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Clinical Trial Results:
A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled, and Open-label Comparator Study of Cotadutide in Participants Who Have Chronic Kidney Disease with Type 2 Diabetes.

Summary
EudraCT number	2020-000255-12
Trial protocol	GB DE
Global end of trial date	08 Mar 2022

Results information
Results version number	v2(current)
This version publication date	21 Mar 2025
First version publication date	20 Mar 2023
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

D5676C00001

ISRCTN number

US NCT number

NCT04515849

WHO universal trial number (UTN)

Sponsor organisation name

AstraZeneca

Sponsor organisation address

Granta Park, Cambridge, United Kingdom, CB21 6GH

Public contact

Global Clinical Lead, AstraZeneca, +1 18772409479, information.center@astrazeneca.com

Scientific contact

Global Clinical Lead, AstraZeneca, +1 18772409479, information.center@astrazeneca.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

21 Jun 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

08 Mar 2022

Global end of trial reached?

Yes

Global end of trial date

08 Mar 2022

Was the trial ended prematurely?

Main objective of the trial

This Phase 2b study is designed to evaluate the efficacy, safety, tolerability, and pharmacokinetic (PK) profile of cotadutide at different dose levels in participants who have CKD with T2DM.

Protection of trial subjects

In the study, fasting was minimised and continuous glucose monitoring (CGM) was used instead of more invasive glucose measures to reduce participant discomfort.

Background therapy

Evidence for comparator

Actual start date of recruitment

31 Aug 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Japan: 26

Country: Number of subjects enrolled

Spain: 61

Country: Number of subjects enrolled

Germany: 34

Country: Number of subjects enrolled

Poland: 16

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

Canada: 59

Country: Number of subjects enrolled

New Zealand: 31

Country: Number of subjects enrolled

Australia: 18

Worldwide total number of subjects

248

EEA total number of subjects

111

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

171

85 years and over

Subject disposition

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Recruitment details

This study was conducted at 79 participating sites in Canada, Australia, New Zealand, Japan, Germany, Poland, Spain and United Kingdom. First subject enrolled 31st August 2020. Last subject last visit: 28th June 2021.

Screening details

This is a parallel treatment, double-blind study with 5 arms.The study had a 14-day run-in period during which participants will be given advice on diet and exercise and asked to wear a CGM sensor, followed by a 26-week treatment period and 28-day follow-up period.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Carer, Data analyst, Assessor, Subject

Are arms mutually exclusive

Yes

Cotadutide 100 ug

Arm description

Participants randomised to Cotadutide 100 ug daily

Arm type

Experimental

Investigational medicinal product name

Cotadutide 100 ug

Investigational medicinal product code

MEDI0382

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

100 ug, subcutaneous

Cotadutide 300 ug

Arm description

Participants randomised to Cotadutide 300 ug daily

Arm type

Experimental

Investigational medicinal product name

Cotadutide 300 ug

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

300 ug, Subcutaneous

Cotadutide 600 ug

Arm description

Participants randomised to Cotadutide 600 ug daily

Arm type

Experimental

Investigational medicinal product name

Cotadutide 600 ug

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

600 ug, subcutaneous

Placebo

Arm description

Participants randomised to placebo daily

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection in pre-filled pen

Routes of administration

Subcutaneous use

Dosage and administration details

subcutaneous

Semaglutide 1 mg

Arm description

Participants radomised to active comparator daily

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 1	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo	Semaglutide 1 mg
Started	52	49	51	51	45
Completed	49	45	50	48	43
Not completed	3	4	1	3	2
Adverse event, serious fatal	2	-	-	-	1
Consent withdrawn by subject	1	2	1	-	-
Other:randomised by error	-	1	-	-	-
Adverse event, non-fatal	-	-	-	1	-
Other:family emergency	-	-	-	1	-
Protocol deviation	-	1	-	-	1

Baseline characteristics

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Reporting group title

Cotadutide 100 ug

Reporting group description

Participants randomised to Cotadutide 100 ug daily

Reporting group title

Cotadutide 300 ug

Reporting group description

Participants randomised to Cotadutide 300 ug daily

Reporting group title

Cotadutide 600 ug

Reporting group description

Participants randomised to Cotadutide 600 ug daily

Reporting group title

Placebo

Reporting group description

Participants randomised to placebo daily

Reporting group title

Semaglutide 1 mg

Reporting group description

Participants radomised to active comparator daily

Reporting group values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo	Semaglutide 1 mg	Total
Number of subjects	52	49	51	51	45	248
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0
Adults (18-64 years)	17	13	23	10	14	77
From 65-84 years	35	36	28	41	31	171
85 years and over	0	0	0	0	0	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	67.2 ( 7.3 )	65.7 ( 8.8 )	66.1 ( 7.4 )	69.5 ( 7.3 )	67.0 ( 7.8 )	-
Sex: Female, Male
Units: Participants
Female	9	3	10	13	12	47
Male	43	46	41	38	33	201
Race (NIH/OMB)
Units: Subjects
AMERICAN INDIAN OR ALASKA NATIVE	0	0	0	0	0	0
ASIAN	10	10	13	10	2	45
BLACK OR AFRICAN AMERICAN	2	0	0	1	2	5
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	2	0	1	1	0	4
OTHER	0	3	1	0	0	4
WHITE	38	36	36	39	41	190

Subject analysis set title

ITT

Subject analysis set type

Intention-to-treat

Subject analysis set description

Intent to treat

Subject analysis sets values	ITT
Number of subjects	248
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	171
From 65-84 years	77
85 years and over	0
Age Continuous
Units: Years
arithmetic mean (standard deviation)	67.1 ( 7.8 )
Sex: Female, Male
Units: Participants
Female
Male
Race (NIH/OMB)
Units: Subjects
AMERICAN INDIAN OR ALASKA NATIVE
ASIAN
BLACK OR AFRICAN AMERICAN
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER
OTHER
WHITE

End points

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Reporting group title

Cotadutide 100 ug

Reporting group description

Participants randomised to Cotadutide 100 ug daily

Reporting group title

Cotadutide 300 ug

Reporting group description

Participants randomised to Cotadutide 300 ug daily

Reporting group title

Cotadutide 600 ug

Reporting group description

Participants randomised to Cotadutide 600 ug daily

Reporting group title

Placebo

Reporting group description

Participants randomised to placebo daily

Reporting group title

Semaglutide 1 mg

Reporting group description

Participants radomised to active comparator daily

Subject analysis set title

ITT

Subject analysis set type

Intention-to-treat

Subject analysis set description

Intent to treat

Primary: Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks

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End point title

Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks ^[1] ^[2]

End point description

Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks. Efficacy endpoints for cotadutide vs. semaglutide are exploratory and are therefore excluded.

End point type

Primary

End point timeframe

Baseline to the end of 14 weeks of dosing

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	49	43	37	43
Units: UACR ratio
least squares mean (confidence interval 95%)	-10.96 (-29.60 to 12.61)	-40.47 (-53.00 to -24.60)	-44.60 (-56.21 to -29.91)	4.60 (-18.02 to 33.46)

No statistical analyses for this end point

Secondary: Percentage change in UACR of cotadutide at different dose levels compared to placebo after 26 weeks

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End point title

Percentage change in UACR of cotadutide at different dose levels compared to placebo after 26 weeks ^[3]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 26 weeks of dosing

Notes
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	49	46	48	49
Units: UACR ratio
least squares mean (confidence interval 95%)	-17.85 (-45.47 to 23.78)	-38.68 (-59.61 to -6.88)	-57.87 (-73.33 to -33.34)	11.79 (-27.85 to 73.22)

No statistical analyses for this end point

Secondary: Percent change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 14 weeks of dosing

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End point title

Percent change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 14 weeks of dosing ^[4]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 14 weeks of dosing

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	37	32	27	35
Units: Absolute value
least squares mean (standard error)	-2.84 ( 0.65 )	-4.15 ( 0.68 )	-5.40 ( 0.73 )	-1.61 ( 0.66 )

No statistical analyses for this end point

Secondary: Percentage change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 26 weeks of dosing

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End point title

Percentage change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 26 weeks of dosing ^[5]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 26 weeks of dosing

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	37	33	27	35
Units: Absolute value
least squares mean (standard error)	-2.60 ( 0.89 )	-5.45 ( 0.92 )	-7.35 ( 0.99 )	-2.23 ( 0.90 )

No statistical analyses for this end point

Secondary: Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 14 of dosing

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End point title

Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 14 of dosing ^[6]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 14 weeks of dosing

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	49	45	48	39
Units: Percent change
least squares mean (standard error)	-0.76 ( 0.12 )	-0.82 ( 0.12 )	-0.65 ( 0.12 )	-0.08 ( 0.12 )

No statistical analyses for this end point

Secondary: Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 26 of dosing

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End point title

Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 26 of dosing ^[7]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 26 weeks of dosing

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	49	46	48	39
Units: Percent change
least squares mean (standard error)	-0.92 ( 0.11 )	-0.92 ( 0.11 )	-0.89 ( 0.11 )	-0.25 ( 0.11 )

No statistical analyses for this end point

Secondary: Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 26 weeks of dosing

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End point title

Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 26 weeks of dosing ^[8]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 26 weeks of dosing

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	45	43	39	45
Units: mmol/L
least squares mean (standard error)	-1.78 ( 0.36 )	-1.76 ( 0.37 )	-1.57 ( 0.39 )	-0.72 ( 0.37 )

No statistical analyses for this end point

Secondary: Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 14 weeks of dosing

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End point title

Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 14 weeks of dosing ^[9]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 14 weeks of dosing

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	42	45	48	49
Units: mmol/L
least squares mean (standard error)	-1.35 ( 0.37 )	-1.57 ( 0.35 )	-1.69 ( 0.40 )	-0.54 ( 0.37 )

No statistical analyses for this end point

Secondary: Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 26 weeks of dosing

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End point title

Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 26 weeks of dosing ^[10]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 26 weeks of dosing

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	25	18	22	30
Units: Percent change
least squares mean (standard error)	-1.735 ( 0.307 )	-1.446 ( 0.334 )	-1.118 ( 0.321 )	-0.273 ( 0.290 )

No statistical analyses for this end point

Secondary: Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 14 weeks of dosing

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End point title

Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 14 weeks of dosing ^[11]

End point description

End point type

Secondary

End point timeframe

Baseline to 14 weeks of dosing

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	30	25	26	30
Units: Percent Change
least squares mean (standard error)	-13.87 ( 3.35 )	-15.79 ( 3.55 )	-13.90 ( 3.52 )	-4.09 ( 3.27 )

No statistical analyses for this end point

Secondary: Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 14 weeks of dosing

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End point title

Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 14 weeks of dosing ^[12]

End point description

End point type

Secondary

End point timeframe

Baseline to end of 14 weeks of dosing

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	30	25	26	30
Units: Percent change
least squares mean (standard error)	-1.556 ( 0.320 )	-1.478 ( 0.337 )	-1.269 ( 0.334 )	-0.440 ( 0.311 )

No statistical analyses for this end point

Secondary: Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 26 weeks of dosing

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End point title

Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 26 weeks of dosing ^[13]

End point description

End point type

Secondary

End point timeframe

Baseline to 26 weeks of dosing

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: In this study, the efficacy efficacy endpoints vs. semaglutide are exploratory and were therefore excluded

End point values	Cotadutide 100 ug	Cotadutide 300 ug	Cotadutide 600 ug	Placebo
Number of subjects analysed	25	18	22	27
Units: Percent change
least squares mean (standard error)	-18.06 ( 3.33 )	-15.38 ( 3.76 )	-11.91 ( 3.51 )	-3.00 ( 3.17 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose of study drug until last study visit

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Cotadutide 300 ug

Reporting group description

Reporting group title

Placebo

Reporting group description

Reporting group title

Semaglutide 1 mg

Reporting group description

Reporting group title

Cotadutide 600 ug

Reporting group description

Reporting group title

Cotadutide 100 ug

Reporting group description

Serious adverse events	Cotadutide 300 ug	Placebo	Semaglutide 1 mg	Cotadutide 600 ug	Cotadutide 100 ug
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 48 (10.42%)	5 / 51 (9.80%)	4 / 45 (8.89%)	5 / 48 (10.42%)	5 / 55 (9.09%)
number of deaths (all causes)	0	0	0	0	2
number of deaths resulting from adverse events	0	0	0	0	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Hypoxia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary mass
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suspected suicide
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Adjustment disorder with anxiety
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Humerus fracture
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Coronary artery disease
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Nervous system disorders
Ischaemic stroke
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Vomiting
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Groin pain
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Diverticulitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vestibular neuronitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Ketosis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Cotadutide 300 ug	Placebo	Semaglutide 1 mg	Cotadutide 600 ug	Cotadutide 100 ug
Total subjects affected by non serious adverse events
subjects affected / exposed	38 / 48 (79.17%)	38 / 51 (74.51%)	39 / 45 (86.67%)	38 / 48 (79.17%)	43 / 55 (78.18%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Haemangioma of liver
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Adrenal neoplasm
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
B-cell lymphoma stage III
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Vascular disorders
Aortic stenosis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Haematoma
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Hot flush
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Hypertension
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	1
Hypotension
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	5 / 45 (11.11%)	3 / 48 (6.25%)	0 / 55 (0.00%)
occurrences all number	1	0	5	4	0
Surgical and medical procedures
Skin neoplasm excision
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Meniscus removal
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Tooth extraction
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
General disorders and administration site conditions
Injection site erythema
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	1
Injection site induration
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Injection site pain
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	1	0	0	1	1
Injection site pruritus
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	1
Asthenia
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	2 / 45 (4.44%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	2	0	2	0	0
Chest pain
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	1
Early satiety
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	0	0	0	2	0
Fatigue
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	1 / 45 (2.22%)	1 / 48 (2.08%)	3 / 55 (5.45%)
occurrences all number	0	1	1	1	3
Injection site bruising
subjects affected / exposed	1 / 48 (2.08%)	2 / 51 (3.92%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	2	0	0	0
Injection site reaction
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	1	0	0	2
Malaise
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	1
Vaccination site pain
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	2	1	0	2	0
Oedema
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Oedema peripheral
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	1 / 45 (2.22%)	0 / 48 (0.00%)	2 / 55 (3.64%)
occurrences all number	1	1	1	0	2
Pain
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	1
Peripheral swelling
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Puncture site haemorrhage
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Pyrexia
subjects affected / exposed	0 / 48 (0.00%)	3 / 51 (5.88%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	3	1	0	0
Reproductive system and breast disorders
Breast tenderness
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea
subjects affected / exposed	1 / 48 (2.08%)	2 / 51 (3.92%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	2	0	0	0
Allergic cough
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Atelectasis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Bronchiectasis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	2
Cough
subjects affected / exposed	1 / 48 (2.08%)	3 / 51 (5.88%)	0 / 45 (0.00%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	1	3	0	2	0
Dyspnoea exertional
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	1	0	1	0
Epistaxis
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	3	0	0	1	0
Nasal congestion
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 48 (2.08%)	2 / 51 (3.92%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	2	0	0	1
Pulmonary congestion
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Rales
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	0	1	0	1	1
Sinus congestion
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Sneezing
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Pulmonary mass
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Psychiatric disorders
Depressed mood
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Cardiovascular somatic symptom disorder
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Irritability
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Insomnia
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	2 / 55 (3.64%)
occurrences all number	1	0	0	0	2
Depression
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Investigations
Amylase increased
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0	0
Blood calcium increased
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Blood bicarbonate increased
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Blood bicarbonate decreased
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	1	0	3	0
Blood creatinine increased
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	2	0	0	0	0
Blood glucose increased
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Blood pressure increased
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Blood pressure decreased
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Blood potassium increased
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	1	0	1
Blood sodium increased
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Cardiac murmur
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Ejection fraction decreased
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Electrocardiogram change
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Pulse absent
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Lipase increased
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0	0
Occult blood positive
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Pedal pulse decreased
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Pulmonary arterial pressure increased
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Glomerular filtration rate decreased
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	2 / 45 (4.44%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	2	0	0
Urine output increased
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Ventricular internal diameter
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Weight decreased
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	1	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	0	0	0	3	1
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Rib fracture
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Procedural pain
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	2	0	0	0	0
Muscle strain
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Limb injury
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	1
Ligament sprain
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Ligament rupture
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Heat stroke
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Heat illness
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	6	0	0	0	0
Fall
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	1	1	0	1	0
Epicondylitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Costal cartilage fracture
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Contusion
subjects affected / exposed	2 / 48 (4.17%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	3	1	0	0	0
Arthropod bite
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Wrist fracture
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Vaccination complication
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Tibia fracture
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Skin wound
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Skin pressure mark
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Skin laceration
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0	0
Skin abrasion
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0	0
Thoracic vertebral fracture
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	0	0	0	2	0
Angina unstable
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Mitral valve incompetence
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Atrial flutter
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Atrioventricular block first degree
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	4	0	0	0	0
Atrioventricular block second degree
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Cardiac septal hypertrophy
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Conduction disorder
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Palpitations
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	0	1	0	1	1
Pericardial effusion
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Sinus tachycardia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Tachycardia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Ventricular tachycardia
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Nervous system disorders
Lethargy
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Akinesia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Cognitive disorder
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Dizziness
subjects affected / exposed	4 / 48 (8.33%)	1 / 51 (1.96%)	1 / 45 (2.22%)	2 / 48 (4.17%)	1 / 55 (1.82%)
occurrences all number	4	1	1	2	1
Dizziness postural
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	1
Headache
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	2 / 45 (4.44%)	3 / 48 (6.25%)	1 / 55 (1.82%)
occurrences all number	1	2	2	5	1
Ischaemic stroke
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Migraine
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Myelopathy
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Neuralgia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Polyneuropathy
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Presyncope
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	1	0	0	1	0
Sciatica
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Syncope
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	1	0	0
Restless legs syndrome
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	0	0	0	2
Blood loss anaemia
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Eye disorders
Eye haemorrhage
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Cataract
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Diabetic retinopathy
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	1
Eye pain
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Glaucoma
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Macular oedema
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Retinal haemorrhage
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Vitreous detachment
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Vitreous floaters
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 45 (2.22%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	1	0	1	1	0
Abdominal discomfort
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Abdominal pain
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	1 / 45 (2.22%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	1	1	1	2	0
Abdominal pain upper
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	1 / 45 (2.22%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	2	0	1	2	0
Chronic gastritis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Constipation
subjects affected / exposed	2 / 48 (4.17%)	2 / 51 (3.92%)	3 / 45 (6.67%)	5 / 48 (10.42%)	7 / 55 (12.73%)
occurrences all number	3	3	4	7	7
Diarrhoea
subjects affected / exposed	7 / 48 (14.58%)	4 / 51 (7.84%)	7 / 45 (15.56%)	6 / 48 (12.50%)	5 / 55 (9.09%)
occurrences all number	10	8	9	9	5
Dyspepsia
subjects affected / exposed	4 / 48 (8.33%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	5	0	0	0	1
Nausea
subjects affected / exposed	7 / 48 (14.58%)	5 / 51 (9.80%)	12 / 45 (26.67%)	14 / 48 (29.17%)	6 / 55 (10.91%)
occurrences all number	9	5	23	18	7
Faeces hard
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Flatulence
subjects affected / exposed	2 / 48 (4.17%)	1 / 51 (1.96%)	0 / 45 (0.00%)	2 / 48 (4.17%)	1 / 55 (1.82%)
occurrences all number	2	1	0	2	1
Gastrointestinal disorder
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	3 / 45 (6.67%)	3 / 48 (6.25%)	1 / 55 (1.82%)
occurrences all number	2	0	4	3	1
Haemorrhoids
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Large intestine polyp
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	0	0	1
Eructation
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	1	0	0
Oral lichen planus
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Toothache
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	2 / 48 (4.17%)	2 / 55 (3.64%)
occurrences all number	0	0	0	2	2
Vomiting
subjects affected / exposed	3 / 48 (6.25%)	2 / 51 (3.92%)	7 / 45 (15.56%)	7 / 48 (14.58%)	2 / 55 (3.64%)
occurrences all number	4	2	9	12	2
Hepatobiliary disorders
Hepatomegaly
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Hepatic cirrhosis
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	1	0	3	0
Actinic keratosis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Blister
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Dermal cyst
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Dermatitis contact
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Diabetic foot
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	1	0	0	1	0
Dry skin
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Eczema
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Lichenification
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Macule
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Night sweats
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Pruritus
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Rash
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	1	0	0	1	1
Scab
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Skin exfoliation
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Skin ulcer
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	3	0	0	1	0
Renal and urinary disorders
Nocturia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Pollakiuria
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Polyuria
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Urinary hesitation
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Urinary incontinence
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Renal mass
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Endocrine disorders
Thyroid mass
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Musculoskeletal and connective tissue disorders
Pain in jaw
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Pain in extremity
subjects affected / exposed	0 / 48 (0.00%)	3 / 51 (5.88%)	1 / 45 (2.22%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	3	1	0	1
Myalgia
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	2 / 45 (4.44%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	4	0	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Muscle spasms
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	1	0	1	0	1
Joint contracture
subjects affected / exposed	2 / 48 (4.17%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	2	0	0	0	0
Flank pain
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	2	0	0	0	0
Back pain
subjects affected / exposed	2 / 48 (4.17%)	4 / 51 (7.84%)	2 / 45 (4.44%)	3 / 48 (6.25%)	2 / 55 (3.64%)
occurrences all number	2	4	2	3	2
Arthritis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Arthralgia
subjects affected / exposed	1 / 48 (2.08%)	3 / 51 (5.88%)	1 / 45 (2.22%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	1	3	2	2	0
Joint swelling
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Tenosynovitis
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Spinal pain
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Onychomycosis
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 48 (0.00%)	3 / 51 (5.88%)	3 / 45 (6.67%)	0 / 48 (0.00%)	2 / 55 (3.64%)
occurrences all number	0	3	3	0	2
Lower respiratory tract infection
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Localised infection
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	1
Giardiasis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	1	0	0
Fungal skin infection
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Eye infection
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Cystitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Conjunctivitis
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	2	1	0	1	0
Cellulitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	0	0	0	1	1
Paronychia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	1	0	1
Vestibular neuronitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	0	1	0
Urinary tract infection
subjects affected / exposed	3 / 48 (6.25%)	1 / 51 (1.96%)	2 / 45 (4.44%)	2 / 48 (4.17%)	0 / 55 (0.00%)
occurrences all number	3	2	2	2	0
Upper respiratory tract infection
subjects affected / exposed	1 / 48 (2.08%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	1	0	0	0
Tooth abscess
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	1	0	1	0
Vulvovaginal candidiasis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Tinea infection
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Sinusitis
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Rhinitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Periodontitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Tonsillitis
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
COVID-19
subjects affected / exposed	1 / 48 (2.08%)	2 / 51 (3.92%)	2 / 45 (4.44%)	1 / 48 (2.08%)	2 / 55 (3.64%)
occurrences all number	1	2	2	1	2
Asymptomatic COVID-19
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	0	0	0	1
Metabolism and nutrition disorders
Hypoglycaemia
subjects affected / exposed	16 / 48 (33.33%)	13 / 51 (25.49%)	4 / 45 (8.89%)	13 / 48 (27.08%)	13 / 55 (23.64%)
occurrences all number	106	148	28	83	88
Hypervolaemia
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	2	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	1 / 55 (1.82%)
occurrences all number	0	1	0	0	1
Hypernatraemia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	0	0	0	1	1
Hyperkalaemia
subjects affected / exposed	1 / 48 (2.08%)	2 / 51 (3.92%)	3 / 45 (6.67%)	1 / 48 (2.08%)	1 / 55 (1.82%)
occurrences all number	1	2	3	1	1
Hyperglycaemia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	1 / 48 (2.08%)	2 / 55 (3.64%)
occurrences all number	0	0	1	1	2
Hypercalcaemia
subjects affected / exposed	0 / 48 (0.00%)	1 / 51 (1.96%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	1	0	0	0
Gout
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	0 / 45 (0.00%)	1 / 48 (2.08%)	2 / 55 (3.64%)
occurrences all number	0	0	0	1	2
Electrolyte imbalance
subjects affected / exposed	1 / 48 (2.08%)	0 / 51 (0.00%)	0 / 45 (0.00%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	1	0	0	0	0
Decreased appetite
subjects affected / exposed	3 / 48 (6.25%)	1 / 51 (1.96%)	8 / 45 (17.78%)	5 / 48 (10.42%)	0 / 55 (0.00%)
occurrences all number	3	1	8	5	0
Hypophagia
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	0 / 48 (0.00%)	0 / 55 (0.00%)
occurrences all number	0	0	1	0	0
Iron deficiency
subjects affected / exposed	0 / 48 (0.00%)	0 / 51 (0.00%)	1 / 45 (2.22%)	1 / 48 (2.08%)	0 / 55 (0.00%)
occurrences all number	0	0	1	1	0

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Were there any global substantial amendments to the protocol? Yes

29 Jun 2020

This global amendment contains revisions to the original global protocol dated (01Apr2020) to remove Cohort 2, which is no longer needed due to completion of Study D5671C00003 earlier than originally planned. Other minor revisions such as clarifications and correction of typos were made. This amendment is considered to be non-substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European Union because it neither significantly impacts the safety or physical/mental integrity of participants nor the scientific value of the study.

04 Jan 2021

This global amendment contains revisions to Amendment 1 of the global protocol dated (29Jun2020) to add time windows for specific visits to make the study more accessible to participants during the current coronavirus disease (COVID-19) pandemic. Other minor revisions such as clarifications and correction of typos were made. This amendment is considered to be non-substantial based on the criteria set forth in Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the European Union because it neither significantly impacts the safety or physical/mental integrity of participants nor the scientific value of the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/39218393

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Clinical trials

Clinical Trial Results: A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled, and Open-label Comparator Study of Cotadutide in Participants Who Have Chronic Kidney Disease with Type 2 Diabetes.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks

Primary: Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks

Secondary: Percentage change in UACR of cotadutide at different dose levels compared to placebo after 26 weeks

Secondary: Percentage change in UACR of cotadutide at different dose levels compared to placebo after 26 weeks

Secondary: Percent change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 14 weeks of dosing

Secondary: Percent change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 14 weeks of dosing

Secondary: Percentage change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 26 weeks of dosing

Secondary: Percentage change in body weight of cotatudide at different dose levels versus placebo from baseline to end of 26 weeks of dosing

Secondary: Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 14 of dosing

Secondary: Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 14 of dosing

Secondary: Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 26 of dosing

Secondary: Percent change in HbA1c of cotadutide at different dose levels versus placebo from baseline to the end of 26 of dosing

Secondary: Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 26 weeks of dosing

Secondary: Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 26 weeks of dosing

Secondary: Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 14 weeks of dosing

Secondary: Change in fasting glucose of cotadutide at different dose levels from baseline versus placebo after 14 weeks of dosing

Secondary: Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 26 weeks of dosing

Secondary: Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 26 weeks of dosing

Secondary: Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 14 weeks of dosing

Secondary: Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 14 weeks of dosing

Secondary: Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 14 weeks of dosing

Secondary: Change in 10-day average glucose levels of cotadutide at different dose levels versus placebo from baseline to end of 14 weeks of dosing

Secondary: Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 26 weeks of dosing

Secondary: Change in percentage time spent in hyperglycaemia over 10 days of cotadutide at different dose levels compared to placebo after 26 weeks of dosing

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled, and Open-label Comparator Study of Cotadutide in Participants Who Have Chronic Kidney Disease with Type 2 Diabetes.