 0H (n=4,13,19)	420293.6 picogram per milliliter (pg/mL) Standard Deviation 154286.55	228313.8 picogram per milliliter (pg/mL) Standard Deviation 101963.47	187730.4 picogram per milliliter (pg/mL) Standard Deviation 173444.62
Soluble Proteins Level TGF-Beta1: Cycle1/Day1 6H (n=4,13,19)	361727.2 picogram per milliliter (pg/mL) Standard Deviation 195371.45	240430.8 picogram per milliliter (pg/mL) Standard Deviation 97194.19	194814.7 picogram per milliliter (pg/mL) Standard Deviation 173849.07
Soluble Proteins Level TGF-Beta1: Cycle1/Day22 (n=4,12,16)	322848.7 picogram per milliliter (pg/mL) Standard Deviation 122214.82	248764.0 picogram per milliliter (pg/mL) Standard Deviation 105171.95	169310.4 picogram per milliliter (pg/mL) Standard Deviation 187249.43
Soluble Proteins Level TGF-Beta1: Cycle2/Day1 (n=3,12,14)	485627.2 picogram per milliliter (pg/mL) Standard Deviation 145104.03	253554.9 picogram per milliliter (pg/mL) Standard Deviation 97795.74	214255.5 picogram per milliliter (pg/mL) Standard Deviation 269963.90
Soluble Proteins Level TGF-Beta1: Cycle3/Day1 (n=2,8,5)	355810.5 picogram per milliliter (pg/mL) Standard Deviation 308789.78	231920.2 picogram per milliliter (pg/mL) Standard Deviation 128882.61	280515.6 picogram per milliliter (pg/mL) Standard Deviation 270982.35
Soluble Proteins Level TGF-Beta1: End of Treatment (n=4,7,11)	292378.4 picogram per milliliter (pg/mL) Standard Deviation 154058.94	235871.6 picogram per milliliter (pg/mL) Standard Deviation 129631.54	249663.6 picogram per milliliter (pg/mL) Standard Deviation 300797.29
Soluble Proteins Level PGF: Baseline (n=4,13,19)	15.6 picogram per milliliter (pg/mL) Standard Deviation 16.56	10.7 picogram per milliliter (pg/mL) Standard Deviation 4.03	9.6 picogram per milliliter (pg/mL) Standard Deviation 4.80
Soluble Proteins Level PGF: Cycle1/Day1 0H (n=4,13,19)	15.3 picogram per milliliter (pg/mL) Standard Deviation 13.03	12.7 picogram per milliliter (pg/mL) Standard Deviation 4.67	9.5 picogram per milliliter (pg/mL) Standard Deviation 4.40
Soluble Proteins Level PGF: Cycle1/Day1 6H (n=4,13,19)	15.7 picogram per milliliter (pg/mL) Standard Deviation 9.90	14.8 picogram per milliliter (pg/mL) Standard Deviation 7.35	14.8 picogram per milliliter (pg/mL) Standard Deviation 7.29
Soluble Proteins Level PGF: Cycle1/Day22 (n=4,12,16)	14.5 picogram per milliliter (pg/mL) Standard Deviation 8.19	9.6 picogram per milliliter (pg/mL) Standard Deviation 3.28	9.9 picogram per milliliter (pg/mL) Standard Deviation 6.58
Soluble Proteins Level PGF:Cycle2/Day1 (n=3,12,14)	9.9 picogram per milliliter (pg/mL) Standard Deviation 1.25	10.1 picogram per milliliter (pg/mL) Standard Deviation 3.77	9.2 picogram per milliliter (pg/mL) Standard Deviation 5.15
Soluble Proteins Level PGF: Cycle3/Day1 (n=2,8,5)	7.2 picogram per milliliter (pg/mL) Standard Deviation 0.28	8.2 picogram per milliliter (pg/mL) Standard Deviation 2.60	6.9 picogram per milliliter (pg/mL) Standard Deviation 1.87
Soluble Proteins Level PGF: End of Treatment (n=4,7,11)	10.3 picogram per milliliter (pg/mL) Standard Deviation 8.28	7.9 picogram per milliliter (pg/mL) Standard Deviation 2.43	8.6 picogram per milliliter (pg/mL) Standard Deviation 5.15
Soluble Proteins Level SVEGF-REC 1: Baseline (n=4,13,19)	152.3 picogram per milliliter (pg/mL) Standard Deviation 29.59	162.3 picogram per milliliter (pg/mL) Standard Deviation 60.10	228.5 picogram per milliliter (pg/mL) Standard Deviation 88.14
Soluble Proteins Level SVEGF-REC 1: Cycle1/Day1 0H (n=4,13,19)	114.0 picogram per milliliter (pg/mL) Standard Deviation 51.72	1397.1 picogram per milliliter (pg/mL) Standard Deviation 4204.03	3196.4 picogram per milliliter (pg/mL) Standard Deviation 10603.61
Soluble Proteins Level SVEGF-REC 1: Cycle1/Day1 6H (n=4,13,19)	116.9 picogram per milliliter (pg/mL) Standard Deviation 16.94	177.1 picogram per milliliter (pg/mL) Standard Deviation 81.20	255.2 picogram per milliliter (pg/mL) Standard Deviation 95.68
Soluble Proteins Level SVEGF-REC 1: Cycle1/Day22 (n=4,12,16)	132.0 picogram per milliliter (pg/mL) Standard Deviation 39.82	170.9 picogram per milliliter (pg/mL) Standard Deviation 93.07	299.4 picogram per milliliter (pg/mL) Standard Deviation 138.60
Soluble Proteins Level BMP-9: Cycle1/Day1 6H (n=4,13,19)	16.7 picogram per milliliter (pg/mL) Standard Deviation 8.95	58.6 picogram per milliliter (pg/mL) Standard Deviation 130.87	33.4 picogram per milliliter (pg/mL) Standard Deviation 15.93
Soluble Proteins Level BMP-9: Cycle1/Day22 (n=4,12,16)	8.9 picogram per milliliter (pg/mL) Standard Deviation 6.39	49.8 picogram per milliliter (pg/mL) Standard Deviation 121.48	25.7 picogram per milliliter (pg/mL) Standard Deviation 12.26

SECONDARY outcome

Timeframe: Baseline, Post-dose (Day 1 of every Cycle up to 28 days after last dose) up to Cycle 30

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

HAHA analysis was performed using validated, sensitive and specific chemiluminescence enzyme-linked immunosorbent assay (ELISA) methodology.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Number of Participants With Human Anti-Human Antibody (HAHA) Baseline	0 participants NA	1 participants 2147607.09	3 participants 2071432.82
Number of Participants With Human Anti-Human Antibody (HAHA) Post-Dose	0 participants NA	0 participants 4649500.22	0 participants 4411233.60

SECONDARY outcome

Timeframe: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)

Population: Response evaluable population included all enrolled participants with measurable disease who received at least 1 dose of PF-03446962 and had an adequate baseline tumor assessment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Number of participants with best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST); Complete response (CR): disappearance of all lesions, Pathological lymph nodes' reduction in short axis (SA) to less than (<)10 millimeter (mm); Partial response (PR): greater than equal to (>=) 30% decrease in sum of longest dimensions (LD) of Target Lesions (TL) taking reference baseline sum LD; Progressive disease (PD):>=20% (>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of >=1 new lesions, unequivocal progression of existing non-TL, or appearance of >=1 new lesion; Stable disease (SD): insufficient shrinkage to qualify for PR, insufficient increase to qualify for PD taking reference smallest sum of the LD since treatment start. Confirmed response=that persist at least 4 weeks after initial documentation.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=18 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Number of Participants With Best Overall Response (BOR) CR	0 participants NA	0 participants 2147607.09	0 participants 2071432.82
Number of Participants With Best Overall Response (BOR) PR	0 participants NA	0 participants 4649500.22	0 participants 4411233.60
Number of Participants With Best Overall Response (BOR) SD	1 participants NA	4 participants 8059603.45	4 participants 8059603.45
Number of Participants With Best Overall Response (BOR) PD	2 participants NA	7 participants 3524102.00	13 participants 3259456.10
Number of Participants With Best Overall Response (BOR) Symptomatic Deterioration	0 participants 1748797.03	0 participants 1095588.29	1 participants 2725448.88
Number of Participants With Best Overall Response (BOR) Early Death	0 participants	1 participants	0 participants
Number of Participants With Best Overall Response (BOR) Indeterminate	1 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)

Population: Response evaluable population included all enrolled participants with measurable disease who received at least 1 dose of PF-03446962 and had an adequate baseline tumor assessment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

Number of participant with clinical benefit response (CBR): CBR was defined as CR, PR, SD >12 weeks, SD<12weeks or PD according to RECIST criteria; Complete response (CR): disappearance of all lesions, Pathological lymph nodes' reduction in short axis (SA) to <10 mm; Partial response (PR): >=30% decrease in sum of longest dimensions (LD) of Target Lesions (TL) taking reference baseline sum LD; Progressive disease (PD):>=20% (>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of >=1 new lesions, unequivocal progression of existing non-TL, or appearance of >=1 new lesion; Stable disease (SD): insufficient shrinkage to qualify for PR, insufficient increase to qualify for PD taking reference smallest sum of the LD since treatment start.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=18 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Number of Participants With Clinical Benefit Response (CBR)	1 participants	4 participants	4 participants

SECONDARY outcome

Timeframe: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)

Population: Response evaluable population included all enrolled participants with measurable disease who received at least 1 dose of PF-03446962 and had an adequate baseline tumor assessment. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure.

PFS was defined as the time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Months) = (first event date minus randomization or the first dose date plus 1) divided by 30.44). PFS was calculated using the median, and 95% Confidence Intervals (CIs) and Progressive disease (PD):>=20% (>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of >=1 new lesions, unequivocal progression of existing non-TL, or appearance of >=1 new lesion.

Outcome measures

Measure	PF-03446962 n=4 Participants PF-03446962 4.5, 7.0 or 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 Participants PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=18 Participants PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Progression Free Survival (PFS)	2.8 months 95% Confidence Interval NA • Interval 1.2 to 2.9	1.8 months 95% Confidence Interval 2147607.09 • Interval 1.3 to 5.6	1.3 months 95% Confidence Interval 2071432.82 • Interval 1.2 to 1.5

Adverse Events

PF-03446962 4.5 mg/kg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

PF-03446962 7.0 mg/kg

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

PF-03446962 10.0 mg/kg

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	PF-03446962 4.5 mg/kg n=4 participants at risk PF-03446962 4.5 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 participants at risk PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 participants at risk PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Hepatobiliary disorders Cholangitis	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Pneumonia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Malnutrition	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.

Other adverse events

Measure	PF-03446962 4.5 mg/kg n=4 participants at risk PF-03446962 4.5 milligram per kilogram (mg/kg) intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 7.0 mg/kg n=13 participants at risk PF-03446962 7.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.	PF-03446962 10.0 mg/kg n=19 participants at risk PF-03446962 10.0 mg/kg intravenous infusion over 1 hour on Day 1 of each cycle. Cycle 1 was of 28 days duration and all subsequent cycles were of 14 days duration.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	10.5% 2/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	21.1% 4/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.8% 3/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Eye disorders Conjunctival haemorrhage	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	23.1% 3/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Eye disorders Eye pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Eye disorders Vision blurred	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal discomfort	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal distension	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Abdominal pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	10.5% 2/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Anorectal disorder	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Ascites	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Constipation	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	21.1% 4/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Duodenal ulcer	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Dyspepsia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Nausea	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Stomatitis	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Gastrointestinal disorders Vomiting	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	10.5% 2/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Asthenia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Chest pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Chills	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Face oedema	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Fatigue	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	10.5% 2/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Injection site extravasation	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Oedema	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Oedema peripheral	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
General disorders Pyrexia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	23.1% 3/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	52.6% 10/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Clostridium difficile colitis	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Enteritis infectious	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Pseudofolliculitis barbae	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Upper respiratory tract infection	50.0% 2/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	10.5% 2/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Infections and infestations Viral infection	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Eschar	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Fall	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Laceration	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Injury, poisoning and procedural complications Procedural site reaction	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Alanine aminotransferase increased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Amylase increased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Aspartate aminotransferase increased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	10.5% 2/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Blood albumin decreased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Blood alkaline phosphatase increased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	21.1% 4/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Blood bilirubin increased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations C-reactive protein increased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Electrocardiogram QT prolonged	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Haemoglobin decreased	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Lipase increased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Lymphocyte count decreased	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Investigations Platelet count decreased	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.8% 3/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	10.5% 2/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Musculoskeletal and connective tissue disorders Periarthritis	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Liver carcinoma ruptured	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Dizziness	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Headache	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.8% 3/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Hypoaesthesia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Monoplegia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Nervous system disorder	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Neuralgia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Psychiatric disorders Insomnia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Atonic urinary bladder	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Azotaemia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Haematuria	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Renal and urinary disorders Proteinuria	50.0% 2/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Reproductive system and breast disorders Menorrhagia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	23.1% 3/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	23.1% 3/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Nasal obstruction	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	5.3% 1/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	15.4% 2/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Acne	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Dry skin	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Purpura	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.00% 0/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	7.7% 1/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.
Skin and subcutaneous tissue disorders Telangiectasia	25.0% 1/4 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	23.1% 3/13 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.	0.00% 0/19 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 subject and as non-serious in another subject, or one subject may have experienced both a serious and non-serious event during the study.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER