Trial Outcomes & Findings for A Study of Lanabecestat (LY3314814) in Participants With Mild Alzheimer's Disease Dementia (NCT NCT02783573)

NCT ID: NCT02783573

Last Updated: 2019-12-03

Results Overview

ADAS-Cog13 (13-item version of ADAS Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment-by-visit interaction, acetylcholinesterase Inhibitor (AChEI) use at baseline, pooled site, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 1722 participants
• Primary outcome timeframe: Baseline, Week 78
• Results posted on: 2019-12-03

Participant Flow

This study consists of Placebo-Controlled Treatment Period (Weeks 0 to 78) and Delayed-Start Period (Weeks 78 to 156).

In Period 1, per the protocol, placebo-controlled groups (Placebo for 78 weeks then Lanabecestat 20 mg; Placebo for 78 weeks then Lanabecestat 50 mg) were combined to form one placebo group. As study terminated early and very few participants entered into the period 2, the arms in period 2 are combined based on dose exposure for ease of comparison.

Participant milestones

Measure	Placebo Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 Milligrams (mg) Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Placebo-Controlled Treatment Period STARTED	562	590	570
Placebo-Controlled Treatment Period Received at Least 1 Dose of Study Drug	558	588	568
Placebo-Controlled Treatment Period COMPLETED	26	28	22
Placebo-Controlled Treatment Period NOT COMPLETED	536	562	548
Delayed-Start Period STARTED	0	17	12
Delayed-Start Period Received at Least 1 Dose of Study Drug	0	14	12
Delayed-Start Period COMPLETED	0	0	0
Delayed-Start Period NOT COMPLETED	0	17	12

Reasons for withdrawal

Measure	Placebo Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 Milligrams (mg) Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Placebo-Controlled Treatment Period Adverse Event	13	17	13
Placebo-Controlled Treatment Period Death	4	2	3
Placebo-Controlled Treatment Period Lack of Efficacy	0	0	2
Placebo-Controlled Treatment Period Lost to Follow-up	3	3	1
Placebo-Controlled Treatment Period Non-Compliance	0	1	0
Placebo-Controlled Treatment Period Other-determined by Investigator	0	1	2
Placebo-Controlled Treatment Period Physician Decision	3	1	3
Placebo-Controlled Treatment Period Protocol Violation	1	2	0
Placebo-Controlled Treatment Period Withdrawal by Subject	15	20	23
Placebo-Controlled Treatment Period Withdrawal due to Caregiver Circumstance	3	3	9
Placebo-Controlled Treatment Period Sponsor Decision	494	512	492
Delayed-Start Period Sponsor Decision	0	17	12

Baseline Characteristics

A Study of Lanabecestat (LY3314814) in Participants With Mild Alzheimer's Disease Dementia

Baseline characteristics by cohort

Measure	Placebo n=562 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=590 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=570 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.	Total n=1722 Participants Total of all reporting groups
Age, Continuous	72.1 Years STANDARD_DEVIATION 7.1 • n=5 Participants	72.3 Years STANDARD_DEVIATION 7.0 • n=7 Participants	72.6 Years STANDARD_DEVIATION 7.0 • n=5 Participants	72.3 Years STANDARD_DEVIATION 7.0 • n=4 Participants
Sex: Female, Male Female	348 Participants n=5 Participants	335 Participants n=7 Participants	340 Participants n=5 Participants	1023 Participants n=4 Participants
Sex: Female, Male Male	214 Participants n=5 Participants	255 Participants n=7 Participants	230 Participants n=5 Participants	699 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	53 Participants n=5 Participants	45 Participants n=7 Participants	55 Participants n=5 Participants	153 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	416 Participants n=5 Participants	442 Participants n=7 Participants	423 Participants n=5 Participants	1281 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	93 Participants n=5 Participants	103 Participants n=7 Participants	92 Participants n=5 Participants	288 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) Asian	64 Participants n=5 Participants	76 Participants n=7 Participants	69 Participants n=5 Participants	209 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) White	387 Participants n=5 Participants	398 Participants n=7 Participants	389 Participants n=5 Participants	1174 Participants n=4 Participants
Race (NIH/OMB) More than one race	72 Participants n=5 Participants	70 Participants n=7 Participants	62 Participants n=5 Participants	204 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	30 Participants n=5 Participants	33 Participants n=7 Participants	32 Participants n=5 Participants	95 Participants n=4 Participants
Region of Enrollment United States	196 Participants n=5 Participants	205 Participants n=7 Participants	199 Participants n=5 Participants	600 Participants n=4 Participants
Region of Enrollment Czechia	42 Participants n=5 Participants	42 Participants n=7 Participants	45 Participants n=5 Participants	129 Participants n=4 Participants
Region of Enrollment Japan	38 Participants n=5 Participants	43 Participants n=7 Participants	38 Participants n=5 Participants	119 Participants n=4 Participants
Region of Enrollment United Kingdom	23 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	68 Participants n=4 Participants
Region of Enrollment Portugal	8 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment Russia	33 Participants n=5 Participants	36 Participants n=7 Participants	31 Participants n=5 Participants	100 Participants n=4 Participants
Region of Enrollment Spain	25 Participants n=5 Participants	25 Participants n=7 Participants	28 Participants n=5 Participants	78 Participants n=4 Participants
Region of Enrollment Canada	32 Participants n=5 Participants	33 Participants n=7 Participants	31 Participants n=5 Participants	96 Participants n=4 Participants
Region of Enrollment South Korea	19 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	59 Participants n=4 Participants
Region of Enrollment Netherlands	9 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants	30 Participants n=4 Participants
Region of Enrollment China	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Taiwan	5 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	24 Participants n=4 Participants
Region of Enrollment Poland	39 Participants n=5 Participants	43 Participants n=7 Participants	40 Participants n=5 Participants	122 Participants n=4 Participants
Region of Enrollment Denmark	7 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Region of Enrollment Italy	23 Participants n=5 Participants	22 Participants n=7 Participants	21 Participants n=5 Participants	66 Participants n=4 Participants
Region of Enrollment Mexico	11 Participants n=5 Participants	9 Participants n=7 Participants	9 Participants n=5 Participants	29 Participants n=4 Participants
Region of Enrollment France	30 Participants n=5 Participants	33 Participants n=7 Participants	30 Participants n=5 Participants	93 Participants n=4 Participants
Region of Enrollment Germany	21 Participants n=5 Participants	22 Participants n=7 Participants	17 Participants n=5 Participants	60 Participants n=4 Participants
ADAS-Cog13 (13-item Alzheimer's Disease Assessment Scale)	30.4 Units on a Scale STANDARD_DEVIATION 7.9 • n=5 Participants	30.6 Units on a Scale STANDARD_DEVIATION 8.3 • n=7 Participants	30.6 Units on a Scale STANDARD_DEVIATION 8.5 • n=5 Participants	30.5 Units on a Scale STANDARD_DEVIATION 8.2 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADAS-Cog13 measure.

ADAS-Cog13 (13-item version of ADAS Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment-by-visit interaction, acetylcholinesterase Inhibitor (AChEI) use at baseline, pooled site, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction.

Outcome measures

Measure	Placebo n=460 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=471 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=464 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score	6.42 Units on a scale Standard Error 1.23	8.93 Units on a scale Standard Error 1.11	6.20 Units on a scale Standard Error 1.32

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADCS-iADL measure.

The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADL score, age at baseline, and baseline iADL score-by-visit interaction.

Outcome measures

Measure	Placebo n=357 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=369 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=347 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items Score (ADCS-iADL)	-3.95 Units on a scale Standard Error 1.27	-6.91 Units on a scale Standard Error 1.29	-7.13 Units on a scale Standard Error 1.40

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for FAQ score.

FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now=1; never did [the activity] but could do now=0; normal=0; has difficulty but does by self=1; requires assistance=2; Dependent =3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline FAQ total score, by-visit interaction and age at baseline.

Outcome measures

Measure	Placebo n=358 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=369 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=347 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in Functional Activities Questionnaire (FAQ) Score	3.93 Units on a scale Standard Error 0.81	5.16 Units on a scale Standard Error 0.85	3.41 Units on a scale Standard Error 0.91

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for iADRS.

The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADRS13 total score, age at baseline, and baseline iADRS13 total score-by-visit interaction.

Outcome measures

Measure	Placebo n=342 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=348 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=333 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score	-10.46 Units on a scale Standard Error 1.97	-15.22 Units on a scale Standard Error 1.90	-12.43 Units on a scale Standard Error 2.08

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CDR-SB.

The CDR-SB is a rater administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which no dementia = 0, questionable dementia = 0.5, mild dementia = 1, moderate dementia = 2 and severe dementia = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher scores indicating greater impairment. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline CDR-SB score, age at baseline, and baseline CDR-SB score-by-visit interaction.

Outcome measures

Measure	Placebo n=369 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=370 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=363 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score	2.32 Units on a scale Standard Error 0.42	2.57 Units on a scale Standard Error 0.41	2.10 Units on a scale Standard Error 0.45

SECONDARY outcome

Timeframe: From Loss of 1 Global Stage through Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CDR global score.

The CDR global score is a composite score calculated using the Washington University CDR-assignment algorithm applied to the 6 individual domain box scores (Morris 1993). The memory domain is considered the primary category that drives the CDR global outcome, and all other domains are secondary. The CDR global score ranges from 0 to 3 (0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia).

Outcome measures

Measure	Placebo n=479 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=500 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=466 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage	379 Days Interval 367.0 to 546.0	367 Days Interval 365.0 to 456.0	449 Days Interval 365.0 to 491.0

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for NPI.

The NPI is a questionnaire administered to caregivers that quantifies behavioral changes. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144, with higher scores indicating a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline NPI score, age at baseline, and baseline NPI score-by-visit interaction.

Outcome measures

Measure	Placebo n=351 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=363 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=342 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in Neuropsychiatric Inventory (NPI) Score	3.45 Units on a scale Standard Error 1.70	3.75 Units on a scale Standard Error 1.84	0.44 Units on a scale Standard Error 1.45

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for MMSE.

The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline MMSE total score, age at baseline, and baseline MMSE total score-by-visit interaction.

Outcome measures

Measure	Placebo n=476 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=495 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=477 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline on the Mini-Mental State Examination (MMSE)	-4.16 Units on a scale Standard Error 0.59	-5.43 Units on a scale Standard Error 0.58	-4.31 Units on a scale Standard Error 0.64

SECONDARY outcome

Timeframe: Baseline, Week 71

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Aβ1-42.

Concentration of the peptide Aβ 1-42 in plasma measured by validated immunoassay. LS Mean was determined by Analysis of covariance (ANCOVA) with last observation carried forward (LOCF), terms for treatment, baseline biomarker and age at baseline.

Outcome measures

Measure	Placebo n=4 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=5 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=5 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42	23.68 Percent change in Aβ1-42 Standard Error 26.76	-13.87 Percent change in Aβ1-42 Standard Error 24.30	-17.04 Percent change in Aβ1-42 Standard Error 23.26

SECONDARY outcome

Timeframe: Baseline, Week 71

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Aβ1-40.

Concentration of the peptide Aβ 1-40 in plasma measured by immunoassay. LS Mean was determined by ANCOVA with LOCF (last observation carried forward), terms for treatment, baseline biomarker and age at baseline.

Outcome measures

Measure	Placebo n=4 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=5 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=5 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40	24.52 Percent change in Aβ1-40 Standard Error 23.08	-37.42 Percent change in Aβ1-40 Standard Error 20.76	-9.63 Percent change in Aβ1-40 Standard Error 20.74

SECONDARY outcome

Timeframe: Baseline, Week 71

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CSF Total Tau.

Cerebrospinal fluid samples were collected for analysis of concentration total tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.

Outcome measures

Measure	Placebo n=4 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=5 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=5 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in CSF Biomarker Total Tau	1.84 Picogram per milliliter (pg/mL) Standard Error 9.75	18.16 Picogram per milliliter (pg/mL) Standard Error 9.77	-11.21 Picogram per milliliter (pg/mL) Standard Error 9.32

SECONDARY outcome

Timeframe: Baseline, Week 71

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CSF Phosphorylated Tau.

Cerebrospinal fluid samples are collected for analysis of concentration of phosphorylated tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.

Outcome measures

Measure	Placebo n=4 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=5 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=5 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in CSF Biomarker Phosphorylated Tau	2.22 Picogram per milliliter (pg/mL) Standard Error 1.54	3.81 Picogram per milliliter (pg/mL) Standard Error 1.49	0.08 Picogram per milliliter (pg/mL) Standard Error 1.41

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for brain amyloid burden.

Amyloid deposition in the brain is one of the defining neuropathologic findings of Alzheimer's disease. Florbetapir exhibits high affinity specific binding to amyloid plaques. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by florbetapir amyloid PET imaging in a subset of participants. The Centiloid scale standardizes quantitative brain amyloid PET results to allow cross-tracer and cross-methodology comparisons. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans. Florbetapir SUVr was converted to the Centiloid scale using the following conversion: Florbetapir Centiloids = 183 x SUVr - 177. LS Mean was determined by using ANCOVA methodology with terms for treatment, baseline biomarker and age at baseline.

Outcome measures

Measure	Placebo n=7 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=10 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=7 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan	-2.43 Units on a scale Standard Error 10.47	-0.21 Units on a scale Standard Error 7.79	-17.63 Units on a scale Standard Error 9.69

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for rCBF.

Florbetapir perfusion evaluated the regional cerebral blood flow (rCBF) as a biomarker of brain function and was performed at the same time as the amyloid florbetapir PET. Cerebral perfusion, especially in temporal and parietal areas, is reduced in AD and this pattern of hypoperfusion closely mirrors the hypometabolism pattern observed using FDG PET. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF (last observation carried forward) and with factors for treatment, baseline biomarker and age at baseline.

Outcome measures

Measure	Placebo n=82 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=65 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=66 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in Regional Cerebral Blood Flow (rCBF) Using Florbetapir Perfusion Scan	-0.03 Standard Uptake Value ratio (SUVr) Standard Error 0.01	-0.03 Standard Uptake Value ratio (SUVr) Standard Error 0.01	-0.03 Standard Uptake Value ratio (SUVr) Standard Error 0.01

SECONDARY outcome

Timeframe: Baseline, Week 78

Population: All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Whole Brain Volume.

Magnetic resonance imaging (MRI) was used to evaluate the effect of lanabecestat on brain atrophy/whole brain volumes. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline volumetric magnetic resonance imaging (vMRI), intracranial volume and age at baseline.

Outcome measures

Measure	Placebo n=221 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg n=215 Participants Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg n=214 Participants Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Change From Baseline in Whole Brain Volume	-15.76 cm^3 (cubic centimeter) Standard Error 0.75	-17.38 cm^3 (cubic centimeter) Standard Error 0.75	-18.84 cm^3 (cubic centimeter) Standard Error 0.76

SECONDARY outcome

Timeframe: Predose, Week 4, 7, 19, 39, 45 and Week 71 post dose

Population: All randomized participants who received at least 1 dose of study drug with evaluable PK data.

The apparent oral clearance of lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.

Outcome measures

Measure	Placebo n=1077 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat	17.4 Liter per hour (L/h) Geometric Coefficient of Variation 38.8	—	—

SECONDARY outcome

Timeframe: Predose, Week 4, 7, 19, 39, 45 and week 71 post dose

Population: All randomized participants who received at least 1 dose of study drug with evaluable PK data.

The central volume of distribution for lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.

Outcome measures

Measure	Placebo n=1077 Participants Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 mg Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 mg Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Population PK: Central Volume of Distribution of Lanabecestat	77.8 Liters (L) Geometric Coefficient of Variation 198	—	—

Adverse Events

Placebo-Period 1

Serious events: 50 serious events

Other events: 48 other events

Deaths: 5 deaths

Lanabecestat 20 Mg-Period 1

Serious events: 50 serious events

Other events: 69 other events

Deaths: 2 deaths

Lanabecestat 50 Mg-Period 1

Serious events: 46 serious events

Other events: 76 other events

Deaths: 3 deaths

Lanabecestat 20 Mg-Period 2

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Lanabecestat 50 Mg-Period 2

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo-Period 1 n=558 participants at risk Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 Mg-Period 1 n=588 participants at risk Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 Mg-Period 1 n=568 participants at risk Participants received lanabecestat 50 mg film-coated oral tablets once daily.	Lanabecestat 20 Mg-Period 2 n=14 participants at risk Participants from placebo group were randomized to receive lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 Mg-Period 2 n=12 participants at risk Participants from placebo group were randomized to receive lanabecestat 50 mg film-coated oral tablets once daily.
Vascular disorders Hypertension	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Blood and lymphatic system disorders Iron deficiency anaemia	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Acute coronary syndrome	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Acute myocardial infarction	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Atrial fibrillation	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Atrial flutter	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Atrioventricular block complete	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Cardiac arrest	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Cardiac failure congestive	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Chronotropic incompetence	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Coronary artery disease	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Myocardial infarction	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Sinus node dysfunction	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.34% 2/588 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Stress cardiomyopathy	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Trifascicular block	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Cardiac disorders Ventricular fibrillation	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Congenital, familial and genetic disorders Gastrointestinal arteriovenous malformation	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Ear and labyrinth disorders Vertigo positional	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Colitis	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Colitis ischaemic	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Constipation	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Diverticulum	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Inguinal hernia	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Peptic ulcer perforation	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Rectal prolapse	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Vomiting	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Chest pain	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Death	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Feeling abnormal	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Non-cardiac chest pain	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Sudden cardiac death	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Hepatobiliary disorders Cholelithiasis	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Immune system disorders Anaphylactic reaction	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Bacteraemia	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Bronchitis viral	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Cellulitis	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Cellulitis orbital	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Epididymitis	0.47% 1/211 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.39% 1/255 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/229 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/7 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Erysipelas	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Liver abscess	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Orchitis	0.47% 1/211 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/255 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/229 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/7 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Pneumonia	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Sepsis	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Sinusitis	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Urinary tract infection	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Infections and infestations Urosepsis	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Animal bite	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Brain contusion	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Fall	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.51% 3/588 • Number of events 3 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.88% 5/568 • Number of events 5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Femur fracture	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Forearm fracture	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Heat exhaustion	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Humerus fracture	0.36% 2/558 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Pelvic fracture	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Post procedural complication	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Pubis fracture	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Rib fracture	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Road traffic accident	0.36% 2/558 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Spinal compression fracture	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Spinal fracture	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Subdural haematoma	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Investigations Prostatic specific antigen increased	0.00% 0/211 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.39% 1/255 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/229 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/7 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Dehydration	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.34% 2/588 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 3 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer recurrent	0.00% 0/347 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/333 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.29% 1/339 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/9 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer stage ii	0.29% 1/347 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/333 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/339 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/9 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.47% 1/211 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.39% 1/255 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/229 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/7 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal oncocytoma	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Brain injury	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Cerebellar haematoma	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Cerebral infarction	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Cerebrovascular accident	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Cognitive disorder	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Coma	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Dementia Alzheimer's type	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Dizziness	0.36% 2/558 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Encephalopathy	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Generalised tonic-clonic seizure	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Haemorrhage intracranial	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Headache	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Presyncope	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Seizure	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Syncope	0.54% 3/558 • Number of events 3 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.51% 3/588 • Number of events 3 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.53% 3/568 • Number of events 4 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Toxic encephalopathy	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Nervous system disorders Transient ischaemic attack	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Product Issues Device malfunction	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Abnormal behaviour	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Acute psychosis	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Adjustment disorder	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Aggression	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Confusional state	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Delirium	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Delusion	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Mental status changes	0.36% 2/558 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Paranoia	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Psychotic disorder	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	8.3% 1/12 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Renal and urinary disorders Acute kidney injury	0.36% 2/558 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Renal and urinary disorders Stress urinary incontinence	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Hiccups	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Vascular disorders Deep vein thrombosis	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Vascular disorders Peripheral ischaemia	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Vascular disorders Thrombosis	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.

Other adverse events

Measure	Placebo-Period 1 n=558 participants at risk Participants received placebo film-coated oral tablets once daily.	Lanabecestat 20 Mg-Period 1 n=588 participants at risk Participants received lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 Mg-Period 1 n=568 participants at risk Participants received lanabecestat 50 mg film-coated oral tablets once daily.	Lanabecestat 20 Mg-Period 2 n=14 participants at risk Participants from placebo group were randomized to receive lanabecestat 20 mg film-coated oral tablets once daily.	Lanabecestat 50 Mg-Period 2 n=12 participants at risk Participants from placebo group were randomized to receive lanabecestat 50 mg film-coated oral tablets once daily.
Eye disorders Glaucoma	0.90% 5/558 • Number of events 5 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.68% 4/588 • Number of events 4 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.53% 3/568 • Number of events 3 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.1% 1/14 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Gastrointestinal disorders Diarrhoea	3.0% 17/558 • Number of events 19 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	4.9% 29/588 • Number of events 35 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	5.1% 29/568 • Number of events 39 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
General disorders Influenza like illness	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.70% 4/568 • Number of events 4 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.1% 1/14 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Injury, poisoning and procedural complications Fall	3.8% 21/558 • Number of events 34 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	5.4% 32/588 • Number of events 37 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	6.0% 34/568 • Number of events 49 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Investigations Blood glucose decreased	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.1% 1/14 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Investigations Thyroxine decreased	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/588 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.35% 2/568 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.1% 1/14 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Metabolism and nutrition disorders Hyperlipidaemia	0.18% 1/558 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.18% 1/568 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.1% 1/14 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Confusional state	0.36% 2/558 • Number of events 2 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.68% 4/588 • Number of events 4 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	1.6% 9/568 • Number of events 9 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	7.1% 1/14 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/12 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Psychiatric disorders Psychotic disorder	0.00% 0/558 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.17% 1/588 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/568 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/14 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	8.3% 1/12 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
Reproductive system and breast disorders Benign prostatic hyperplasia	1.9% 4/211 • Number of events 4 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	1.6% 4/255 • Number of events 4 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	1.3% 3/229 • Number of events 3 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	20.0% 1/5 • Number of events 1 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.	0.00% 0/7 • Up To 156 Weeks All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.

Additional Information

AstraZeneca Information Center

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor shall review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.
• Publication restrictions are in place

Restriction type: OTHER