Trial Outcomes & Findings for Endovenous Corticosteroid Pulses in Moderate Ulcerative Colitis (NCT NCT02921555)

Last Updated: 2025-02-21

Results Overview

The percentage of patients with steroid-free, endoscopic remission, with no rescue therapies. It has been measured by Mayo endoscopic subscore (MES). MES= 0 (no friability and granularity and intact vascular pattern). MES= 1 (mild erythema or decreased vascular pattern). MES= 2 (marked erythema, absent vascular pattern, friability, and erosions). MES= 3 (spontaneous bleeding and ulceration)

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

75 participants

Primary outcome timeframe

Change from baseline at week 8

Results posted on

2025-02-21

Participant Flow

Participant milestones

Participant milestones
Measure	Methylprednisolone & Prednisone Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Overall Study STARTED	36	39
Overall Study COMPLETED	36	39
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Endovenous Corticosteroid Pulses in Moderate Ulcerative Colitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Total n=75 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	30 Participants n=5 Participants	35 Participants n=7 Participants	65 Participants n=5 Participants
Age, Categorical >=65 years	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	47 years n=5 Participants	50 years n=7 Participants	49 years n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Race/Ethnicity, Customized Not responded	36 Participants n=5 Participants	39 Participants n=7 Participants	75 Participants n=5 Participants
Region of Enrollment Spain	36 participants n=5 Participants	39 participants n=7 Participants	75 participants n=5 Participants
Active smokers	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Familial inflammatory bowel disease	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Extensive ulcerative colitis	21 Participants n=5 Participants	17 Participants n=7 Participants	38 Participants n=5 Participants
Oral mesalazine at inclusion	28 Participants n=5 Participants	31 Participants n=7 Participants	59 Participants n=5 Participants
Number of patients with Mayo Complete score at baseline	12 participants n=5 Participants	9 participants n=7 Participants	21 participants n=5 Participants
Severe endoscopic activity	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Change from baseline at week 8

Population: All patients participating in the study had to undergo an endoscopic assessment of at least \>25cm from the anal verge at baseline and after 8 weeks.

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Percentage of Participants With Endoscopic and Clincal Remission	11 participants	10 participants

PRIMARY outcome

Timeframe: Change from baseline at week 54

Population: All patients participating in the study had to undergo an endoscopic assessment of at least \>25cm from the anal verge at baseline and after 54 weeks.

The proportions of patients with steroid-free, endoscopic remission, with no rescue therapies. It has been measured by Mayo endoscopic subscore (MES). MES= 0 (no friability and granularity and intact vascular pattern). MES= 1 (mild erythema or decreased vascular pattern). MES= 2 (marked erythema, absent vascular pattern, friability, and erosions). MES= 3 (spontaneous bleeding and ulceration)

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Percentage of Participants With Endoscopic and Clinical Remission	31 Percentage of participants	36 Percentage of participants

SECONDARY outcome

Timeframe: Change from baseline at week 8.

Population: All patients participating in the study had to undergo a clinical assessment at baseline and after 8 weeks.

It was measured as a decrease in the Mayo index score from baseline of at least 3 points; and a decrease of at least 30% in the rectal bleeding variable of at least 1 point or with an absolute value of 0 or 1. The Mayo index score is composed of four parts: rectal bleeding, stool frequency, physician assessment, and endoscopy appearance. Each part is rated from 0 to 3, giving a total score of 0 to 12. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease.

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Percentage of Patients With Clinical Remission	36 percentage of participants Interval 28.0 to 44.0	39 percentage of participants Interval 31.0 to 47.0

SECONDARY outcome

Timeframe: 12 months

Population: Information on adverse events (AEs) were collected at all study visits via spontaneous patient reporting and patient interviews at each visit.

Adverse events (AEs) were collected during the study, from informed consent until the last visit.

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Number of Participants With Adverse Events	25 Participants	21 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Information on adverse events (AEs) were collected at all study visits via spontaneous patient reporting and patient interviews at each visit.

Serious Adverse Events (SAEs) were defined as any adverse event or adverse drug reaction that resulted in death, is life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, or caused a congenital anomaly/birth defect.

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Number of Participants With Serious Adverse Events	1 Participants	6 Participants

SECONDARY outcome

Timeframe: Baseline

Population: Laboratory assessments were conducted at baseline, and blood samples were collected for C-reactive protein determination.

Clinical assessments included the analytical laboratory test. Blood samples were taken for haematology, and C-reactive protein (mg/L) levels were measured.

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Levels of C-reactive Protein	8 mg/L Interval 4.0 to 16.0	11 mg/L Interval 4.0 to 27.0

SECONDARY outcome

Timeframe: Baseline

Population: Analytical laboratory test at baseline were performed in all participants at baseline. Blood samples were taken for haematology, and Serum albumin was determined.

Clinical assessments included the analytical laboratory test. Blood samples were taken for haematology, and Serum albumin determination.

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Levels of Serum Albumin	41 g/L Interval 38.0 to 43.0	40 g/L Interval 36.0 to 45.0

SECONDARY outcome

Timeframe: Baseline

Population: FC concentration was measured using the quantitative, chemiluminescent, sandwich immunoassay Calprotectin (LIASON® DiaSorin, Italy), with a measuring range of 5-8,000 mg/g.

Faecal samples were collected at baseline, frozen and stored at -20 Celsius degrees (ºC) for central measurement of faecal calprotectin (FC).

Outcome measures

Outcome measures
Measure	Methylprednisolone & Prednisone n=36 Participants Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 Participants A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Levels of Faecal Calprotectin	1,230 mg/g	1,710 mg/g

Adverse Events

Methylprednisolone & Prednisone

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Prednisone

Serious events: 6 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Methylprednisolone & Prednisone n=36 participants at risk Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 participants at risk A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Gastrointestinal disorders Ulcerative colitis	0.00% 0/36 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	5.1% 2/39 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Injury, poisoning and procedural complications pyrexia	0.00% 0/36 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	5.1% 2/39 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm of the ampulla of Vater	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	0.00% 0/39 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) neurogenic tumor	0.00% 0/36 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	2.6% 1/39 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Infections and infestations Epstein Barr virus infection	0.00% 0/36 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	2.6% 1/39 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.

Other adverse events

Additional Information

Dr. Eugeni Domènech

Grupo Español de Trabajo en Enfermedad de Crohn y colitis Ulcerosa

Phone: 635899553

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Methylprednisolone & Prednisone n=36 participants at risk Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone Methylprednisolone : Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d) Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)	Prednisone n=39 participants at risk A decreasing conventional course of oral prednisone Prednisone: Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)
Metabolism and nutrition disorders hyperlipidaemia	30.6% 11/36 • Number of events 11 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	12.8% 5/39 • Number of events 5 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Blood and lymphatic system disorders Anaemia	11.1% 4/36 • Number of events 4 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	15.4% 6/39 • Number of events 6 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Nervous system disorders Sleeplessness	19.4% 7/36 • Number of events 7 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	7.7% 3/39 • Number of events 3 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Nervous system disorders Excitability	11.1% 4/36 • Number of events 4 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	17.9% 7/39 • Number of events 7 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Endocrine disorders Hyperglucemia	8.3% 3/36 • Number of events 3 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	7.7% 3/39 • Number of events 3 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Nervous system disorders Headache	5.6% 2/36 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	5.1% 2/39 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Blood and lymphatic system disorders Arterial hypertension	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	7.7% 3/39 • Number of events 3 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Infections and infestations infections	8.3% 3/36 • Number of events 3 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	2.6% 1/39 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Gastrointestinal disorders Heartburn	5.6% 2/36 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	5.1% 2/39 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Vascular disorders dizziness	0.00% 0/36 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	7.7% 3/39 • Number of events 3 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Metabolism and nutrition disorders Hypertransaminaemia	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	5.1% 2/39 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Musculoskeletal and connective tissue disorders Arthromyalgia	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	5.1% 2/39 • Number of events 2 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumours	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	2.6% 1/39 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Respiratory, thoracic and mediastinal disorders Cough	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	0.00% 0/39 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Eye disorders Transient diplopia	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	0.00% 0/39 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Vascular disorders Limb oedema	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	0.00% 0/39 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Blood and lymphatic system disorders Hyponatraemia	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	0.00% 0/39 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Endocrine disorders Acne	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	0.00% 0/39 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.
Renal and urinary disorders Acute renal dysfunction	2.8% 1/36 • Number of events 1 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.	0.00% 0/39 • 12 months Clinically important AEs or adverse drug reactions were also considered serious regardless of whether they met the defined criteria and included important medical events requiring intervention to prevent one of the outcomes defined as serious.