Trial Outcomes & Findings for A Safety Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic Despite Treatment With H1 Antihistamines, H2 Blockers, and/or Leukotriene Receptor Antagonists (NCT NCT01264939)

Last Updated: 2013-11-26

Results Overview

The percentage of participants with serious adverse events and other adverse events is summarized by MedDRA preferred terms and organ classes in the Reported Adverse Events section below.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

336 participants

Primary outcome timeframe

Baseline to the end of study (up to 40 weeks)

Results posted on

2013-11-26

Participant Flow

Randomized population: All randomized participants regardless of whether they received any study drug. One patient in the placebo group was withdrawn after randomization but before receiving treatment due to an adverse event. This patient is 1 of 18 in this reporting group who did not complete the study.

Participant milestones

Participant milestones
Measure	Placebo Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Overall Study STARTED	84	252
Overall Study COMPLETED	66	224
Overall Study NOT COMPLETED	18	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Overall Study Adverse Event	1	3
Overall Study Lost to Follow-up	0	3
Overall Study Physician Decision	1	1
Overall Study Patient/Guardian Decision	8	10
Overall Study Disease Progression	8	11

Baseline Characteristics

A Safety Study of Xolair (Omalizumab) in Patients With Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic Despite Treatment With H1 Antihistamines, H2 Blockers, and/or Leukotriene Receptor Antagonists

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.	Total n=335 Participants Total of all reporting groups
Age Continuous	44.3 years STANDARD_DEVIATION 14.7 • n=93 Participants	42.7 years STANDARD_DEVIATION 13.9 • n=4 Participants	43.1 years STANDARD_DEVIATION 14.1 • n=27 Participants
Sex: Female, Male Female	55 Participants n=93 Participants	186 Participants n=4 Participants	241 Participants n=27 Participants
Sex: Female, Male Male	28 Participants n=93 Participants	66 Participants n=4 Participants	94 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to the end of study (up to 40 weeks)

Population: Safety population: All randomized participants who received at least 1 dose of study drug.

The percentage of participants with serious adverse events and other adverse events is summarized by MedDRA preferred terms and organ classes in the Reported Adverse Events section below.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Percentage of Participants With Adverse Events	78.3 Percentage of participants	83.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching. A negative change score indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Change From Baseline to Week 12 in the Weekly Itch Severity Score	-4.01 Units on a scale Standard Deviation 5.87	-8.55 Units on a scale Standard Deviation 6.01

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity. A negative change score indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Change From Baseline to Week 12 in the Urticaria Activity Score Over 7 Days (UAS7)	-8.50 Units on a scale Standard Deviation 11.71	-19.01 Units on a scale Standard Deviation 13.15

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

The weekly hives score is the sum of the daily hives scores over 7 days and ranges from 0 to 21. The number of hives is measured twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 12 hives per 12 hours). The daily hives score is the average of the morning and evening scores. The Baseline score is the sum of the daily hives scores over the 7 days prior to the first treatment. A higher score indicates more hives. A negative change score indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Change From Baseline to Week 12 in the Weekly Number of Hives Score	-4.49 Units on a scale Standard Deviation 6.33	-10.46 Units on a scale Standard Deviation 7.74

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug. Only patients with a MID response were included in the analysis.

The time to the MID response is the number of weeks from the start of treatment (Baseline) until the time point at which the first MID response occurs. The MID response is defined as a reduction ≥ 5 points from Baseline in the weekly itch severity score. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Time to Minimally Important Difference (MID) Response in the Weekly Itch Severity Score by Week 12	5.0 Weeks Interval 3.0 to 7.0	2.0 Weeks Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Percentage of Participants With a UAS7 Score ≤ 6 at Week 12	12.0 Percentage of participants	52.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

The percentage of participants with an itch severity score at 12 Weeks at least 5 points lower than at Baseline. The weekly itch severity score is the sum of the daily itch severity scores over 7 days and ranges from 0 to 21. The daily itch severity score is the average of the morning and evening scores on a scale of 0 (none) to 3 (severe). The Baseline weekly itch severity score is the sum of the daily itch severity scores over the 7 days prior to the first treatment. A higher itch severity score indicates more severe itching.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Percentage of Weekly Itch Severity Score MID Responders at Week 12	39.8 Percentage of participants	69.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

The weekly size of the largest hive score is the sum of the daily size of the largest hive scores over 7 days and ranges from 0 to 21. The daily size of the largest hive score is assessed twice daily (morning and evening) on a scale of 0 (none) to 3 (\> 2.5 cm). The daily size of the largest hive score is the average of the morning and evening scores. The Baseline weekly size of the largest hive score is calculated over the 7 days prior to the first treatment. A higher score indicates larger hives. A negative change score indicates a reduction in hive size.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Change From Baseline to Week 12 in the Weekly Size of the Largest Hive Score	-3.09 Units on a scale Standard Deviation 5.46	-8.82 Units on a scale Standard Deviation 7.23

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug and who had a DLQI score at Week 12.

The DLQI is a 10-item dermatology-specific health-related quality of life measure. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspects of their lives on a scale of 0 (Not at all) to 3 (Very much). The overall DLQI is the sum of the responses to the 10 items and ranges from 0 to 30. A lower score indicates a better quality of life. A negative change score indicates improvement.

Outcome measures

Outcome measures
Measure	Placebo n=64 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=216 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Change From Baseline in the Overall Dermatology Life Quality Index (DLQI) Score at Week 12	-5.11 Units on a scale Standard Deviation 7.53	-9.69 Units on a scale Standard Deviation 6.85

SECONDARY outcome

Timeframe: Week 4 to Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug. Patients who withdrew before the Week 4 visit or who had missing responses for more than 40% of the daily diary entries between the Week 4 visit and the Week 12 visit were not included in the analysis.

The percentage of angioedema-free days from Weeks 4 to 12 was defined as the number of days for which a patient responded "No" to the angioedema question in the daily diary divided by the total number of days with a non-missing diary entry, starting at the Week 4 visit and ending the day prior to the Week 12 visit.

Outcome measures

Outcome measures
Measure	Placebo n=68 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=224 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Percentage of Angioedema-free Days From Week 4 to Week 12	88.1 Percentage of days Standard Deviation 18.9	91.0 Percentage of days Standard Deviation 21.0

SECONDARY outcome

Timeframe: Week 12

Population: Modified intent-to-treat population: All randomized patients who received at least 1 dose of study drug.

A complete responder was defined as a participant with a UAS7 score = 0 at Week 12. The UAS7 is the sum of the daily urticarial activity scores over 7 days and ranges from 0 to 42. The daily urticarial activity score is the average of the morning and evening urticarial activity scores and ranges from 0 to 6. The urticarial activity score is the sum of ratings on a scale of 0 to 3 (0=none to 3=intense/severe) for (1) the number of wheals (hives) and (2) itch intensity over the previous 12 hours, ranges from 0 to 6, and is measured twice daily (morning and evening). The Baseline score is the sum of the daily urticarial activity scores over the 7 days prior to the first treatment. A higher urticarial activity score indicates more urticaria activity.

Outcome measures

Outcome measures
Measure	Placebo n=83 Participants Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 Participants Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Percentage of Complete Responders (UAS7 = 0) at Week 12	4.8 Percentage of participants	33.7 Percentage of participants

Adverse Events

Placebo

Serious events: 5 serious events

Other events: 41 other events

Deaths: 0 deaths

Omalizumab 300 mg

Serious events: 18 serious events

Other events: 142 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=83 participants at risk Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 participants at risk Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Gastrointestinal disorders Nausea	6.0% 5/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	6.0% 15/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Gastrointestinal disorders Diarrhoea	6.0% 5/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	5.2% 13/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Sinusitis	10.8% 9/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	12.3% 31/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Nasopharyngitis	9.6% 8/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	11.9% 30/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Upper respiratory tract infection	4.8% 4/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	11.5% 29/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Urinary tract infection	1.2% 1/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	6.0% 15/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Nervous system disorders Headache	7.2% 6/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	10.7% 27/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.4% 7/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	4.4% 11/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Respiratory, thoracic and mediastinal disorders Sinus congestion	6.0% 5/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	1.2% 3/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Skin and subcutaneous tissue disorders Idiopathic urticaria	12.0% 10/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	14.7% 37/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Skin and subcutaneous tissue disorders Urticaria	3.6% 3/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	5.6% 14/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.

Additional Information

Medical Communications

Genentech, Inc.

Phone: 800 821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=83 participants at risk Participants received placebo subcutaneously every 4 weeks during the 24 week treatment period.	Omalizumab 300 mg n=252 participants at risk Participants received omalizumab 300 mg subcutaneously every 4 weeks during the 24 week treatment period.
Cardiac disorders Angina unstable	1.2% 1/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.00% 0/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Gastrointestinal disorders Gastric ulcer	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Gastrointestinal disorders Gastritis erosive	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Hepatobiliary disorders Cholelithiasis	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Immune system disorders Hypersensitivity	1.2% 1/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.00% 0/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Gastroenteritis	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Retroperitoneal infection	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Gastroenteritis viral	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Viral infection	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Pelvic abscess	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Lower respiratory tract infection	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Infections and infestations Urinary tract infection	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Injury, poisoning and procedural complications Multiple drug overdose	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Investigations Blood glucose increased	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Investigations Blood pressure increased	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Metabolism and nutrition disorders Hyperglycaemia	1.2% 1/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.00% 0/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Psychiatric disorders Depression	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.2% 1/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.00% 0/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Skin and subcutaneous tissue disorders Angioedema	1.2% 1/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	1.6% 4/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Skin and subcutaneous tissue disorders Urticaria	1.2% 1/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.79% 2/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Skin and subcutaneous tissue disorders Idiopathic urticaria	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.
Vascular disorders Intermittent claudication	0.00% 0/83 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.	0.40% 1/252 • Adverse events were reported that started on or after the first treatment date through the end of the study (up to 40 weeks). Safety population: All randomized participants who received at least 1 dose of study drug. Multiple occurrences of a specific adverse event for a patient were counted once in the frequency for the adverse event.