Trial Outcomes & Findings for Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo (NCT NCT00762411)
NCT ID: NCT00762411
Last Updated: 2015-02-16
Results Overview
The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
COMPLETED
PHASE3
1111 participants
Baseline (randomization), 76 weeks
2015-02-16
Participant Flow
Participant milestones
| Measure |
140 mg LY450139
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Initial Treatment
STARTED
|
556
|
555
|
|
Initial Treatment
Intent-to-treat (ITT)
|
555
|
553
|
|
Initial Treatment
COMPLETED
|
22
|
34
|
|
Initial Treatment
NOT COMPLETED
|
534
|
521
|
|
Delayed Start
STARTED
|
22
|
34
|
|
Delayed Start
COMPLETED
|
5
|
8
|
|
Delayed Start
NOT COMPLETED
|
17
|
26
|
|
Safety Follow Up (SFU)-Optional
STARTED
|
312
|
430
|
|
Safety Follow Up (SFU)-Optional
COMPLETED
|
228
|
312
|
|
Safety Follow Up (SFU)-Optional
NOT COMPLETED
|
84
|
118
|
Reasons for withdrawal
| Measure |
140 mg LY450139
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Initial Treatment
Death
|
7
|
6
|
|
Initial Treatment
Adverse Event
|
132
|
40
|
|
Initial Treatment
Protocol Violation
|
4
|
1
|
|
Initial Treatment
Withdrawal by Subject
|
65
|
52
|
|
Initial Treatment
Physician Decision
|
1
|
0
|
|
Initial Treatment
Sponsor Decision
|
293
|
401
|
|
Initial Treatment
Lost to Follow-up
|
5
|
0
|
|
Initial Treatment
Caregiver Decision
|
21
|
16
|
|
Initial Treatment
Abnormal Lab/ECG Result
|
6
|
4
|
|
Initial Treatment
Entry Criteria Exclusion
|
0
|
1
|
|
Delayed Start
Adverse Event
|
0
|
4
|
|
Delayed Start
Protocol Violation
|
0
|
1
|
|
Delayed Start
Sponsor Decision
|
16
|
20
|
|
Delayed Start
Caregiver Decision
|
1
|
1
|
|
Safety Follow Up (SFU)-Optional
Death
|
1
|
8
|
|
Safety Follow Up (SFU)-Optional
Adverse Event
|
0
|
1
|
|
Safety Follow Up (SFU)-Optional
Withdrawal by Subject
|
21
|
46
|
|
Safety Follow Up (SFU)-Optional
Lost to Follow-up
|
6
|
1
|
|
Safety Follow Up (SFU)-Optional
Caregiver Decision
|
8
|
8
|
|
Safety Follow Up (SFU)-Optional
No safety visit or SFU
|
48
|
54
|
Baseline Characteristics
Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo
Baseline characteristics by cohort
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
Total
n=1108 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
73.4 years
STANDARD_DEVIATION 8.0 • n=5 Participants
|
73.0 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
73.2 years
STANDARD_DEVIATION 8.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
316 Participants
n=5 Participants
|
327 Participants
n=7 Participants
|
643 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
239 Participants
n=5 Participants
|
226 Participants
n=7 Participants
|
465 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
358 participants
n=5 Participants
|
354 participants
n=7 Participants
|
712 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African
|
11 participants
n=5 Participants
|
8 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
33 participants
n=5 Participants
|
29 participants
n=7 Participants
|
62 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
East Asian
|
150 participants
n=5 Participants
|
160 participants
n=7 Participants
|
310 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
West Asian
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
18 participants
n=5 Participants
|
21 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
20 participants
n=5 Participants
|
18 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
50 participants
n=5 Participants
|
49 participants
n=7 Participants
|
99 participants
n=5 Participants
|
|
Region of Enrollment
China
|
22 participants
n=5 Participants
|
22 participants
n=7 Participants
|
44 participants
n=5 Participants
|
|
Region of Enrollment
France
|
28 participants
n=5 Participants
|
29 participants
n=7 Participants
|
57 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
24 participants
n=5 Participants
|
20 participants
n=7 Participants
|
44 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
19 participants
n=5 Participants
|
16 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
14 participants
n=5 Participants
|
11 participants
n=7 Participants
|
25 participants
n=5 Participants
|
|
Region of Enrollment
Japan
|
64 participants
n=5 Participants
|
69 participants
n=7 Participants
|
133 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
38 participants
n=5 Participants
|
43 participants
n=7 Participants
|
81 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
26 participants
n=5 Participants
|
24 participants
n=7 Participants
|
50 participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
20 participants
n=5 Participants
|
17 participants
n=7 Participants
|
37 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
15 participants
n=5 Participants
|
19 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Region of Enrollment
Serbia
|
5 participants
n=5 Participants
|
8 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Taiwan
|
25 participants
n=5 Participants
|
24 participants
n=7 Participants
|
49 participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
25 participants
n=5 Participants
|
23 participants
n=7 Participants
|
48 participants
n=5 Participants
|
|
Region of Enrollment
Ukraine
|
19 participants
n=5 Participants
|
20 participants
n=7 Participants
|
39 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
123 participants
n=5 Participants
|
120 participants
n=7 Participants
|
243 participants
n=5 Participants
|
|
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) Score (n=507, 533)
|
24.5 units on a scale
STANDARD_DEVIATION 9.1 • n=5 Participants
|
24.2 units on a scale
STANDARD_DEVIATION 9.1 • n=7 Participants
|
24.3 units on a scale
STANDARD_DEVIATION 9.1 • n=5 Participants
|
|
Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory Score (n=505, 529)
|
58.8 units on a scale
STANDARD_DEVIATION 13.3 • n=5 Participants
|
59.1 units on a scale
STANDARD_DEVIATION 13.8 • n=7 Participants
|
58.9 units on a scale
STANDARD_DEVIATION 13.5 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks
|
7.37 units on a scale
Standard Error 0.79
|
6.77 units on a scale
Standard Error 0.72
|
PRIMARY outcome
Timeframe: Baseline (randomization), 16 weeks following treatment cessationPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
The cognitive subscale of ADAS (ADAS Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=312 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=430 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug
|
4.81 units on a scale
Standard Error 0.70
|
4.85 units on a scale
Standard Error 0.63
|
PRIMARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
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 total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks
|
-10.49 units on a scale
Standard Error 0.98
|
-9.77 units on a scale
Standard Error 0.90
|
PRIMARY outcome
Timeframe: Baseline (randomization), 16 weeks following treatment cessationPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
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 total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=312 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=430 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug
|
-8.88 units on a scale
Standard Error 0.93
|
-7.68 units on a scale
Standard Error 0.84
|
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=22 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=34 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks
|
3.05 units on a scale
Standard Error 1.10
|
4.00 units on a scale
Standard Error 0.92
|
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the participant's behavior. Total score ranges from 12 to 144; higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks
|
2.94 units on a scale
Standard Error 1.04
|
3.84 units on a scale
Standard Error 0.95
|
SECONDARY outcome
Timeframe: Baseline (randomization), up to 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Assesses healthcare resource utilization (formal and informal care). Information gathered on both caregivers (care-giving time, work status) and participants (accommodation and healthcare resource utilization) was gathered from baseline and follow-up interviews. Reported number of hospitalizations per participant up to 76 weeks. Least Squares (LS) Mean value was controlled for age and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks
|
0.72 number of hospitalizations
Standard Error 0.14
|
0.82 number of hospitalizations
Standard Error 0.16
|
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression; each has 3 severity levels (no, some, severe problems) coded to a 1-digit number (1-3). Digits are combined into 5-digit number describing health state. Numerals 1-3 are not added for total score. VAS assesses caregiver's impression of participant's overall health state; scores range: 0 to 100. Lower scores indicate greater disease severity. Least Squares (LS) Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in the EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) at 76 Weeks
|
-4.46 units on a scale
Standard Error 1.78
|
-3.38 units on a scale
Standard Error 1.64
|
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Assess QoL for AD: participant rates mood, relationships, memory, finances, physical condition, and overall QoL assessment. Each of 13 items, rated on a 4-point scale. Sum of items=total score (range: 13 to 52). Higher scores indicate greater QoL. Participant's primary caregiver asked to complete same measure. Least Squares (LS) Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks
|
-1.83 units on a scale
Standard Error 0.47
|
-1.05 units on a scale
Standard Error 0.43
|
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
MMSE is a brief screening instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges from 0 to 30; lower score indicates greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks
|
-3.56 units on a scale
Standard Error 0.38
|
-3.35 units on a scale
Standard Error 0.35
|
SECONDARY outcome
Timeframe: Baseline (randomization), 52 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
Concentration of amino acid peptide known as Aβ 1-42 in plasma. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks
|
-16.03 picogram per milliliter (pg/mL)
Standard Error 28.33
|
76.37 picogram per milliliter (pg/mL)
Standard Error 24.73
|
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
Measurement of local cerebral glucose metabolism by PET using the radioactive tracer 18F-FDG. The outcome reported is the composite summary of the standard uptake value ratio (SUVR) normalized to the Pons. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=74 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=80 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks
|
-0.13 ratio
Standard Error 0.05
|
-0.08 ratio
Standard Error 0.03
|
SECONDARY outcome
Timeframe: Baseline (randomization), up to 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
The vMRI assessment of right and left hippocampal volume is reported. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks
Right Hippocampal Volume
|
-158.50 cubic millimeter (mm^3)
Standard Error 29.44
|
-73.60 cubic millimeter (mm^3)
Standard Error 24.18
|
|
Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks
Left Hippocampal Volume
|
-84.41 cubic millimeter (mm^3)
Standard Error 61.96
|
-111.27 cubic millimeter (mm^3)
Standard Error 49.22
|
SECONDARY outcome
Timeframe: Baseline (randomization), up to 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
A radioactive tracer for PET that is a ligand for amyloid called \[18F\]-AV-45. This permits the visualization of amyloid in the brains of Alzheimer's participants. The outcome reported is the composite summary of the standard uptake value ratio (SUVR) normalized to the cerebellar gray matter. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks
|
-0.36 ratio
Standard Error 0.23
|
0.16 ratio
Standard Error 0.11
|
SECONDARY outcome
Timeframe: Baseline (randomization), up to 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Concentration of total tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks
|
-11.60 picogram per milliliter (pg/mL)
Standard Error 39.39
|
117.88 picogram per milliliter (pg/mL)
Standard Error 53.58
|
SECONDARY outcome
Timeframe: 6 weeks, 12 weeks, and 52 weeksPopulation: All participants randomized to LY450139 with sufficient dosing information and concentration data to allow estimation of pharmacokinetic parameters.
Model estimated apparent oral clearance. Clearance is defined as the volume of plasma which is completely cleared of drug (LY450139) per unit time.
Outcome measures
| Measure |
140 mg LY450139
n=517 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
LY450139 Population Pharmacokinetics: Clearance of LY450139
|
18.9 liters per hour (L/h)
Geometric Coefficient of Variation 26.6
|
—
|
SECONDARY outcome
Timeframe: 6 weeks, 12 weeks, and 52 weeksPopulation: All participants randomized to LY450139 with sufficient dosing information and concentration data to allow estimation of pharmacokinetic parameters.
Model-estimated apparent volume of distribution. Volume of distribution is a measure of the extent to which drug distributes in the body.
Outcome measures
| Measure |
140 mg LY450139
n=517 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139
|
66.1 liters (L)
Geometric Coefficient of Variation 26.2
|
—
|
SECONDARY outcome
Timeframe: Baseline (randomization), 4 weeks following treatment cessationPopulation: August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Semi-structured interview. Participant's cognitive status rated across 6 domains of functioning: memory, orientation, judgment/problem solving, community affairs, home/hobbies, personal care. Severity score assigned for each of 6 domains; total score (SB) ranges: 0 to 18. Higher scores=greater disease severity. Least Squares Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care medication. LY450139 dosing stopped due to evidence of dose-dependent cognitive/functional worsening. Participants followed off-dose for 32 weeks, but CDR-SB not assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (randomization), 4 weeks following treatment cessationPopulation: August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
NPI assesses psychopathology in participants with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with participant's behavior. Total score ranges from 12 to 144; higher scores indicate greater disease severity. The Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but NPI was not assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (randomization), 4 weeks following treatment cessationPopulation: August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Assesses healthcare resource utilization (formal and informal care). Information gathered on both care-giving time, work status) and participants (accommodation, healthcare resource utilization) is collected. Reported number of participant hospitalizations. Least Squares (LS) Mean value controlled for age and investigator. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but RUD-Lite was not assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (randomization), 4 weeks following treatment cessationPopulation: August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression. 3 severity levels: no, some, severe problems. VAS assesses caregiver's impression of participant's health state; score ranges: 0 to 100. Lower scores=greater disease severity. Least Squares (LS) Mean value controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but EQ-5D VAS was not assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (randomization), 4 weeks following treatment cessationPopulation: August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Assess QoL for AD; participant rates mood, relationships, memory, finances, physical condition, and overall QoL assessment. Each of 13 items rated on a 4-point scale. Sum of items=total score (range: 13-52). Higher scores=greater QoL. Participant's primary caregiver asked to complete same measure. Least Squares Mean value controlled for baseline, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but QoL-AD not assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (randomization), 4 weeks following treatment cessationPopulation: August 2010: all dosing was stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening of LY450139-treated participants. Participants were followed off-dose for 32 weeks. No analysis was performed at 4 weeks after cessation of drug since this outcome measure was not assessed during the follow-up period.
Used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures) in elderly participants. Total score ranges: 0 to 30. Lower score indicates greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication. All LY450139 dosing was stopped due to evidence of dose-dependent cognitive/functional worsening. Participants were followed off-dose for 32 weeks, but MMSE was not assessed.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
ADAS-Cog12 is ADAS-Cog11 augmented with delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=22 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=34 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks
|
10.09 units on a scale
Standard Error 3.29
|
10.34 units on a scale
Standard Error 2.67
|
SECONDARY outcome
Timeframe: Baseline (randomization), 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication.
ADAS-Cog14 is ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks
|
9.23 units on a scale
Standard Error 0.90
|
8.32 units on a scale
Standard Error 0.82
|
SECONDARY outcome
Timeframe: Baseline (randomization), up to 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Concentration of p-tau in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks
|
7.94 picogram per milliliter (pg/mL)
Standard Error 3.06
|
14.75 picogram per milliliter (pg/mL)
Standard Error 4.68
|
SECONDARY outcome
Timeframe: Baseline (randomization), up to 76 weeksPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication, last observation carried forward (LOCF).
Concentration of an amino acid peptide known as Aβ 1-42 in spinal fluid. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator.
Outcome measures
| Measure |
140 mg LY450139
n=555 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=553 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks
|
19.20 picogram per milliliter (pg/mL)
Standard Error 26.03
|
-21.39 picogram per milliliter (pg/mL)
Standard Error 35.35
|
SECONDARY outcome
Timeframe: Baseline (randomization), 16 weeks following treatment cessationPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
ADAS-Cog12 is ADAS-Cog11 augmented with delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, and concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=312 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=430 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug
|
5.33 units on a scale
Standard Error 0.74
|
5.14 units on a scale
Standard Error 0.67
|
SECONDARY outcome
Timeframe: Baseline (randomization), 16 weeks following treatment cessationPopulation: Intent to treat (ITT) population: All randomized participants who received at least 1 dose of study medication and had both baseline and post-baseline evaluable data.
ADAS-Cog14 is ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Squares (LS) Mean value was controlled for baseline value, age, investigator, visit, concomitant standard of care (SOC) medication.
Outcome measures
| Measure |
140 mg LY450139
n=312 Participants
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
Placebo
n=430 Participants
Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.
|
|---|---|---|
|
Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug
|
6.00 units on a scale
Standard Error 0.82
|
5.89 units on a scale
Standard Error 0.73
|
Adverse Events
Placebo- (Initial Treatment Period [NT])
140 mg LY450139- NT
Placebo- (Delayed Start Period [DO])
140 mg LY450139- DO
Placebo-Safety Follow Up Period (SFU)
140 mg LY450139 - SFU
Serious adverse events
| Measure |
Placebo- (Initial Treatment Period [NT])
n=555 participants at risk
Participants received placebo orally once daily for the first 76 weeks.
|
140 mg LY450139- NT
n=556 participants at risk
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 76.
|
Placebo- (Delayed Start Period [DO])
n=34 participants at risk
After Week 76, participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
140 mg LY450139- DO
n=22 participants at risk
After Week 76, participants received 140 mg LY450139 orally once daily until Week 88.
|
Placebo-Safety Follow Up Period (SFU)
n=430 participants at risk
For SFU, study drug had been stopped and period was optional to enter; Participants entered from Placebo initial treatment or delayed start or did not enter SFU.
|
140 mg LY450139 - SFU
n=312 participants at risk
For SFU, study drug had been stopped and period was optional to enter; Participants entered from 140 mg LY450139 initial treatment or delayed start or did not enter SFU.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia folate deficiency
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Cardiac disorders
Angina pectoris
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Cardiac disorders
Aortic valve stenosis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Cardiac disorders
Bradycardia
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Cardiac disorders
Cardiac arrest
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Cardiac disorders
Cardiac failure acute
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Cardiac disorders
Myocardial ischaemia
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.47%
2/430 • Number of events 2
|
0.00%
0/312
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Eye disorders
Cataract
|
0.36%
2/555 • Number of events 2
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Eye disorders
Retinal artery occlusion
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
4.5%
1/22 • Number of events 1
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.18%
1/555 • Number of events 1
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.00%
0/555
|
0.00%
0/556
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Gastrointestinal disorders
Enterocolitis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Pancreatitis
|
0.18%
1/555 • Number of events 1
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/555
|
0.00%
0/556
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
General disorders
Accidental death
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
General disorders
Chest pain
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
General disorders
Death
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
General disorders
Sudden cardiac death
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/555
|
0.18%
1/556 • Number of events 2
|
0.00%
0/34
|
4.5%
1/22 • Number of events 1
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Hepatobiliary disorders
Cholangitis
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Hepatobiliary disorders
Cholecystitis
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Hepatobiliary disorders
Cholecystitis chronic
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.18%
1/555 • Number of events 1
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Hepatobiliary disorders
Hepatitis toxic
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Anal abscess
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Appendicitis
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Infections and infestations
Bronchitis
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Infections and infestations
Clostridial infection
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Cystitis
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Infections and infestations
Diabetic gangrene
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Meningitis bacterial
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Pneumonia
|
0.36%
2/555 • Number of events 2
|
2.2%
12/556 • Number of events 13
|
0.00%
0/34
|
0.00%
0/22
|
0.47%
2/430 • Number of events 2
|
0.32%
1/312 • Number of events 1
|
|
Infections and infestations
Pneumonia staphylococcal
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Pyelonephritis acute
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Salmonella sepsis
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Sepsis
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Septic shock
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Staphylococcal infection
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Urinary tract infection
|
0.54%
3/555 • Number of events 3
|
0.72%
4/556 • Number of events 4
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Urosepsis
|
0.36%
2/555 • Number of events 2
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Fall
|
0.54%
3/555 • Number of events 3
|
0.54%
3/556 • Number of events 3
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.36%
2/555 • Number of events 3
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Fractured sacrum
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Heat exhaustion
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Post lumbar puncture syndrome
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.18%
1/555 • Number of events 1
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.64%
2/312 • Number of events 2
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.18%
1/555 • Number of events 1
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Thoracic vertebral fracture
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Investigations
Blood glucose increased
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Investigations
Medical observation
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Metabolism and nutrition disorders
Dehydration
|
0.36%
2/555 • Number of events 2
|
0.54%
3/556 • Number of events 3
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Metabolism and nutrition disorders
Food intolerance
|
0.00%
0/555
|
0.00%
0/556
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/555
|
0.00%
0/556
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bile duct cancer
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.18%
1/555 • Number of events 1
|
0.54%
3/556 • Number of events 3
|
0.00%
0/34
|
0.00%
0/22
|
0.47%
2/430 • Number of events 2
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.30%
1/328 • Number of events 1
|
0.00%
0/317
|
0.00%
0/20
|
0.00%
0/12
|
0.00%
0/251
|
0.00%
0/184
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic cancer metastatic
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Keratoacanthoma
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung cancer metastatic
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neurilemmoma
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.18%
1/555 • Number of events 1
|
0.54%
3/556 • Number of events 3
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.36%
2/555 • Number of events 2
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Cerebral infarction
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Nervous system disorders
Coma
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Convulsion
|
0.18%
1/555 • Number of events 1
|
0.54%
3/556 • Number of events 3
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Nervous system disorders
Dementia alzheimer's type
|
0.36%
2/555 • Number of events 2
|
0.36%
2/556 • Number of events 2
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Guillain-barre syndrome
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.18%
1/555 • Number of events 1
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Hydrocephalus
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Loss of consciousness
|
0.36%
2/555 • Number of events 2
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Nervous system disorders
Normal pressure hydrocephalus
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Status epilepticus
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Syncope
|
0.72%
4/555 • Number of events 4
|
0.90%
5/556 • Number of events 5
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.32%
1/312 • Number of events 1
|
|
Nervous system disorders
Thalamus haemorrhage
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Psychiatric disorders
Aggression
|
0.18%
1/555 • Number of events 1
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Psychiatric disorders
Agitation
|
0.18%
1/555 • Number of events 1
|
0.36%
2/556 • Number of events 2
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Psychiatric disorders
Confusional state
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Psychiatric disorders
Delirium
|
0.00%
0/555
|
0.36%
2/556 • Number of events 2
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Psychiatric disorders
Hallucination
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Renal and urinary disorders
Calculus ureteric
|
0.18%
1/555 • Number of events 1
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Renal and urinary disorders
Urethral caruncle
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Reproductive system and breast disorders
Prostatitis
|
0.00%
0/227
|
0.42%
1/239 • Number of events 1
|
0.00%
0/14
|
0.00%
0/10
|
0.00%
0/179
|
0.78%
1/128 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.23%
1/430 • Number of events 1
|
0.00%
0/312
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/555
|
0.00%
0/556
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Social circumstances
Activities of daily living impaired
|
0.00%
0/555
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Vascular disorders
Aortic dissection
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.32%
1/312 • Number of events 1
|
|
Vascular disorders
Arteriosclerosis obliterans
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/555
|
0.18%
1/556 • Number of events 1
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Vascular disorders
Haematoma
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Vascular disorders
Hypertension
|
0.18%
1/555 • Number of events 1
|
0.00%
0/556
|
2.9%
1/34 • Number of events 1
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
Other adverse events
| Measure |
Placebo- (Initial Treatment Period [NT])
n=555 participants at risk
Participants received placebo orally once daily for the first 76 weeks.
|
140 mg LY450139- NT
n=556 participants at risk
Participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 76.
|
Placebo- (Delayed Start Period [DO])
n=34 participants at risk
After Week 76, participants received 60 mg LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.
|
140 mg LY450139- DO
n=22 participants at risk
After Week 76, participants received 140 mg LY450139 orally once daily until Week 88.
|
Placebo-Safety Follow Up Period (SFU)
n=430 participants at risk
For SFU, study drug had been stopped and period was optional to enter; Participants entered from Placebo initial treatment or delayed start or did not enter SFU.
|
140 mg LY450139 - SFU
n=312 participants at risk
For SFU, study drug had been stopped and period was optional to enter; Participants entered from 140 mg LY450139 initial treatment or delayed start or did not enter SFU.
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
33/555 • Number of events 42
|
10.4%
58/556 • Number of events 72
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Hiatus hernia
|
0.00%
0/555
|
0.00%
0/556
|
5.9%
2/34 • Number of events 2
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Nausea
|
3.4%
19/555 • Number of events 24
|
8.8%
49/556 • Number of events 53
|
5.9%
2/34 • Number of events 2
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Gastrointestinal disorders
Vomiting
|
3.1%
17/555 • Number of events 22
|
5.9%
33/556 • Number of events 46
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Nasopharyngitis
|
4.0%
22/555 • Number of events 24
|
5.0%
28/556 • Number of events 31
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/555
|
0.00%
0/556
|
8.8%
3/34 • Number of events 3
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Investigations
Prostatic specific antigen increased
|
0.00%
0/227
|
0.00%
0/239
|
7.1%
1/14 • Number of events 1
|
0.00%
0/10
|
0.00%
0/179
|
0.00%
0/128
|
|
Investigations
Weight decreased
|
2.9%
16/555 • Number of events 16
|
7.6%
42/556 • Number of events 42
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.9%
16/555 • Number of events 16
|
9.4%
52/556 • Number of events 53
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Dizziness
|
2.7%
15/555 • Number of events 15
|
5.4%
30/556 • Number of events 32
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Nervous system disorders
Headache
|
4.3%
24/555 • Number of events 29
|
7.2%
40/556 • Number of events 45
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Skin and subcutaneous tissue disorders
Hair colour changes
|
0.72%
4/555 • Number of events 4
|
9.5%
53/556 • Number of events 53
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.90%
5/555 • Number of events 6
|
6.5%
36/556 • Number of events 42
|
0.00%
0/34
|
0.00%
0/22
|
0.00%
0/430
|
0.00%
0/312
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60