Trial Outcomes & Findings for The Effect of Glucagon-like-peptide 1 (GLP-1) Receptor Agonism on Diabetic Kidney Disease (NCT NCT01847313)

NCT ID: NCT01847313

Last Updated: 2019-02-08

Results Overview

Spot urine sample for MCP-1 and creatinine

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 20 participants
• Primary outcome timeframe: Up to 26 weeks
• Results posted on: 2019-02-08

Participant Flow

All subjects were recruited from St Vincent's University Hospital, Dublin, Ireland

Participant milestones

Measure	Liraglutide Liraglutide 0.6 mg daily administration for 6 months	Control Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
Overall Study STARTED	10	10
Overall Study COMPLETED	10	8
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Liraglutide Liraglutide 0.6 mg daily administration for 6 months	Control Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
Overall Study Death	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Liraglutide n=10 Participants Liraglutide 0.6 mg daily administration for 6 months	Control n=10 Participants Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist	Total n=20 Participants Total of all reporting groups
Age, Continuous	65 years STANDARD_DEVIATION 7 • n=10 Participants	64 years STANDARD_DEVIATION 10 • n=10 Participants	65 years STANDARD_DEVIATION 9 • n=20 Participants
Sex: Female, Male Female	3 Participants n=10 Participants	3 Participants n=10 Participants	6 Participants n=20 Participants
Sex: Female, Male Male	7 Participants n=10 Participants	7 Participants n=10 Participants	14 Participants n=20 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Ireland	10 Participants n=10 Participants	10 Participants n=10 Participants	20 Participants n=20 Participants
BMI	30 kg/m2 STANDARD_DEVIATION 5 • n=10 Participants	34 kg/m2 STANDARD_DEVIATION 4 • n=10 Participants	32 kg/m2 STANDARD_DEVIATION 5 • n=20 Participants
Duration of diabetes	8 years STANDARD_DEVIATION 1 • n=10 Participants	9 years STANDARD_DEVIATION 2 • n=10 Participants	9 years STANDARD_DEVIATION 2 • n=20 Participants
HbA1c	53 mmol/mol STANDARD_DEVIATION 7 • n=10 Participants	52 mmol/mol STANDARD_DEVIATION 7 • n=10 Participants	53 mmol/mol STANDARD_DEVIATION 7 • n=20 Participants
Systolic blood pressure	136 mmHg STANDARD_DEVIATION 14 • n=10 Participants	140 mmHg STANDARD_DEVIATION 20 • n=10 Participants	138 mmHg STANDARD_DEVIATION 17 • n=20 Participants
Diastolic Blood Pressure	82 mmHg STANDARD_DEVIATION 8 • n=10 Participants	81 mmHg STANDARD_DEVIATION 12 • n=10 Participants	81 mmHg STANDARD_DEVIATION 10 • n=20 Participants
Estimated glomerular filtration rate	69 ml/min/1.73m2 STANDARD_DEVIATION 7 • n=10 Participants	79 ml/min/1.73m2 STANDARD_DEVIATION 11 • n=10 Participants	74 ml/min/1.73m2 STANDARD_DEVIATION 10 • n=20 Participants
Urinary albumin excretion rate	106.9 µg/min STANDARD_DEVIATION 109.5 • n=10 Participants	122.8 µg/min STANDARD_DEVIATION 142.1 • n=10 Participants	114.9 µg/min STANDARD_DEVIATION 123.7 • n=20 Participants
MCP-1:Creatinine Ratio in Urine	32.8 ng/mmol STANDARD_DEVIATION 25.7 • n=9 Participants • Liraglutide group contained an analytical outlier which was excluded from further analysis.	20.8 ng/mmol STANDARD_DEVIATION 6.0 • n=8 Participants • Liraglutide group contained an analytical outlier which was excluded from further analysis.	27.2 ng/mmol STANDARD_DEVIATION 19.6 • n=17 Participants • Liraglutide group contained an analytical outlier which was excluded from further analysis.
sCD163:creatinine ratio in urine	51 pg/mmol STANDARD_DEVIATION 60 • n=10 Participants • Baseline measure not reported for subjects that died or withdrew	37 pg/mmol STANDARD_DEVIATION 38 • n=8 Participants • Baseline measure not reported for subjects that died or withdrew	44 pg/mmol STANDARD_DEVIATION 51 • n=18 Participants • Baseline measure not reported for subjects that died or withdrew
sCD163 in serum	96 ng/ml STANDARD_DEVIATION 45 • n=10 Participants • Measure Analysis Population Description: Baseline measure not reported for subjects that died or withdrew	106 ng/ml STANDARD_DEVIATION 47 • n=8 Participants • Measure Analysis Population Description: Baseline measure not reported for subjects that died or withdrew	100 ng/ml STANDARD_DEVIATION 45 • n=18 Participants • Measure Analysis Population Description: Baseline measure not reported for subjects that died or withdrew

PRIMARY outcome

Timeframe: Up to 26 weeks

Population: Liraglutide group contained an analytical outlier which was excluded from further analysis.

Spot urine sample for MCP-1 and creatinine

Outcome measures

Measure	Liraglutide n=9 Participants Liraglutide 0.6 mg daily administration for 6 months	Control n=8 Participants Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
MCP-1:Creatinine Ratio in Urine	27.9 ng/mmol Standard Deviation 14.3	24.3 ng/mmol Standard Deviation 15.4

SECONDARY outcome

Timeframe: Up to 26 weeks

Spot urine sample for albumin and creatinine

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 26 weeks

Albuminuria as Measured by 24 Hour Albumin Excretion Rate

Outcome measures

Measure	Liraglutide n=9 Participants Liraglutide 0.6 mg daily administration for 6 months	Control n=7 Participants Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
Urinary Albumin Excretion Rate	144.1 µg/min Standard Deviation 232.6	132.4 µg/min Standard Deviation 101.3

SECONDARY outcome

Timeframe: Up to 26 weeks

Serum sample for sCD163

Outcome measures

Measure	Liraglutide n=10 Participants Liraglutide 0.6 mg daily administration for 6 months	Control n=8 Participants Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
sCD163 in Serum	82 ng/ml Standard Deviation 34	84 ng/ml Standard Deviation 23

SECONDARY outcome

Timeframe: Up to 26 weeks

Spot urine sample for MCP-1 and creatinine

Outcome measures

Measure	Liraglutide n=10 Participants Liraglutide 0.6 mg daily administration for 6 months	Control n=8 Participants Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
sCD163:Creatinine Ratio in Urine	27.9 pg/mmol Standard Deviation 14.0	24.3 pg/mmol Standard Deviation 15.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 34 weeks

Adverse event data collection

Outcome measures

Outcome data not reported

Adverse Events

Liraglutide

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Control

Serious events: 1 serious events

Other events: 7 other events

Deaths: 1 deaths

Serious adverse events

Measure	Liraglutide n=10 participants at risk Liraglutide 0.6 mg daily administration for 6 months	Control n=10 participants at risk Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
Cardiac disorders Heart failure	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Cardiac disorders Paroxysmal atrial fibrillation	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.

Other adverse events

Measure	Liraglutide n=10 participants at risk Liraglutide 0.6 mg daily administration for 6 months	Control n=10 participants at risk Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
Renal and urinary disorders Acute kidney injury	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Blood and lymphatic system disorders Hypokalaemia	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	20.0% 2/10 • Number of events 2 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Gastrointestinal disorders Diarrhoea	20.0% 2/10 • Number of events 2 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Gastrointestinal disorders Gastroenteritis	20.0% 2/10 • Number of events 2 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Infections and infestations Viral illness	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 2 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Gastrointestinal disorders Dyspepsia	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Metabolism and nutrition disorders Hypoglycaemia	20.0% 2/10 • Number of events 7 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 9 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Gastrointestinal disorders Gastritis	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Nervous system disorders Dizziness	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Reproductive system and breast disorders Erectile dysfunction	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Skin and subcutaneous tissue disorders Ingrown toenail	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Infections and infestations Upper respiratory tract infection	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Cardiac disorders Palpitations	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Gastrointestinal disorders Mouth ulcer	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Gastrointestinal disorders Loose stool	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Infections and infestations Lower respiratory tract infection	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Infections and infestations Sinusitis	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.
Blood and lymphatic system disorders Hyponatraemia	10.0% 1/10 • Number of events 1 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.	0.00% 0/10 • Starting from the first administration of the IMP through to the End of Study Visit (30 weeks) all Adverse Event and Serious Adverse event information was collected at each visit. AEs were collected by the PI and Sub-investigators and recorded in the CRF/site file/medical record. AEs/SAEs were recorded in the CRF module for AE in verbatim terms. In case of several signs/symptoms, a single syndrome or diagnosis was recorded. In the event of an AE, investigators adjudicated whether the AE was serious, the start date, the stop date, whether the AE was related to study drug or procedure, AE-related actions taken with the study drug, the severity of the AE and outcome.

Additional Information

Prof Carel le Roux

University College Dublin

Phone: +353 1 716 6831

Email: carel.leroux@ucd.ie

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place