We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02783573
Recruitment Status : Terminated (An independent assessment concluded the trial was not likely to meet the primary endpoint upon completion and therefore, trial stopped for futility.)
First Posted : May 26, 2016
Results First Posted : August 6, 2019
Last Update Posted : December 3, 2019
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Alzheimer's Disease
Interventions Drug: Lanabecestat
Drug: Placebo
Enrollment 1722
Recruitment Details This study consists of Placebo-Controlled Treatment Period (Weeks 0 to 78) and Delayed-Start Period (Weeks 78 to 156).
Pre-assignment Details In Period 1, per the protocol, placebo-controlled groups (Placebo for 78 weeks then Lanabecestat 20 mg; Placebo for 78 weeks then Lanabecestat 50 mg) were combined to form one placebo group. As study terminated early and very few participants entered into the period 2, the arms in period 2 are combined based on dose exposure for ease of comparison.
Arm/Group Title Placebo Lanabecestat 20 Milligrams (mg) Lanabecestat 50 mg
Hide Arm/Group Description Participants received placebo film-coated oral tablets once daily. Participants received lanabecestat 20 mg film-coated oral tablets once daily. Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Period Title: Placebo-Controlled Treatment Period
Started 562 590 570
Received at Least 1 Dose of Study Drug 558 588 568
Completed 26 28 22
Not Completed 536 562 548
Reason Not Completed
Adverse Event             13             17             13
Death             4             2             3
Lack of Efficacy             0             0             2
Lost to Follow-up             3             3             1
Non-Compliance             0             1             0
Other-determined by Investigator             0             1             2
Physician Decision             3             1             3
Protocol Violation             1             2             0
Withdrawal by Subject             15             20             23
Withdrawal due to Caregiver Circumstance             3             3             9
Sponsor Decision             494             512             492
Period Title: Delayed-Start Period
Started 0 [1] 17 [2] 12 [2]
Received at Least 1 Dose of Study Drug 0 14 12
Completed 0 0 0
Not Completed 0 17 12
Reason Not Completed
Sponsor Decision             0             17             12
[1]
Participants from placebo group were randomized to Lanabecestat 20 mg and 50 mg.
[2]
Participants completed period 1 may not have entered period 2 due to early termination of the study.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg Total
Hide Arm/Group Description Participants received placebo film-coated oral tablets once daily. Participants received lanabecestat 20 mg film-coated oral tablets once daily. Participants received lanabecestat 50 mg film-coated oral tablets once daily. Total of all reporting groups
Overall Number of Baseline Participants 562 590 570 1722
Hide Baseline Analysis Population Description
All randomized participants who received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 562 participants 590 participants 570 participants 1722 participants
72.1  (7.1) 72.3  (7.0) 72.6  (7.0) 72.3  (7.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 562 participants 590 participants 570 participants 1722 participants
Female
348
  61.9%
335
  56.8%
340
  59.6%
1023
  59.4%
Male
214
  38.1%
255
  43.2%
230
  40.4%
699
  40.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 562 participants 590 participants 570 participants 1722 participants
Hispanic or Latino
53
   9.4%
45
   7.6%
55
   9.6%
153
   8.9%
Not Hispanic or Latino
416
  74.0%
442
  74.9%
423
  74.2%
1281
  74.4%
Unknown or Not Reported
93
  16.5%
103
  17.5%
92
  16.1%
288
  16.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 562 participants 590 participants 570 participants 1722 participants
American Indian or Alaska Native
5
   0.9%
7
   1.2%
6
   1.1%
18
   1.0%
Asian
64
  11.4%
76
  12.9%
69
  12.1%
209
  12.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.2%
3
   0.5%
4
   0.2%
Black or African American
4
   0.7%
5
   0.8%
9
   1.6%
18
   1.0%
White
387
  68.9%
398
  67.5%
389
  68.2%
1174
  68.2%
More than one race
72
  12.8%
70
  11.9%
62
  10.9%
204
  11.8%
Unknown or Not Reported
30
   5.3%
33
   5.6%
32
   5.6%
95
   5.5%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
 Number Analyzed 562 participants 590 participants 570 participants 1722 participants
United States
196
  34.9%
205
  34.7%
199
  34.9%
600
  34.8%
Czechia
42
   7.5%
42
   7.1%
45
   7.9%
129
   7.5%
Japan
38
   6.8%
43
   7.3%
38
   6.7%
119
   6.9%
United Kingdom
23
   4.1%
22
   3.7%
23
   4.0%
68
   3.9%
Portugal
8
   1.4%
8
   1.4%
8
   1.4%
24
   1.4%
Russia
33
   5.9%
36
   6.1%
31
   5.4%
100
   5.8%
Spain
25
   4.4%
25
   4.2%
28
   4.9%
78
   4.5%
Canada
32
   5.7%
33
   5.6%
31
   5.4%
96
   5.6%
South Korea
19
   3.4%
20
   3.4%
20
   3.5%
59
   3.4%
Netherlands
9
   1.6%
9
   1.5%
12
   2.1%
30
   1.7%
China
1
   0.2%
0
   0.0%
1
   0.2%
2
   0.1%
Taiwan
5
   0.9%
10
   1.7%
9
   1.6%
24
   1.4%
Poland
39
   6.9%
43
   7.3%
40
   7.0%
122
   7.1%
Denmark
7
   1.2%
8
   1.4%
8
   1.4%
23
   1.3%
Italy
23
   4.1%
22
   3.7%
21
   3.7%
66
   3.8%
Mexico
11
   2.0%
9
   1.5%
9
   1.6%
29
   1.7%
France
30
   5.3%
33
   5.6%
30
   5.3%
93
   5.4%
Germany
21
   3.7%
22
   3.7%
17
   3.0%
60
   3.5%
ADAS-Cog13 (13-item Alzheimer's Disease Assessment Scale)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a Scale
Number Analyzed 562 participants 590 participants 570 participants 1722 participants
30.4  (7.9) 30.6  (8.3) 30.6  (8.5) 30.5  (8.2)
[1]
Measure Description: ADAS-Cog13, a 13-item rating scale, measured the severity of cognitive dysfunction in persons with Alzheimer's disease (AD). Scores ranged from 0 to 85, with a higher score indicating worse cognitive functioning.
1.Primary Outcome
Title Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score
Hide Description ADAS-Cog13 (13-item version of ADAS Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment-by-visit interaction, acetylcholinesterase Inhibitor (AChEI) use at baseline, pooled site, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADAS-Cog13 measure.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 460 471 464
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
6.42  (1.23) 8.93  (1.11) 6.20  (1.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.129
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 2.51
Confidence Interval (2-Sided) 95%
-0.752 to 5.776
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.903
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-3.725 to 3.296
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.76
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items Score (ADCS-iADL)
Hide Description The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADL score, age at baseline, and baseline iADL score-by-visit interaction.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADCS-iADL measure.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 357 369 347
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-3.95  (1.27) -6.91  (1.29) -7.13  (1.40)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.100
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -2.95
Confidence Interval (2-Sided) 95%
-6.488 to 0.580
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.78
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.092
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -3.18
Confidence Interval (2-Sided) 95%
-6.876 to 0.525
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.86
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Functional Activities Questionnaire (FAQ) Score
Hide Description FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now=1; never did [the activity] but could do now=0; normal=0; has difficulty but does by self=1; requires assistance=2; Dependent =3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline FAQ total score, by-visit interaction and age at baseline.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for FAQ score.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 358 369 347
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
3.93  (0.81) 5.16  (0.85) 3.41  (0.91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.285
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
-1.045 to 3.499
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-2.889 to 1.843
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.19
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score
Hide Description The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADRS13 total score, age at baseline, and baseline iADRS13 total score-by-visit interaction.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for iADRS.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 342 348 333
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-10.46  (1.97) -15.22  (1.90) -12.43  (2.08)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -4.77
Confidence Interval (2-Sided) 95%
-10.103 to 0.56
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.486
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -1.97
Confidence Interval (2-Sided) 95%
-7.573 to 3.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.82
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
Hide Description The CDR-SB is a rater administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which no dementia = 0, questionable dementia = 0.5, mild dementia = 1, moderate dementia = 2 and severe dementia = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher scores indicating greater impairment. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline CDR-SB score, age at baseline, and baseline CDR-SB score-by-visit interaction.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CDR-SB.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 369 370 363
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
2.32  (0.42) 2.57  (0.41) 2.10  (0.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.663
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.890 to 1.391
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.57
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.717
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-1.423 to 0.983
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.60
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage
Hide Description The CDR global score is a composite score calculated using the Washington University CDR-assignment algorithm applied to the 6 individual domain box scores (Morris 1993). The memory domain is considered the primary category that drives the CDR global outcome, and all other domains are secondary. The CDR global score ranges from 0 to 3 (0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia).
Time Frame From Loss of 1 Global Stage through Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CDR global score.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 479 500 466
Median (95% Confidence Interval)
Unit of Measure: Days
379
(367 to 546)
367
(365 to 456)
449
(365 to 491)
7.Secondary Outcome
Title Change From Baseline in Neuropsychiatric Inventory (NPI) Score
Hide Description The NPI is a questionnaire administered to caregivers that quantifies behavioral changes. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144, with higher scores indicating a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline NPI score, age at baseline, and baseline NPI score-by-visit interaction.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for NPI.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 351 363 342
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
3.45  (1.70) 3.75  (1.84) 0.44  (1.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.899
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
-4.297 to 4.889
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -3.01
Confidence Interval (2-Sided) 95%
-7.267 to 1.238
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.16
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline on the Mini-Mental State Examination (MMSE)
Hide Description The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline MMSE total score, age at baseline, and baseline MMSE total score-by-visit interaction.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for MMSE.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 476 495 477
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-4.16  (0.59) -5.43  (0.58) -4.31  (0.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.126
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -1.26
Confidence Interval (2-Sided) 95%
-2.891 to 0.362
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.862
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-1.867 to 1.566
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.86
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42
Hide Description Concentration of the peptide Aβ 1-42 in plasma measured by validated immunoassay. LS Mean was determined by Analysis of covariance (ANCOVA) with last observation carried forward (LOCF), terms for treatment, baseline biomarker and age at baseline.
Time Frame Baseline, Week 71
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Aβ1-42.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 4 5 5
Least Squares Mean (Standard Error)
Unit of Measure: Percent change in Aβ1-42
23.68  (26.76) -13.87  (24.30) -17.04  (23.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.343
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -37.55
Confidence Interval (2-Sided) 95%
-122.35 to 47.26
Parameter Dispersion
Type: Standard Error of the Mean
Value: 37.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.276
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -40.72
Confidence Interval (2-Sided) 95%
-120.17 to 38.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 35.12
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40
Hide Description Concentration of the peptide Aβ 1-40 in plasma measured by immunoassay. LS Mean was determined by ANCOVA with LOCF (last observation carried forward), terms for treatment, baseline biomarker and age at baseline.
Time Frame Baseline, Week 71
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Aβ1-40.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 4 5 5
Least Squares Mean (Standard Error)
Unit of Measure: Percent change in Aβ1-40
24.52  (23.08) -37.42  (20.76) -9.63  (20.74)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -61.94
Confidence Interval (2-Sided) 95%
-132.75 to 8.87
Parameter Dispersion
Type: Standard Error of the Mean
Value: 31.30
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.303
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -34.15
Confidence Interval (2-Sided) 95%
-104.88 to 36.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 31.27
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in CSF Biomarker Total Tau
Hide Description Cerebrospinal fluid samples were collected for analysis of concentration total tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.
Time Frame Baseline, Week 71
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CSF Total Tau.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 4 5 5
Least Squares Mean (Standard Error)
Unit of Measure: Picogram per milliliter (pg/mL)
1.84  (9.75) 18.16  (9.77) -11.21  (9.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.283
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 16.32
Confidence Interval (2-Sided) 95%
-16.015 to 48.659
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.349
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -13.05
Confidence Interval (2-Sided) 95%
-42.929 to 16.820
Parameter Dispersion
Type: Standard Error of the Mean
Value: 13.21
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in CSF Biomarker Phosphorylated Tau
Hide Description Cerebrospinal fluid samples are collected for analysis of concentration of phosphorylated tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.
Time Frame Baseline, Week 71
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for CSF Phosphorylated Tau.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 4 5 5
Least Squares Mean (Standard Error)
Unit of Measure: Picogram per milliliter (pg/mL)
2.22  (1.54) 3.81  (1.49) 0.08  (1.41)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.494
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
-3.457 to 6.640
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.323
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -2.13
Confidence Interval (2-Sided) 95%
-6.743 to 2.481
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.04
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan
Hide Description Amyloid deposition in the brain is one of the defining neuropathologic findings of Alzheimer's disease. Florbetapir exhibits high affinity specific binding to amyloid plaques. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by florbetapir amyloid PET imaging in a subset of participants. The Centiloid scale standardizes quantitative brain amyloid PET results to allow cross-tracer and cross-methodology comparisons. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans. Florbetapir SUVr was converted to the Centiloid scale using the following conversion: Florbetapir Centiloids = 183 x SUVr - 177. LS Mean was determined by using ANCOVA methodology with terms for treatment, baseline biomarker and age at baseline.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for brain amyloid burden.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 7 10 7
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
-2.43  (10.47) -0.21  (7.79) -17.63  (9.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.873
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 2.22
Confidence Interval (2-Sided) 95%
-26.569 to 31.017
Parameter Dispersion
Type: Standard Error of the Mean
Value: 13.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.337
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -15.20
Confidence Interval (2-Sided) 95%
-47.488 to 17.096
Parameter Dispersion
Type: Standard Error of the Mean
Value: 15.43
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Regional Cerebral Blood Flow (rCBF) Using Florbetapir Perfusion Scan
Hide Description Florbetapir perfusion evaluated the regional cerebral blood flow (rCBF) as a biomarker of brain function and was performed at the same time as the amyloid florbetapir PET. Cerebral perfusion, especially in temporal and parietal areas, is reduced in AD and this pattern of hypoperfusion closely mirrors the hypometabolism pattern observed using FDG PET. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF (last observation carried forward) and with factors for treatment, baseline biomarker and age at baseline.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for rCBF.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 82 65 66
Least Squares Mean (Standard Error)
Unit of Measure: Standard Uptake Value ratio (SUVr)
-0.03  (0.01) -0.03  (0.01) -0.03  (0.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.927
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.015 to 0.017
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.930
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.015 to 0.017
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.01
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Whole Brain Volume
Hide Description Magnetic resonance imaging (MRI) was used to evaluate the effect of lanabecestat on brain atrophy/whole brain volumes. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline volumetric magnetic resonance imaging (vMRI), intracranial volume and age at baseline.
Time Frame Baseline, Week 78
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least one dose of study drug and have baseline and at least one post-baseline data for Whole Brain Volume.
Arm/Group Title Placebo Lanabecestat 20 mg Lanabecestat 50 mg
Hide Arm/Group Description:
Participants received placebo film-coated oral tablets once daily.
Participants received lanabecestat 20 mg film-coated oral tablets once daily.
Participants received lanabecestat 50 mg film-coated oral tablets once daily.
Overall Number of Participants Analyzed 221 215 214
Least Squares Mean (Standard Error)
Unit of Measure: cm^3 (cubic centimeter)
-15.76  (0.75) -17.38  (0.75) -18.84  (0.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 20 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.127
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -1.62
Confidence Interval (2-Sided) 95%
-3.708 to 0.464
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Lanabecestat 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference (Final Values)
Estimated Value -3.08
Confidence Interval (2-Sided) 95%
-5.172 to -0.991
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.06
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat
Hide Description The apparent oral clearance of lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.
Time Frame Predose, Week 4, 7, 19, 39, 45 and Week 71 post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug with evaluable PK data.
Arm/Group Title Lanabecestat
Hide Arm/Group Description:
Participants received Lanabecestat film-coated tablets orally.
Overall Number of Participants Analyzed 1077
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liter per hour (L/h)
17.4
(38.8%)
17.Secondary Outcome
Title Population PK: Central Volume of Distribution of Lanabecestat
Hide Description The central volume of distribution for lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.
Time Frame Predose, Week 4, 7, 19, 39, 45 and week 71 post dose
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug with evaluable PK data.
Arm/Group Title Lanabecestat
Hide Arm/Group Description:
Participants received Lanabecestat film-coated tablets orally.
Overall Number of Participants Analyzed 1077
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters (L)
77.8
(198%)
Time Frame Up To 156 Weeks
Adverse Event Reporting Description All randomized participants who received at least one dose of study drug. There are gender specific adverse events, only occurring in male or female participants. The number of participants exposed has been adjusted accordingly.
 
Arm/Group Title Placebo-Period 1 Lanabecestat 20 Mg-Period 1 Lanabecestat 50 Mg-Period 1 Lanabecestat 20 Mg-Period 2 Lanabecestat 50 Mg-Period 2
Hide Arm/Group Description Participants received placebo film-coated oral tablets once daily. Participants received lanabecestat 20 mg film-coated oral tablets once daily. Participants received lanabecestat 50 mg film-coated oral tablets once daily. Participants from placebo group were randomized to receive lanabecestat 20 mg film-coated oral tablets once daily. Participants from placebo group were randomized to receive lanabecestat 50 mg film-coated oral tablets once daily.
All-Cause Mortality
Placebo-Period 1 Lanabecestat 20 Mg-Period 1 Lanabecestat 50 Mg-Period 1 Lanabecestat 20 Mg-Period 2 Lanabecestat 50 Mg-Period 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/558 (0.90%)      2/588 (0.34%)      3/568 (0.53%)      0/14 (0.00%)      0/12 (0.00%)    
Hide Serious Adverse Events
Placebo-Period 1 Lanabecestat 20 Mg-Period 1 Lanabecestat 50 Mg-Period 1 Lanabecestat 20 Mg-Period 2 Lanabecestat 50 Mg-Period 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   50/558 (8.96%)      50/588 (8.50%)      46/568 (8.10%)      0/14 (0.00%)      1/12 (8.33%)    
Blood and lymphatic system disorders           
Iron deficiency anaemia † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cardiac disorders           
Acute coronary syndrome † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Acute myocardial infarction † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Atrial fibrillation † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 2/568 (0.35%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Atrial flutter † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Atrioventricular block complete † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Cardiac arrest † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cardiac failure congestive † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Cardio-respiratory arrest † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Chronotropic incompetence † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Coronary artery disease † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Myocardial infarction † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Sinus node dysfunction † 1  0/558 (0.00%)  0 2/588 (0.34%)  2 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Stress cardiomyopathy † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Trifascicular block † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Ventricular fibrillation † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Congenital, familial and genetic disorders           
Gastrointestinal arteriovenous malformation † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Ear and labyrinth disorders           
Vertigo positional † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorders           
Colitis † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Colitis ischaemic † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Constipation † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 2/568 (0.35%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Diverticulum † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal haemorrhage † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Inguinal hernia † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Intestinal obstruction † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Peptic ulcer perforation † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Rectal prolapse † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Vomiting † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
General disorders           
Chest pain † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Death † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Feeling abnormal † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Non-cardiac chest pain † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Sudden cardiac death † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Hepatobiliary disorders           
Cholecystitis acute † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Cholelithiasis † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Immune system disorders           
Anaphylactic reaction † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Infections and infestations           
Bacteraemia † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Bronchitis viral † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cellulitis † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cellulitis orbital † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Epididymitis † 1  1/211 (0.47%)  1 1/255 (0.39%)  1 0/229 (0.00%)  0 0/5 (0.00%)  0 0/7 (0.00%)  0
Erysipelas † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Liver abscess † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Orchitis † 1  1/211 (0.47%)  1 0/255 (0.00%)  0 0/229 (0.00%)  0 0/5 (0.00%)  0 0/7 (0.00%)  0
Pneumonia † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Sepsis † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Sinusitis † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Urinary tract infection † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Urosepsis † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Injury, poisoning and procedural complications           
Animal bite † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Ankle fracture † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Brain contusion † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Clavicle fracture † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Craniocerebral injury † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Fall † 1  1/558 (0.18%)  1 3/588 (0.51%)  3 5/568 (0.88%)  5 0/14 (0.00%)  0 0/12 (0.00%)  0
Femoral neck fracture † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Femur fracture † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Fibula fracture † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Forearm fracture † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Heat exhaustion † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Hip fracture † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Humerus fracture † 1  2/558 (0.36%)  2 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Lumbar vertebral fracture † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Pelvic fracture † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Post procedural complication † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Pubis fracture † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 2/568 (0.35%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Rib fracture † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 2/568 (0.35%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Road traffic accident † 1  2/558 (0.36%)  2 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Spinal compression fracture † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Spinal fracture † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Subdural haematoma † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Tibia fracture † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Upper limb fracture † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Wrist fracture † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Investigations           
Prostatic specific antigen increased † 1  0/211 (0.00%)  0 1/255 (0.39%)  1 0/229 (0.00%)  0 0/5 (0.00%)  0 0/7 (0.00%)  0
Metabolism and nutrition disorders           
Decreased appetite † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Dehydration † 1  0/558 (0.00%)  0 2/588 (0.34%)  2 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Hypoglycaemia † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Hyponatraemia † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 2/568 (0.35%)  3 0/14 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Cervical spinal stenosis † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Muscle haemorrhage † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Muscle spasms † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Myalgia † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Osteoarthritis † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Adenocarcinoma of colon † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Adenocarcinoma pancreas † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Bladder transitional cell carcinoma † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Brain neoplasm † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Breast cancer † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Colon cancer † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Colorectal cancer † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Invasive ductal breast carcinoma † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Lung adenocarcinoma † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Ovarian cancer recurrent † 1  0/347 (0.00%)  0 0/333 (0.00%)  0 1/339 (0.29%)  1 0/9 (0.00%)  0 0/5 (0.00%)  0
Ovarian cancer stage ii † 1  1/347 (0.29%)  1 0/333 (0.00%)  0 0/339 (0.00%)  0 0/9 (0.00%)  0 0/5 (0.00%)  0
Pancreatic carcinoma † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Papillary thyroid cancer † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Prostate cancer † 1  1/211 (0.47%)  1 1/255 (0.39%)  1 0/229 (0.00%)  0 0/5 (0.00%)  0 0/7 (0.00%)  0
Renal oncocytoma † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Squamous cell carcinoma of the tongue † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Nervous system disorders           
Brain injury † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cerebellar haematoma † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cerebral infarction † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cerebrovascular accident † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 2/568 (0.35%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Cognitive disorder † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Coma † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Dementia Alzheimer's type † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Dizziness † 1  2/558 (0.36%)  2 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Encephalopathy † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Generalised tonic-clonic seizure † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Haemorrhage intracranial † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Headache † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Presyncope † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Seizure † 1  1/558 (0.18%)  1 1/588 (0.17%)  2 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Syncope † 1  3/558 (0.54%)  3 3/588 (0.51%)  3 3/568 (0.53%)  4 0/14 (0.00%)  0 0/12 (0.00%)  0
Toxic encephalopathy † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Transient ischaemic attack † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Product Issues           
Device malfunction † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Psychiatric disorders           
Abnormal behaviour † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Acute psychosis † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Adjustment disorder † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Aggression † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Confusional state † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Delirium † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 2/568 (0.35%)  2 0/14 (0.00%)  0 0/12 (0.00%)  0
Delusion † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Mental status changes † 1  2/558 (0.36%)  2 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Paranoia † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Psychotic disorder † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 1/12 (8.33%)  1
Renal and urinary disorders           
Acute kidney injury † 1  2/558 (0.36%)  2 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Stress urinary incontinence † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Chronic obstructive pulmonary disease † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Hiccups † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Hypoxia † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Lung disorder † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Pleural effusion † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Pneumonia aspiration † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Pneumothorax † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Pulmonary embolism † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 1/568 (0.18%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Respiratory arrest † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Vascular disorders           
Deep vein thrombosis † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Hypertension † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Peripheral ischaemia † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Thrombosis † 1  1/558 (0.18%)  1 0/588 (0.00%)  0 0/568 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo-Period 1 Lanabecestat 20 Mg-Period 1 Lanabecestat 50 Mg-Period 1 Lanabecestat 20 Mg-Period 2 Lanabecestat 50 Mg-Period 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   48/558 (8.60%)      69/588 (11.73%)      76/568 (13.38%)      5/14 (35.71%)      1/12 (8.33%)    
Eye disorders           
Glaucoma † 1  5/558 (0.90%)  5 4/588 (0.68%)  4 3/568 (0.53%)  3 1/14 (7.14%)  1 0/12 (0.00%)  0
Gastrointestinal disorders           
Diarrhoea † 1  17/558 (3.05%)  19 29/588 (4.93%)  35 29/568 (5.11%)  39 0/14 (0.00%)  0 0/12 (0.00%)  0
General disorders           
Influenza like illness † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 4/568 (0.70%)  4 1/14 (7.14%)  1 0/12 (0.00%)  0
Injury, poisoning and procedural complications           
Fall † 1  21/558 (3.76%)  34 32/588 (5.44%)  37 34/568 (5.99%)  49 0/14 (0.00%)  0 0/12 (0.00%)  0
Investigations           
Blood glucose decreased † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 0/568 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Thyroxine decreased † 1  0/558 (0.00%)  0 0/588 (0.00%)  0 2/568 (0.35%)  2 1/14 (7.14%)  1 0/12 (0.00%)  0
Metabolism and nutrition disorders           
Hyperlipidaemia † 1  1/558 (0.18%)  1 1/588 (0.17%)  1 1/568 (0.18%)  1 1/14 (7.14%)  1 0/12 (0.00%)  0
Psychiatric disorders           
Confusional state † 1  2/558 (0.36%)  2 4/588 (0.68%)  4 9/568 (1.58%)  9 1/14 (7.14%)  1 0/12 (0.00%)  0
Psychotic disorder † 1  0/558 (0.00%)  0 1/588 (0.17%)  1 0/568 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Reproductive system and breast disorders           
Benign prostatic hyperplasia † 1  4/211 (1.90%)  4 4/255 (1.57%)  4 3/229 (1.31%)  3 1/5 (20.00%)  1 0/7 (0.00%)  0
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
An independent assessment concluded the trial was not likely to meet the primary endpoint upon completion and therefore, trial stopped for futility.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor shall review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: AstraZeneca Information Center
Organization: AstraZeneca
Phone: 1-877-240-9479
EMail: information.center@astrazeneca.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02783573    
Other Study ID Numbers: 16024
I8D-MC-AZET ( Other Identifier: Eli Lilly and Company )
2015-005625-39 ( EudraCT Number )
First Submitted: May 24, 2016
First Posted: May 26, 2016
Results First Submitted: June 11, 2019
Results First Posted: August 6, 2019
Last Update Posted: December 3, 2019