Trial Outcomes & Findings for Efficacy and Safety of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Chronic Migraine (NCT NCT03303079)

NCT ID: NCT03303079

Last Updated: 2021-06-15

Results Overview

Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 571 participants
• Primary outcome timeframe: Baseline, 12 weeks
• Results posted on: 2021-06-15

Participant Flow

Participant milestones

Measure	TEV-48125 (675/225/225 mg) Group TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Overall Study STARTED	189	191	191
Overall Study COMPLETED	182	180	179
Overall Study NOT COMPLETED	7	11	12

Reasons for withdrawal

Measure	TEV-48125 (675/225/225 mg) Group TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Overall Study Adverse Event	0	1	3
Overall Study Protocol Violation	5	4	7
Overall Study Withdrawal by Subject	2	4	2
Overall Study Other than specified	0	2	0

Baseline Characteristics

Efficacy and Safety of Subcutaneous Administration of TEV-48125 for the Preventive Treatment of Chronic Migraine

Baseline characteristics by cohort

Measure	TEV-48125 (675/225/225 mg) Group n=189 Participants TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=191 Participants TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=191 Participants Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).	Total n=571 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	187 Participants n=5 Participants	184 Participants n=7 Participants	190 Participants n=5 Participants	561 Participants n=4 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Age, Continuous	42.7 years STANDARD_DEVIATION 10.2 • n=5 Participants	43.5 years STANDARD_DEVIATION 10.2 • n=7 Participants	42.1 years STANDARD_DEVIATION 10.2 • n=5 Participants	42.8 years STANDARD_DEVIATION 10.2 • n=4 Participants
Sex: Female, Male Female	163 Participants n=5 Participants	165 Participants n=7 Participants	163 Participants n=5 Participants	491 Participants n=4 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	26 Participants n=7 Participants	28 Participants n=5 Participants	80 Participants n=4 Participants
Race/Ethnicity, Customized Asian	189 Participants n=5 Participants	191 Participants n=7 Participants	191 Participants n=5 Participants	571 Participants n=4 Participants
Region of Enrollment Japan	159 participants n=5 Participants	159 participants n=7 Participants	161 participants n=5 Participants	479 participants n=4 Participants
Region of Enrollment South Korea	30 participants n=5 Participants	32 participants n=7 Participants	30 participants n=5 Participants	92 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, 12 weeks

Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity

Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.

Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.

Outcome measures

Measure	TEV-48125 (675/225/225 mg) Group n=187 Participants TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=189 Participants TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=190 Participants Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)	-4.12 days/month Standard Error 0.43	-4.14 days/month Standard Error 0.43	-2.45 days/month Standard Error 0.43

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity

Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.

Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.

Outcome measures

Measure	TEV-48125 (675/225/225 mg) Group n=187 Participants TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=189 Participants TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=190 Participants Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP	-4.90 days/month Standard Error 0.50	-4.07 days/month Standard Error 0.49	-2.79 days/month Standard Error 0.49

SECONDARY outcome

Timeframe: 12 weeks

Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity "Overall Number of Participants Analyzed" = the number of subjects meeting responder criteria

Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.

Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.

Outcome measures

Measure	TEV-48125 (675/225/225 mg) Group n=54 Participants TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=55 Participants TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=25 Participants Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP	29.0 percentage of participants	29.1 percentage of participants	13.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity

Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications).

Outcome measures

Measure	TEV-48125 (675/225/225 mg) Group n=187 Participants TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=189 Participants TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=190 Participants Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP	-3.74 days/month Standard Error 0.44	-3.87 days/month Standard Error 0.43	-2.44 days/month Standard Error 0.43

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity

Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who had experienced headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as mild, moderate, or severe.

Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications."

Outcome measures

Measure	TEV-48125 (675/225/225 mg) Group n=149 Participants TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=149 Participants TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=149 Participants Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Mean Change From Baseline in the Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-week Period After the First Dose of IMP in Subjects Not Receiving Concomitant Preventive Migraine Medications	-3.74 days/month Standard Error 0.44	-3.87 days/month Standard Error 0.43	-2.44 days/month Standard Error 0.43

SECONDARY outcome

Timeframe: Baseline, 4 weeks

Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of headache days of at least moderate severity

Subjects assessed the impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress, using the HIT-6. The HIT-6 total score will be obtained from summation of the 6 question points.Each question is answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always).

Outcome measures

Measure	TEV-48125 (675/225/225 mg) Group n=182 Participants TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=180 Participants TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=179 Participants Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Mean Change From Baseline in Disability Score, as Measured by 6-Item Headache Impact Test (HIT-6) at 4 Weeks After the Final (Third) Dose of IMP	-8.06 score on a scale Standard Error 0.70	-8.03 score on a scale Standard Error 0.68	-6.49 score on a scale Standard Error 0.68

Adverse Events

TEV-48125 (675/225/225 mg) Group

Serious events: 3 serious events

Other events: 115 other events

Deaths: 0 deaths

TEV-48125 (675 mg/Placebo/Placebo) Group

Serious events: 1 serious events

Other events: 116 other events

Deaths: 0 deaths

Placebo Group

Serious events: 1 serious events

Other events: 117 other events

Deaths: 0 deaths

Serious adverse events

Measure	TEV-48125 (675/225/225 mg) Group n=188 participants at risk TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=190 participants at risk TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=191 participants at risk Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Injury, poisoning and procedural complications Brain contusion	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Asthma	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Influenza	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Intestinal haemorrhage	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once

Other adverse events

Measure	TEV-48125 (675/225/225 mg) Group n=188 participants at risk TEV-48125 will be subcutaneously administered once monthly for 3 months (675/225/225 mg).	TEV-48125 (675 mg/Placebo/Placebo) Group n=190 participants at risk TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/ placebo/placebo).	Placebo Group n=191 participants at risk Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo).
Blood and lymphatic system disorders Iron deficiency anaemia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Blood and lymphatic system disorders Anaemia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Cardiac disorders Palpitations	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Cardiac disorders Prinzmetal angina	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Cardiac disorders Bundle branch block right	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Cardiac disorders Left ventricular hypertrophy	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Ear and labyrinth disorders Deafness neurosensory	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Ear and labyrinth disorders Vertigo	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Ear and labyrinth disorders Meniere's disease	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Ear and labyrinth disorders Tinnitus	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Dry eye	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Astigmatism	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Conjunctival cyst	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Conjunctivitis allergic	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Ocular discomfort	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Asthenopia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Blepharospasm	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Chalazion	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Eye disorders Retinopathy solar	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Chronic gastritis	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Diarrhoea	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	2.1% 4/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Constipation	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Gastrooesophageal reflux disease	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Nausea	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	2.6% 5/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Tooth loss	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Abdominal discomfort	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Abdominal pain	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Abdominal pain upper	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Cheilitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Dyspepsia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Enterocolitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Gastritis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Toothache	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Anal fissure	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Colitis ischaemic	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Dental caries	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Epigastric discomfort	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Gastric polyps	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Haemorrhoids	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Lumbar hernia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Periodontal inflammation	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Salivary gland mass	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Stomatitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Gastrointestinal disorders Vomiting	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site induration	17.6% 33/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	12.1% 23/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	12.6% 24/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site erythema	15.4% 29/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	12.1% 23/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	11.0% 21/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site pain	7.4% 14/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	12.6% 24/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	8.9% 17/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site pruritus	5.3% 10/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	2.6% 5/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site swelling	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site haemorrhage	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site rash	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Malaise	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Pyrexia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Chest pain	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Generalised oedema	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site bruising	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site dermatitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Injection site inflammation	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Non-cardiac chest pain	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
General disorders Thirst	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Immune system disorders Seasonal allergy	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Nasopharyngitis	16.0% 30/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	21.1% 40/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	18.8% 36/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Influenza	2.1% 4/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Upper respiratory tract infection	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Gastroenteritis	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Herpes virus infection	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Bronchitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Conjunctivitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Gingivitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Kaposi's varicelliform eruption	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Oral herpes	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Sinusitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Tonsillitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Vulvitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Cystitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	2.1% 4/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Helicobacter infection	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Herpes simplex	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Hordeolum	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Parotitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Pharyngitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Pharyngotonsillitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Pneumonia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Pulpitis dental	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Streptococcal infection	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Infections and infestations Urinary tract infection	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Contusion	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Fracture	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Stab wound	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Wound	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Arthropod sting	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Dental restoration failure	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Muscle contusion	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Injury, poisoning and procedural complications Procedural pain	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Urine leukocyte esterase positive	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Weight decreased	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Alanine aminotransferase increased	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Aspartate aminotransferase increased	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Blood urine present	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Gamma-glutamyltransferase increased	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Blood bilirubin increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Blood creatine phosphokinase increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Blood glucose increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Blood potassium increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Blood pressure increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Eosinophil count increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Weight increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations White blood cell count increased	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Metabolism and nutrition disorders Hyperglycaemia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Metabolism and nutrition disorders Vitamin D deficiency	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Investigations Decreased appetite	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Metabolism and nutrition disorders Diabetic complication	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Back pain	2.7% 5/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Pain in extremity	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Myalgia	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Neck pain	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Muscle spasms	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Temporomandibular joint syndrome	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Tenosynovitis	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Limb discomfort	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Osteopenia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Spinal deformity	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Dizziness	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Headache	1.6% 3/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Syncope	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Cognitive disorder	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Hypersomnia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Hypoaesthesia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Migraine	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Monoplegia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Paraesthesia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Presyncope	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Amnestic disorder	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Dizziness postural	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Intercostal neuralgia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Memory impairment	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Neuralgia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Nervous system disorders Somnolence	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Psychiatric disorders Depression	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Psychiatric disorders Alcoholic hangover	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Psychiatric disorders Insomnia	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Psychiatric disorders Mental fatigue	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Psychiatric disorders Panic disorder	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Psychiatric disorders Sleep disorder	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Psychiatric disorders Suicidal ideation	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Renal and urinary disorders Haematuria	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Renal and urinary disorders Proteinuria	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Reproductive system and breast disorders Dysmenorrhoea	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Reproductive system and breast disorders Menorrhagia	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Reproductive system and breast disorders Vaginal haemorrhage	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Reproductive system and breast disorders Premenstrual syndrome	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Asthma	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	2.1% 4/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Cough	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.1% 2/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.6% 3/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Reflux laryngitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Throat tightness	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Eczema	1.1% 2/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Dermatitis contact	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	1.0% 2/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Drug eruption	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Dry skin	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Miliaria	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Pruritus	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Urticaria	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Erythema	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.52% 1/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Onycholysis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Rash	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Seborrhoeic dermatitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Skin and subcutaneous tissue disorders Solar dermatitis	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Vascular disorders Peripheral coldness	0.53% 1/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once
Vascular disorders Neurogenic shock	0.00% 0/188 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.53% 1/190 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once	0.00% 0/191 • Double-blind treatment period (12 weeks) Safety set (SS):Subjects who received the IMP at least once

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: CL_OPCJ_RDA_Team@otsuka.jp

Results disclosure agreements

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