A Safety Study in Participants With Advanced Solid Tumors

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Terminated

CT.gov ID

NCT01284335

Collaborator

(none)

234

Enrollment

Locations

Arms

Duration (Months)

12.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine a safe dose of LY573636 (tasisulam) when used in 5 separate combinations with an approved cancer medication for treating participants with advanced cancer. Data from this study will be reviewed for any side effects or anti-tumor activity that may be associated with the LY573636 combination treatments.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: Gemcitabine Drug: Docetaxel Drug: Temozolomide Drug: Cisplatin Drug: Erlotinib Drug: LY573636	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

234 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Multicenter, Dose-escalation Study of LY573636-sodium in Combination With 1) Gemcitabine HCl or 2) Docetaxel or 3) Temozolomide or 4) Cisplatin, or 5) Erlotinib in Patients With Advanced Solid Tumors

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Oct 1, 2012

Actual Study Completion Date :

May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gemcitabine plus LY573636	Drug: Gemcitabine 1000 mg/m2 administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Other Names: LY18011 Drug: LY573636 Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Other Names: Tasisulam LY573636-sodium
Experimental: Docetaxel plus LY573636	Drug: Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Drug: LY573636 Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Other Names: Tasisulam LY573636-sodium
Experimental: Temozolomide plus LY573636	Drug: Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Drug: LY573636 Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Other Names: Tasisulam LY573636-sodium
Experimental: Cisplatin plus LY573636	Drug: Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Drug: LY573636 Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Other Names: Tasisulam LY573636-sodium
Experimental: Erlotinib plus LY573636	Drug: Erlotinib 150 mg administered orally days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Drug: LY573636 Individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Other Names: Tasisulam LY573636-sodium

Outcome Measures

Primary Outcome Measures

Number of Participants With Dose-Limiting Toxicities Cycle 1 [Baseline to Cycle 1 (Up to Day 28)]
A Dose-Limiting Toxicity (DLT) is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade 4 neutropenia lasting more than 5 days. Grade 4 neutropenia with fever or Grade 4 thrombocytopenia, regardless of duration; Grade ≥3 thrombocytopenia with bleeding, regardless of duration; Grade ≥3 nonhematologic toxicity (excluding nausea/vomiting or diarrhea that can be controlled with medication, and alopecia). Grade 3 electrolyte toxicity (for example, hypokalemia, hypophosphatemia) will not be considered a DLT unless it is considered related to the study drug or combination and does not resolve with standard replacement treatments within 42 days after Cycle 1 Day 1. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section.

Secondary Outcome Measures

Pharmacokinetic (PK): Concentration Maximum (Cmax) [Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.]
Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) [Baseline to Study Completion (Up to 2 years)]
Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions; Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions.
Number of Participants With a Clinically Significant Effects [Baseline to Study Completion (Up to 2 years)]
Clinically significant effects are reported if a Grade 3 or higher treatment emergent adverse event (TEAE) and observed in ≥10% of participants or a toxicity possibly related to study drug based on Common Terminology Criteria for Adverse Events (CTCAE). A summary of other nonserious AEs and all SAEs, regardless of causality is located in the Reported Adverse Event section.
PK: Area Under the Curve Albumin (AUCalb) [Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.]
Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants who have histologically confirmed solid malignancy or lymphoma that is unresectable and/or metastatic for which monotherapy with gemcitabine HCl, docetaxel, temozolomide, cisplatin, or erlotinib would otherwise be appropriate
Must have tumor progression after receiving standard/approved chemotherapy or limited treatment options
Must have measurable or nonmeasurable disease
Have given written informed consent prior to any study-specific procedures
Must have adequate hepatic, hematologic and renal function
Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy or other investigational therapy for at least 4 weeks (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and recovered from the acute effects of therapy. Endocrine therapies for the treatment of prostate cancer may be continued, at the discretion of the investigator. Whole brain radiation must have been completed 90 days before starting study therapy. Participants without evidence of brain metastases who have received prophylactic whole brain irradiation as part of standard of care for small cell lung cancer may be included in the study with a shorter washout period pending approval by the Lilly physician.
Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 6 months following the last dose of study drug.
Females with child-bearing potential must have had a negative serum pregnancy test within 7 days prior to the first dose of study drug.
Must have a serum albumin level greater than or equal to 3.0 g/dL (30 g/L).
Must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale

Exclusion Criteria:

Have received treatment within 30 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication
Have serious preexisting medical conditions that in the opinion of the investigator would preclude participation in the study
Participants with active central nervous system or brain metastasis at the time of study entry. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before study entry to rule out brain metastasis. Participants with stable CNS metastasis not requiring steroids may be eligible.
Have a current hematologic malignancy (other than lymphoma)
Participants with serious concomitant disorders, including active bacterial, fungal, or viral infection, incompatible with the study)
Participants actively receiving warfarin (Coumadin®) therapy
Participants who have previously completed or withdrawn from any study investigating LY573636
Participants with a known hypersensitivity to one of the combination drugs cannot be enrolled to the treatment arm which includes that chemotherapeutic combination
Females who are pregnant or breast feeding
Have known positive test results of HIV, hepatitis B, or hepatitis C
Participants receiving amiodarone, quinidine, propofol, or clozapine.
Participants receiving treatment with strong or moderate inhibitors of CYP2C19, including proton-pump inhibitors (PPIs). Esomeprazole or pantoprazole are allowed if not administered 72 hours before or after LY573636 administration.

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.	Birmingham	Alabama	United States	35233
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.	Fayetteville	Arkansas	United States	72703
3	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.	Denver	Colorado	United States	80218
4	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.	Orlando	Florida	United States	32806
5	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.	Park Ridge	Illinois	United States	60068
6	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.	Indianapolis	Indiana	United States	46219
7	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.	Las Vegas	Nevada	United States	89169
8	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.	Albany	New York	United States	12206
9	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.	Kettering	Ohio	United States	45429
10	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.	Portland	Oregon	United States	97213
11	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.	Greenville	South Carolina	United States	29605
12	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.	Austin	Texas	United States	78731
13	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.	Dallas	Texas	United States	75246
14	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.	The Woodlands	Texas	United States	77380
15	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.	Tyler	Texas	United States	75702
16	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.	Norfolk	Virginia	United States	23502
17	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.	Spokane	Washington	United States	99218
18	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.	Vancouver	Washington	United States	98684
19	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.	Yakima	Washington	United States	98902

Sponsors and Collaborators

Eli Lilly and Company

Investigators

Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 or 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:

NCT01284335

Other Study ID Numbers:

12267
H8K-MC-JZAK

First Posted:

Jan 27, 2011

Last Update Posted:

Jan 10, 2019

Last Verified:

Dec 1, 2018

Keywords provided by Eli Lilly and Company

Advanced solid tumors

Unresectable

Metastatic

Limited treatment options

Measurable or nonmeasurable disease

Additional relevant MeSH terms:

Neoplasms

Gemcitabine

Docetaxel

Erlotinib Hydrochloride

Temozolomide

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	Study completion was defined as when the recommended dose of LY573636 (tasisulam) was defined for each treatment arm or if a decision was made to stop enrollment in the study for business reasons.

Arm/Group Title	Arm A Tasisulam + Gemcitabine Dose Escalation	Arm A Tasisulam + Gemcitabine Dose Confirmation	Arm B* Tasisulam + Docetaxel Dose Escalation	Arm B1 Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Confirmation	Arm C Tasisulam + Temozolomide Dose Escalation	Arm C Tasisulam + Temozolomide Dose Confirmation	Arm D* Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Confirmation	Arm E Tasisulam + Erlotinib Dose Escalation	Arm E Tasisulam + Erlotinib Dose Confirmation
Arm/Group Description	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam and Docetaxel 60 mg/m2 administered concurrently intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam Day 4 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam and 75 mg/m2 cisplatin administered IV on Day 1 in 21-day cycles.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Period Title: Overall Study
STARTED	25	33	5	5	24	26	19	6	4	14	45	16	12
Received at Least One Dose of Study Drug	25	33	5	5	24	26	19	6	4	14	45	16	12
COMPLETED	25	33	5	5	24	26	19	6	4	14	45	16	12
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Arm A Tasisulam + Gemcitabine Dose Escalation	Arm A Tasisulam + Gemcitabine Dose Confirmation	Arm B* Tasisulam + Docetaxel Dose Escalation	Arm B1 Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Confirmation	Arm C Tasisulam + Temozolomide Dose Escalation	Arm C Tasisulam + Temozolomide Dose Confirmation	Arm D* Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Confirmation	Arm E Tasisulam + Erlotinib Dose Escalation	Arm E Tasisulam + Erlotinib Dose Confirmation	Total
Arm/Group Description	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam and Docetaxel 60 mg/m2 administered concurrently intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam Day 4 of a 28 day cycle. Participant's may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam and 75 mg/m2 cisplatin administered IV on Day 1 in 21-day cycles.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Total of all reporting groups
Overall Participants	25	33	5	5	24	26	19	6	4	14	45	16	12	234
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	63.2	65.5	66.3	78.8	64.2	62.7	63.3	65.7	48.46	54.88	67.36	57.84	61.63	63.6
Sex: Female, Male (Count of Participants)
Female	12 48%	19 57.6%	3 60%	2 40%	10 41.7%	17 65.4%	4 21.1%	3 50%	3 75%	7 50%	21 46.7%	9 56.3%	7 58.3%	117 50%
Male	13 52%	14 42.4%	2 40%	3 60%	14 58.3%	9 34.6%	15 78.9%	3 50%	1 25%	7 50%	24 53.3%	7 43.8%	5 41.7%	117 50%
Race/Ethnicity, Customized (Count of Participants)
African	1 4%	2 6.1%	1 20%	2 40%	2 8.3%	3 11.5%	0 0%	0 0%	0 0%	2 14.3%	6 13.3%	3 18.8%	0 0%	22 9.4%
Caucasian	23 92%	30 90.9%	3 60%	3 60%	22 91.7%	21 80.8%	17 89.5%	6 100%	3 75%	10 71.4%	36 80%	12 75%	11 91.7%	197 84.2%
East Asian	1 4%	0 0%	0 0%	0 0%	0 0%	1 3.8%	2 10.5%	0 0%	0 0%	1 7.1%	1 2.2%	1 6.3%	0 0%	7 3%
West Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.2%	0 0%	0 0%	1 0.4%
Hispanic	0 0%	1 3%	1 20%	0 0%	0 0%	1 3.8%	0 0%	0 0%	1 25%	1 7.1%	1 2.2%	0 0%	1 8.3%	7 3%
Region of Enrollment (Count of Participants)
United States	25 100%	33 100%	5 100%	5 100%	24 100%	26 100%	19 100%	6 100%	4 100%	14 100%	45 100%	16 100%	12 100%	234 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-Limiting Toxicities Cycle 1
Description	A Dose-Limiting Toxicity (DLT) is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade 4 neutropenia lasting more than 5 days. Grade 4 neutropenia with fever or Grade 4 thrombocytopenia, regardless of duration; Grade ≥3 thrombocytopenia with bleeding, regardless of duration; Grade ≥3 nonhematologic toxicity (excluding nausea/vomiting or diarrhea that can be controlled with medication, and alopecia). Grade 3 electrolyte toxicity (for example, hypokalemia, hypophosphatemia) will not be considered a DLT unless it is considered related to the study drug or combination and does not resolve with standard replacement treatments within 42 days after Cycle 1 Day 1. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section.
Time Frame	Baseline to Cycle 1 (Up to Day 28)

Outcome Measure Data

Analysis Population Description
All participants who received at least one dose of study drug Tasisulam in dose escalation phase and experienced a dose-limiting toxicity.

Arm/Group Title	Arm A Tasisulam + Gemcitabine Dose Escalation	Arm A Tasisulam + Gemcitabine Dose Confirmation	Arm B* Tasisulam + Docetaxel Dose Escalation	Arm B1 Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Confirmation	Arm C Tasisulam + Temozolomide Dose Escalation	Arm C Tasisulam + Temozolomide Dose Confirmation	Arm D* Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Confirmation	Arm E Tasisulam + Erlotinib Dose Escalation	Arm E Tasisulam + Erlotinib Dose Confirmation
Arm/Group Description	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam and Docetaxel 60 mg/m2 administered concurrently intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam Day 4 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam and 75 mg/m2 cisplatin administered IV on Day 1 in 21-day cycles.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Measure Participants	25	33	5	5	24	26	19	6	4	14	45	16	12
Count of Participants [Participants]	4 16%	0 0%	4 80%	4 80%	3 12.5%	0 0%	3 15.8%	0 0%	0 0%	2 14.3%	0 0%	1 6.3%	0 0%

2. Secondary Outcome

Title	Pharmacokinetic (PK): Concentration Maximum (Cmax)
Description	Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
Time Frame	Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.

Outcome Measure Data

Analysis Population Description
All participants who received at least one dose of study drug Tasisulam and had evaluable PK data

Arm/Group Title	Tasisulam
Arm/Group Description	Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criterion are met.
Measure Participants	217
Cycle 1	306 (20.03)
Cycle 2	250 (31.39)

3. Secondary Outcome

Title	Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response)
Description	Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions; Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions.
Time Frame	Baseline to Study Completion (Up to 2 years)

Outcome Measure Data

Analysis Population Description
All participants who received study drug Tasisulam and had CR or PR tumor response at dose confirmation phase.

Arm/Group Title	Arm A Tasisulam + Gemcitabine Dose Confirmation	Arm B* Tasisulam + Docetaxel Dose Confirmation	Arm C Tasisulam + Temozolomide Dose Confirmation	Arm D Tasisulam + Cisplatin Dose Confirmation	Arm E Tasisulam + Erlotinib Dose Confirmation
Arm/Group Description	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam and Docetaxel 60 mg/m2 administered concurrently intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Measure Participants	33	26	6	45	12
Non-Small Cell Lung Cancer (NSCLC)	0.0 0%	20.0 60.6%	5.0 100%	0.0 0%
Other	14.3 57.2%	6.3 19.1%	0.0 0%	10.0 200%	14.3 59.6%
Pancreas	13.3 53.2%	0 0%	0.0 0%
Small Cell Lung Cancer (SCLC)	7.1 28.4%

4. Secondary Outcome

Title	Number of Participants With a Clinically Significant Effects
Description	Clinically significant effects are reported if a Grade 3 or higher treatment emergent adverse event (TEAE) and observed in ≥10% of participants or a toxicity possibly related to study drug based on Common Terminology Criteria for Adverse Events (CTCAE). A summary of other nonserious AEs and all SAEs, regardless of causality is located in the Reported Adverse Event section.
Time Frame	Baseline to Study Completion (Up to 2 years)

Outcome Measure Data

Analysis Population Description
All participants who received at least one dose of study drug Tasisulam and experienced a Grade 3 or higher TEAE or drug toxicity possibly related to study drug.

Arm/Group Title	Arm A Tasisulam + Gemcitabine Dose Escalation	Arm A Tasisulam + Gemcitabine Dose Confirmation	Arm B1 Tasisulam + Docetaxel Dose Escalation	Arm B* Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Escalation	Arm B2 Tasisulam + Docetaxel Dose Confirmation	Arm C Tasisulam + Temozolomide Dose Escalation	Arm C Tasisulam + Temozolomide Dose Confirmation	Arm D* Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Escalation	Arm D Tasisulam + Cisplatin Dose Confirmation	Arm E Tasisulam + Erlotinib Dose Escalation	Arm E Tasisulam + Erlotinib Dose Confirmation
Arm/Group Description	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participants height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participants height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam and Docetaxel 60 mg/m2 administered concurrently intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met	Tasisulam and 75 mg/m2 cisplatin administered IV on Day 1 in 21-day cycles.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.	Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Measure Participants	25	33	5	5	24	26	19	6	4	14	45	16	12
TEAE >/= Grade 3	15 60%	18 54.5%	0 0%	0 0%	16 66.7%	19 73.1%	11 57.9%	6 100%	0 0%	8 57.1%	30 66.7%	5 31.3%	7 58.3%
Toxicity >/= Grade 3	13 52%	18 54.5%	5 100%	4 80%	18 75%	26 100%	13 68.4%	6 100%	1 25%	7 50%	30 66.7%	5 31.3%	7 58.3%

5. Secondary Outcome

Title	PK: Area Under the Curve Albumin (AUCalb)
Description	Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
Time Frame	Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.

Outcome Measure Data

Analysis Population Description
All participants who received at least one dose of study drug Tasisulam and had evaluable PK data.

Arm/Group Title	Tasisulam
Arm/Group Description	Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters
Measure Participants	217
Cycle 1	946 (427.2)
Cycle 2	648 (765.92)

Adverse Events

	Arm A Tasisulam + Gemcitabine Dose Escalation		Arm A Tasisulam + Gemcitabine Dose Confirmation		Arm B* Tasisulam + Docetaxel Dose Escalation		Arm B1 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Confirmation		Arm C Tasisulam + Temozolomide Dose Escalation		Arm C Tasisulam + Temozolomide Dose Confirmation		Arm D* Tasisulam + Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Confirmation		Arm E Tasisulam + Erlotinib Dose Escalation		Arm E Tasisulam + Erlotinib Dose Confirmation
Time Frame
Adverse Event Reporting Description

Arm/Group Title	Arm A Tasisulam + Gemcitabine Dose Escalation		Arm A Tasisulam + Gemcitabine Dose Confirmation		Arm B* Tasisulam + Docetaxel Dose Escalation		Arm B1 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Confirmation		Arm C Tasisulam + Temozolomide Dose Escalation		Arm C Tasisulam + Temozolomide Dose Confirmation		Arm D* Tasisulam + Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Confirmation		Arm E Tasisulam + Erlotinib Dose Escalation		Arm E Tasisulam + Erlotinib Dose Confirmation
Arm/Group Description	Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.		Gemcitabine 1000 milligrams meter squared (mg/m2) administered intravenously on Days 1 and 15 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.		Tasisulam and Docetaxel 60 mg/m2 administered concurrently intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.		Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met. Tasisulam Day 4 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met.		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Docetaxel 60 mg/m2 administered intravenously over 60 minutes on Day 4 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Temozolomide 200 mg/m2 administered orally on days 1-5 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.		Tasisulam and 75 mg/m2 cisplatin administered IV on Day 1 in 21-day cycles.		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Cisplatin 75 mg/m2 administered intravenously on Day 1 of the 28-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.		Tasisulam individualized dose is dependent on participant's height, weight, gender and is adjusted to target a specific exposure range corrected for a participant's laboratory parameters. Intravenous dosing is done on Day 1 of a 28 day cycle. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria are met. Erlotinib 150 mg administered orally (PO) days 1-28 of a 28 day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
All Cause Mortality
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/25 (8%)		8/33 (24.2%)		1/5 (20%)		1/5 (20%)		0/24 (0%)		4/26 (15.4%)		3/19 (15.8%)		3/6 (50%)		1/4 (25%)		2/14 (14.3%)		7/45 (15.6%)		3/16 (18.8%)		3/12 (25%)
Serious Adverse Events
	Arm A Tasisulam + Gemcitabine Dose Escalation		Arm A Tasisulam + Gemcitabine Dose Confirmation		Arm B* Tasisulam + Docetaxel Dose Escalation		Arm B1 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Confirmation		Arm C Tasisulam + Temozolomide Dose Escalation		Arm C Tasisulam + Temozolomide Dose Confirmation		Arm D* Tasisulam + Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Confirmation		Arm E Tasisulam + Erlotinib Dose Escalation		Arm E Tasisulam + Erlotinib Dose Confirmation
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/25 (36%)		14/33 (42.4%)		1/5 (20%)		2/5 (40%)		9/24 (37.5%)		12/26 (46.2%)		8/19 (42.1%)		4/6 (66.7%)		1/4 (25%)		4/14 (28.6%)		19/45 (42.2%)		6/16 (37.5%)		7/12 (58.3%)
Blood and lymphatic system disorders
Anaemia	2/25 (8%)	4	2/33 (6.1%)	3	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	5	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	4	0/16 (0%)	0	0/12 (0%)	0
Febrile neutropenia	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	4	0/16 (0%)	0	0/12 (0%)	0
Leukopenia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Neutropenia	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	3/24 (12.5%)	3	0/26 (0%)	0	3/19 (15.8%)	4	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Thrombocytopenia	1/25 (4%)	1	1/33 (3%)	2	0/5 (0%)	0	1/5 (20%)	2	1/24 (4.2%)	2	0/26 (0%)	0	3/19 (15.8%)	4	1/6 (16.7%)	1	0/4 (0%)	0	1/14 (7.1%)	1	2/45 (4.4%)	2	0/16 (0%)	0	2/12 (16.7%)	4
Cardiac disorders
Atrial fibrillation	0/25 (0%)	0	2/33 (6.1%)	3	0/5 (0%)	0	1/5 (20%)	2	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Cardiac arrest	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Cardiac failure congestive	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	0/16 (0%)	0	0/12 (0%)	0
Cardiopulmonary failure	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Pericardial effusion	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Ventricular tachycardia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Congenital, familial and genetic disorders
Hydrocele	0/13 (0%)	0	1/14 (7.1%)	2	0/2 (0%)	0	0/3 (0%)	0	0/14 (0%)	0	0/9 (0%)	0	0/15 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/24 (0%)	0	0/7 (0%)	0	0/5 (0%)	0
Endocrine disorders
Adrenal haemorrhage	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Ascites	0/25 (0%)	0	2/33 (6.1%)	3	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Colitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Constipation	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Diarrhoea	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Dysphagia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Erosive oesophagitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Gastritis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Gastrointestinal haemorrhage	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	1/12 (8.3%)	1
Haematochezia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Ileus	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Intestinal obstruction	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	3
Intestinal perforation	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Jejunal ulcer	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Large intestinal obstruction	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Nausea	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	3	0/16 (0%)	0	0/12 (0%)	0
Oesophageal haemorrhage	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Oesophageal obstruction	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Small intestinal obstruction	2/25 (8%)	5	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Stomatitis	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Vomiting	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	5	0/16 (0%)	0	0/12 (0%)	0
General disorders
Asthenia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Complication associated with device	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
General physical health deterioration	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Mucosal inflammation	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Non-cardiac chest pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Oedema peripheral	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pyrexia	2/25 (8%)	3	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Hepatobiliary disorders
Bile duct obstruction	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hyperbilirubinaemia	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Jaundice cholestatic	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Immune system disorders
Anaphylactic reaction	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Infections and infestations
Bacterial sepsis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Cellulitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Diverticulitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Endocarditis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Herpes zoster	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Infection	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Neutropenic sepsis	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pneumonia	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Postoperative wound infection	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pseudomonal bacteraemia	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Sepsis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Septic shock	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Systemic candida	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Urinary tract infection	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	1/4 (25%)	1	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Injury, poisoning and procedural complications
Acute haemolytic transfusion reaction	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Rib fracture	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Spinal compression fracture	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Transfusion reaction	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Wound dehiscence	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Investigations
Platelet count decreased	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	3/45 (6.7%)	4	0/16 (0%)	0	1/12 (8.3%)	1
Diabetes mellitus	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Hyperglycaemia	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hypoglycaemia	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hypokalaemia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Hypomagnesaemia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Hyponatraemia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Hypovolaemia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	0/16 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Back pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Rhabdomyolysis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Malignant pleural effusion	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Metastases to central nervous system	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Tumour haemorrhage	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Nervous system disorders
Aphasia	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Cerebrovascular accident	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Depressed level of consciousness	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Dizziness	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Haemorrhagic stroke	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Peripheral motor neuropathy	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Presyncope	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Seizure	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Vasogenic cerebral oedema	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Psychiatric disorders
Confusional state	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Mental status changes	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	2	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Psychotic disorder	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Renal and urinary disorders
Obstructive uropathy	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Renal failure	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	2/24 (8.3%)	2	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Acute respiratory failure	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Aspiration	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Bronchitis chronic	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Chronic obstructive pulmonary disease	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Dyspnoea	0/25 (0%)	0	2/33 (6.1%)	4	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	1/45 (2.2%)	1	0/16 (0%)	0	1/12 (8.3%)	1
Dyspnoea exertional	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Epistaxis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Haemoptysis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hypoxia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	1/16 (6.3%)	2	0/12 (0%)	0
Lung infiltration	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pleural effusion	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	0/16 (0%)	0	0/12 (0%)	0
Pneumonia aspiration	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	1/12 (8.3%)	1
Pneumonitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pneumothorax	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Pulmonary embolism	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Pulmonary haemorrhage	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Respiratory distress	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Respiratory failure	0/25 (0%)	0	1/33 (3%)	1	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Vascular disorders
Hypertensive crisis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Hypotension	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hypovolaemic shock	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Thrombosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Venous thrombosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm A Tasisulam + Gemcitabine Dose Escalation		Arm A Tasisulam + Gemcitabine Dose Confirmation		Arm B* Tasisulam + Docetaxel Dose Escalation		Arm B1 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Escalation		Arm B2 Tasisulam + Docetaxel Dose Confirmation		Arm C Tasisulam + Temozolomide Dose Escalation		Arm C Tasisulam + Temozolomide Dose Confirmation		Arm D* Tasisulam + Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Escalation		Arm D Tasisulam+ Cisplatin Dose Confirmation		Arm E Tasisulam + Erlotinib Dose Escalation		Arm E Tasisulam + Erlotinib Dose Confirmation
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/25 (96%)		33/33 (100%)		5/5 (100%)		5/5 (100%)		24/24 (100%)		26/26 (100%)		19/19 (100%)		6/6 (100%)		4/4 (100%)		14/14 (100%)		43/45 (95.6%)		16/16 (100%)		11/12 (91.7%)
Blood and lymphatic system disorders
Anaemia	11/25 (44%)	66	13/33 (39.4%)	28	3/5 (60%)	5	4/5 (80%)	11	11/24 (45.8%)	45	11/26 (42.3%)	82	6/19 (31.6%)	21	2/6 (33.3%)	4	0/4 (0%)	0	5/14 (35.7%)	13	19/45 (42.2%)	71	8/16 (50%)	27	4/12 (33.3%)	14
Febrile neutropenia	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	3	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Leukocytosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Leukopenia	4/25 (16%)	11	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	2/24 (8.3%)	6	4/26 (15.4%)	7	2/19 (10.5%)	4	1/6 (16.7%)	1	0/4 (0%)	0	1/14 (7.1%)	4	4/45 (8.9%)	12	0/16 (0%)	0	2/12 (16.7%)	5
Lymphopenia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	6	1/26 (3.8%)	1	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	0/16 (0%)	0	1/12 (8.3%)	2
Neutropenia	13/25 (52%)	48	7/33 (21.2%)	30	4/5 (80%)	5	3/5 (60%)	17	14/24 (58.3%)	59	17/26 (65.4%)	84	6/19 (31.6%)	16	2/6 (33.3%)	3	1/4 (25%)	10	5/14 (35.7%)	24	19/45 (42.2%)	64	2/16 (12.5%)	6	5/12 (41.7%)	11
Thrombocytopenia	12/25 (48%)	41	11/33 (33.3%)	28	1/5 (20%)	1	0/5 (0%)	0	5/24 (20.8%)	7	11/26 (42.3%)	30	8/19 (42.1%)	33	4/6 (66.7%)	8	0/4 (0%)	0	6/14 (42.9%)	14	26/45 (57.8%)	89	4/16 (25%)	7	4/12 (33.3%)	24
Thrombocytosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Cardiac disorders
Angina pectoris	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Atrial fibrillation	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	4	0/16 (0%)	0	0/12 (0%)	0
Cardiac failure congestive	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Left ventricular dysfunction	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Palpitations	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	4	0/16 (0%)	0	0/12 (0%)	0
Sinus tachycardia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	3	1/16 (6.3%)	2	0/12 (0%)	0
Tachycardia	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	1/5 (20%)	2	3/24 (12.5%)	4	2/26 (7.7%)	11	1/19 (5.3%)	1	0/6 (0%)	0	1/4 (25%)	3	0/14 (0%)	0	4/45 (8.9%)	4	2/16 (12.5%)	2	1/12 (8.3%)	2
Ear and labyrinth disorders
Deafness	0/25 (0%)	0	1/33 (3%)	6	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	2/14 (14.3%)	13	2/45 (4.4%)	7	0/16 (0%)	0	0/12 (0%)	0
Hypoacusis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	3	0/16 (0%)	0	1/12 (8.3%)	3
Tinnitus	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	2	4/14 (28.6%)	22	4/45 (8.9%)	8	0/16 (0%)	0	0/12 (0%)	0
Vertigo	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	9	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Eye disorders
Chorioretinal disorder	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Dry eye	1/25 (4%)	14	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	7	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	1/16 (6.3%)	9	0/12 (0%)	0
Eye discharge	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	3	0/16 (0%)	0	0/12 (0%)	0
Eye haemorrhage	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Eye pain	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	3	0/16 (0%)	0	0/12 (0%)	0
Lacrimation increased	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	5	0/5 (0%)	0	1/24 (4.2%)	3	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	3	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Macular detachment	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Orbital oedema	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Periorbital oedema	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	6	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Vision blurred	1/25 (4%)	4	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	7	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	1/45 (2.2%)	9	0/16 (0%)	0	0/12 (0%)	0
Visual impairment	0/25 (0%)	0	2/33 (6.1%)	8	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	4	0/16 (0%)	0	0/12 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/25 (4%)	2	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	3	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	9	0/16 (0%)	0	1/12 (8.3%)	6
Abdominal distension	1/25 (4%)	1	2/33 (6.1%)	4	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	2/6 (33.3%)	3	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	3
Abdominal hernia	1/25 (4%)	22	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	3	1/19 (5.3%)	8	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	3	0/16 (0%)	0	0/12 (0%)	0
Abdominal pain	4/25 (16%)	11	5/33 (15.2%)	9	0/5 (0%)	0	2/5 (40%)	4	3/24 (12.5%)	12	4/26 (15.4%)	15	2/19 (10.5%)	4	1/6 (16.7%)	2	2/4 (50%)	13	2/14 (14.3%)	6	3/45 (6.7%)	11	2/16 (12.5%)	5	1/12 (8.3%)	2
Abdominal pain lower	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	5	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Abdominal pain upper	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	6	1/26 (3.8%)	1	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	4	0/16 (0%)	0	0/12 (0%)	0
Ascites	2/25 (8%)	4	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	4	1/45 (2.2%)	2	3/16 (18.8%)	5	0/12 (0%)	0
Constipation	7/25 (28%)	26	16/33 (48.5%)	64	1/5 (20%)	7	2/5 (40%)	4	7/24 (29.2%)	24	13/26 (50%)	57	7/19 (36.8%)	25	2/6 (33.3%)	3	3/4 (75%)	6	4/14 (28.6%)	9	11/45 (24.4%)	48	3/16 (18.8%)	31	3/12 (25%)	15
Diarrhoea	13/25 (52%)	22	9/33 (27.3%)	51	2/5 (40%)	4	4/5 (80%)	11	9/24 (37.5%)	18	7/26 (26.9%)	31	4/19 (21.1%)	6	1/6 (16.7%)	2	1/4 (25%)	1	1/14 (7.1%)	2	13/45 (28.9%)	99	10/16 (62.5%)	49	4/12 (33.3%)	20
Dry mouth	1/25 (4%)	1	2/33 (6.1%)	4	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	1/4 (25%)	3	0/14 (0%)	0	1/45 (2.2%)	2	0/16 (0%)	0	2/12 (16.7%)	9
Dyspepsia	1/25 (4%)	3	1/33 (3%)	8	1/5 (20%)	2	0/5 (0%)	0	1/24 (4.2%)	1	4/26 (15.4%)	17	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	1/14 (7.1%)	2	2/45 (4.4%)	3	2/16 (12.5%)	6	1/12 (8.3%)	2
Dysphagia	2/25 (8%)	2	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	6	1/16 (6.3%)	2	1/12 (8.3%)	5
Flatulence	3/25 (12%)	5	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	2/14 (14.3%)	8	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Gastrointestinal haemorrhage	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Gastrooesophageal reflux disease	0/25 (0%)	0	2/33 (6.1%)	11	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	43	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	11	1/16 (6.3%)	9	2/12 (16.7%)	5
Gingival bleeding	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	1/19 (5.3%)	8	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Haemorrhoids	2/25 (8%)	2	2/33 (6.1%)	12	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	6	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	4	0/12 (0%)	0
Large intestinal stenosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Lip ulceration	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Mouth ulceration	2/25 (8%)	4	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Nausea	10/25 (40%)	50	7/33 (21.2%)	42	3/5 (60%)	3	3/5 (60%)	7	10/24 (41.7%)	21	10/26 (38.5%)	72	7/19 (36.8%)	22	0/6 (0%)	0	3/4 (75%)	20	4/14 (28.6%)	13	19/45 (42.2%)	126	6/16 (37.5%)	11	4/12 (33.3%)	6
Oesophageal haemorrhage	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Oesophageal stenosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Oesophageal ulcer	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	1/16 (6.3%)	2	0/12 (0%)	0
Oral discomfort	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Oral pain	1/25 (4%)	1	1/33 (3%)	1	1/5 (20%)	1	2/5 (40%)	3	2/24 (8.3%)	11	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pancreatic insufficiency	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Pancreatitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Rectal haemorrhage	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	6	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Stomatitis	4/25 (16%)	6	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	4/24 (16.7%)	7	3/26 (11.5%)	11	1/19 (5.3%)	1	2/6 (33.3%)	2	0/4 (0%)	0	1/14 (7.1%)	1	1/45 (2.2%)	2	1/16 (6.3%)	2	0/12 (0%)	0
Toothache	1/25 (4%)	5	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Vomiting	6/25 (24%)	13	3/33 (9.1%)	4	2/5 (40%)	3	1/5 (20%)	2	7/24 (29.2%)	15	4/26 (15.4%)	14	4/19 (21.1%)	4	1/6 (16.7%)	1	1/4 (25%)	2	2/14 (14.3%)	6	15/45 (33.3%)	44	2/16 (12.5%)	3	6/12 (50%)	11
General disorders
Application site dermatitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	6	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Asthenia	5/25 (20%)	12	4/33 (12.1%)	14	0/5 (0%)	0	0/5 (0%)	0	3/24 (12.5%)	9	1/26 (3.8%)	1	3/19 (15.8%)	7	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	9/45 (20%)	78	2/16 (12.5%)	3	2/12 (16.7%)	4
Chest discomfort	2/25 (8%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	4	0/26 (0%)	0	1/19 (5.3%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Chest pain	1/25 (4%)	1	1/33 (3%)	1	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	1/45 (2.2%)	1	1/16 (6.3%)	1	0/12 (0%)	0
Chills	2/25 (8%)	2	3/33 (9.1%)	3	2/5 (40%)	3	1/5 (20%)	1	1/24 (4.2%)	1	0/26 (0%)	0	2/19 (10.5%)	2	0/6 (0%)	0	1/4 (25%)	4	0/14 (0%)	0	1/45 (2.2%)	1	1/16 (6.3%)	1	2/12 (16.7%)	2
Decreased activity	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Discomfort	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Face oedema	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	4	1/16 (6.3%)	2	0/12 (0%)	0
Fatigue	17/25 (68%)	76	17/33 (51.5%)	90	3/5 (60%)	11	4/5 (80%)	8	16/24 (66.7%)	70	16/26 (61.5%)	97	13/19 (68.4%)	36	1/6 (16.7%)	2	3/4 (75%)	12	7/14 (50%)	37	27/45 (60%)	163	7/16 (43.8%)	26	5/12 (41.7%)	20
Feeling hot	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Gait disturbance	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	6	0/16 (0%)	0	1/12 (8.3%)	2
Influenza like illness	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	4	0/16 (0%)	0	0/12 (0%)	0
Infusion site pain	1/25 (4%)	1	2/33 (6.1%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	3	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	4/45 (8.9%)	8	1/16 (6.3%)	1	0/12 (0%)	0
Injection site pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	1/26 (3.8%)	1	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Malaise	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Mucosal inflammation	6/25 (24%)	11	4/33 (12.1%)	9	1/5 (20%)	3	1/5 (20%)	1	7/24 (29.2%)	20	4/26 (15.4%)	42	3/19 (15.8%)	4	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	2/16 (12.5%)	13	1/12 (8.3%)	8
Non-cardiac chest pain	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	4/45 (8.9%)	7	0/16 (0%)	0	0/12 (0%)	0
Oedema	0/25 (0%)	0	2/33 (6.1%)	11	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	1/14 (7.1%)	2	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Oedema peripheral	4/25 (16%)	7	3/33 (9.1%)	13	2/5 (40%)	6	2/5 (40%)	3	5/24 (20.8%)	15	6/26 (23.1%)	100	0/19 (0%)	0	1/6 (16.7%)	1	1/4 (25%)	1	2/14 (14.3%)	2	6/45 (13.3%)	9	5/16 (31.3%)	13	1/12 (8.3%)	2
Pain	0/25 (0%)	0	2/33 (6.1%)	6	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	4	2/45 (4.4%)	9	0/16 (0%)	0	0/12 (0%)	0
Peripheral swelling	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	1/5 (20%)	1	3/24 (12.5%)	11	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	1/12 (8.3%)	6
Pyrexia	5/25 (20%)	5	5/33 (15.2%)	26	2/5 (40%)	5	0/5 (0%)	0	3/24 (12.5%)	3	1/26 (3.8%)	2	1/19 (5.3%)	1	1/6 (16.7%)	1	0/4 (0%)	0	2/14 (14.3%)	4	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Temperature intolerance	1/25 (4%)	3	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Thirst	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Xerosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	6	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Hepatobiliary disorders
Hyperbilirubinaemia	1/25 (4%)	3	3/33 (9.1%)	5	0/5 (0%)	0	1/5 (20%)	2	1/24 (4.2%)	3	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	3	0/16 (0%)	0	1/12 (8.3%)	3
Immune system disorders
Anaphylactic reaction	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Seasonal allergy	0/25 (0%)	0	2/33 (6.1%)	10	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	9
Infections and infestations
Angular cheilitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	3
Bronchitis	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Candida infection	0/25 (0%)	0	2/33 (6.1%)	3	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	3	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Cellulitis	0/25 (0%)	0	2/33 (6.1%)	2	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Clostridium difficile infection	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	4
Cystitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Fungal infection	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Fungal skin infection	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	2/12 (16.7%)	5
Gastroenteritis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Herpes zoster	1/25 (4%)	2	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	4	1/26 (3.8%)	2	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	8	0/16 (0%)	0	1/12 (8.3%)	3
Localised infection	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Nail infection	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Oral herpes	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Pharyngitis	0/25 (0%)	0	1/33 (3%)	3	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	40	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pneumonia	2/25 (8%)	2	0/33 (0%)	0	1/5 (20%)	2	1/5 (20%)	2	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	3	0/16 (0%)	0	0/12 (0%)	0
Pseudomonal bacteraemia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Sepsis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	2	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Sinusitis	2/25 (8%)	3	2/33 (6.1%)	5	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	3	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Subcutaneous abscess	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	6	0/12 (0%)	0
Upper respiratory tract infection	2/25 (8%)	4	3/33 (9.1%)	4	0/5 (0%)	0	0/5 (0%)	0	5/24 (20.8%)	10	1/26 (3.8%)	2	1/19 (5.3%)	2	0/6 (0%)	0	1/4 (25%)	2	1/14 (7.1%)	1	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Urinary tract infection	6/25 (24%)	7	2/33 (6.1%)	4	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	2	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	4	1/16 (6.3%)	1	0/12 (0%)	0
Viral infection	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	3	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Vulvovaginal mycotic infection	0/12 (0%)	0	0/19 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/10 (0%)	0	0/17 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	2/21 (9.5%)	3	0/9 (0%)	0	0/7 (0%)	0
Vulvovaginitis	0/12 (0%)	0	1/19 (5.3%)	1	0/3 (0%)	0	0/2 (0%)	0	0/10 (0%)	0	0/17 (0%)	0	0/4 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/21 (0%)	0	0/9 (0%)	0	0/7 (0%)	0
Injury, poisoning and procedural complications
Contusion	1/25 (4%)	1	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	4	1/26 (3.8%)	1	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	2/16 (12.5%)	2	1/12 (8.3%)	2
Corneal abrasion	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Infusion related reaction	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Radiation pneumonitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	2
Investigations
Alanine aminotransferase increased	1/25 (4%)	2	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	3/12 (25%)	3
Aspartate aminotransferase increased	3/25 (12%)	4	2/33 (6.1%)	2	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	1/26 (3.8%)	1	1/19 (5.3%)	3	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	3	0/16 (0%)	0	2/12 (16.7%)	2
Blood alkaline phosphatase increased	1/25 (4%)	2	2/33 (6.1%)	5	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	2/12 (16.7%)	4
Blood bilirubin increased	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	1/16 (6.3%)	1	1/12 (8.3%)	1
Blood creatine increased	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Blood creatinine increased	3/25 (12%)	9	3/33 (9.1%)	5	2/5 (40%)	2	0/5 (0%)	0	4/24 (16.7%)	15	1/26 (3.8%)	1	2/19 (10.5%)	12	1/6 (16.7%)	1	0/4 (0%)	0	3/14 (21.4%)	13	12/45 (26.7%)	66	0/16 (0%)	0	3/12 (25%)	10
Blood urea increased	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	4	0/16 (0%)	0	0/12 (0%)	0
Blood urine present	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Carbon dioxide decreased	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Haemoglobin decreased	0/25 (0%)	0	2/33 (6.1%)	5	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	11	0/16 (0%)	0	0/12 (0%)	0
International normalised ratio increased	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	3	0/16 (0%)	0	0/12 (0%)	0
Neutrophil count decreased	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	1/16 (6.3%)	2	0/12 (0%)	0
Oxygen saturation decreased	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Platelet count decreased	1/25 (4%)	2	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Precancerous cells present	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Prothrombin time prolonged	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Urine leukocyte esterase	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	3	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Weight decreased	5/25 (20%)	13	5/33 (15.2%)	17	0/5 (0%)	0	0/5 (0%)	0	4/24 (16.7%)	7	1/26 (3.8%)	8	2/19 (10.5%)	5	1/6 (16.7%)	2	0/4 (0%)	0	2/14 (14.3%)	5	4/45 (8.9%)	8	3/16 (18.8%)	6	1/12 (8.3%)	2
Weight increased	1/25 (4%)	7	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	6	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
White blood cell count decreased	2/25 (8%)	6	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	2	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	7/25 (28%)	22	6/33 (18.2%)	27	0/5 (0%)	0	2/5 (40%)	6	8/24 (33.3%)	23	8/26 (30.8%)	30	6/19 (31.6%)	19	2/6 (33.3%)	2	2/4 (50%)	5	3/14 (21.4%)	14	15/45 (33.3%)	36	9/16 (56.3%)	24	5/12 (41.7%)	14
Dehydration	4/25 (16%)	10	2/33 (6.1%)	2	1/5 (20%)	1	0/5 (0%)	0	6/24 (25%)	7	3/26 (11.5%)	10	3/19 (15.8%)	3	0/6 (0%)	0	0/4 (0%)	0	3/14 (21.4%)	6	6/45 (13.3%)	10	2/16 (12.5%)	4	4/12 (33.3%)	7
Diabetes mellitus	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	3	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	9	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Glucose tolerance impaired	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hypercalcaemia	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	1/16 (6.3%)	2	2/12 (16.7%)	3
Hyperglycaemia	3/25 (12%)	5	2/33 (6.1%)	6	0/5 (0%)	0	1/5 (20%)	7	2/24 (8.3%)	2	3/26 (11.5%)	5	1/19 (5.3%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	4	0/16 (0%)	0	0/12 (0%)	0
Hyperkalaemia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hyperuricaemia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	4	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Hypoalbuminaemia	3/25 (12%)	9	6/33 (18.2%)	13	0/5 (0%)	0	2/5 (40%)	5	5/24 (20.8%)	11	9/26 (34.6%)	66	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	4/14 (28.6%)	15	11/45 (24.4%)	22	6/16 (37.5%)	13	3/12 (25%)	7
Hypocalcaemia	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	5/45 (11.1%)	11	0/16 (0%)	0	0/12 (0%)	0
Hypokalaemia	7/25 (28%)	13	4/33 (12.1%)	15	1/5 (20%)	1	1/5 (20%)	2	6/24 (25%)	17	9/26 (34.6%)	26	1/19 (5.3%)	1	0/6 (0%)	0	1/4 (25%)	1	3/14 (21.4%)	10	12/45 (26.7%)	25	8/16 (50%)	19	5/12 (41.7%)	11
Hypomagnesaemia	1/25 (4%)	3	0/33 (0%)	0	0/5 (0%)	0	4/5 (80%)	7	5/24 (20.8%)	7	4/26 (15.4%)	19	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	9/45 (20%)	10	1/16 (6.3%)	1	3/12 (25%)	9
Hyponatraemia	2/25 (8%)	3	3/33 (9.1%)	4	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	8	3/26 (11.5%)	6	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	3	7/45 (15.6%)	9	1/16 (6.3%)	1	0/12 (0%)	0
Hypophosphataemia	5/25 (20%)	11	3/33 (9.1%)	5	0/5 (0%)	0	4/5 (80%)	8	7/24 (29.2%)	24	3/26 (11.5%)	7	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	10/45 (22.2%)	17	2/16 (12.5%)	3	3/12 (25%)	4
Hypovolaemia	3/25 (12%)	4	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Type 2 diabetes mellitus	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	4	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Vitamin d deficiency	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	5	2/16 (12.5%)	3	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	4/25 (16%)	23	1/33 (3%)	9	1/5 (20%)	3	0/5 (0%)	0	4/24 (16.7%)	9	2/26 (7.7%)	9	1/19 (5.3%)	14	0/6 (0%)	0	1/4 (25%)	6	1/14 (7.1%)	10	2/45 (4.4%)	4	1/16 (6.3%)	2	2/12 (16.7%)	6
Back pain	5/25 (20%)	14	4/33 (12.1%)	5	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	13	6/26 (23.1%)	13	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	6	2/14 (14.3%)	20	4/45 (8.9%)	12	2/16 (12.5%)	4	2/12 (16.7%)	11
Flank pain	2/25 (8%)	7	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Joint stiffness	1/25 (4%)	19	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	0/26 (0%)	0	1/19 (5.3%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Muscle spasms	1/25 (4%)	2	3/33 (9.1%)	9	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	70	2/19 (10.5%)	4	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	7	0/16 (0%)	0	1/12 (8.3%)	7
Muscular weakness	1/25 (4%)	2	2/33 (6.1%)	4	1/5 (20%)	3	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Musculoskeletal chest pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	2/26 (7.7%)	6	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	2/45 (4.4%)	3	2/16 (12.5%)	2	1/12 (8.3%)	4
Musculoskeletal discomfort	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	2/12 (16.7%)	2
Musculoskeletal pain	2/25 (8%)	6	0/33 (0%)	0	1/5 (20%)	2	1/5 (20%)	7	0/24 (0%)	0	2/26 (7.7%)	2	1/19 (5.3%)	2	0/6 (0%)	0	1/4 (25%)	3	1/14 (7.1%)	1	3/45 (6.7%)	5	0/16 (0%)	0	0/12 (0%)	0
Myalgia	3/25 (12%)	10	1/33 (3%)	7	1/5 (20%)	3	0/5 (0%)	0	2/24 (8.3%)	7	2/26 (7.7%)	8	1/19 (5.3%)	6	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	1/12 (8.3%)	1
Neck pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	3/26 (11.5%)	19	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Pain in extremity	3/25 (12%)	5	1/33 (3%)	8	1/5 (20%)	2	0/5 (0%)	0	2/24 (8.3%)	4	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	4	0/14 (0%)	0	2/45 (4.4%)	8	1/16 (6.3%)	3	1/12 (8.3%)	9
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	5	0/16 (0%)	0	1/12 (8.3%)	1
Squamous cell carcinoma	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Tumour associated fever	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	4
Tumour pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	3	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Nervous system disorders
Amnesia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	2/26 (7.7%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Balance disorder	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Dizziness	2/25 (8%)	2	1/33 (3%)	1	1/5 (20%)	1	2/5 (40%)	4	1/24 (4.2%)	1	3/26 (11.5%)	4	2/19 (10.5%)	4	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	6/45 (13.3%)	50	0/16 (0%)	0	6/12 (50%)	33
Dysgeusia	2/25 (8%)	4	8/33 (24.2%)	37	0/5 (0%)	0	1/5 (20%)	2	4/24 (16.7%)	18	2/26 (7.7%)	8	3/19 (15.8%)	7	1/6 (16.7%)	1	1/4 (25%)	4	2/14 (14.3%)	8	5/45 (11.1%)	17	1/16 (6.3%)	2	2/12 (16.7%)	7
Headache	3/25 (12%)	13	2/33 (6.1%)	2	4/5 (80%)	5	0/5 (0%)	0	3/24 (12.5%)	4	3/26 (11.5%)	13	3/19 (15.8%)	8	1/6 (16.7%)	2	1/4 (25%)	6	0/14 (0%)	0	3/45 (6.7%)	4	0/16 (0%)	0	3/12 (25%)	16
Lethargy	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	3	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Memory impairment	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Neuralgia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	4
Neuropathy peripheral	3/25 (12%)	7	2/33 (6.1%)	18	1/5 (20%)	1	1/5 (20%)	2	3/24 (12.5%)	7	4/26 (15.4%)	62	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	4	0/14 (0%)	0	3/45 (6.7%)	11	1/16 (6.3%)	1	0/12 (0%)	0
Paraesthesia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	1/16 (6.3%)	24	0/12 (0%)	0
Peripheral sensory neuropathy	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	1/5 (20%)	2	0/24 (0%)	0	1/26 (3.8%)	6	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	2/45 (4.4%)	6	0/16 (0%)	0	0/12 (0%)	0
Restless legs syndrome	0/25 (0%)	0	1/33 (3%)	9	0/5 (0%)	0	1/5 (20%)	3	1/24 (4.2%)	5	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Sinus headache	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Speech disorder	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Syncope	2/25 (8%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	2	0/16 (0%)	0	0/12 (0%)	0
Product Issues
Device occlusion	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	22	0/12 (0%)	0
Psychiatric disorders
Anxiety	3/25 (12%)	3	2/33 (6.1%)	14	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	4	4/26 (15.4%)	10	0/19 (0%)	0	3/6 (50%)	5	1/4 (25%)	2	3/14 (21.4%)	6	3/45 (6.7%)	5	2/16 (12.5%)	41	1/12 (8.3%)	1
Confusional state	2/25 (8%)	2	1/33 (3%)	2	0/5 (0%)	0	1/5 (20%)	5	1/24 (4.2%)	1	2/26 (7.7%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	3	0/16 (0%)	0	0/12 (0%)	0
Depression	2/25 (8%)	7	2/33 (6.1%)	11	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	12	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	5	1/14 (7.1%)	4	1/45 (2.2%)	3	3/16 (18.8%)	7	1/12 (8.3%)	1
Disorientation	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Insomnia	4/25 (16%)	14	2/33 (6.1%)	6	0/5 (0%)	0	1/5 (20%)	3	3/24 (12.5%)	14	6/26 (23.1%)	16	4/19 (21.1%)	11	0/6 (0%)	0	1/4 (25%)	2	1/14 (7.1%)	6	5/45 (11.1%)	22	3/16 (18.8%)	5	3/12 (25%)	22
Stress	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	2	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Renal and urinary disorders
Bladder pain	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Dysuria	3/25 (12%)	5	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	1/16 (6.3%)	1	0/12 (0%)	0
Haematuria	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	2	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	5
Hydronephrosis	1/25 (4%)	2	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	3
Pollakiuria	1/25 (4%)	1	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	3	2/19 (10.5%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	9	1/16 (6.3%)	1	0/12 (0%)	0
Ureteric obstruction	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	1	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Urinary hesitation	2/25 (8%)	3	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	8	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Urinary incontinence	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	0/13 (0%)	0	2/14 (14.3%)	8	0/2 (0%)	0	0/3 (0%)	0	0/14 (0%)	0	0/9 (0%)	0	0/15 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/24 (0%)	0	0/7 (0%)	0	0/5 (0%)	0
Testicular pain	1/13 (7.7%)	2	0/14 (0%)	0	0/2 (0%)	0	0/3 (0%)	0	0/14 (0%)	0	0/9 (0%)	0	0/15 (0%)	0	0/3 (0%)	0	0/1 (0%)	0	0/7 (0%)	0	0/24 (0%)	0	0/7 (0%)	0	0/5 (0%)	0
Vaginal haemorrhage	0/12 (0%)	0	1/19 (5.3%)	2	0/3 (0%)	0	0/2 (0%)	0	0/10 (0%)	0	0/17 (0%)	0	1/4 (25%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/21 (0%)	0	0/9 (0%)	0	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	2	1/24 (4.2%)	1	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Chronic obstructive pulmonary disease	2/25 (8%)	4	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Cough	4/25 (16%)	11	11/33 (33.3%)	43	2/5 (40%)	5	0/5 (0%)	0	7/24 (29.2%)	22	4/26 (15.4%)	10	6/19 (31.6%)	13	1/6 (16.7%)	2	1/4 (25%)	4	2/14 (14.3%)	2	10/45 (22.2%)	39	0/16 (0%)	0	3/12 (25%)	12
Dry throat	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	1	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Dysphonia	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	1	0/19 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	7	0/16 (0%)	0	0/12 (0%)	0
Dyspnoea	9/25 (36%)	29	9/33 (27.3%)	35	1/5 (20%)	3	2/5 (40%)	5	7/24 (29.2%)	20	8/26 (30.8%)	88	5/19 (26.3%)	7	1/6 (16.7%)	1	0/4 (0%)	0	2/14 (14.3%)	4	10/45 (22.2%)	21	4/16 (25%)	7	2/12 (16.7%)	5
Dyspnoea exertional	4/25 (16%)	15	2/33 (6.1%)	5	1/5 (20%)	1	0/5 (0%)	0	2/24 (8.3%)	14	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	3	2/45 (4.4%)	6	1/16 (6.3%)	5	1/12 (8.3%)	14
Emphysema	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	13	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Epistaxis	2/25 (8%)	2	3/33 (9.1%)	5	1/5 (20%)	3	0/5 (0%)	0	2/24 (8.3%)	11	4/26 (15.4%)	9	2/19 (10.5%)	9	1/6 (16.7%)	2	1/4 (25%)	11	0/14 (0%)	0	6/45 (13.3%)	6	2/16 (12.5%)	9	1/12 (8.3%)	2
Haemoptysis	1/25 (4%)	2	2/33 (6.1%)	14	0/5 (0%)	0	2/5 (40%)	3	1/24 (4.2%)	2	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	2/16 (12.5%)	5	0/12 (0%)	0
Hiccups	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	1	1/4 (25%)	1	1/14 (7.1%)	5	2/45 (4.4%)	11	0/16 (0%)	0	0/12 (0%)	0
Hypoxia	3/25 (12%)	7	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	3/24 (12.5%)	6	1/26 (3.8%)	5	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	3/45 (6.7%)	3	0/16 (0%)	0	0/12 (0%)	0
Nasal congestion	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	5	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	3/14 (21.4%)	7	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Nasal mucosal disorder	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	1	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Oropharyngeal pain	4/25 (16%)	5	4/33 (12.1%)	13	3/5 (60%)	5	0/5 (0%)	0	1/24 (4.2%)	1	0/26 (0%)	0	1/19 (5.3%)	1	1/6 (16.7%)	3	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	0/16 (0%)	0	0/12 (0%)	0
Paranasal sinus hypersecretion	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	2/19 (10.5%)	6	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	5
Pharyngeal erythema	1/25 (4%)	4	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	13	0/12 (0%)	0
Pleural effusion	1/25 (4%)	1	0/33 (0%)	0	1/5 (20%)	1	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	1/14 (7.1%)	3	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Productive cough	0/25 (0%)	0	2/33 (6.1%)	5	1/5 (20%)	1	0/5 (0%)	0	2/24 (8.3%)	9	0/26 (0%)	0	1/19 (5.3%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	1	0/12 (0%)	0
Pulmonary hypertension	2/25 (8%)	12	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Rhinitis allergic	0/25 (0%)	0	1/33 (3%)	4	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	6	1/19 (5.3%)	1	0/6 (0%)	0	1/4 (25%)	5	0/14 (0%)	0	1/45 (2.2%)	2	0/16 (0%)	0	0/12 (0%)	0
Rhinorrhoea	0/25 (0%)	0	0/33 (0%)	0	2/5 (40%)	5	0/5 (0%)	0	1/24 (4.2%)	2	1/26 (3.8%)	1	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Sinus congestion	1/25 (4%)	1	2/33 (6.1%)	8	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	2	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	1/16 (6.3%)	2	1/12 (8.3%)	5
Wheezing	0/25 (0%)	0	2/33 (6.1%)	4	0/5 (0%)	0	1/5 (20%)	2	2/24 (8.3%)	13	1/26 (3.8%)	11	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	7	1/16 (6.3%)	3	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	3/25 (12%)	10	6/33 (18.2%)	28	1/5 (20%)	6	2/5 (40%)	10	7/24 (29.2%)	43	8/26 (30.8%)	77	1/19 (5.3%)	2	2/6 (33.3%)	3	0/4 (0%)	0	1/14 (7.1%)	6	6/45 (13.3%)	26	0/16 (0%)	0	2/12 (16.7%)	11
Dermatitis acneiform	1/25 (4%)	8	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	3	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	6/16 (37.5%)	25	0/12 (0%)	0
Dry skin	0/25 (0%)	0	1/33 (3%)	9	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	16	1/26 (3.8%)	2	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	4/16 (25%)	19	0/12 (0%)	0
Ecchymosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	2/45 (4.4%)	4	1/16 (6.3%)	1	1/12 (8.3%)	1
Erythema	1/25 (4%)	1	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	2	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	3/12 (25%)	14
Hirsutism	0/12 (0%)	0	0/19 (0%)	0	0/3 (0%)	0	0/2 (0%)	0	0/10 (0%)	0	0/17 (0%)	0	1/4 (25%)	3	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/21 (0%)	0	0/9 (0%)	0	0/7 (0%)	0
Hyperhidrosis	0/25 (0%)	0	2/33 (6.1%)	2	1/5 (20%)	1	0/5 (0%)	0	1/24 (4.2%)	1	1/26 (3.8%)	1	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	1	1/14 (7.1%)	1	1/45 (2.2%)	1	1/16 (6.3%)	1	0/12 (0%)	0
Nail bed inflammation	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	1/12 (8.3%)	1
Nail disorder	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	2	1/5 (20%)	3	1/24 (4.2%)	8	2/26 (7.7%)	5	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	9	0/16 (0%)	0	0/12 (0%)	0
Night sweats	1/25 (4%)	3	2/33 (6.1%)	4	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	2	1/16 (6.3%)	6	1/12 (8.3%)	5
Palmar-plantar erythrodysaesthesia syndrome	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	1/12 (8.3%)	1
Petechiae	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	2/12 (16.7%)	4
Pruritus	0/25 (0%)	0	1/33 (3%)	1	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	9	2/26 (7.7%)	8	3/19 (15.8%)	6	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Rash	2/25 (8%)	8	2/33 (6.1%)	10	0/5 (0%)	0	0/5 (0%)	0	8/24 (33.3%)	17	2/26 (7.7%)	8	2/19 (10.5%)	6	1/6 (16.7%)	2	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	5/16 (31.3%)	18	7/12 (58.3%)	45
Rash maculo-papular	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	2/16 (12.5%)	4	0/12 (0%)	0
Skin exfoliation	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	13	0/19 (0%)	0	0/6 (0%)	0	1/4 (25%)	3	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Skin fissures	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Skin hyperpigmentation	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	1/5 (20%)	5	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	3	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Urticaria	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	1/26 (3.8%)	5	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Vascular disorders
Deep vein thrombosis	2/25 (8%)	5	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	5	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Flushing	1/25 (4%)	1	1/33 (3%)	1	1/5 (20%)	3	0/5 (0%)	0	2/24 (8.3%)	4	0/26 (0%)	0	1/19 (5.3%)	1	0/6 (0%)	0	1/4 (25%)	2	0/14 (0%)	0	0/45 (0%)	0	2/16 (12.5%)	5	0/12 (0%)	0
Haematoma	0/25 (0%)	0	0/33 (0%)	0	1/5 (20%)	5	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Hot flush	0/25 (0%)	0	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	9	0/16 (0%)	0	0/12 (0%)	0
Hypertension	1/25 (4%)	7	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	1/24 (4.2%)	3	0/26 (0%)	0	1/19 (5.3%)	2	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	2	2/45 (4.4%)	3	1/16 (6.3%)	1	1/12 (8.3%)	1
Hypotension	7/25 (28%)	9	2/33 (6.1%)	2	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	2	3/26 (11.5%)	4	2/19 (10.5%)	2	1/6 (16.7%)	1	0/4 (0%)	0	0/14 (0%)	0	3/45 (6.7%)	4	3/16 (18.8%)	7	1/12 (8.3%)	2
Pallor	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	1/14 (7.1%)	1	0/45 (0%)	0	0/16 (0%)	0	0/12 (0%)	0
Phlebitis	1/25 (4%)	2	1/33 (3%)	2	0/5 (0%)	0	0/5 (0%)	0	2/24 (8.3%)	3	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	1	0/16 (0%)	0	0/12 (0%)	0
Thrombophlebitis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	1/45 (2.2%)	7	1/16 (6.3%)	6	0/12 (0%)	0
Thrombosis	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	2	0/12 (0%)	0
Vasodilatation	0/25 (0%)	0	0/33 (0%)	0	0/5 (0%)	0	0/5 (0%)	0	0/24 (0%)	0	0/26 (0%)	0	0/19 (0%)	0	0/6 (0%)	0	0/4 (0%)	0	0/14 (0%)	0	0/45 (0%)	0	1/16 (6.3%)	17	0/12 (0%)	0

Limitations/Caveats

This study was terminated early due to termination of development of the tasisulam compound. All participants were considered to have completed the study upon the completion of one cycle of treatment.

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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.

Results Point of Contact

Name/Title	Chief Medical Officer
Organization	Eli Lilly and Company
Phone	800-545-5979
Email

Responsible Party:

Eli Lilly and Company

ClinicalTrials.gov Identifier:

NCT01284335

Other Study ID Numbers:

12267
H8K-MC-JZAK

First Posted:

Jan 27, 2011

Last Update Posted:

Jan 10, 2019

Last Verified:

Dec 1, 2018

A Safety Study in Participants With Advanced Solid Tumors

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Certain Agreements

Results Point of Contact