A Study for Participants With Advanced Cancer

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01214629
• Collaborator: (none)
• Enrollment: 54
• Locations: 2
• Arms: 2
• Duration (Months): 58
• Patients Per Site: 27
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study is being conducted to determine the safety of LY2523355 for the treatment of advanced and/or metastatic cancer (including Non-Hodgkin's lymphoma).

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer; Metastatic Cancer	Drug: LY2523355; Drug: LY2523355; Drug: pegfilgrastim	Phase 1

Detailed Description

This study is a multi-center, non-randomized, open label, dose-escalation, Phase 1 study of intravenous LY2523355 in participants with advanced and/or metastatic cancer (including Non-Hodgkin's Lymphoma) for whom no treatment of higher priority exists.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study of LY2523355 in Patients With Advanced Cancer
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2523355	Drug: LY2523355; Administered intravenously as a 1-hour infusion on Days 1, 2, 3 of each 21-day cycle for at least 2 cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met. Starting dose for LY2523355 alone arm is 0.125 milligrams per meter square per day (mg/m²/day).
Experimental: LY2523355 + pegfilgrastim	Drug: LY2523355; Administered intravenously as a 1-hour infusion on Days 1, 2, 3 of each 21-day cycle for at least 2 cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met. Starting dose for LY2523355 + pegfilgrastim is 4 mg/m²/day.; Drug: pegfilgrastim; 6 milligrams (mg) administered subcutaneously on Day 4 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received.

Outcome Measures

Primary Outcome Measures

1. Recommended Dose for Phase 2 Studies [Baseline, daily up to 21 days in Cycle 1]

   Recommended Phase 2 dose was determined by the maximum tolerated dose (MTD). The MTD was defined as the dose that caused <1/3 of all participants treated with the study drug to experience a dose-limiting toxicity (DLT). A DLT was defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 3.0 Grade ≥3 nonhematological toxicity possibly or likely related to the study drug (except for nausea/vomiting/diarrhea without maximal symptomatic/prophylactic treatment); any CTCAE v 3.0 Grade ≥3 thrombocytopenia with bleeding; any CTCAE v3.0 Grade 4 hematological toxicity of >5 days duration; any febrile neutropenia.

Secondary Outcome Measures

1. Number of Participants With Clinically Significant Effects [Baseline to study completion including 30-day follow-up up to 647 days,any AE reported]

   Adverse events (AEs) were considered clinically significant effects. Data presented are the number of participants who experienced serious AEs (SAEs), other non-serious AEs and deaths during the study, including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

2. Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose [Cycle 1 Day 1(21-day cycle):End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime]

   Cmax following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.

3. Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses [Cycle 1, Day 3(21-day cycle): End of infusion]

   Cmax following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.

4. Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose [Cycle 1,Day 1(21-day cycle): End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime]

   AUC(0-∞) following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.

5. Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses [Cycle 1, Day 3(21-day cycle): End of infusion]

   AUC(0-∞) following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.

6. Number of Participants With Tumor Response [Baseline to measured disease progression or discontinuation up to 617 days]

   Data presented are the number of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions. PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a diagnosis of advanced and/or metastatic cancer (solid tumors or Non-Hodgkin's lymphoma) that is refractory to standard therapy or for which no proven effective therapy exists. Participants entering Part B of the study must also have a tumor that is safely amenable to serial biopsies

• Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST, Therasse et al. 2000) or Revised International Working Group Lymphoma Response Criteria (Cheson et al. 2007)

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 28 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment

• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug

• Females with child bearing potential must have had a negative urine or serum pregnancy test less than or equal to 7 days prior to the first dose of study drug

• Have an estimated life expectancy of greater than or equal to 12 weeks

Exclusion Criteria:

• Have symptomatic, untreated or uncontrolled central nervous system (CNS) metastases. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastases is not required

• Have current acute or chronic leukemia

• Have had an autologous or allogenic bone marrow transplant

• Have the following conduction abnormalities: PR >250 milliseconds (msec), second degree or complete atrioventricular (AV) block, intraventricular conduction delay (IVCD) with QRS ≥120 msec, left branch bundle block (LBBB), right branch bundle block (RBBB), Wolf-Parkinson- White syndrome (WPW), left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), or other conduction abnormality that in the opinion of the investigator would preclude safe participation in this study.

• Females who are pregnant or lactating

• Known hypersensitivity to pegfilgrastim or filgrastim

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Albuquerque	New Mexico	United States	87131
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Philadelphia	Pennsylvania	United States	19111

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01214629
• Other Study ID Numbers: 11618; I1Y-MC-JFBA
• First Posted: Oct 5, 2010
• Last Update Posted: Aug 6, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by Eli Lilly and Company: Advanced Cancer; Metastatic Cancer; Cancer
• Additional relevant MeSH terms: Neoplasms; Neoplasm Metastasis

Study Results

Participant Flow

Pre-assignment Detail	Participants who completed 2 cycles of treatment are considered having completed study.

Arm/Group Title	0.125 mg/m²/Day LY	0.25 mg/m²/Day LY	0.5 mg/m²/Day LY	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	4.0 mg/m²/Day LY + 6 mg PEG	6.0 mg/m²/Day LY + 6 mg PEG	7.0 mg/m²/Day LY + 6 mg PEG
Arm/Group Description	0.125 milligrams per meter square per day (mg/m²/day) LY2523355 (LY) was administered as an intravenous (IV) infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until progressive disease (PD), unacceptable toxicity or other withdrawal criterion is met.	0.25 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	0.5 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 milligrams (mg) pegfilgrastim (PEG) was administered subcutaneously (SC) on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.
Period Title: Overall Study
STARTED	1	1	1	3	3	13	5	3	3	18	3
Received at Least 1 Dose of Study Drug	1	1	1	3	3	13	5	3	3	18	3
COMPLETED	0	0	1	1	1	9	4	2	2	11	1
NOT COMPLETED	1	1	0	2	2	4	1	1	1	7	2

Baseline Characteristics

Arm/Group Title	0.125 mg/m²/Day LY	0.25 mg/m²/Day LY	0.5 mg/m²/Day LY	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	4.0 mg/m²/Day LY + 6 mg PEG	6.0 mg/m²/Day LY + 6 mg PEG	7.0 mg/m²/Day LY + 6 mg PEG	Total
Arm/Group Description	0.125 milligrams per meter square per day (mg/m²/day) LY2523355 (LY) was administered as an intravenous (IV) infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until progressive disease (PD), unacceptable toxicity or other withdrawal criterion is met	0.25 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	0.5 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 milligrams (mg) pegfilgrastim (PEG) was administered subcutaneously (SC) on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	Total of all reporting groups
Overall Participants	1	1	1	3	3	13	5	3	3	18	3	54
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.01 (NA)	71.20 (NA)	52.37 (NA)	60.78 (12.84)	61.30 (13.91)	59.79 (8.75)	63.38 (12.50)	67.26 (5.88)	66.97 (17.19)	56.82 (12.09)	60.13 (0.49)	60.27 (10.78)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	1 100%	3 100%	3 100%	9 69.2%	3 60%	1 33.3%	3 100%	12 66.7%	2 66.7%	37 68.5%
Male	1 100%	1 100%	0 0%	0 0%	0 0%	4 30.8%	2 40%	2 66.7%	0 0%	6 33.3%	1 33.3%	17 31.5%
Race/Ethnicity, Customized (Count of Participants)
African	1 100%	0 0%	0 0%	0 0%	1 33.3%	3 23.1%	0 0%	0 0%	0 0%	3 16.7%	1 33.3%	9 16.7%
Caucasian	0 0%	0 0%	1 100%	3 100%	2 66.7%	10 76.9%	5 100%	3 100%	2 66.7%	10 55.6%	2 66.7%	38 70.4%
East Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hispanic	0 0%	1 100%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 33.3%	3 16.7%	0 0%	5 9.3%
Native American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 11.1%	0 0%	2 3.7%
Region of Enrollment (Count of Participants)
United States	1 100%	1 100%	1 100%	3 100%	3 100%	13 100%	5 100%	3 100%	3 100%	18 100%	3 100%	54 100%

Outcome Measures

1. Primary Outcome

Title	Recommended Dose for Phase 2 Studies
Description	Recommended Phase 2 dose was determined by the maximum tolerated dose (MTD). The MTD was defined as the dose that caused <1/3 of all participants treated with the study drug to experience a dose-limiting toxicity (DLT). A DLT was defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 3.0 Grade ≥3 nonhematological toxicity possibly or likely related to the study drug (except for nausea/vomiting/diarrhea without maximal symptomatic/prophylactic treatment); any CTCAE v 3.0 Grade ≥3 thrombocytopenia with bleeding; any CTCAE v3.0 Grade 4 hematological toxicity of >5 days duration; any febrile neutropenia.
Time Frame	Baseline, daily up to 21 days in Cycle 1

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	LY2523355	LY2523355 + Pegfilgrastim
Arm/Group Description	0.125 to 6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle)	4.0 to 7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 with 6 mg pegfilgrastim administered SC on Day 4 of Cycle 1 (21-day Cycle).
Measure Participants	30	24
Number [mg/m²/day]	4.0	6.0

2. Secondary Outcome

Title	Number of Participants With Clinically Significant Effects
Description	Adverse events (AEs) were considered clinically significant effects. Data presented are the number of participants who experienced serious AEs (SAEs), other non-serious AEs and deaths during the study, including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time Frame	Baseline to study completion including 30-day follow-up up to 647 days,any AE reported

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	0.125 mg/m²/Day LY	0.25 mg/m²/Day LY	0.5 mg/m²/Day LY	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	4.0 mg/m²/Day LY + 6 mg PEG	6.0 mg/m²/Day LY + 6 mg PEG	7.0 mg/m²/Day LY + 6 mg PEG
Arm/Group Description	0.125 mg/m²/day LY2523355 (LY) was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	0.25 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	0.5 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim (PEG) was administered subcutaneously (SC) on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.
Measure Participants	1	1	1	3	3	13	5	3	3	18	3
SAEs	0 0%	0 0%	0 0%	1 33.3%	0 0%	5 38.5%	3 60%	3 100%	0 0%	11 61.1%	3 100%
AEs	1 100%	1 100%	0 0%	2 66.7%	3 100%	13 100%	5 100%	3 100%	3 100%	18 100%	3 100%
Death	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.6%	0 0%

3. Secondary Outcome

Title	Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose
Description	Cmax following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time Frame	Cycle 1 Day 1(21-day cycle):End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime

Outcome Measure Data

Analysis Population Description

All enrolled participants who received 1 dose of LY2523355 on Day 1 of Cycle 1 with evaluable pharmacokinetic data to enable determination of the LY2523355 plasma Cmax on Day 1 of Cycle 1.

Arm/Group Title	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	7.0 mg/m²/Day LY
Arm/Group Description	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).
Measure Participants	3	3	16	5	21	3
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	32.6 (36)	61.7 (10)	120 (40)	127 (28)	168 (39)	222 (33)

4. Secondary Outcome

Title	Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses
Description	Cmax following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time Frame	Cycle 1, Day 3(21-day cycle): End of infusion

Outcome Measure Data

Analysis Population Description

All enrolled participants who received more than 1 dose of LY2523355 and had evaluable pharmacokinetic data to enable determination of the LY2523355 Cmax on Day 3 of Cycle 1.

Arm/Group Title	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	7.0 mg/m²/Day LY
Arm/Group Description	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle).	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle).	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle) or 4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 with 6 mg pegfilgrastim administered SC on Day 4 of Cycle 1 (21-day cycle).	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle).	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle) or 6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 with 6 mg pegfilgrastim administered SC on Day 4 of Cycle 1 (21-day cycle).	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 with 6 mg pegfilgrastim administered SC on Day 4 of Cycle 1 (21-day cycle).
Measure Participants	3	3	16	5	20	3
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	29.8 (32)	73.6 (47)	126 (49)	129 (34)	193 (37)	231 (23)

5. Secondary Outcome

Title	Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose
Description	AUC(0-∞) following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time Frame	Cycle 1,Day 1(21-day cycle): End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime

Outcome Measure Data

Analysis Population Description

All enrolled participants who received 1 dose of LY2523355 on Day 1 of Cycle 1 with evaluable pharmacokinetic data to enable calculation of the LY2523355 AUC(0-∞) on Day 1 of Cycle 1.

Arm/Group Title	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	7.0 mg/m²/Day LY
Arm/Group Description	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Day 1 of Cycle 1 (21-day cycle).
Measure Participants	3	3	16	5	21	3
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour/milliliter (ng*h/mL)]	81.8 (33)	159 (21)	324 (41)	379 (23)	443 (40)	642 (50)

6. Secondary Outcome

Title	Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses
Description	AUC(0-∞) following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.
Time Frame	Cycle 1, Day 3(21-day cycle): End of infusion

Outcome Measure Data

Analysis Population Description

All enrolled participants who received more than 1 dose of LY2523355 and had evaluable pharmacokinetic data to enable calculation of the LY2523355 AUC(0-∞) on Day 3 of Cycle 1.

Arm/Group Title	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	7.0 mg/m²/Day LY
Arm/Group Description	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle).	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle).	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle) or 4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 with 6 mg pegfilgrastim administered SC on Day 4 of Cycle 1 (21-day cycle).	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle).	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of Cycle 1 (21-day cycle) or 6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 with 6 mg pegfilgrastim administered SC on Day 4 of Cycle 1 (21-day cycle).	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 with 6 mg pegfilgrastim administered SC on Day 4 of Cycle 1 (21-day cycle).
Measure Participants	3	3	16	5	20	3
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	109 (19)	220 (30)	484 (46)	593 (45)	649 (52)	1090 (54)

7. Secondary Outcome

Title	Number of Participants With Tumor Response
Description	Data presented are the number of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions. PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions.
Time Frame	Baseline to measured disease progression or discontinuation up to 617 days

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug.

Arm/Group Title	0.125 mg/m²/Day LY	0.25 mg/m²/Day LY	0.5 mg/m²/Day LY	1.0 mg/m²/Day LY	2.0 mg/m²/Day LY	4.0 mg/m²/Day LY	5.0 mg/m²/Day LY	6.0 mg/m²/Day LY	4.0 mg/m²/Day LY + 6 mg PEG	6.0 mg/m²/Day LY + 6 mg PEG	7.0 mg/m²/Day LY + 6 mg PEG
Arm/Group Description	0.125 mg/m²/day LY2523355 (LY) was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	0.25 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	0.5 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim (PEG) was administered subcutaneously (SC) on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD unacceptable toxicity or other withdrawal criterion is met.	6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.	7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.
Measure Participants	1	1	1	3	3	13	5	3	3	18	3
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 20%	0 0%	0 0%	1 5.6%	0 0%

Adverse Events

Arm/Group Title	0.125 mg/m²/Day LY		0.25 mg/m²/Day LY		0.5 mg/m²/Day LY		1.0 mg/m²/Day LY		2.0 mg/m²/Day LY		4.0 mg/m²/Day LY		4.0 mg/m²/Day LY + 6 mg PEG		5.0 mg/m²/Day LY		6.0 mg/m²/Day LY		6.0 mg/m²/Day LY + 6 mg PEG		7.0 mg/m²/Day LY + 6 mg PEG
Arm/Group Description	0.125 mg/m²/day LY2523355 (LY) was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		0.25 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		0.5 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		1.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		2.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		4.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 milligrams (mg) pegfilgrastim (PEG) was administered subcutaneously (SC) on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		5.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		6.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.		7.0 mg/m²/day LY2523355 was administered as an IV infusion over 1 hour on Days 1, 2 and 3 of each 21-day cycle for at least 2 cycles. 6 mg pegfilgrastim was administered SC on Day 4 of each 21-day cycle for at least 2 cycles and for any subsequent cycles of LY2523355 received. Participants could continue on study drug until PD, unacceptable toxicity or other withdrawal criterion is met.
All Cause Mortality
	0.125 mg/m²/Day LY		0.25 mg/m²/Day LY		0.5 mg/m²/Day LY		1.0 mg/m²/Day LY		2.0 mg/m²/Day LY		4.0 mg/m²/Day LY		4.0 mg/m²/Day LY + 6 mg PEG		5.0 mg/m²/Day LY		6.0 mg/m²/Day LY		6.0 mg/m²/Day LY + 6 mg PEG		7.0 mg/m²/Day LY + 6 mg PEG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	0.125 mg/m²/Day LY		0.25 mg/m²/Day LY		0.5 mg/m²/Day LY		1.0 mg/m²/Day LY		2.0 mg/m²/Day LY		4.0 mg/m²/Day LY		4.0 mg/m²/Day LY + 6 mg PEG		5.0 mg/m²/Day LY		6.0 mg/m²/Day LY		6.0 mg/m²/Day LY + 6 mg PEG		7.0 mg/m²/Day LY + 6 mg PEG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/3 (33.3%)		0/3 (0%)		5/13 (38.5%)		0/3 (0%)		3/5 (60%)		3/3 (100%)		11/18 (61.1%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Febrile neutropenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
Leukopenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	3/3 (100%)	3	0/18 (0%)	0	0/3 (0%)	0
Neutropenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Cardiac disorders
Atrial fibrillation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Diarrhoea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/18 (0%)	0	1/3 (33.3%)	1
Gastrointestinal haemorrhage	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Ileus	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Nausea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Oesophageal ulcer	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Vomiting	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
General disorders
Chest pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Mucosal inflammation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
Pyrexia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	3/18 (16.7%)	3	0/3 (0%)	0
Infections and infestations
Infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	2/3 (66.7%)	2	0/18 (0%)	0	0/3 (0%)	0
Neutropenic infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Pneumonia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Sepsis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Investigations
International normalised ratio increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Metabolism and nutrition disorders
Failure to thrive	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Hypokalaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/18 (0%)	0	1/3 (33.3%)	1
Hyponatraemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Nervous system disorders
Cerebrovascular accident	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
Convulsion	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Headache	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Renal and urinary disorders
Hydronephrosis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Renal tubular necrosis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Haemoptysis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Hypoventilation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Pleural effusion	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	0.125 mg/m²/Day LY		0.25 mg/m²/Day LY		0.5 mg/m²/Day LY		1.0 mg/m²/Day LY		2.0 mg/m²/Day LY		4.0 mg/m²/Day LY		4.0 mg/m²/Day LY + 6 mg PEG		5.0 mg/m²/Day LY		6.0 mg/m²/Day LY		6.0 mg/m²/Day LY + 6 mg PEG		7.0 mg/m²/Day LY + 6 mg PEG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		0/1 (0%)		2/3 (66.7%)		3/3 (100%)		13/13 (100%)		3/3 (100%)		5/5 (100%)		3/3 (100%)		18/18 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	5/13 (38.5%)	5	0/3 (0%)	0	2/5 (40%)	2	1/3 (33.3%)	1	6/18 (33.3%)	7	0/3 (0%)	0
Febrile neutropenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Haemolysis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Leukopenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	8/13 (61.5%)	12	1/3 (33.3%)	2	5/5 (100%)	8	0/3 (0%)	0	5/18 (27.8%)	7	0/3 (0%)	0
Lymphopenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	5/13 (38.5%)	7	0/3 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	1	4/18 (22.2%)	8	0/3 (0%)	0
Neutropenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	7/13 (53.8%)	11	0/3 (0%)	0	3/5 (60%)	4	0/3 (0%)	0	7/18 (38.9%)	9	1/3 (33.3%)	1
Thrombocytopenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	3	0/3 (0%)	0
Cardiac disorders
Arrhythmia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Atrial fibrillation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Atrial tachycardia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Palpitations	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	3	0/3 (0%)	0
Sinus arrhythmia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Sinus bradycardia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	2	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Sinus tachycardia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	4	0/3 (0%)	0
Tachycardia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	1/18 (5.6%)	1	0/3 (0%)	0
Ear and labyrinth disorders
Ear pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/18 (0%)	0	0/3 (0%)	0
Eye disorders
Cataract	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Eye irritation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Abdominal pain lower	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Anal inflammation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Anorectal discomfort	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Ascites	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Cheilitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Constipation	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	3/13 (23.1%)	4	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	4/18 (22.2%)	4	1/3 (33.3%)	1
Diarrhoea	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	4/13 (30.8%)	4	0/3 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	1	6/18 (33.3%)	6	0/3 (0%)	0
Dyspepsia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	3/18 (16.7%)	3	0/3 (0%)	0
Dysphagia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Flatulence	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Food poisoning	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Gastritis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Gastrointestinal haemorrhage	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Gastrooesophageal reflux disease	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Melaena	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Nausea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	6/13 (46.2%)	7	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	6/18 (33.3%)	8	2/3 (66.7%)	2
Proctalgia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Stomatitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	2/5 (40%)	2	2/3 (66.7%)	2	6/18 (33.3%)	7	2/3 (66.7%)	2
Vomiting	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	2	0/3 (0%)	0	4/13 (30.8%)	4	0/3 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	7/18 (38.9%)	12	1/3 (33.3%)	2
General disorders
Asthenia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Axillary pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Chest discomfort	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	1/3 (33.3%)	1	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Chest pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	3/18 (16.7%)	3	0/3 (0%)	0
Chills	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	3	1/3 (33.3%)	1	1/5 (20%)	1	1/3 (33.3%)	1	4/18 (22.2%)	5	0/3 (0%)	0
Early satiety	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Fatigue	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	6/13 (46.2%)	6	1/3 (33.3%)	1	2/5 (40%)	2	0/3 (0%)	0	7/18 (38.9%)	7	1/3 (33.3%)	1
Feeling hot	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Gait disturbance	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Local swelling	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Mucosal inflammation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	3	0/3 (0%)	0
Nodule	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Oedema	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Oedema peripheral	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	3/18 (16.7%)	4	0/3 (0%)	0
Pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	3/18 (16.7%)	3	0/3 (0%)	0
Pyrexia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	2/3 (66.7%)	2	5/18 (27.8%)	8	0/3 (0%)	0
Hepatobiliary disorders
Bile duct obstruction	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hyperbilirubinaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Infections and infestations
Bacterial sepsis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Candidiasis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Cellulitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Fungal infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Nasopharyngitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	2/3 (66.7%)	2	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Oral candidiasis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Oral herpes	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Skin infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Tooth infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Upper respiratory tract infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Urinary tract infection	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	2/18 (11.1%)	4	0/3 (0%)	0
Injury, poisoning and procedural complications
Procedural pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Radius fracture	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Rib fracture	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Thermal burn	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Alanine aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
Aspartate aminotransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	2	1/3 (33.3%)	1
Blood alkaline phosphatase	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	2	0/3 (0%)	0
Blood alkaline phosphatase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Blood bilirubin increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Blood chloride increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Blood creatinine	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	4	0/3 (0%)	0
Blood creatinine decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	2	0/3 (0%)	0
Blood creatinine increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Blood uric acid decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Gamma-glutamyltransferase increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Haemoglobin	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Haemoglobin decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	1	0/18 (0%)	0	1/3 (33.3%)	1
International normalised ratio decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
International normalised ratio increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Neutrophil count increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	5	0/3 (0%)	0
Platelet count	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	3	0/3 (0%)	0
Platelet count decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Prothrombin time prolonged	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Weight decreased	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	1/3 (33.3%)	1	1/5 (20%)	1	1/3 (33.3%)	1	2/18 (11.1%)	2	1/3 (33.3%)	1
Weight increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
White blood cell count decreased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
White blood cell count increased	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	4/18 (22.2%)	6	0/3 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/1 (100%)	1	1/1 (100%)	1	0/1 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	2/13 (15.4%)	2	0/3 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	5/18 (27.8%)	5	0/3 (0%)	0
Dehydration	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	1	5/18 (27.8%)	5	1/3 (33.3%)	1
Hypercholesterolaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	2	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Hyperglycaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	1/3 (33.3%)	1	1/5 (20%)	1	0/3 (0%)	0	3/18 (16.7%)	5	0/3 (0%)	0
Hyperkalaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	2	0/3 (0%)	0
Hyperuricaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hypoalbuminaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	3/18 (16.7%)	6	0/3 (0%)	0
Hypocalcaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	4/18 (22.2%)	4	0/3 (0%)	0
Hypoglycaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hypokalaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	6/18 (33.3%)	8	0/3 (0%)	0
Hypomagnesaemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	6	0/3 (0%)	0
Hyponatraemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	4	0/3 (0%)	0
Hypophosphataemia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	4/18 (22.2%)	4	0/3 (0%)	0
Back pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0	0/3 (0%)	0	3/18 (16.7%)	3	0/3 (0%)	0
Bone pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Flank pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Groin pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Muscle spasms	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	2	0/3 (0%)	0
Muscular weakness	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	4	0/3 (0%)	0
Musculoskeletal chest pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Musculoskeletal pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Musculoskeletal stiffness	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
Myalgia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	2/13 (15.4%)	3	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Neck pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Pain in extremity	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Pain in jaw	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/18 (0%)	0	0/3 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Nervous system disorders
Ataxia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Dizziness	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	3/18 (16.7%)	5	0/3 (0%)	0
Dysgeusia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Headache	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Paraesthesia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Peripheral sensory neuropathy	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Sciatica	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Sinus headache	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Somnolence	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Viith nerve paralysis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/3 (33.3%)	1	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Psychiatric disorders
Agitation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Anxiety	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Confusional state	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Depression	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Insomnia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Mental status changes	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Renal and urinary disorders
Dysuria	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/18 (0%)	0	0/3 (0%)	0
Haematuria	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Haemoglobinuria	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Micturition urgency	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	2	0/3 (0%)	0
Pollakiuria	1/1 (100%)	1	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	1/18 (5.6%)	1	1/3 (33.3%)	1
Reproductive system and breast disorders
Breast pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Genital discomfort	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
Perineal pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Cough	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	2/18 (11.1%)	2	0/3 (0%)	0
Dyspnoea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	1/3 (33.3%)	1	1/5 (20%)	1	0/3 (0%)	0	1/18 (5.6%)	2	0/3 (0%)	0
Dyspnoea exertional	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Epistaxis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hiccups	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hypoxia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	1/18 (5.6%)	1	0/3 (0%)	0
Nasal congestion	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Oropharyngeal pain	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	2/3 (66.7%)	2	1/18 (5.6%)	1	0/3 (0%)	0
Rhinorrhoea	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Throat irritation	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	1	5/18 (27.8%)	5	1/3 (33.3%)	1
Dermatitis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Exfoliative rash	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hair growth abnormal	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hyperhidrosis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Hyperkeratosis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	0/3 (0%)	0
Night sweats	0/1 (0%)	0	1/1 (100%)	1	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Palmar-plantar erythrodysaesthesia syndrome	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	1/3 (33.3%)	1
Pruritus	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	3/13 (23.1%)	3	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	4/18 (22.2%)	4	1/3 (33.3%)	1
Rash	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/13 (7.7%)	1	0/3 (0%)	0	2/5 (40%)	2	1/3 (33.3%)	1	5/18 (27.8%)	7	0/3 (0%)	0
Skin chapped	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/18 (0%)	0	1/3 (33.3%)	1
Skin discolouration	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Surgical and medical procedures
Tooth extraction	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Vascular disorders
Hot flush	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	3/18 (16.7%)	3	0/3 (0%)	0
Hypertension	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0
Hypotension	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	1/3 (33.3%)	1	2/5 (40%)	2	0/3 (0%)	0	4/18 (22.2%)	5	0/3 (0%)	0
Thrombosis	0/1 (0%)	0	0/1 (0%)	0	0/1 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/13 (0%)	0	0/3 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/18 (5.6%)	1	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.