Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Efficacy of AZD2014

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01026402
• Collaborator: (none)
• Enrollment: 172
• Locations: 2
• Arm: 1
• Duration (Months): 56
• Patients Per Site: 86
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

The main purpose of the study is to establish a safe dose of the drug by providing information on any potential side effects this drug may cause and collecting data about how a patient's cancer responds to the drug. The study will also assess the blood levels and action of AZD2014 in the body over a period of time and will indicate whether the drug has an effect on the types of cancer the patients have.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Malignancies	Drug: AZD2014	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 172 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTor Kinase Inhibitor AZD2014 Administered Orally to Patients With Advanced Solid Malignancies
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

Arm

Intervention/Treatment

Experimental: AZD2014 AZD2014 dose escalation phase in Part A and expansion phase in Part B.

Drug: AZD2014; Dose escalation phase: a single dose taken orally (solution or tablet) of AZD2014 on single dose day 1 (visit 2), followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or Single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal. Expansion phase: twice daily dosing from day 1 until discontinuation or withdrawal or a single dose taken orally of AZD2014 on single dose day 1 (visit 2), followed by a single dose on second single dose day 1 (visit 3) after a washout period (48 hours - 7 days) followed by once or twice daily continuous dosing after a washout period (48 hours - 7 days) at visit 4, until discontinuation or withdrawal or single or multiple doses taken orally (solution or tablet) of AZD2014 taken intermittently until discontinuation or withdrawal.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities (DLTs) [Up to 21 days from first multiple dose]

   Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in >1 patient

Secondary Outcome Measures

1. Best Objective Response [Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months]

   Best Objective Response per Response Evaluation Criteria in Solid Tumours Criteria (RECIST) 1.1 for target and non target lesions assessed by CT, MRI or X-ray; Complete Response (CR), Disappearance of all target lesions since baseline; Partial Response (PR), At least a 30 percent decrease in the sum of diameters of target lesions; Progressive Disease (PD), At least a 20 percent increase in the sum of diameters of target lesions and an absolute increase of at least 5mm

2. Maximum Concentration (Cmax) Single Dose [Following Single Dose up to 12, 24 or 48 hours post dose]

   Maximum concentration following single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

3. Area Under the Curve (AUC) Single Dose [Following Single Dose up to 12, 24 or 48 hours post dose]

   Area under the curve following single dose Continuous dosing - AUC parameter used Intermittent dosing - AUC(0-12) used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

4. Maximum Concentration (Cmax) at Steady State [Multiple dosing to steady state (up to 12 or 48 hours post dose)]

   Cmax at steady state (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

5. Area Under the Curve (AUC) at Steady State [Multiple dosing to steady state (up to 12 or 48 hours post dose)]

   AUC at steady state Continuous dosing - AUCss used Intermittent dosing - Weekly AUC used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

6. Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose [Pre dose through to 12 hours post dose]

   Fraction dose excreted unchanged in the urine from 0-12 hours after a single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

7. Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State [Pre dose through to 24 hours post dose]

   Fraction dose excreted unchanged in the urine from 0-12 hours after dosing (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

8. Urine PK - Renal Clearance (Renal CL) Single Dose [Pre dose through to 24 hours post dose]

   Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

9. Urine PK - Renal Clearance (Renal CL) at Steady State [Pre dose through to 24 hours post dose]

   Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)

10. Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose [predose and 2 hours after a single dose]

    Phosphorylation levels of 4EBP1 from peripheral blood mononuclear cell (Patients with undetectable values at baseline have been excluded)

11. Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose [predose and 2 hours after a single dose]

    Phosphorylation levels of AKT from PRP (Patients with undetectable values at baseline have been excluded)

12. Partial Metabolic Response (PMR), Cycle 1 [Cycle 1 Day 8]

    Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

13. Partial Metabolic Response (PMR), Cycle 2 [Cycle 2 Day 8]

    Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

14. Complete Metabolic Response (CMR), Cycle 1 [Cycle 1 Day 8]

    Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

15. Complete Metabolic Response (CMR), Cycle 2 [Cycle 2 Day 8]

    Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 150 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histological or cytological confirmation of a solid, malignant tumour that is refractory to standard therapies or for which no standard therapies exist

• At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment

• World Health Organisation performance status 0-2 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks

Exclusion Criteria:

• Patients with severe laboratory abnormalities for haematology, liver or renal function. Also treatment with any haemopoietic growth factors are not allowed within two weeks prior to first dose of study drug

• Patients with abnormal fasting glucose, type I or uncontrolled type II diabetes

• Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Manchester		United Kingdom
2	Research Site	Sutton		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Dr. Udai Banerji, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT
• Study Director: Elisabeth Oelmann, AstraZeneca

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01026402
• Other Study ID Numbers: D2270C00001; 2009-015244-42
• First Posted: Dec 4, 2009
• Last Update Posted: Feb 11, 2016
• Last Verified: Jan 1, 2016

• Keywords provided by AstraZeneca: Phase I; cancer; advanced solid malignancies; dose escalation; AZD2014; mTor kinase inhibitor; safety; pharmacokinetics
• Additional relevant MeSH terms: Neoplasms

Study Results

Participant Flow

Recruitment Details	First Subject In: 30th December 2009 Last Subject Last visit: 18th August 2014 2 sites located in the UK Number of participants analyzed in Dose Limiting Toxicity (DLT) outcome measure are patients evaluable for DLT assessment Note - in the Clinical Study Report, combined groups are discussed (e.g. Part A 125mg BD Int and Part B 125mg BD tab Int)
Pre-assignment Detail	A total of 172 patients were enrolled. 135 of these patients passed screening assessments and were dosed

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Period Title: Overall Study
STARTED	6	8	33	18	3	5	8	3	7	3	7	8	8	6	3	5	4
COMPLETED	6	8	33	18	3	5	8	3	7	3	7	8	8	6	3	5	4
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Total
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Total of all reporting groups
Overall Participants	6	8	33	18	3	5	8	3	7	3	7	8	8	6	3	5	4	135
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.2 (15.8)	58.3 (14.1)	57.2 (10.3)	58.6 (14.2)	51.7 (11.5)	50.0 (16.1)	59.4 (11.0)	51.3 (18.9)	65.6 (9.8)	59.0 (18.7)	67.3 (7.9)	57.6 (5.4)	53.8 (9.9)	54.2 (14.2)	42.7 (9.0)	47.4 (14.8)	50.0 (8.2)	56.9 (12.3)
Sex: Female, Male (Count of Participants)
Female	2 33.3%	8 100%	22 66.7%	8 44.4%	2 66.7%	4 80%	6 75%	2 66.7%	4 57.1%	3 100%	4 57.1%	4 50%	6 75%	5 83.3%	3 100%	3 60%	2 50%	88 65.2%
Male	4 66.7%	0 0%	11 33.3%	10 55.6%	1 33.3%	1 20%	2 25%	1 33.3%	3 42.9%	0 0%	3 42.9%	4 50%	2 25%	1 16.7%	0 0%	2 40%	2 50%	47 34.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs)
Description	Maximum Tolerated Dose (MTD) was determined by testing various doses and schedules of AZD2014 in cohorts of 3-6 evaluable patients. MTD reflects the highest dose of drug at each schedule that did not cause a DLT in >1 patient
Time Frame	Up to 21 days from first multiple dose

Outcome Measure Data

Analysis Population Description

Safety Analysis Set - All patients that received at least 1 dose of AZD2014. This includes dosed patients who are not evaluable for dose escalation decision purposes.

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	6	0	0	3	3	6	2	2	3	6	6	5	6	3	4	4
Number [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	2 40%	2 25%	0 0%	0 0%	0 0%	2 28.6%	0 0%	3 37.5%	2 33.3%	4 133.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part A 25mg BD Soln Cont, Part A 50mg BD Soln Cont, Part A 70mg BD Soln Cont, Part A 100mg BD Soln Cont
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose
	Estimated Value	50
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	50mg twice daily continuous dosing 20 evaluable patients

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part A 75mg QD Soln Cont, Part A 125mg QD Soln Cont, Part A 100mg QD Tab Cont, Part A 125mg QD Tab Cont, Part A 175mg QD Tab Cont
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose
	Estimated Value	100
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	100mg once daily continuous dosing 16 evaluable patients

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part A 100mg BD Tab Int, Part A 125mg BD Tab Int, Part A 170mg BD Tab Int, Part A 225mg BD Tab Int, Part B 125mg BD Tab Int, Part B 170mg BD Tab Int
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum Tolerated Dose
	Estimated Value	125
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	125mg twice daily intermittent dosing (2 days on, 5 days off) 29 evaluable patients

2. Secondary Outcome

Title	Best Objective Response
Description	Best Objective Response per Response Evaluation Criteria in Solid Tumours Criteria (RECIST) 1.1 for target and non target lesions assessed by CT, MRI or X-ray; Complete Response (CR), Disappearance of all target lesions since baseline; Partial Response (PR), At least a 30 percent decrease in the sum of diameters of target lesions; Progressive Disease (PD), At least a 20 percent increase in the sum of diameters of target lesions and an absolute increase of at least 5mm
Time Frame	Assessed every 8 weeks until progression or withdrawal, whichever came first, estimated to be up to 4 months

Outcome Measure Data

Analysis Population Description

Efficacy analysis set - Patients who received at least 1 dose of AZD2014 and have a baseline tumour assessment

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	8	33	18	3	5	8	3	7	3	7	8	8	6	3	5	4
Responders	0 0%	0 0%	2 6.1%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Non-responders	6 100%	8 100%	31 93.9%	18 100%	3 100%	5 100%	8 100%	3 100%	7 100%	3 100%	7 100%	8 100%	8 100%	6 100%	3 100%	5 100%	4 100%
Stable disease ≥8 wks (a subset of non-responders)	2 33.3%	1 12.5%	12 36.4%	7 38.9%	1 33.3%	1 20%	4 50%	0 0%	1 14.3%	0 0%	3 42.9%	2 25%	1 12.5%	1 16.7%	0 0%	2 40%	0 0%

3. Secondary Outcome

Title	Maximum Concentration (Cmax) Single Dose
Description	Maximum concentration following single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Following Single Dose up to 12, 24 or 48 hours post dose

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	8	19	0	3	4	8	3	7	3	7	8	8	6	3	5	4	18	18
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	435 (41.98)	1313 (43.62)	1089 (62.43)	1476 (78.18)	4046 (22.46)	2048 (47.26)	2989 (20.69)	3251 (54.69)	1868 (32.82)	1826 (62.99)	3293 (74.44)	5223 (39.53)	2849 (61.7)	4395 (14.92)	2382 (38.8)	2787 (71.97)	856.3 (73.47)	643.7 (54.10)

4. Secondary Outcome

Title	Area Under the Curve (AUC) Single Dose
Description	Area under the curve following single dose Continuous dosing - AUC parameter used Intermittent dosing - AUC(0-12) used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Following Single Dose up to 12, 24 or 48 hours post dose

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	8	17	0	3	4	8	3	6	3	7	8	8	6	3	5	4	17	16
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	1640 (51.92)	5308 (63.35)	3520 (81.37)	8866 (50.78)	20790 (39.4)	11160 (64.18)	23450 (24)	31670 (61.45)	11850 (11.29)	8364 (118.6)	18630 (74.75)	33840 (60.95)	15390 (50.33)	30030 (14.13)	8967 (32.54)	9671 (65.88)	3690 (98.07)	3411 (66.71)

5. Secondary Outcome

Title	Maximum Concentration (Cmax) at Steady State
Description	Cmax at steady state (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Multiple dosing to steady state (up to 12 or 48 hours post dose)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	6	11	0	2	3	6	0	0	3	6	6	3	6	1	2	0	14	0
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	746.9 (72.42)	1822 (38.78)	1704 (85.92)	NA (NA)	5517 (29.14)	2730 (47.23)	3258 (25.20)	3534 (25.08)	7557 (38.19)	11400 (24.23)	5649 (27.38)	NA (NA)	NA (NA)	1162 (46.37)

6. Secondary Outcome

Title	Area Under the Curve (AUC) at Steady State
Description	AUC at steady state Continuous dosing - AUCss used Intermittent dosing - Weekly AUC used (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Multiple dosing to steady state (up to 12 or 48 hours post dose)

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	6	11	0	1	1	6	0	0	3	6	6	3	5	1	2	0	11	0
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	2984 (78.71)	6436 (57.04)	7532 (120.5)	NA (NA)	NA (NA)	17230 (64.89)	77690 (41.93)	78150 (73.52)	177100 (79.93)	380200 (52.06)	89530 (27.06)	NA (NA)	NA (NA)	5275 (53.17)

7. Secondary Outcome

Title	Urine PK - Fraction Dose Excreted (fe(0-12)) Single Dose
Description	Fraction dose excreted unchanged in the urine from 0-12 hours after a single dose (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Pre dose through to 12 hours post dose

Outcome Measure Data

Analysis Population Description

PK analysis set - A subset of Safety Analysis set who have reportable plasma concentrations and PK parameter data and who have no important protocol deviations/AEs that may impact PK

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	5	7	0	0	2	4	4	0	6	0	5	6	7	1	1	5	3	0	0
Mean (Standard Deviation) [Percent concentration]	0.3709 (0.2953)	0.5459 (0.4828)	NA (NA)	0.7094 (0.3569)	0.7728 (0.4854)	0.8344 (0.5690)	0.8991 (0.7350)	0.4744 (0.2252)	1.106 (0.8091)	NA (NA)	NA (NA)	0.3288 (0.1359)	0.7680 (0.7217)

8. Secondary Outcome

Title	Urine PK - Fraction Dose Excreted (fe(0-12)) at Steady State
Description	Fraction dose excreted unchanged in the urine from 0-12 hours after dosing (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Pre dose through to 24 hours post dose

Outcome Measure Data

Analysis Population Description

PK analysis set - A subset of Safety Analysis set who have reportable plasma concentrations and PK parameter data and who have no important protocol deviations/AEs that may impact PK

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	0	0	0	0	2	3	6	0	0	0	0	0	0	0	0	0	0	0	0
Mean (Standard Deviation) [Percent concentration]	NA (NA)	0.9056 (0.6456)	1.026 (0.3658)

9. Secondary Outcome

Title	Urine PK - Renal Clearance (Renal CL) Single Dose
Description	Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Pre dose through to 24 hours post dose

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	5	6	0	0	2	4	3	0	5	0	6	6	7	1	1	5	3	0	0
Mean (Standard Deviation) [L/h]	0.07304 (0.07247)	0.03994 (0.02933)	NA (NA)	0.04338 (0.009039)	0.07526 (0.03353)	0.08576 (0.02948)	0.1081 (0.01434)	0.06049 (0.05774)	0.07377 (0.05802)	NA (NA)	NA (NA)	0.03083 (0.01394)	0.09813 (0.04768)

10. Secondary Outcome

Title	Urine PK - Renal Clearance (Renal CL) at Steady State
Description	Renal Clearance (n varies between PK outcome measures as a subset of the PK analysis set was used with reportable AZD2014 plasma concentrations and PK parameters at that visit who have no important adverse events or protocol deviations that may impact PK at that visit, which means that different amounts of data were available for different parameters depending on what visits the parameter covered)
Time Frame	Pre dose through to 24 hours post dose

Outcome Measure Data

Analysis Population Description

PK analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont	Part B 50mg BD Tablet Fasted	Part B 50mg BD Tablet Fed
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	5	5	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Mean (Standard Deviation) [L/h]	0.03702 (0.02688)	0.04242 (0.01126)	NA (NA)

11. Secondary Outcome

Title	Percent Change From Baseline in p4EBP1 at 2 Hours Post Dose
Description	Phosphorylation levels of 4EBP1 from peripheral blood mononuclear cell (Patients with undetectable values at baseline have been excluded)
Time Frame	predose and 2 hours after a single dose

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	0	6	13	16	2	5	6	3	7	3	4	7	7	5	2	5	4
Median (Full Range) [Percent change]	-47.422	-31.067	-21.710	-78.760	-74.053	-66.855	-68.966	-82.249	-57.317	-76.977	-67.275	-55.847	-42.632	-64.855	-57.143	-62.775

12. Secondary Outcome

Title	Percent Change From Baseline in pAKT (S473) in Platelet Rich Plasma (PRP) at 2 Hours Post Dose
Description	Phosphorylation levels of AKT from PRP (Patients with undetectable values at baseline have been excluded)
Time Frame	predose and 2 hours after a single dose

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	5	8	32	18	3	5	8	3	7	3	5	8	8	3	2	5	4
Median (Full Range) [Percent change]	-63.633	-76.202	-65.375	-62.942	-67.349	-82.737	-76.364	-49.476	-86.422	-57.326	-63.350	-62.839	-85.376	-92.031	-66.958	-90.374	-88.343

13. Secondary Outcome

Title	Partial Metabolic Response (PMR), Cycle 1
Description	Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Time Frame	Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	8	33	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Number [Participants]	0 0%	0 0%	4 12.1%

14. Secondary Outcome

Title	Partial Metabolic Response (PMR), Cycle 2
Description	Partial metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Time Frame	Cycle 2 Day 8

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	8	33	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Number [Participants]	0 0%	0 0%	5 15.2%

15. Secondary Outcome

Title	Complete Metabolic Response (CMR), Cycle 1
Description	Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Time Frame	Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	8	33	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Number [Participants]	0 0%	0 0%	0 0%

16. Secondary Outcome

Title	Complete Metabolic Response (CMR), Cycle 2
Description	Complete metabolic responses measured by 2-[F-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) (or FDG-PET/Computed Tomography (CT)) with a comparison to baseline (pre-dose)
Time Frame	Cycle 2 Day 8

Outcome Measure Data

Analysis Population Description

Efficacy analysis set

Arm/Group Title	Part A 25mg BD Soln Cont	Part A 50mg BD Soln Cont	Part B 50mg BD Soln Cont	Part B Fed/Fasted 50mg BD Tab Cont	Part A 75mg QD Soln Cont	Part A 125mg QD Soln Cont	Part A 100mg QD Tab Cont	Part A 125mg QD Tab Cont	Part A 175mg QD Tab Cont	Part A 100mg BD Tab Int	Part A 125mg BD Tab Int	Part A 170mg BD Tab Int	Part A 225mg BD Tab Int	Part B 125mg BD Tab Int	Part B 170mg BD Tab Int	Part A 70mg BD Soln Cont	Part A 100mg BD Soln Cont
Arm/Group Description	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous BD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Continuous QD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Intermittent BD dosing	Continuous BD dosing	Continuous BD dosing
Measure Participants	6	8	33	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Number [Participants]	0 0%	0 0%	0 0%

Adverse Events

Time Frame	At each visit from screening through to 30 day follow up (estimated to be up to 4 months, plus 30 days follow up)
Adverse Event Reporting Description	Continuous BD solution dosing cohorts 25mg, 50mg, 70mg, 100mg Continuous BD tablet dosing cohort Fed/Fasted 50mg Continuous QD solution dosing cohorts 75mg, 125mg Continuous Qd tablet dosing cohorts 100mg, 125mg, 175mg Intermmittent BD tablet dosing cohorts 100mg, 125mg, 170mg, 225mg
Arm/Group Title	Part A - AZD2014 100 mg BD Solution		Part A - AZD2014 100 mg QD Tablet		Part A - AZD2014 125 mg QD Solution		Part A - AZD2014 125 mg QD Tablet		Part A - AZD2014 175 mg QD Tablet		Part A - AZD2014 25 mg BD Solution		Part A - AZD2014 50 mg BD Solution		Part A - AZD2014 70 mg BD Solution		Part A - AZD2014 75 mg QD Solution		Part A - Intermittent AZD2014 100 mg BD Tablet		Part A - Intermittent AZD2014 125 mg BD Tablet		Part A - Intermittent AZD2014 170 mg BD Tablet		Part A - Intermittent AZD2014 225 mg BD Tablet		Part B - AZD2014 50 mg BD Solution		Part B - AZD2014 50 mg BD Tablet Fasted/Fed		Part B - AZD2014 BD 50 mg Tablet Fed/Fasted		Part B - Intermittent AZD2014 125 mg BD Tablet		Part B - Intermittent AZD2014 170 mg BD Tablet
Arm/Group Description	Continuous BD dosing		Continuous QD dosing		Continous QD dosing		Continuous QD dosing		Continuous QD dosing		Continuous BD dosing		Continuous BD dosing		Continuous BD dosing		Continuous QD dosing		Intermittent BD dosing		Intermittent BD dosing		Intermittent BD dosing		Intermittent BD dosing		Continuous BD dosing		Continuous BD dosing		Continuous BD dosing		Intermittent BD dosing		Intermittent BD dosing
All Cause Mortality
	Part A - AZD2014 100 mg BD Solution		Part A - AZD2014 100 mg QD Tablet		Part A - AZD2014 125 mg QD Solution		Part A - AZD2014 125 mg QD Tablet		Part A - AZD2014 175 mg QD Tablet		Part A - AZD2014 25 mg BD Solution		Part A - AZD2014 50 mg BD Solution		Part A - AZD2014 70 mg BD Solution		Part A - AZD2014 75 mg QD Solution		Part A - Intermittent AZD2014 100 mg BD Tablet		Part A - Intermittent AZD2014 125 mg BD Tablet		Part A - Intermittent AZD2014 170 mg BD Tablet		Part A - Intermittent AZD2014 225 mg BD Tablet		Part B - AZD2014 50 mg BD Solution		Part B - AZD2014 50 mg BD Tablet Fasted/Fed		Part B - AZD2014 BD 50 mg Tablet Fed/Fasted		Part B - Intermittent AZD2014 125 mg BD Tablet		Part B - Intermittent AZD2014 170 mg BD Tablet
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part A - AZD2014 100 mg BD Solution		Part A - AZD2014 100 mg QD Tablet		Part A - AZD2014 125 mg QD Solution		Part A - AZD2014 125 mg QD Tablet		Part A - AZD2014 175 mg QD Tablet		Part A - AZD2014 25 mg BD Solution		Part A - AZD2014 50 mg BD Solution		Part A - AZD2014 70 mg BD Solution		Part A - AZD2014 75 mg QD Solution		Part A - Intermittent AZD2014 100 mg BD Tablet		Part A - Intermittent AZD2014 125 mg BD Tablet		Part A - Intermittent AZD2014 170 mg BD Tablet		Part A - Intermittent AZD2014 225 mg BD Tablet		Part B - AZD2014 50 mg BD Solution		Part B - AZD2014 50 mg BD Tablet Fasted/Fed		Part B - AZD2014 BD 50 mg Tablet Fed/Fasted		Part B - Intermittent AZD2014 125 mg BD Tablet		Part B - Intermittent AZD2014 170 mg BD Tablet
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		4/8 (50%)		0/5 (0%)		2/3 (66.7%)		4/7 (57.1%)		5/6 (83.3%)		0/8 (0%)		2/5 (40%)		1/3 (33.3%)		1/3 (33.3%)		3/7 (42.9%)		3/8 (37.5%)		6/8 (75%)		11/33 (33.3%)		4/9 (44.4%)		3/9 (33.3%)		3/6 (50%)		2/3 (66.7%)
Cardiac disorders
Myocardial infarction	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Palpitations	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Tachycardia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Abdominal pain lower	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Constipation	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Diarrhoea	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	1/3 (33.3%)	1
Haematemesis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Large intestinal obstruction	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Nausea	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	2/8 (25%)	2	2/33 (6.1%)	2	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Stomatitis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Vomiting	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	3	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
General disorders
Fatigue	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Pyrexia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Hepatobiliary disorders
Hyperbilirubinaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Infections and infestations
Abdominal infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Biliary sepsis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Device related infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Lower respiratory tract infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pneumonia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Sepsis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Urinary tract infection	0/4 (0%)	0	1/8 (12.5%)	2	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/33 (3%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Urinary tract infection bacterial	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Urinary tract infection pseudomonal	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypercalcaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Hyperglycaemia	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Musculoskeletal chest pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	2	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Pain in extremity	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Nervous system disorders
Cerebral infarction	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Headache	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Lethargy	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Peripheral motor neuropathy	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Psychiatric disorders
Confusional state	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Renal and urinary disorders
Haematuria	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Ureteric fistula	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Reproductive system and breast disorders
Vaginal fistula	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/4 (25%)	1	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1
Haemoptysis	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pleural effusion	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pneumothorax	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pulmonary embolism	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Rash maculo-papular	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	2/3 (66.7%)	2	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	3	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Vascular disorders
Deep vein thrombosis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Other (Not Including Serious) Adverse Events
	Part A - AZD2014 100 mg BD Solution		Part A - AZD2014 100 mg QD Tablet		Part A - AZD2014 125 mg QD Solution		Part A - AZD2014 125 mg QD Tablet		Part A - AZD2014 175 mg QD Tablet		Part A - AZD2014 25 mg BD Solution		Part A - AZD2014 50 mg BD Solution		Part A - AZD2014 70 mg BD Solution		Part A - AZD2014 75 mg QD Solution		Part A - Intermittent AZD2014 100 mg BD Tablet		Part A - Intermittent AZD2014 125 mg BD Tablet		Part A - Intermittent AZD2014 170 mg BD Tablet		Part A - Intermittent AZD2014 225 mg BD Tablet		Part B - AZD2014 50 mg BD Solution		Part B - AZD2014 50 mg BD Tablet Fasted/Fed		Part B - AZD2014 BD 50 mg Tablet Fed/Fasted		Part B - Intermittent AZD2014 125 mg BD Tablet		Part B - Intermittent AZD2014 170 mg BD Tablet
	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	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		8/8 (100%)		5/5 (100%)		3/3 (100%)		7/7 (100%)		6/6 (100%)		8/8 (100%)		5/5 (100%)		3/3 (100%)		3/3 (100%)		7/7 (100%)		8/8 (100%)		8/8 (100%)		32/33 (97%)		9/9 (100%)		9/9 (100%)		6/6 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	1/4 (25%)	1	3/8 (37.5%)	3	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/8 (25%)	2	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	3/7 (42.9%)	3	1/8 (12.5%)	2	2/8 (25%)	4	6/33 (18.2%)	7	4/9 (44.4%)	4	2/9 (22.2%)	2	2/6 (33.3%)	2	1/3 (33.3%)	1
Eosinophilia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Leukocytosis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Leukopenia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Lymphadenopathy	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Neutropenia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	3/8 (37.5%)	3	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1
Thrombocytopenia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	1/9 (11.1%)	1	1/9 (11.1%)	1	1/6 (16.7%)	1	0/3 (0%)	0
Cardiac disorders
Tachycardia	1/4 (25%)	2	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	2	1/8 (12.5%)	2	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Ear and labyrinth disorders
Cerumen impaction	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Deafness unilateral	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Ear discomfort	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Ear pain	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypoacusis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Eye disorders
Conjunctival haemorrhage	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dry eye	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Extraocular muscle paresis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Eye pain	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Halo vision	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Iritis	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Lacrimation increased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Ocular hyperaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Vision blurred	0/4 (0%)	0	1/8 (12.5%)	4	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	3	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Abdominal distension	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Abdominal pain	0/4 (0%)	0	2/8 (25%)	2	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	3/33 (9.1%)	4	1/9 (11.1%)	3	1/9 (11.1%)	1	0/6 (0%)	0	2/3 (66.7%)	2
Abdominal pain lower	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Abdominal pain upper	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	2/7 (28.6%)	2	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	3	1/9 (11.1%)	2	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Anal fissure	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Anorectal discomfort	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Cheilitis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Colonic fistula	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Constipation	1/4 (25%)	1	3/8 (37.5%)	3	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	2/6 (33.3%)	2	2/8 (25%)	2	0/5 (0%)	0	1/3 (33.3%)	2	2/3 (66.7%)	2	3/7 (42.9%)	4	2/8 (25%)	2	3/8 (37.5%)	4	10/33 (30.3%)	15	4/9 (44.4%)	4	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Diarrhoea	1/4 (25%)	1	4/8 (50%)	5	2/5 (40%)	3	2/3 (66.7%)	2	4/7 (57.1%)	7	2/6 (33.3%)	3	2/8 (25%)	3	3/5 (60%)	3	0/3 (0%)	0	0/3 (0%)	0	6/7 (85.7%)	6	4/8 (50%)	7	3/8 (37.5%)	5	16/33 (48.5%)	23	4/9 (44.4%)	4	3/9 (33.3%)	3	3/6 (50%)	4	2/3 (66.7%)	2
Dry mouth	1/4 (25%)	3	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	3/7 (42.9%)	3	1/6 (16.7%)	1	3/8 (37.5%)	3	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	5/33 (15.2%)	5	3/9 (33.3%)	3	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Dyspepsia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	3/33 (9.1%)	3	1/9 (11.1%)	2	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dysphagia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Epigastric discomfort	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Faecal incontinence	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Flatulence	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/8 (25%)	2	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Gastrooesophageal reflux disease	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Glossitis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Glossodynia	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Haematemesis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Haemorrhoids	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	2	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0
Lip dry	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Lip pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Mouth ulceration	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	4/33 (12.1%)	4	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Nausea	4/4 (100%)	6	5/8 (62.5%)	14	4/5 (80%)	4	1/3 (33.3%)	2	5/7 (71.4%)	6	2/6 (33.3%)	2	3/8 (37.5%)	4	3/5 (60%)	3	2/3 (66.7%)	4	1/3 (33.3%)	1	4/7 (57.1%)	6	7/8 (87.5%)	11	6/8 (75%)	9	16/33 (48.5%)	23	3/9 (33.3%)	4	4/9 (44.4%)	5	4/6 (66.7%)	4	2/3 (66.7%)	2
Oedema mouth	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Oesophageal pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Oral mucosal erythema	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Oral pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Paraesthesia oral	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Proctalgia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Retching	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Stomatitis	2/4 (50%)	2	0/8 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	3/8 (37.5%)	3	3/5 (60%)	4	2/3 (66.7%)	3	1/3 (33.3%)	1	1/7 (14.3%)	1	1/8 (12.5%)	1	1/8 (12.5%)	1	8/33 (24.2%)	9	1/9 (11.1%)	1	0/9 (0%)	0	2/6 (33.3%)	2	1/3 (33.3%)	1
Toothache	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Vomiting	4/4 (100%)	5	3/8 (37.5%)	4	5/5 (100%)	6	3/3 (100%)	6	2/7 (28.6%)	2	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	5/8 (62.5%)	12	5/8 (62.5%)	8	10/33 (30.3%)	15	2/9 (22.2%)	3	3/9 (33.3%)	4	2/6 (33.3%)	4	1/3 (33.3%)	1
General disorders
Application site vesicles	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Asthenia	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Catheter site related reaction	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Chest discomfort	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Chills	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	2	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Device occlusion	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Facial pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Fatigue	2/4 (50%)	2	7/8 (87.5%)	8	4/5 (80%)	5	2/3 (66.7%)	3	3/7 (42.9%)	4	2/6 (33.3%)	2	5/8 (62.5%)	5	1/5 (20%)	1	2/3 (66.7%)	3	2/3 (66.7%)	2	3/7 (42.9%)	3	5/8 (62.5%)	6	4/8 (50%)	6	23/33 (69.7%)	23	5/9 (55.6%)	6	3/9 (33.3%)	3	5/6 (83.3%)	5	0/3 (0%)	0
Influenza like illness	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Local swelling	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Localised oedema	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Mucosal inflammation	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	6/33 (18.2%)	7	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Non-cardiac chest pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Oedema peripheral	1/4 (25%)	1	2/8 (25%)	2	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	2/8 (25%)	2	0/8 (0%)	0	2/33 (6.1%)	2	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pelvic mass	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Peripheral swelling	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pyrexia	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	2	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	2/5 (40%)	3	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	2/8 (25%)	2	2/8 (25%)	4	1/33 (3%)	2	1/9 (11.1%)	2	1/9 (11.1%)	1	1/6 (16.7%)	1	1/3 (33.3%)	1
Hepatobiliary disorders
Hepatomegaly	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hyperbilirubinaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Infections and infestations
Candida infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Catheter site infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Cystitis	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Device related infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Ear infection	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Gastroenteritis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Herpes zoster	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Influenza	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Lower respiratory tract infection	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	3	4/33 (12.1%)	4	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Lung infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	2	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Nasopharyngitis	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Onychomycosis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Oral candidiasis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	3	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Oral herpes	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Otitis media	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	2	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Paronychia	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pelvic sepsis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pharyngitis	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Rash pustular	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Sinusitis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Soft tissue infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Upper respiratory tract infection	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	2	0/6 (0%)	0	2/8 (25%)	2	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	1/9 (11.1%)	1	1/6 (16.7%)	1	0/3 (0%)	0
Urinary tract infection	0/4 (0%)	0	3/8 (37.5%)	4	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	2/3 (66.7%)	4	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	4	3/9 (33.3%)	5	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Urinary tract infection enterococcal	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Viral infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Viral upper respiratory tract infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Vulvovaginal candidiasis	0/4 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Wound infection	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Wound infection staphylococcal	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Injury, poisoning and procedural complications
Anal injury	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Contusion	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Excoriation	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Fall	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Incision site pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Procedural pain	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Scar	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	2	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Skin wound	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Thermal burn	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Tooth fracture	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Wound	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Investigations
Alanine aminotransferase increased	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	2	1/8 (12.5%)	1	2/33 (6.1%)	2	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Aspartate aminotransferase increased	2/4 (50%)	2	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	3/33 (9.1%)	3	2/9 (22.2%)	2	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood alkaline phosphatase increased	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/8 (25%)	2	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	2/9 (22.2%)	2	1/9 (11.1%)	1	1/6 (16.7%)	1	0/3 (0%)	0
Blood bicarbonate increased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	2	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood bilirubin increased	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood calcium increased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood creatine phosphokinase increased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood creatinine increased	2/4 (50%)	2	1/8 (12.5%)	2	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	2	3/8 (37.5%)	5	3/33 (9.1%)	4	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood glucose increased	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Blood potassium increased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood triglycerides increased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood urea increased	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Blood urine present	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Body temperature increased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Breath sounds abnormal	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Electrocardiogram QT prolonged	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Electrocardiogram ST segment depression	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Electrocardiogram T wave inversion	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Fungal test positive	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Gamma-glutamyltransferase increased	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	4/9 (44.4%)	4	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Heart rate abnormal	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Pulmonary physical examination abnormal	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Visual field tests	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Weight decreased	2/4 (50%)	2	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	2/6 (33.3%)	2	0/8 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	2/33 (6.1%)	2	3/9 (33.3%)	3	2/9 (22.2%)	2	2/6 (33.3%)	2	0/3 (0%)	0
White blood cell count decreased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	4/4 (100%)	5	3/8 (37.5%)	4	4/5 (80%)	4	2/3 (66.7%)	3	5/7 (71.4%)	5	3/6 (50%)	3	5/8 (62.5%)	6	2/5 (40%)	2	1/3 (33.3%)	1	2/3 (66.7%)	2	2/7 (28.6%)	2	3/8 (37.5%)	3	4/8 (50%)	5	12/33 (36.4%)	14	4/9 (44.4%)	5	4/9 (44.4%)	5	2/6 (33.3%)	2	1/3 (33.3%)	1
Dehydration	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	2/9 (22.2%)	2	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Hypercalcaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	2	0/3 (0%)	0
Hypercholesterolaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	2/8 (25%)	2	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hyperglycaemia	1/4 (25%)	1	3/8 (37.5%)	3	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	2/8 (25%)	2	0/5 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	2/7 (28.6%)	3	4/8 (50%)	5	3/8 (37.5%)	3	2/33 (6.1%)	2	0/9 (0%)	0	1/9 (11.1%)	1	1/6 (16.7%)	1	2/3 (66.7%)	2
Hypernatraemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypertriglyceridaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypoalbuminaemia	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	3/33 (9.1%)	3	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Hypocalcaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypoglycaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypokalaemia	0/4 (0%)	0	2/8 (25%)	3	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	4	1/8 (12.5%)	1	1/5 (20%)	1	1/3 (33.3%)	1	1/3 (33.3%)	1	1/7 (14.3%)	1	2/8 (25%)	3	2/8 (25%)	2	5/33 (15.2%)	6	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Hypomagnesaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	1	1/8 (12.5%)	1	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hyponatraemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Hypophosphataemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	2	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	2/7 (28.6%)	3	2/8 (25%)	2	4/8 (50%)	10	0/33 (0%)	0	1/9 (11.1%)	1	1/9 (11.1%)	1	2/6 (33.3%)	3	0/3 (0%)	0
Polydipsia	0/4 (0%)	0	1/8 (12.5%)	2	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/4 (0%)	0	2/8 (25%)	2	1/5 (20%)	1	1/3 (33.3%)	1	1/7 (14.3%)	1	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Back pain	2/4 (50%)	2	1/8 (12.5%)	2	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	2	2/8 (25%)	2	6/33 (18.2%)	7	2/9 (22.2%)	4	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Chest wall mass	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Flank pain	1/4 (25%)	1	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	2	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Groin pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Joint swelling	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Muscle spasms	1/4 (25%)	1	2/8 (25%)	3	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Muscular weakness	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Musculoskeletal chest pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	5/33 (15.2%)	5	3/9 (33.3%)	3	2/9 (22.2%)	2	2/6 (33.3%)	2	2/3 (66.7%)	2
Musculoskeletal pain	1/4 (25%)	1	0/8 (0%)	0	2/5 (40%)	2	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	1/33 (3%)	2	1/9 (11.1%)	2	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Myalgia	1/4 (25%)	1	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Neck pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	2/9 (22.2%)	2	0/6 (0%)	0	0/3 (0%)	0
Pain in extremity	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pubic pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Infected neoplasm	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Lipoma	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Metastatic pain	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Neoplasm recurrence	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Tumour pain	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Nervous system disorders
Ataxia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Balance disorder	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Brachial plexopathy	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dizziness	0/4 (0%)	0	3/8 (37.5%)	5	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	0/33 (0%)	0	1/9 (11.1%)	1	2/9 (22.2%)	2	0/6 (0%)	0	1/3 (33.3%)	1
Dizziness postural	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dysgeusia	0/4 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	2	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	4/7 (57.1%)	4	1/8 (12.5%)	1	1/8 (12.5%)	1	5/33 (15.2%)	5	2/9 (22.2%)	2	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Dyskinesia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Facial neuralgia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Head discomfort	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Headache	0/4 (0%)	0	1/8 (12.5%)	2	1/5 (20%)	1	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	2	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	3/7 (42.9%)	4	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	2/6 (33.3%)	3	0/3 (0%)	0
Hypoaesthesia	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypokinesia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Lethargy	2/4 (50%)	4	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	3/8 (37.5%)	3	2/5 (40%)	2	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	4/33 (12.1%)	5	1/9 (11.1%)	1	1/9 (11.1%)	1	0/6 (0%)	0	1/3 (33.3%)	1
Loss of consciousness	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Meralgia paraesthetica	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Migraine	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	4	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Neuralgia	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Neuropathy peripheral	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Paraesthesia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Sciatica	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Sinus headache	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Somnolence	0/4 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	1/7 (14.3%)	1	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Psychiatric disorders
Anxiety	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Confusional state	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Depressed mood	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Depression	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hallucination	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Insomnia	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Libido decreased	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Renal and urinary disorders
Bladder spasm	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dysuria	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	0/8 (0%)	0	2/8 (25%)	2	1/33 (3%)	1	2/9 (22.2%)	2	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Haematuria	0/4 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hyperphosphaturia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Nocturia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	2/33 (6.1%)	3	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pollakiuria	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	2/33 (6.1%)	4	1/9 (11.1%)	1	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Polyuria	0/4 (0%)	0	1/8 (12.5%)	2	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Proteinuria	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Renal failure acute	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	2/9 (22.2%)	2	0/6 (0%)	0	0/3 (0%)	0
Renal impairment	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Urinary incontinence	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Reproductive system and breast disorders
Breast pain	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dysmenorrhoea	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pelvic pain	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Scrotal oedema	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Vaginal discharge	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Catarrh	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Chronic obstructive pulmonary disease	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Cough	0/4 (0%)	0	3/8 (37.5%)	3	0/5 (0%)	0	0/3 (0%)	0	3/7 (42.9%)	4	3/6 (50%)	3	0/8 (0%)	0	1/5 (20%)	1	1/3 (33.3%)	1	0/3 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	1	1/8 (12.5%)	2	8/33 (24.2%)	8	1/9 (11.1%)	1	0/9 (0%)	0	3/6 (50%)	4	0/3 (0%)	0
Dysphonia	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	2/6 (33.3%)	4	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	2/9 (22.2%)	2	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dyspnoea	1/4 (25%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	2/7 (28.6%)	2	1/6 (16.7%)	1	1/8 (12.5%)	1	1/5 (20%)	1	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	2/8 (25%)	3	1/8 (12.5%)	1	6/33 (18.2%)	7	1/9 (11.1%)	1	0/9 (0%)	0	1/6 (16.7%)	1	1/3 (33.3%)	1
Dyspnoea exertional	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	4	1/9 (11.1%)	1	3/9 (33.3%)	3	1/6 (16.7%)	1	0/3 (0%)	0
Haemoptysis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hyperoxia	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Oropharyngeal pain	1/4 (25%)	1	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	3/33 (9.1%)	3	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Pleural effusion	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pneumonitis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pneumothorax	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pulmonary embolism	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1
Rhinorrhoea	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Wheezing	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	1/5 (20%)	1	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Skin and subcutaneous tissue disorders
Decubitus ulcer	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dermatitis acneiform	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Drug eruption	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Dry skin	0/4 (0%)	0	2/8 (25%)	2	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	2/8 (25%)	2	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	1/8 (12.5%)	1	1/8 (12.5%)	1	4/33 (12.1%)	4	2/9 (22.2%)	2	1/9 (11.1%)	1	0/6 (0%)	0	1/3 (33.3%)	1
Eczema	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	2/33 (6.1%)	2	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Erythema	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	2/8 (25%)	2	3/5 (60%)	3	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Ingrowing nail	0/4 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Nail growth abnormal	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Night sweats	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Onycholysis	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pruritus	0/4 (0%)	0	2/8 (25%)	2	1/5 (20%)	1	2/3 (66.7%)	2	1/7 (14.3%)	1	0/6 (0%)	0	2/8 (25%)	2	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	9/33 (27.3%)	10	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Pruritus allergic	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Rash	0/4 (0%)	0	3/8 (37.5%)	3	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	2/8 (25%)	2	1/5 (20%)	1	0/3 (0%)	0	1/3 (33.3%)	1	1/7 (14.3%)	1	0/8 (0%)	0	1/8 (12.5%)	1	10/33 (30.3%)	16	2/9 (22.2%)	2	2/9 (22.2%)	2	0/6 (0%)	0	0/3 (0%)	0
Rash erythematous	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Rash macular	0/4 (0%)	0	0/8 (0%)	0	1/5 (20%)	2	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/6 (0%)	0	0/3 (0%)	0
Rash maculo-papular	0/4 (0%)	0	1/8 (12.5%)	1	1/5 (20%)	1	0/3 (0%)	0	2/7 (28.6%)	2	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	1	3/33 (9.1%)	3	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Rash papular	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Rash pruritic	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	1/7 (14.3%)	1	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Skin fissures	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Skin hypertrophy	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Skin ulcer	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Urticaria	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Vascular disorders
Flushing	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Haemorrhage	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Hypertension	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	2	0/6 (0%)	0	0/3 (0%)	0
Hypotension	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	1/3 (33.3%)	1	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	3	2/33 (6.1%)	2	1/9 (11.1%)	1	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Lymphoedema	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/33 (3%)	1	0/9 (0%)	0	0/9 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0
Peripheral ischaemia	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	1/6 (16.7%)	1	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Thrombophlebitis	0/4 (0%)	0	1/8 (12.5%)	1	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0
Vasodilatation	0/4 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/6 (0%)	0	0/8 (0%)	0	0/5 (0%)	0	0/3 (0%)	0	0/3 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/33 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/6 (0%)	0	0/3 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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