Trial Outcomes & Findings for A Study of Gantenerumab in Participants With Prodromal Alzheimer's Disease (NCT NCT01224106)

Last Updated: 2021-12-13

Results Overview

The CDR (Clinical Dementia Rating) is obtained through semi-structured interviews of participants and informants, and cognitive functioning is rated in six domains of functioning: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a five-point scale of functioning as follows: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment. The CDR-SOB (Clinical Dementia Rating-Sum of Boxes) is based on summing each of the domain box scores with total scores ranging from 0-18, where lower total scores represent better outcomes and higher total scores represent worse outcomes.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

799 participants

Primary outcome timeframe

Baseline, Week 104

Results posted on

2021-12-13

Participant Flow

The study was conducted at 128 centers in 24 countries.

A total of 799 participants were randomised in this study. Of these, a total of 797 participants were enrolled and received at least one dose of any study drug and represented the Safety population during the Double-Blind Treatment Phase (Parts 1 and 2 of the study). From the Double-Blind Treatment Phase, a total of 154 participants (at 53 sites) were enrolled into Open-Label Extension (OLE) Phase (Part 3 of the study).

Participant milestones

Participant milestones
Measure	Placebo (Parts 1 and 2) Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 105 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Double-Blind Treatment Phase STARTED	266	271	260	0	0
Double-Blind Treatment Phase COMPLETED	187	185	180	0	0
Double-Blind Treatment Phase NOT COMPLETED	79	86	80	0	0
Open-Label Extension (OLE) Phase STARTED	0	0	0	49	105
Open-Label Extension (OLE) Phase COMPLETED	0	0	0	33	71
Open-Label Extension (OLE) Phase NOT COMPLETED	0	0	0	16	34

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo (Parts 1 and 2) Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 105 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Double-Blind Treatment Phase Death	3	0	0	0	0
Double-Blind Treatment Phase Physician Decision	6	5	4	0	0
Double-Blind Treatment Phase Adverse Event	0	5	3	0	0
Double-Blind Treatment Phase Other	0	0	1	0	0
Double-Blind Treatment Phase Participant/legal guardian decision	7	8	8	0	0
Double-Blind Treatment Phase Parts 1 and 2 Termination by Sponsor	62	68	63	0	0
Double-Blind Treatment Phase Lost to Follow-up	1	0	1	0	0
Open-Label Extension (OLE) Phase Death	0	0	0	1	3
Open-Label Extension (OLE) Phase Adverse Event	0	0	0	2	6
Open-Label Extension (OLE) Phase Physician Decision	0	0	0	2	7
Open-Label Extension (OLE) Phase Withdrawal by Subject	0	0	0	6	15
Open-Label Extension (OLE) Phase Other	0	0	0	5	3

Baseline Characteristics

Participants in the OLE Phase of this study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo (Parts 1 and 2) n=266 Participants Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 105 mg (Parts 1 and 2) n=271 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=260 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) n=49 Participants Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) n=105 Participants Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Total n=951 Participants Total of all reporting groups
Race/Ethnicity, Customized Hispanic	41 Participants n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	39 Participants n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	47 Participants n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	10 Participants n=49 Participants • Participants in the OLE Phase of this study.	17 Participants n=105 Participants • Participants in the OLE Phase of this study.	127 Participants n=797 Participants • Participants in the Double-Blind Treatment Phase of this study.
Age, Continuous	69.5 years STANDARD_DEVIATION 7.5 • n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	70.3 years STANDARD_DEVIATION 7.0 • n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	71.3 years STANDARD_DEVIATION 7.1 • n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	75.5 years STANDARD_DEVIATION 5.8 • n=49 Participants • Participants in the OLE Phase of this study.	73.7 years STANDARD_DEVIATION 7.3 • n=105 Participants • Participants in the OLE Phase of this study.	74.3 years STANDARD_DEVIATION 6.9 • n=154 Participants • Participants in the OLE Phase of this study.
Sex: Female, Male Female	0 Participants Participants in the OLE Phase of this study.	0 Participants Participants in the OLE Phase of this study.	0 Participants Participants in the OLE Phase of this study.	27 Participants n=49 Participants • Participants in the OLE Phase of this study.	64 Participants n=105 Participants • Participants in the OLE Phase of this study.	91 Participants n=154 Participants • Participants in the OLE Phase of this study.
Sex: Female, Male Male	0 Participants Participants in the OLE Phase of this study.	0 Participants Participants in the OLE Phase of this study.	0 Participants Participants in the OLE Phase of this study.	22 Participants n=49 Participants • Participants in the OLE Phase of this study.	41 Participants n=105 Participants • Participants in the OLE Phase of this study.	63 Participants n=154 Participants • Participants in the OLE Phase of this study.
Race/Ethnicity, Customized Non-Hispanic	217 Participants n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	221 Participants n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	210 Participants n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	39 Participants n=49 Participants • Participants in the OLE Phase of this study.	88 Participants n=105 Participants • Participants in the OLE Phase of this study.	127 Participants n=154 Participants • Participants in the OLE Phase of this study.
Race/Ethnicity, Customized American Indian or Alaska native	1 Participants n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	6 Participants n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	5 Participants n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	0 Participants n=49 Participants • Participants in the OLE Phase of this study.	3 Participants n=105 Participants • Participants in the OLE Phase of this study.	3 Participants n=154 Participants • Participants in the OLE Phase of this study.
Race/Ethnicity, Customized Asian	9 Participants n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	4 Participants n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	7 Participants n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	2 Participants n=49 Participants • Participants in the OLE Phase of this study.	0 Participants n=105 Participants • Participants in the OLE Phase of this study.	2 Participants n=154 Participants • Participants in the OLE Phase of this study.
Race/Ethnicity, Customized Black	1 Participants n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	2 Participants n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	2 Participants n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	—	—	5 Participants n=797 Participants • Participants in the Double-Blind Treatment Phase of this study.
Race/Ethnicity, Customized White	239 Participants n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	252 Participants n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	239 Participants n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	42 Participants n=49 Participants • Participants in the OLE Phase of this study.	101 Participants n=105 Participants • Participants in the OLE Phase of this study.	143 Participants n=154 Participants • Participants in the OLE Phase of this study.
Race/Ethnicity, Customized Not Available	24 Participants n=266 Participants • Participants in the Double-Blind Treatment Phase of this study.	18 Participants n=271 Participants • Participants in the Double-Blind Treatment Phase of this study.	10 Participants n=260 Participants • Participants in the Double-Blind Treatment Phase of this study.	—	—	52 Participants n=797 Participants • Participants in the Double-Blind Treatment Phase of this study.
Race/Ethnicity, Customized Unknown	—	—	—	5 Participants n=49 Participants • Participants in the OLE Phase of this study.	1 Participants n=105 Participants • Participants in the OLE Phase of this study.	6 Participants n=154 Participants • Participants in the OLE Phase of this study.

PRIMARY outcome

Timeframe: Baseline, Week 104

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=105 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=100 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=104 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 104 (Double-Blind Treatment Phase)	1.41 Scores on a Scale Standard Deviation 2.02	1.47 Scores on a Scale Standard Deviation 1.89	—	1.19 Scores on a Scale Standard Deviation 1.68

PRIMARY outcome

Timeframe: Baseline up until a maximum of 5 years

An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=105 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=49 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) AEs	100 Participants	—	—	46 Participants
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (OLE Phase) SAEs	28 Participants	—	—	18 Participants

SECONDARY outcome

Timeframe: Baseline, Week 104

The ADAS-Cog-11 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. Most of these are assessed by tests although some are rated by the clinician on a 5-point scale. The score range for ADAS-Cog-11 is from 0 to 70 with higher scores representing severe dysfunction.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=104 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=100 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=105 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 104 (Double-Blind Treatment Phase)	3.52 Scores on a Scale Standard Deviation 6.28	3.97 Scores on a Scale Standard Deviation 6.89	—	3.68 Scores on a Scale Standard Deviation 6.64

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.

Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=95 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=91 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=91 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Time to Onset of Dementia at Week 104 (Double-Blind Treatment Phase)	62.98 Days Interval 56.0 to 69.16	70.64 Days Interval 63.34 to 76.75	—	63.64 Days Interval 56.63 to 69.82

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. The Placebo Match Gantenerumab 225mg (Parts 1 and 2) arm consisted of participants with the ApoE 2e4 mutation who were excluded from the Gantenerumab 225 mg (Parts 1 and 2) arm. Data presented below is only for participants included in the actual analysis.

The Cambridge Neuropsychological Test Automated Battery (CANTAB) ® is a cognitive test battery that incorporates a variety of executive and memory tasks in order to assess neuropsychological function. The end outcome as reported below, is a Z-Composite Score. The score range of the Z-Composite Score is from (-) infinity to (+) infinity with a score of zero representing the population mean, lower (negative) scores representing poorer cognitive outcomes and higher (positive) scores representing better cognitive outcomes.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=87 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=80 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=73 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=90 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite Score at Week 104 (Double-Blind Treatment Phase)	-1.37 Z-Score Standard Deviation 2.74	-1.4 Z-Score Standard Deviation 3.11	-1.93 Z-Score Standard Deviation 3.08	-1.72 Z-Score Standard Deviation 2.99

SECONDARY outcome

Timeframe: Baseline, Week 104

FCSRT assesses verbal episodic memory. Performances in free recalls, cued recalls and in a recognition task were analyzed, as the process of encoding is controlled. Participants were asked to remember a list of 16 words. Three tasks of free and cued recalls, as well as 1 recognition task and one delayed recall give the scores. Total recall was obtained by the addition of cued recalls to free recalls. Maximum score is 48 for immediate: 16 words multiplied by (\*) 3 corresponding to immediate free recall + immediate cued recall + immediate recognition test. Maximum score is 64 (better score) when delayed recall: 16 words\*4. The minimum score is 0 (worse).

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=102 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=97 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=79 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=100 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 104 (Double-Blind Treatment Phase)	-4.11 Scores on a Scale Standard Deviation 8.57	-6.42 Scores on a Scale Standard Deviation 8.45	-4.05 Scores on a Scale Standard Deviation 8.68	-4.05 Scores on a Scale Standard Deviation 8.73

SECONDARY outcome

Timeframe: Baseline, Week 104

Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=104 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=99 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=84 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=105 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 104 (Double-Blind Treatment Phase)	4.89 Scores on a Scale Standard Deviation 6.2	4.03 Scores on a Scale Standard Deviation 5.75	3.6 Scores on a Scale Standard Deviation 4.93	3.59 Scores on a Scale Standard Deviation 4.93

SECONDARY outcome

Timeframe: Baseline, Week 104

The CDR-GS represents a semi-structured interview which rates impairment in 6 categories (memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care) on a 5-point scale in which CDR 0 = no dementia and CDR 0.5, 1, 2 or 3 = questionable, mild, moderate or severe dementia respectively. The range in scores for the CDR-GS is from 0 to 3 and a high score on the CDR-GS would indicate a high disease severity.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=105 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=100 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=83 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=104 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in CDR-Global Score at Week 104 (Double-Blind Treatment Phase)	0.18 Scores on a Scale Standard Deviation 0.36	0.14 Scores on a Scale Standard Deviation 0.33	0.1 Scores on a Scale Standard Deviation 0.31	0.1 Scores on a Scale Standard Deviation 0.29

SECONDARY outcome

Timeframe: Baseline, Week 104

The NPI is a retrospective (to 1 month) caregiver-informant interview assessing frequency and severity of 12 neuropsychiatric symptom domains. The NPI score is based on the sum of the severity ratings (0=absent, 1=mild, 3=severe). The 12 symptom domains include delusions, hallucinations, agitation/aggression, dysphoria/depression, anxiety, euphoria/elation, apathy/indifference, disinhibition, irritability/lability, aberrant motor behaviors, nighttime behavioral disturbances, and appetite/eating abnormalities. The NPI severity score is based on severity ratings (0=absent, 1=mild to 3=severe).

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=105 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=99 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=82 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=103 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Neuropsychiatric Inventory (NPI) Questionnaire Score at Week 104 (Double-Blind Treatment Phase)	0.39 Scores on a Scale Standard Deviation 2.57	0.34 Scores on a Scale Standard Deviation 2.84	0.72 Scores on a Scale Standard Deviation 3.35	0.6 Scores on a Scale Standard Deviation 3.22

SECONDARY outcome

Timeframe: Baseline, Week 104

CSF biomarker phospho-tau (p-tau) is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=71 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=66 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=56 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=72 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase) p-tau (Week 104)	-4.78 Percentage Change Standard Deviation 11.9	-7.34 Percentage Change Standard Deviation 10.09	2.84 Percentage Change Standard Deviation 23.19	2.77 Percentage Change Standard Deviation 20.69
Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase) t-tau (Week 104)	-1.36 Percentage Change Standard Deviation 12.89	-2.12 Percentage Change Standard Deviation 11.01	3.46 Percentage Change Standard Deviation 22.32	3.43 Percentage Change Standard Deviation 19.95
Percentage Change From Baseline in Cerebrospinal Fluid Biomarkers (Phosphorylated-tau [P-tau], Amyloid Beta 1-42 [Abeta 1-42], Total Tau [T-tau]) at Week 104 (Double-Blind Treatment Phase) Abeta (Week 104)	2.45 Percentage Change Standard Deviation 24.57	15.2 Percentage Change Standard Deviation 45.24	4.3 Percentage Change Standard Deviation 39.31	4.87 Percentage Change Standard Deviation 36.14

SECONDARY outcome

Timeframe: Baseline, Week 104

Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 104 using magnetic resonance imaging.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=124 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=119 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=107 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=131 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) HRV (Week 104)	-7.52 Percentage Change Standard Deviation 3.96	-7.34 Percentage Change Standard Deviation 3.84	-7.7 Percentage Change Standard Deviation 4.01	-7.61 Percentage Change Standard Deviation 4.03
Percentage Change From Baseline in Hippocampal Volume at Week 104 (Double-Blind Treatment Phase) HLV (Week 104)	-7.76 Percentage Change Standard Deviation 3.74	-7.27 Percentage Change Standard Deviation 3.78	-8.12 Percentage Change Standard Deviation 4.19	-7.8 Percentage Change Standard Deviation 4.28

SECONDARY outcome

Timeframe: Baseline, Week 156

The different regions of the brain that were analyzed included cerebellum gray, whole cerebellum, composite white matter, subcortical white matter, pons and composite reference.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=4 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=10 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) n=4 Participants Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=6 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) Cerebellum gray (Week 156)	2.7 Percentage Change Standard Deviation 10.59	-8.36 Percentage Change Standard Deviation 9.11	5.95 Percentage Change Standard Deviation 11.13	6.26 Percentage Change Standard Deviation 9.1
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) Whole Cerebellum (Week 156)	2.07 Percentage Change Standard Deviation 8.65	-8.44 Percentage Change Standard Deviation 8.06	5.17 Percentage Change Standard Deviation 8.66	5.41 Percentage Change Standard Deviation 7.13
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) Composite White Matter (Week 156)	-0.87 Percentage Change Standard Deviation 2.95	-4.86 Percentage Change Standard Deviation 6.35	3.07 Percentage Change Standard Deviation 2.07	2.75 Percentage Change Standard Deviation 3.18
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) Subcortical White Matter (Week 156)	1.69 Percentage Change Standard Deviation 4.45	-0.42 Percentage Change Standard Deviation 8.26	4.59 Percentage Change Standard Deviation 0.55	4.83 Percentage Change Standard Deviation 4.95
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) Pons (Week 156)	-2.83 Percentage Change Standard Deviation 3.39	-6.99 Percentage Change Standard Deviation 5.65	2.1 Percentage Change Standard Deviation 2.73	1.72 Percentage Change Standard Deviation 2.51
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (Double-Blind Treatment Phase) Composite Reference (Week 156)	1.19 Percentage Change Standard Deviation 5.63	-6.75 Percentage Change Standard Deviation 6.1	4.46 Percentage Change Standard Deviation 4.49	4.5 Percentage Change Standard Deviation 3.48

SECONDARY outcome

Timeframe: Pre-Dose: Weeks 8, 20, 44, 68 and 100; Post-Dose: Weeks 1, 53 and 101

Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB. Data presented below is only for participants included in the actual analysis and note that participants who received dose reduction were excluded from this PK analysis.

The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with participants grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=227 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=239 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 1 (Post-Dose)	7.4 µg/ml (micrograms per milliliter) Standard Deviation 4.28	—	—	3.56 µg/ml (micrograms per milliliter) Standard Deviation 2.36
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 8 (Pre-Dose)	5.92 µg/ml (micrograms per milliliter) Standard Deviation 3.16	—	—	2.87 µg/ml (micrograms per milliliter) Standard Deviation 1.84
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 20 (Pre-Dose)	7.66 µg/ml (micrograms per milliliter) Standard Deviation 4.14	—	—	3.7 µg/ml (micrograms per milliliter) Standard Deviation 2.15
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 44 (Pre-Dose)	8.22 µg/ml (micrograms per milliliter) Standard Deviation 4.51	—	—	4.08 µg/ml (micrograms per milliliter) Standard Deviation 2.44
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 53 (Post-Dose)	15 µg/ml (micrograms per milliliter) Standard Deviation 9.34	—	—	6.77 µg/ml (micrograms per milliliter) Standard Deviation 3.94
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 68 (Pre-Dose)	8.91 µg/ml (micrograms per milliliter) Standard Deviation 4.86	—	—	3.95 µg/ml (micrograms per milliliter) Standard Deviation 2.35
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 100 (Pre-Dose)	9.4 µg/ml (micrograms per milliliter) Standard Deviation 4.69	—	—	4.35 µg/ml (micrograms per milliliter) Standard Deviation 2.34
Gantenerumab Plasma Concentrations at Different Time Points (Double-Blind Treatment Phase) Week 101 (Post-Dose)	16.63 µg/ml (micrograms per milliliter) Standard Deviation 7.96	—	—	7.32 µg/ml (micrograms per milliliter) Standard Deviation 3.53

SECONDARY outcome

Timeframe: Baseline, Week 104

Population: The Intent-To-Treat (ITT) population was defined as all participants who had received any dose of study treatment and had at least one post-baseline assessment of CDR-SOB.

The MMSE is a brief, practical screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. A positive change score indicates improvement.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=105 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=99 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=104 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 104 (Double-Blind Treatment Phase)	-2.46 Scores on a Scale Standard Deviation 3.68	-2.25 Scores on a Scale Standard Deviation 3.31	—	-2.31 Scores on a Scale Standard Deviation 3.23

SECONDARY outcome

Timeframe: Baseline up until a maximum of 4.5 years

Population: The Safety population was defined as all participants who had received at least one dose of study drug, regardless of whether the participant withdrew prematurely or not. All safety data was analyzed according to study drug actually received.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=271 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=260 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=266 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) AEs	241 Participants	240 Participants	—	250 Participants
Number of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) (Double-Blind Treatment Phase) SAEs	48 Participants	46 Participants	—	55 Participants

SECONDARY outcome

Timeframe: Baseline up until a maximum of 4.5 years

Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Gantenerumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=266 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=256 Participants Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=259 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) Baseline ADAs	7.5 Percentage of Participants	5.5 Percentage of Participants	—	5.8 Percentage of Participants
Percentage of Participants With Anti-Drug Antibodies (ADAs) (Double-Blind Treatment Phase) Treatment Emergent ADAs	7.0 Percentage of Participants	6.4 Percentage of Participants	—	5.0 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 156

Population: The Safety population was defined as all participants who had received at least one dose of Gantenerumab during the OLE phase. All participants in the Safety population also had at least one post-OLE baseline MRI. Data presented below is only for participants included in the actual analysis.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=51 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=21 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog-11) Scores at Week 156 (OLE Phase)	8.9 Scores on a Scale Standard Deviation 9.7	—	—	5.8 Scores on a Scale Standard Deviation 7.3

SECONDARY outcome

Timeframe: Baseline, Week 156

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=52 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=21 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Total Score at Week 156 (OLE Phase)	2.8 Scores on a Scale Standard Deviation 3.0	—	—	3.3 Scores on a Scale Standard Deviation 2.4

SECONDARY outcome

Timeframe: Baseline, Week 156

The ADAS-Cog-13 assesses multiple cognitive domains including memory, comprehension, praxis, orientation, and spontaneous speech. The score range for ADAS-Cog-13 is from 0 to 85 with higher scores representing severe dysfunction.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=51 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=21 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Alzheimer Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog-13) Scores at Week 156 (OLE Phase)	10.4 Scores on a Scale Standard Deviation 10.6	—	—	8.0 Scores on a Scale Standard Deviation 8.2

SECONDARY outcome

Timeframe: Baseline, Week 156

Time to Onset of Dementia was defined as the time interval between the first treatment date and the date that participant is assessed as having Alzheimer-type dementia by investigators.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=14 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=3 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Time to Onset of Dementia at Week 156 (OLE Phase)	50.82 Days Interval 32.04 to 66.87	—	—	38.18 Days Interval 9.9 to 66.97

SECONDARY outcome

Timeframe: Baseline, Week 156

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=51 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=22 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Free and Cued Selective Reminding Test (FCSRT) Score at Week 156 (OLE Phase)	-4.1 Scores on a Scale Standard Deviation 8.3	—	—	-7.7 Scores on a Scale Standard Deviation 9.3

SECONDARY outcome

Timeframe: Baseline, Week 156

Participants completed the FAQ for physical function. Overall scores ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=52 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=22 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Functional Activities Questionnaire (FAQ) Score at Week 156 (OLE Phase)	6.8 Scores on a Scale Standard Deviation 6.8	—	—	8.1 Scores on a Scale Standard Deviation 5.3

SECONDARY outcome

Timeframe: Baseline, Week 156

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=52 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=21 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in CDR-Global Score at Week 156 (OLE Phase)	0.5 Scores on a Scale Standard Deviation 0.6	—	—	0.6 Scores on a Scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: Baseline, Week 152

Change from baseline in hippocampal right volume (HRV) and hippocampal left volume (HLV) were analysed at Week 152 using magnetic resonance imaging.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=51 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=18 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) HRV (Week 152)	16.1 Percentage Change Standard Deviation 8.2	—	—	16.7 Percentage Change Standard Deviation 8.4
Percentage Change From Baseline in Hippocampal Volume at Week 152 (OLE Phase) HLV (Week 152)	18.0 Percentage Change Standard Deviation 8.9	—	—	16.2 Percentage Change Standard Deviation 13.0

SECONDARY outcome

Timeframe: Baseline, Week 156

The regions of the brain that were analyzed included cerebellum gray and composite reference.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=2 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) Cerebellum gray (Week 156)	—	—	—	-0.2 Percentage Change Standard Deviation 0.2
Percentage Change From Baseline in Cortical Composite Sustained Uptake Volume Ratio (SUVr) in Different Brain Regions at Week 156 (OLE Phase) Composite Reference (Week 156)	—	—	—	-41.4 Percentage Change Standard Deviation 29.9

SECONDARY outcome

Timeframe: Pre-Dose: Weeks 64, 100, 104, 136, 156 and 208; Post-Dose: Week 101

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=99 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Week 64 (Pre-Dose)	—	—	—	33.0 µg/ml (micrograms per milliliter) Standard Deviation 21.7
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Week 100 (Pre-Dose)	—	—	—	39.2 µg/ml (micrograms per milliliter) Standard Deviation 22.7
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Week 101 (Post-Dose)	—	—	—	80.5 µg/ml (micrograms per milliliter) Standard Deviation 37.8
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Week 104 (Pre-Dose)	—	—	—	40.5 µg/ml (micrograms per milliliter) Standard Deviation 22.5
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Week 136 (Pre-Dose)	—	—	—	45.2 µg/ml (micrograms per milliliter) Standard Deviation 22.4
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Week 156 (Pre-Dose)	—	—	—	39.6 µg/ml (micrograms per milliliter) Standard Deviation 28.2
Gantenerumab Plasma Concentrations at Different Time Points (OLE Phase) Week 208 (Pre-Dose)	—	—	—	37.1 µg/ml (micrograms per milliliter) Standard Deviation 29.2

SECONDARY outcome

Timeframe: Baseline, Week 156

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=53 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=22 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Mean Change From Baseline in Mini Mental State Exam (MMSE) Score at Week 156 (OLE Phase)	-4.7 Scores on a Scale Standard Deviation 4.6	—	—	-4.3 Scores on a Scale Standard Deviation 4.3

SECONDARY outcome

Timeframe: Baseline up until a maximum of 5 years

Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.

Outcome measures

Outcome measures
Measure	Gantenerumab 105 mg (Parts 1 and 2) n=104 Participants Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo Match Gantenerumab 225 mg (Parts 1 and 2) Participants with Alzheimer's disease received matching Placebo to Gantenerumab 225 mg by SC injection q4w for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) n=49 Participants Participants with Alzheimer's disease received Placebo SC injection (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.
Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) Baseline ADAs	5.8 Percentage of Participants	—	—	2.0 Percentage of Participants
Percentage of Participants With Anti-Drug Antibodies (ADAs) (OLE Phase) Treatment Emergent ADAs	2.9 Percentage of Participants	—	—	2.2 Percentage of Participants

Adverse Events

Placebo (Parts 1 and 2)

Serious events: 55 serious events

Other events: 163 other events

Deaths: 6 deaths

Gantenerumab 105 mg (Parts 1 and 2)

Serious events: 48 serious events

Other events: 188 other events

Deaths: 0 deaths

Gantenerumab 225 mg (Parts 1 and 2)

Serious events: 46 serious events

Other events: 189 other events

Deaths: 2 deaths

Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE])

Serious events: 18 serious events

Other events: 40 other events

Deaths: 1 deaths

Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE])

Serious events: 28 serious events

Other events: 87 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Placebo (Parts 1 and 2) n=266 participants at risk Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 105 mg (Parts 1 and 2) n=271 participants at risk Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=260 participants at risk Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) n=49 participants at risk Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) n=105 participants at risk Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Injury, poisoning and procedural complications Ankle fracture	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Femur fracture	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Laceration	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Ligament rupture	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Blood and lymphatic system disorders Anaemia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Acute myocardial infarction	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Arrhythmia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Cardiac disorders Atrial flutter	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Bradycardia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Cardiac disorders Cardiac failure	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Mitral valve incompetence	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Myocardial infarction	0.75% 2/266 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Cardiac disorders Supraventricular tachycardia	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Ear and labyrinth disorders Deafness unilateral	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Constipation	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Gastric haemorrhage	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Gastric ulcer	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Inguinal hernia	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Intestinal obstruction	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Asthenia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
General disorders Chest pain	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Gait disturbance	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Sudden death	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Infections and infestations Abdominal abscess	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Atypical pneumonia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations COVID-19	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Diverticulitis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Infections and infestations Infection	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Lower respiratory tract infection	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Otitis media	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Pelvic abscess	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Respiratory tract infection	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Infections and infestations Sepsis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Urinary tract infection	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Fall	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	4.1% 2/49 • Number of events 2 • Baseline up until a maximum of 9.5 years	3.8% 4/105 • Number of events 4 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Head injury	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Hip fracture	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.77% 2/260 • Number of events 2 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Joint injury	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Muscle strain	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Procedural pain	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Rib fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Investigations Body temperature increased	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Metabolism and nutrition disorders Dehydration	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Osteitis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Osteoarthritis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary cancer metastatic	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.75% 2/266 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell carcinoma	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders ARIA-E	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	1.9% 2/105 • Number of events 2 • Baseline up until a maximum of 9.5 years
Nervous system disorders Balance disorder	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Cerebellar infarction	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Cerebral haematoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Cerebral haemorrhage	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Dementia with Lewy bodies	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Epilepsy	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	1.9% 2/105 • Number of events 2 • Baseline up until a maximum of 9.5 years
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Nervous system disorders Headache	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Neuropathy peripheral	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Partial seizures	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Retrograde amnesia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Seizure	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Nervous system disorders Speech disorder	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Nervous system disorders Thalamic infarction	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Agitation	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Confusional state	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	2.9% 3/105 • Number of events 3 • Baseline up until a maximum of 9.5 years
Respiratory, thoracic and mediastinal disorders Delirium	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Delusion	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Neuropsychiatric symptoms	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Suicidal behaviour	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Reproductive system and breast disorders Prostatomegaly	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.77% 2/260 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Surgical and medical procedures Rotator cuff repair	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Surgical and medical procedures Urethral caruncle removal	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Vascular disorders Deep vein thrombosis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Vascular disorders Peripheral artery aneurysm	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Vascular disorders Peripheral ischaemia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Acute coronary syndrome	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Angina pectoris	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Angina unstable	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Arteriosclerosis coronary artery	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Atrial fibrillation	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Atrial thrombosis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Atrioventricular block second degree	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Cardiac ventricular thrombosis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Coronary artery disease	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.74% 2/271 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Myocardial rupture	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Cardiac disorders Sinus arrest	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Endocrine disorders Diabetes insipidus	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Eye disorders Retinal detachment	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.74% 2/271 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Eye disorders Visual impairment	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Abdominal distension	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Abdominal pain	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Diarrhoea	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Gastritis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Hiatus hernia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Pancreatic mass	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Umbilical hernia	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Device dislocation	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Malaise	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Pain	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Pyrexia	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Hepatobiliary disorders Cholecystitis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Hepatobiliary disorders Cholelithiasis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Immune system disorders Anaphylactic reaction	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Immune system disorders Type I hypersensitivity	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Investigations Blood pressure increased	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 4 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Investigations C-reactive protein increased	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Arthritis reactive	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Renal and urinary disorders Bladder obstruction	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Renal and urinary disorders Haematuria	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Reproductive system and breast disorders Cystocele	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Reproductive system and breast disorders Ovarian cyst	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Surgical and medical procedures Hip arthroplasty	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Surgical and medical procedures Knee arthroplasty	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Surgical and medical procedures Spinal decompression	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Vascular disorders Hypotension	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Vascular disorders Malignant hypertension	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Amyotrophic lateral sclerosis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Ischaemic stroke	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.77% 2/260 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Monoparesis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Presyncope	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Radial nerve palsy	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Syncope	0.75% 2/266 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Transient global amnesia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Transient ischaemic attack	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.77% 2/260 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Appendicitis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Bacterial sepsis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Cellulitis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Cholecystitis infective	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Cystitis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Erysipelas	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Gastroenteritis	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Gastroenteritis viral	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Lyme disease	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Pleural infection bacterial	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Pneumonia	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Post procedural infection	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Infections and infestations Subcutaneous abscess	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone sarcoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage II	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal tract adenoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioma	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intestinal adenocarcinoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pharyngeal neoplasm benign	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal oncocytoma	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage unspecified	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Post procedural haematuria	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Radiation mucositis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Radius fracture	0.75% 2/266 • Number of events 2 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Road traffic accident	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Tibia fracture	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Urinary retention postoperative	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Nervous system disorders Dizziness	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Anxiety	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.38% 1/260 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Behavioral and psychological symptoms of dementia	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Depression	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Major depression	0.38% 1/266 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Suicide attempt	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Surgical and medical procedures Urethral dilation procedure	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.37% 1/271 • Number of events 1 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years

Other adverse events

Other adverse events
Measure	Placebo (Parts 1 and 2) n=266 participants at risk Participants with Alzheimer's disease received Placebo by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 105 mg (Parts 1 and 2) n=271 participants at risk Participants with Alzheimer's disease received Gantenerumab 105 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Gantenerumab 225 mg (Parts 1 and 2) n=260 participants at risk Participants with Alzheimer's disease received Gantenerumab 225 mg by SC injection every 4 weeks (Q4W) for 104 weeks or approximately 2 years during Part 1 of the study. Participants who completed the Week 104 visit were given an option to continue the treatment received during Part 1, for 2 additional years in Part 2.	Placebo (Parts 1 and 2) Switched to Gantenerumab Up to 1200mg (Part 3 Open-Label Extension [OLE]) n=49 participants at risk Participants with Alzheimer's disease who had received Placebo by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.	Gantenerumab Up to 1200 mg (Part 3 Open-Label Extension [OLE]) n=105 participants at risk Participants with Alzheimer's disease who had received Gantenerumab by SC injection in Part 1 or Part 2, now received Gantenerumab at doses up to 1200 mg by SC injection every 4 weeks (Q4W) for up to 5 additional years.
Eye disorders Cataract	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	8.2% 4/49 • Number of events 5 • Baseline up until a maximum of 9.5 years	1.9% 2/105 • Number of events 3 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Diarrhoea	4.9% 13/266 • Number of events 18 • Baseline up until a maximum of 9.5 years	5.5% 15/271 • Number of events 22 • Baseline up until a maximum of 9.5 years	5.8% 15/260 • Number of events 18 • Baseline up until a maximum of 9.5 years	6.1% 3/49 • Number of events 3 • Baseline up until a maximum of 9.5 years	10.5% 11/105 • Number of events 14 • Baseline up until a maximum of 9.5 years
Gastrointestinal disorders Vomiting	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	10.2% 5/49 • Number of events 5 • Baseline up until a maximum of 9.5 years	5.7% 6/105 • Number of events 9 • Baseline up until a maximum of 9.5 years
General disorders Injection site erythema	1.1% 3/266 • Number of events 3 • Baseline up until a maximum of 9.5 years	10.7% 29/271 • Number of events 133 • Baseline up until a maximum of 9.5 years	13.5% 35/260 • Number of events 114 • Baseline up until a maximum of 9.5 years	34.7% 17/49 • Number of events 196 • Baseline up until a maximum of 9.5 years	34.3% 36/105 • Number of events 359 • Baseline up until a maximum of 9.5 years
Infections and infestations Bronchitis	3.8% 10/266 • Number of events 10 • Baseline up until a maximum of 9.5 years	3.7% 10/271 • Number of events 12 • Baseline up until a maximum of 9.5 years	5.4% 14/260 • Number of events 18 • Baseline up until a maximum of 9.5 years	6.1% 3/49 • Number of events 3 • Baseline up until a maximum of 9.5 years	6.7% 7/105 • Number of events 9 • Baseline up until a maximum of 9.5 years
Infections and infestations Herpes zoster	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	8.2% 4/49 • Number of events 4 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Infections and infestations Influenza	4.9% 13/266 • Number of events 14 • Baseline up until a maximum of 9.5 years	4.8% 13/271 • Number of events 18 • Baseline up until a maximum of 9.5 years	5.8% 15/260 • Number of events 17 • Baseline up until a maximum of 9.5 years	6.1% 3/49 • Number of events 4 • Baseline up until a maximum of 9.5 years	6.7% 7/105 • Number of events 8 • Baseline up until a maximum of 9.5 years
Infections and infestations Nasopharyngitis	6.4% 17/266 • Number of events 34 • Baseline up until a maximum of 9.5 years	11.1% 30/271 • Number of events 40 • Baseline up until a maximum of 9.5 years	7.7% 20/260 • Number of events 35 • Baseline up until a maximum of 9.5 years	14.3% 7/49 • Number of events 7 • Baseline up until a maximum of 9.5 years	14.3% 15/105 • Number of events 23 • Baseline up until a maximum of 9.5 years
Infections and infestations Upper respiratory tract infection	4.1% 11/266 • Number of events 14 • Baseline up until a maximum of 9.5 years	4.8% 13/271 • Number of events 15 • Baseline up until a maximum of 9.5 years	6.9% 18/260 • Number of events 21 • Baseline up until a maximum of 9.5 years	10.2% 5/49 • Number of events 5 • Baseline up until a maximum of 9.5 years	9.5% 10/105 • Number of events 19 • Baseline up until a maximum of 9.5 years
Infections and infestations Urinary tract infection	9.4% 25/266 • Number of events 37 • Baseline up until a maximum of 9.5 years	5.9% 16/271 • Number of events 25 • Baseline up until a maximum of 9.5 years	8.5% 22/260 • Number of events 38 • Baseline up until a maximum of 9.5 years	8.2% 4/49 • Number of events 6 • Baseline up until a maximum of 9.5 years	14.3% 15/105 • Number of events 25 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Contusion	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	8.2% 4/49 • Number of events 4 • Baseline up until a maximum of 9.5 years	4.8% 5/105 • Number of events 5 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Fall	10.5% 28/266 • Number of events 42 • Baseline up until a maximum of 9.5 years	8.5% 23/271 • Number of events 32 • Baseline up until a maximum of 9.5 years	10.4% 27/260 • Number of events 38 • Baseline up until a maximum of 9.5 years	26.5% 13/49 • Number of events 20 • Baseline up until a maximum of 9.5 years	16.2% 17/105 • Number of events 29 • Baseline up until a maximum of 9.5 years
Injury, poisoning and procedural complications Skin laceration	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	6.7% 7/105 • Number of events 8 • Baseline up until a maximum of 9.5 years
Investigations Weight decreased	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	4.1% 2/49 • Number of events 2 • Baseline up until a maximum of 9.5 years	5.7% 6/105 • Number of events 7 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 21/266 • Number of events 29 • Baseline up until a maximum of 9.5 years	4.4% 12/271 • Number of events 14 • Baseline up until a maximum of 9.5 years	6.2% 16/260 • Number of events 17 • Baseline up until a maximum of 9.5 years	4.1% 2/49 • Number of events 2 • Baseline up until a maximum of 9.5 years	7.6% 8/105 • Number of events 8 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Back pain	9.8% 26/266 • Number of events 33 • Baseline up until a maximum of 9.5 years	5.9% 16/271 • Number of events 18 • Baseline up until a maximum of 9.5 years	10.0% 26/260 • Number of events 32 • Baseline up until a maximum of 9.5 years	4.1% 2/49 • Number of events 2 • Baseline up until a maximum of 9.5 years	9.5% 10/105 • Number of events 10 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	6.1% 3/49 • Number of events 3 • Baseline up until a maximum of 9.5 years	0.95% 1/105 • Number of events 1 • Baseline up until a maximum of 9.5 years
Nervous system disorders Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits	11.7% 31/266 • Number of events 51 • Baseline up until a maximum of 9.5 years	21.4% 58/271 • Number of events 92 • Baseline up until a maximum of 9.5 years	13.8% 36/260 • Number of events 64 • Baseline up until a maximum of 9.5 years	14.3% 7/49 • Number of events 12 • Baseline up until a maximum of 9.5 years	16.2% 17/105 • Number of events 44 • Baseline up until a maximum of 9.5 years
Nervous system disorders Amyloid related imaging abnormality-oedema/effusion	0.75% 2/266 • Number of events 2 • Baseline up until a maximum of 9.5 years	6.6% 18/271 • Number of events 20 • Baseline up until a maximum of 9.5 years	13.1% 34/260 • Number of events 36 • Baseline up until a maximum of 9.5 years	24.5% 12/49 • Number of events 21 • Baseline up until a maximum of 9.5 years	27.6% 29/105 • Number of events 45 • Baseline up until a maximum of 9.5 years
Nervous system disorders Dizziness	7.9% 21/266 • Number of events 21 • Baseline up until a maximum of 9.5 years	7.7% 21/271 • Number of events 27 • Baseline up until a maximum of 9.5 years	10.0% 26/260 • Number of events 35 • Baseline up until a maximum of 9.5 years	8.2% 4/49 • Number of events 5 • Baseline up until a maximum of 9.5 years	13.3% 14/105 • Number of events 18 • Baseline up until a maximum of 9.5 years
Nervous system disorders Headache	13.5% 36/266 • Number of events 50 • Baseline up until a maximum of 9.5 years	12.5% 34/271 • Number of events 47 • Baseline up until a maximum of 9.5 years	9.6% 25/260 • Number of events 36 • Baseline up until a maximum of 9.5 years	14.3% 7/49 • Number of events 11 • Baseline up until a maximum of 9.5 years	11.4% 12/105 • Number of events 18 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Agitation	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	6.1% 3/49 • Number of events 4 • Baseline up until a maximum of 9.5 years	7.6% 8/105 • Number of events 10 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Anxiety	6.8% 18/266 • Number of events 23 • Baseline up until a maximum of 9.5 years	7.4% 20/271 • Number of events 20 • Baseline up until a maximum of 9.5 years	6.2% 16/260 • Number of events 16 • Baseline up until a maximum of 9.5 years	4.1% 2/49 • Number of events 2 • Baseline up until a maximum of 9.5 years	6.7% 7/105 • Number of events 8 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Confusional state	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	10.2% 5/49 • Number of events 5 • Baseline up until a maximum of 9.5 years	7.6% 8/105 • Number of events 8 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Irritability	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	2.0% 1/49 • Number of events 1 • Baseline up until a maximum of 9.5 years	5.7% 6/105 • Number of events 9 • Baseline up until a maximum of 9.5 years
Respiratory, thoracic and mediastinal disorders Cough	4.9% 13/266 • Number of events 14 • Baseline up until a maximum of 9.5 years	4.1% 11/271 • Number of events 13 • Baseline up until a maximum of 9.5 years	5.0% 13/260 • Number of events 13 • Baseline up until a maximum of 9.5 years	10.2% 5/49 • Number of events 5 • Baseline up until a maximum of 9.5 years	7.6% 8/105 • Number of events 12 • Baseline up until a maximum of 9.5 years
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/266 • Baseline up until a maximum of 9.5 years	0.00% 0/271 • Baseline up until a maximum of 9.5 years	0.00% 0/260 • Baseline up until a maximum of 9.5 years	6.1% 3/49 • Number of events 3 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Vascular disorders Hypertension	6.8% 18/266 • Number of events 20 • Baseline up until a maximum of 9.5 years	4.1% 11/271 • Number of events 11 • Baseline up until a maximum of 9.5 years	7.7% 20/260 • Number of events 23 • Baseline up until a maximum of 9.5 years	4.1% 2/49 • Number of events 2 • Baseline up until a maximum of 9.5 years	7.6% 8/105 • Number of events 11 • Baseline up until a maximum of 9.5 years
Psychiatric disorders Depression	4.9% 13/266 • Number of events 14 • Baseline up until a maximum of 9.5 years	8.5% 23/271 • Number of events 23 • Baseline up until a maximum of 9.5 years	9.6% 25/260 • Number of events 25 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
General disorders Fatigue	3.0% 8/266 • Number of events 8 • Baseline up until a maximum of 9.5 years	2.6% 7/271 • Number of events 7 • Baseline up until a maximum of 9.5 years	5.8% 15/260 • Number of events 20 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.0% 16/266 • Number of events 18 • Baseline up until a maximum of 9.5 years	2.2% 6/271 • Number of events 7 • Baseline up until a maximum of 9.5 years	1.9% 5/260 • Number of events 5 • Baseline up until a maximum of 9.5 years	0.00% 0/49 • Baseline up until a maximum of 9.5 years	0.00% 0/105 • Baseline up until a maximum of 9.5 years

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER