NAVIGATE-AD: A Study of LY3202626 on Disease Progression in Participants With Mild Alzheimer's Disease Dementia
Sponsor
Eli Lilly and Company (Industry)
Overall Status
Terminated
CT.gov ID
NCT02791191
Collaborator
(none)
316
76
3
24.5
4.2
0.2
Study Details
Study Description
Brief Summary
The main purpose of this study is to evaluate the safety and the effect on brain tau of the study drug LY3202626 in participants with mild Alzheimer's disease (AD) dementia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
316 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Effect of LY3202626 on Alzheimer's Disease Progression as Measured by Cerebral ¹⁸F-AV-1451 Tau-PET in Mild Alzheimer's Disease Dementia
Actual Study Start Date
:
Jun 16, 2016
Actual Primary Completion Date
:
Jul 2, 2018
Actual Study Completion Date
:
Jul 2, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose 1 LY3202626 3 mg LY3202626 given orally once daily for 52 weeks. |
Drug: LY3202626
Administered orally
|
| Experimental: Dose 2 LY3202626 12 mg LY3202626 given orally once daily for 52 weeks. |
Drug: LY3202626
Administered orally
|
| Experimental: Placebo Placebo given orally once daily for 52 weeks. |
Drug: Placebo
Administered orally
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks [Baseline, Week 52]
The 18F-AV-1451 PET tracer assesses change from baseline in the pharmacodynamic effect of 3 mg and 12 mg doses of LY3202626 in participants with mild Alzheimer's disease (AD), compared with placebo at Week 52.The SUVr of ¹⁸F-AV-1451 was modeled using analysis of covariance (ANCOVA) to include the fixed, categorical effects of treatment dose, and the continuous, fixed covariate of baseline Tau PET SUVr and age at baseline.
Secondary Outcome Measures
- Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings [Week 52]
Percentage of participants with treatment-emergent MRI findings at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction.
- Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) [Week 52]
Percentage of participants with presence of amyloid-related imaging abnormalities-edema (ARIA-E, also known as vasogenic edema) and percentage of an increase in amyloid-related imaging abnormalities-hemorrhage (ARIA-H, also known as also known as microhemorrhage) at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction.
- Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores [Baseline through Week 52]
The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
- Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626 [Week 2, 4, and 12: Predose and Postdose prior to departing; Week 8 and 16: Postdose after arriving and prior to departing; Week 24: Postdose after cognitive testing]
PK: AUC [T,SS] of LY3202626
- Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration [Baseline, Week 52]
A mixed model repeated measures (MMRM) analysis will be used to evaluate the change from baseline to Week 52 in plasma Aβ₁-₄₀, Aβ₁-₄₂, and Aβ 1-x. The model for the fixed effects will include terms for the following independent effects: log transformed baseline plasma Aβ, treatment, visit, treatment-by-visit interaction.
- Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃) [Baseline, Week 52]
The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS that was used as the primary efficacy measure consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS--Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. A mixed model repeated measures (MMRM) was used in analysis. The model included fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.
- Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL) [Baseline, Week 52]
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 (instrumental activity items 7-23) of daily living by participants. The range for the ADCS-iADL is 0-56 with higher scores reflecting better performance. ADCS-iADL was analyzed using mixed-model repeated measures (MMRM), Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction.
- Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) [Baseline, Week 52]
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 9score range 0 to 85 with higher scores reflecting worse performance and the ADCS-iADL (score range 0-56 with higher scores reflecting better performance). The iADRS score ranges from 0 to 141 with lower scores indicating worse performance. iADRS was analyzed using mixed-model repeated measures (MMRM); Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction.
Eligibility Criteria
Criteria
Ages Eligible for Study:
55 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Present with mild AD dementia based on the National Institute on Aging (NIA) and the Alzheimer's Association (AA) disease diagnostic criteria as determined by a qualified clinician approved by the Sponsor or designee.
-
Mini-Mental State Examination score of 20 to 26 inclusive at screening visit.
-
Has a florbetapir PET scan consistent with the presence of amyloid pathology at screening.
Exclusion Criteria:
-
Significant neurological disease affecting the central nervous system (CNS), other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures (except febrile childhood seizures).
-
Ocular pathology that significantly limits ability to reliably evaluate vision or the retina.
-
Use of strong inducers of cytochrome P450 3A (CYP3A).
-
Sensitivity to florbetapir or ¹⁸F-AV-1451.
-
Contraindication to MRI or PET or poor venous access for blood draws.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Irvine Clinical Research Center | Irvine | California | United States | 92614 |
| 2 | Sutter Medical Group | Sacramento | California | United States | 95816 |
| 3 | Pacific Research Network Inc | San Diego | California | United States | 92103 |
| 4 | Sharp Mesa Vista Hospital | San Diego | California | United States | 92123 |
| 5 | Ray Dolby Brain Health Center/Sutter Health/CPMC | San Francisco | California | United States | 94114 |
| 6 | Syrentis Clinical Research | Santa Ana | California | United States | 92705 |
| 7 | North Bay Neuroscience Institute | Sebastopol | California | United States | 95472 |
| 8 | New England Institute for Clinical Research | Stamford | Connecticut | United States | 06905 |
| 9 | Christiana Care Health Service | Wilmington | Delaware | United States | 19801 |
| 10 | Clinical Neuroscience Solutions Inc | Jacksonville | Florida | United States | 32256 |
| 11 | Compass Research | Melbourne | Florida | United States | 32940 |
| 12 | Florida International Research Center | Miami | Florida | United States | 33173 |
| 13 | New Horizon Research Center | Miami | Florida | United States | 33175 |
| 14 | The Neurology Research Group, LLC | Miami | Florida | United States | 33176 |
| 15 | Suncoast Clinical Research | New Port Richey | Florida | United States | 34652 |
| 16 | Renstar Medical Research | Ocala | Florida | United States | 34470 |
| 17 | Sensible Healthcare | Ocoee | Florida | United States | 34761 |
| 18 | Meridien Research | Spring Hill | Florida | United States | 34609 |
| 19 | Axiom Research | Tampa | Florida | United States | 33609 |
| 20 | United Osteoporosis Center | Gainesville | Georgia | United States | 30501 |
| 21 | Fort Wayne Neurological Center | Fort Wayne | Indiana | United States | 46804 |
| 22 | Indiana University School of Medicine | Indianapolis | Indiana | United States | 46202 |
| 23 | Cotton O'Neil Clinic | Topeka | Kansas | United States | 66606 |
| 24 | Heartland Research Associates | Wichita | Kansas | United States | 67205 |
| 25 | Johns Hopkins University School of Medicine | Baltimore | Maryland | United States | 21224 |
| 26 | Boston Center for Memory | Newton | Massachusetts | United States | 02459 |
| 27 | Missouri Memory Center | Bolivar | Missouri | United States | 65613 |
| 28 | Clinical Research Professionals | Chesterfield | Missouri | United States | 63005 |
| 29 | Millenium Psychiatric Associates LLC | Creve Coeur | Missouri | United States | 63141 |
| 30 | St Lukes Hospital | Kansas City | Missouri | United States | 64111 |
| 31 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63108 |
| 32 | Las Vegas Medical Research | Las Vegas | Nevada | United States | 89113 |
| 33 | Memory Enhancement Center of America, Inc. | Eatontown | New Jersey | United States | 07724 |
| 34 | Pyramid Clinical Research | Monroe | New Jersey | United States | 08831 |
| 35 | Advanced Memory Research Institute of New Jersey | Toms River | New Jersey | United States | 08755 |
| 36 | Bio Behavioral Health | Toms River | New Jersey | United States | 08755 |
| 37 | Albany Medical College | Albany | New York | United States | 12206 |
| 38 | Dent Neurological Institute | Amherst | New York | United States | 14226 |
| 39 | Valley Medical Primary Care | Centerville | Ohio | United States | 45459 |
| 40 | University of Cincinnati Health Neurology | Dayton | Ohio | United States | 45417 |
| 41 | Neurology Diagnostics, Inc. | Dayton | Ohio | United States | 45459 |
| 42 | Insight Clinical Trials | Shaker Heights | Ohio | United States | 44122 |
| 43 | Abington Neurological Associates | Abington | Pennsylvania | United States | 19090 |
| 44 | Lehigh Center for Clinical Research | Allentown | Pennsylvania | United States | 18104 |
| 45 | Clinical Trial Center, LLC, Psychiatry | Jenkintown | Pennsylvania | United States | 19046 |
| 46 | Clinical Trials of South Carolina | Charleston | South Carolina | United States | 29406 |
| 47 | Baylor AT&T Memory Center | Dallas | Texas | United States | 75231 |
| 48 | Nantz National Alzheimer Center | Houston | Texas | United States | 77030 |
| 49 | University of Texas Health Services Center - Houston | Houston | Texas | United States | 77054 |
| 50 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Box Hill | Australia | 3128 | |
| 51 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Chermside | Australia | 4032 | |
| 52 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Darlinghurst | Australia | 2010 | |
| 53 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Erina | Australia | 2250 | |
| 54 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Glen Iris | Australia | 3146 | |
| 55 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Heidelberg | Australia | 3084 | |
| 56 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Herston | Australia | 4029 | |
| 57 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nedlands | Australia | 6009 | |
| 58 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Parkville | Australia | 3050 | |
| 59 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | West Perth | Australia | 6005 | |
| 60 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Gatineau | Canada | J8T 8J1 | |
| 61 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ottawa | Canada | KIN 5C8 | |
| 62 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Verdun | Canada | H4H 1R3 | |
| 63 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Akashi | Japan | 673-0891 | |
| 64 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Hachioji | Japan | 193-0998 | |
| 65 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Ikeda | Japan | 563-0058 | |
| 66 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kasukabe-shi | Japan | 344-0036 | |
| 67 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Kyoto | Japan | 606-0851 | |
| 68 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nagoya | Japan | 451-8511 | |
| 69 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Nerima-ku | Japan | 179-0072 | |
| 70 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Osaka | Japan | 533-0004 | |
| 71 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Osaka | Japan | 559-0004 | |
| 72 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Setagaya-ku | Japan | 158-8531 | |
| 73 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Takamatsu | Japan | 760-8557 | |
| 74 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Tokyo | Japan | 156-0041 | |
| 75 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Wako | Japan | 351-0111 | |
| 76 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Yokosuka-shi | Japan | 238-0042 |
Sponsors and Collaborators
- Eli Lilly and Company
Investigators
- Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02791191
Other Study ID Numbers:
- 16223
- I7X-MC-LLCF
First Posted:
Jun 6, 2016
Last Update Posted:
Apr 19, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Eli Lilly and Company
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Period Title: Overall Study | |||
| STARTED | 55 | 128 | 133 |
| Received One Dose of Study Drug | 55 | 127 | 133 |
| COMPLETED | 17 | 17 | 13 |
| NOT COMPLETED | 38 | 111 | 120 |
Baseline Characteristics
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. | Total of all reporting groups |
| Overall Participants | 55 | 128 | 133 | 316 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
73.91
(6.72)
|
72.73
(7.15)
|
72.54
(7.80)
|
72.86
(7.36)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
29
52.7%
|
86
67.2%
|
77
57.9%
|
192
60.8%
|
| Male |
26
47.3%
|
42
32.8%
|
56
42.1%
|
124
39.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
1
1.8%
|
5
3.9%
|
7
5.3%
|
13
4.1%
|
| Not Hispanic or Latino |
50
90.9%
|
108
84.4%
|
112
84.2%
|
270
85.4%
|
| Unknown or Not Reported |
4
7.3%
|
15
11.7%
|
14
10.5%
|
33
10.4%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
8
14.5%
|
18
14.1%
|
13
9.8%
|
39
12.3%
|
| Native Hawaiian or Other Pacific Islander |
1
1.8%
|
0
0%
|
1
0.8%
|
2
0.6%
|
| Black or African American |
1
1.8%
|
5
3.9%
|
4
3%
|
10
3.2%
|
| White |
45
81.8%
|
104
81.3%
|
113
85%
|
262
82.9%
|
| More than one race |
0
0%
|
1
0.8%
|
2
1.5%
|
3
0.9%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||
| Canada |
0
0%
|
1
0.8%
|
1
0.8%
|
2
0.6%
|
| United States |
43
78.2%
|
86
67.2%
|
105
78.9%
|
234
74.1%
|
| Japan |
7
12.7%
|
18
14.1%
|
12
9%
|
37
11.7%
|
| Australia |
5
9.1%
|
23
18%
|
15
11.3%
|
43
13.6%
|
| Flortaucipir Standard Uptake Value Ratio (SUVr) (standard uptake value ratio (SUVr)) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [standard uptake value ratio (SUVr)] |
1.32
(0.24)
|
1.36
(0.28)
|
1.42
(0.35)
|
1.38
(0.31)
|
Outcome Measures
| Title | Change From Baseline in ¹⁸F-AV-1451 Positron Emission Tomography (PET) Standard Uptake Value Ratio (SUVr) at 52 Weeks |
|---|---|
| Description | The 18F-AV-1451 PET tracer assesses change from baseline in the pharmacodynamic effect of 3 mg and 12 mg doses of LY3202626 in participants with mild Alzheimer's disease (AD), compared with placebo at Week 52.The SUVr of ¹⁸F-AV-1451 was modeled using analysis of covariance (ANCOVA) to include the fixed, categorical effects of treatment dose, and the continuous, fixed covariate of baseline Tau PET SUVr and age at baseline. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug, and have baseline and at least one post-baseline scan. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 15 | 15 | 11 |
| Mean (Standard Deviation) [Standard Uptake Value Ratio (SUVr)] |
0.02
(0.04)
|
0.03
(0.04)
|
0.01
(0.08)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.418 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.231 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Percentage of Participants With Emergent Magnetic Resonance Imaging (MRI) Findings |
|---|---|
| Description | Percentage of participants with treatment-emergent MRI findings at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction. |
| Time Frame | Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 41 | 75 | 62 |
| White Matter Disease |
2.4
4.4%
|
1.3
1%
|
1.6
1.2%
|
| Cortical Infarct |
2.4
4.4%
|
0.0
0%
|
0.0
0%
|
| Cortical Superficial Siderous |
0.0
0%
|
1.3
1%
|
0.0
0%
|
| Lacunar Infarct |
0.0
0%
|
0.0
0%
|
1.6
1.2%
|
| Other Infarct |
0.0
0%
|
0.0
0%
|
1.6
1.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | White Matter Disease | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | White Matter Disease | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.404 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Cortical Superficial Siderous | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Lacunar Infarct | |
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Lacunar Infarct | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.457 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Other Infarct | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Other Infarct | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.457 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) |
|---|---|
| Description | Percentage of participants with presence of amyloid-related imaging abnormalities-edema (ARIA-E, also known as vasogenic edema) and percentage of an increase in amyloid-related imaging abnormalities-hemorrhage (ARIA-H, also known as also known as microhemorrhage) at Week 52 are summarized here. The mixed-effect model for repeated measures (MMRM) analysis was adjusted for fixed effects of treatment, visit (categorical covariate), treatment-by-visit interaction, baseline age, baseline score (continuous covariate) and baseline-by-visit interaction. |
| Time Frame | Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 41 | 75 | 62 |
| Presence of Vasogenic Edema |
0.0
0%
|
0.0
0%
|
1.6
1.2%
|
| Increase in Microhemorrhages |
4.7
8.5%
|
6.3
4.9%
|
7.5
5.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Vasogenic Edema | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Vasogenic Edema | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.457 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Increase in Microhemorrhage | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.703 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Increase in Microhemorrhage | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 1.000 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Percentage of Participants With Suicidal Ideation and Behaviors Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) Scores |
|---|---|
| Description | The Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions, which includes a wish to be dead and 4 different categories of active suicidal ideation. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation and behavior are defined as treatment-emergent (TE) if not present during the period up through randomization. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. |
| Time Frame | Baseline through Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had at least one post-baseline C-SSRS measure. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 55 | 127 | 133 |
| TE Suicidal Ideation |
7.27
13.2%
|
7.09
5.5%
|
3.76
2.8%
|
| TE Suicidal Behavior |
1.82
3.3%
|
0.79
0.6%
|
0.00
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Treatment Emergent Suicidal Ideation | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.452 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.279 |
| Comments | TE Suicidal Ideation | |
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Emergence of Suicidal Behavior | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.293 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Emergence of Suicidal Behavior | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.486 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Pharmacokinetics (PK): Area Under the Plasma Concentration-Time Curve at Steady State (AUC [T,SS]) of LY3202626 |
|---|---|
| Description | PK: AUC [T,SS] of LY3202626 |
| Time Frame | Week 2, 4, and 12: Predose and Postdose prior to departing; Week 8 and 16: Postdose after arriving and prior to departing; Week 24: Postdose after cognitive testing |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and have evaluable PK data. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 |
|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. |
| Measure Participants | 55 | 127 |
| Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)] |
158
(55.1)
|
641
(58.0)
|
| Title | Change From Baseline in Plasma Amyloid Beta Aβ₁-₄₀, ₁-₄₂, and 1-x Concentration |
|---|---|
| Description | A mixed model repeated measures (MMRM) analysis will be used to evaluate the change from baseline to Week 52 in plasma Aβ₁-₄₀, Aβ₁-₄₂, and Aβ 1-x. The model for the fixed effects will include terms for the following independent effects: log transformed baseline plasma Aβ, treatment, visit, treatment-by-visit interaction. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug, and have baseline and at least one post-baseline measure. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 55 | 127 | 133 |
| Amyloid Beta |
-258.7
(64)
|
-286.1
(85.9)
|
-12.0
(80.5)
|
| Amyloid Beta 1-40 |
-157.3
(65.6)
|
-149.3
(38.0)
|
-17.0
(38.2)
|
| Amyloid Beta 1-42 |
-46.3
(38.7)
|
-50.0
(34.1)
|
0.0
(5.8)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Amyloid Beta | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | Amyloid Beta | |
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Amyloid Beta 1-40 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Amyloid Beta 1-40 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | Amyloid Beta 1-42 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | Amyloid Beta 1-42 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <.001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog₁₃) |
|---|---|
| Description | The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS that was used as the primary efficacy measure consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS--Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. A mixed model repeated measures (MMRM) was used in analysis. The model included fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug, and have baseline and at least one post-baseline ADAS-Cog₁₃ measure. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 17 | 19 | 15 |
| Least Squares Mean (Standard Error) [units on a scale] |
3.05
(1.40)
|
1.88
(1.33)
|
2.97
(1.51)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.970 |
| Comments | ||
| Method | Mixed Model Repeated Measures | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.586 |
| Comments | ||
| Method | Mixed Model Repeated Meausres | |
| Comments | ||
| Title | Change From Baseline on the Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL) |
|---|---|
| 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 (instrumental activity items 7-23) of daily living by participants. The range for the ADCS-iADL is 0-56 with higher scores reflecting better performance. ADCS-iADL was analyzed using mixed-model repeated measures (MMRM), Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug, and have baseline and at least one post-baseline ADCS-iADL measure. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 17 | 19 | 15 |
| Least Squares Mean (Standard Error) [units on a scale] |
-3.97
(1.34)
|
-4.63
(1.24)
|
-7.32
(1.38)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.088 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.150 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) |
|---|---|
| Description | 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 9score range 0 to 85 with higher scores reflecting worse performance and the ADCS-iADL (score range 0-56 with higher scores reflecting better performance). The iADRS score ranges from 0 to 141 with lower scores indicating worse performance. iADRS was analyzed using mixed-model repeated measures (MMRM); Least Square (LS) Mean was controlled for treatment, visit, treatment-by-visit interaction, baseline age, baseline score and baseline-by-visit interaction. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug, and have baseline and at least one post-baseline iADRS measure. |
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo |
|---|---|---|---|
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks. | Placebo administered orally once daily for 52 weeks. |
| Measure Participants | 16 | 19 | 15 |
| Least Squares Mean (Standard Error) [units on a scale] |
-6.01
(2.07)
|
-6.45
(1.90)
|
-10.32
(2.15)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 3 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.153 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 12 mg LY3202626, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.176 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
Adverse Events
| Time Frame | Up to 56 Weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All randomized participants. | |||||
| Arm/Group Title | 3 mg LY3202626 | 12 mg LY3202626 | Placebo | |||
| Arm/Group Description | 3 mg LY3202626 administered orally once daily for 52 weeks. | 12 mg LY3202626 administered orally once daily for 52 weeks | Placebo administered orally once daily for 52 weeks. | |||
All Cause Mortality |
||||||
| 3 mg LY3202626 | 12 mg LY3202626 | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/55 (0%) | 0/127 (0%) | 0/133 (0%) | |||
Serious Adverse Events |
||||||
| 3 mg LY3202626 | 12 mg LY3202626 | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/55 (18.2%) | 8/127 (6.3%) | 10/133 (7.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Haemorrhagic anaemia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Cardiac disorders | ||||||
| Angina pectoris | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Cardiac failure congestive | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Coronary artery disease | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Duodenal ulcer | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Gastrointestinal haemorrhage | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Small intestinal obstruction | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| General disorders | ||||||
| Chest discomfort | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Gait disturbance | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Pyrexia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Infections and infestations | ||||||
| Cystitis | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Influenza | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Pneumonia | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Pyuria | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Accidental overdose | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Ankle fracture | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Confusion postoperative | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Fall | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Hip fracture | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Spinal compression fracture | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Diabetes mellitus inadequate control | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Hypocalcaemia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Lactic acidosis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| Spinal column stenosis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Nervous system disorders | ||||||
| Metabolic encephalopathy | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Syncope | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Transient global amnesia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Product Issues | ||||||
| Device breakage | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Psychiatric disorders | ||||||
| Aggression | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Suicidal ideation | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Suicide attempt | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Urinary retention | 1/55 (1.8%) | 3 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| 3 mg LY3202626 | 12 mg LY3202626 | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 46/55 (83.6%) | 97/127 (76.4%) | 91/133 (68.4%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Thrombocytopenia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Cardiac disorders | ||||||
| Angina pectoris | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Arrhythmia | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Atrial fibrillation | 3/55 (5.5%) | 3 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Atrioventricular block first degree | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Bradycardia | 1/55 (1.8%) | 1 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Cardiac failure congestive | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Coronary artery disease | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Left ventricular failure | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Tachyarrhythmia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Ear and labyrinth disorders | ||||||
| Cerumen impaction | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Otorrhoea | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Tinnitus | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 3/133 (2.3%) | 3 |
| Vertigo | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Endocrine disorders | ||||||
| Goitre | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Hyperparathyroidism secondary | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Hypothyroidism | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Eye disorders | ||||||
| Cataract | 3/55 (5.5%) | 3 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 2 |
| Cataract nuclear | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Conjunctival haemorrhage | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Corneal oedema | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Diplopia | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Dyschromatopsia | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Erythropsia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Eye pain | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Eye swelling | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Eyelid cyst | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Eyelid oedema | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Glaucoma | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Lacrimation increased | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Lenticular opacities | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Macular degeneration | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Macular fibrosis | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Macular oedema | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Normal tension glaucoma | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Ocular hyperaemia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Optic disc disorder | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Optic disc haemorrhage | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Photopsia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Posterior capsule opacification | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Retinal drusen | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Retinal haemorrhage | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Visual acuity reduced | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Visual impairment | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Vitreous detachment | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Abdominal distension | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Abdominal hernia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Abdominal pain | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Abdominal pain upper | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Abdominal tenderness | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Aphthous ulcer | 2/55 (3.6%) | 2 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Barrett's oesophagus | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Constipation | 2/55 (3.6%) | 2 | 5/127 (3.9%) | 5 | 1/133 (0.8%) | 2 |
| Dental caries | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Diarrhoea | 2/55 (3.6%) | 2 | 6/127 (4.7%) | 7 | 6/133 (4.5%) | 7 |
| Dry mouth | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Dyspepsia | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Dysphagia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Faeces discoloured | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Flatulence | 2/55 (3.6%) | 2 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Functional gastrointestinal disorder | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Gastric ulcer haemorrhage | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 2/133 (1.5%) | 2 |
| Haemorrhoids | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Hiatus hernia | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Hyperchlorhydria | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Large intestinal obstruction | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Nausea | 1/55 (1.8%) | 1 | 2/127 (1.6%) | 2 | 4/133 (3%) | 4 |
| Oral disorder | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Toothache | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 0/133 (0%) | 0 |
| Vomiting | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| General disorders | ||||||
| Asthenia | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Chest discomfort | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Chest pain | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Chills | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Crying | 2/55 (3.6%) | 2 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Fatigue | 0/55 (0%) | 0 | 5/127 (3.9%) | 5 | 7/133 (5.3%) | 7 |
| Feeling abnormal | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Feeling cold | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Feeling jittery | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Gait disturbance | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 2/133 (1.5%) | 2 |
| Influenza like illness | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Injection site rash | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Malaise | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Non-cardiac chest pain | 0/55 (0%) | 0 | 6/127 (4.7%) | 7 | 1/133 (0.8%) | 1 |
| Oedema | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Oedema peripheral | 1/55 (1.8%) | 1 | 4/127 (3.1%) | 5 | 2/133 (1.5%) | 2 |
| Pain | 0/55 (0%) | 0 | 2/127 (1.6%) | 3 | 0/133 (0%) | 0 |
| Peripheral swelling | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Pyrexia | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 0/133 (0%) | 0 |
| Unevaluable event | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Vessel puncture site haematoma | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hepatobiliary disorders | ||||||
| Cholecystitis chronic | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Cholelithiasis | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Immune system disorders | ||||||
| Allergy to animal | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Hypersensitivity | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Mite allergy | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Mycotic allergy | 1/55 (1.8%) | 2 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Seasonal allergy | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Infections and infestations | ||||||
| Acute sinusitis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Bronchitis | 2/55 (3.6%) | 2 | 1/127 (0.8%) | 1 | 3/133 (2.3%) | 3 |
| Cellulitis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Clostridium difficile infection | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Conjunctivitis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Dermatitis infected | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Diverticulitis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| External ear cellulitis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Folliculitis | 2/55 (3.6%) | 2 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Fungal skin infection | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Gastroenteritis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Hepatitis e | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Herpes zoster | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Hordeolum | 2/55 (3.6%) | 2 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Influenza | 2/55 (3.6%) | 2 | 4/127 (3.1%) | 4 | 3/133 (2.3%) | 3 |
| Laryngitis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Localised infection | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Lower respiratory tract infection | 0/55 (0%) | 0 | 1/127 (0.8%) | 3 | 0/133 (0%) | 0 |
| Nail bed infection bacterial | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Nasopharyngitis | 7/55 (12.7%) | 7 | 14/127 (11%) | 16 | 7/133 (5.3%) | 7 |
| Onychomycosis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Oral herpes | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Otitis externa | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Otitis media | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Pharyngitis | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Rhinitis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Sinusitis | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Tinea versicolour | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Tooth infection | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Upper respiratory tract infection | 5/55 (9.1%) | 5 | 6/127 (4.7%) | 6 | 7/133 (5.3%) | 8 |
| Urinary tract infection | 3/55 (5.5%) | 5 | 7/127 (5.5%) | 8 | 3/133 (2.3%) | 3 |
| Viral infection | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Viral upper respiratory tract infection | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Vulvovaginal candidiasis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Arthropod bite | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Back injury | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Compression fracture | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Contusion | 1/55 (1.8%) | 1 | 11/127 (8.7%) | 12 | 4/133 (3%) | 4 |
| Eye contusion | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Fall | 1/55 (1.8%) | 2 | 8/127 (6.3%) | 12 | 8/133 (6%) | 9 |
| Fracture displacement | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Incision site pain | 1/55 (1.8%) | 2 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Joint dislocation | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Joint injury | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Laceration | 0/55 (0%) | 0 | 4/127 (3.1%) | 4 | 2/133 (1.5%) | 2 |
| Ligament sprain | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Limb injury | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Lower limb fracture | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Meniscus injury | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Muscle rupture | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Overdose | 1/55 (1.8%) | 2 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Post procedural haematuria | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Post procedural swelling | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Rib fracture | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 3/133 (2.3%) | 3 |
| Skin abrasion | 3/55 (5.5%) | 3 | 1/127 (0.8%) | 1 | 2/133 (1.5%) | 2 |
| Spinal compression fracture | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Synovial rupture | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Upper limb fracture | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Wrist fracture | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Aspartate aminotransferase increased | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Biopsy skin | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Blood alkaline phosphatase increased | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Blood cholesterol increased | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Blood creatine phosphokinase increased | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Blood creatinine increased | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Blood pressure increased | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Cardiac murmur | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Colonoscopy | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Cystoscopy | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Electrocardiogram qt prolonged | 1/55 (1.8%) | 1 | 3/127 (2.4%) | 3 | 1/133 (0.8%) | 1 |
| Fibrin d dimer increased | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Haemoglobin decreased | 2/55 (3.6%) | 2 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Hepatic enzyme increased | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Low density lipoprotein increased | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Mammogram abnormal | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Oxygen saturation decreased | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Staphylococcus test positive | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Transaminases increased | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Tri-iodothyronine decreased | 1/55 (1.8%) | 1 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Weight decreased | 2/55 (3.6%) | 2 | 1/127 (0.8%) | 1 | 3/133 (2.3%) | 3 |
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 1/133 (0.8%) | 1 |
| Dehydration | 2/55 (3.6%) | 2 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Diabetes mellitus | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Dyslipidaemia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Gout | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hypercalcaemia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hypercholesterolaemia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hyperglycaemia | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Hyperlipidaemia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Hypoglycaemia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Hypokalaemia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Vitamin d deficiency | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/55 (3.6%) | 2 | 4/127 (3.1%) | 4 | 8/133 (6%) | 8 |
| Arthritis | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Back pain | 1/55 (1.8%) | 1 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Bursitis | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Exostosis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Foot deformity | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Intervertebral disc degeneration | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Intervertebral disc protrusion | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Joint space narrowing | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Joint swelling | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Mobility decreased | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Muscle spasms | 4/55 (7.3%) | 4 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Musculoskeletal pain | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Myalgia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Neck pain | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Osteoarthritis | 1/55 (1.8%) | 1 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Osteopenia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Osteoporosis | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Pain in extremity | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 3/133 (2.3%) | 3 |
| Periarthritis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Rheumatoid arthritis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Rotator cuff syndrome | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Scoliosis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Spinal osteoarthritis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Synovial cyst | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Tendonitis | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Acrochordon | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Basal cell carcinoma | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Bowen's disease | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Breast cancer | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Dysplastic naevus | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Seborrhoeic keratosis | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Skin papilloma | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Squamous cell carcinoma | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 4/133 (3%) | 4 |
| Nervous system disorders | ||||||
| Amyloid related imaging abnormality-microhaemorrhages and haemosiderin deposits | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Amyloid related imaging abnormality-oedema/effusion | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Aphasia | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 0/133 (0%) | 0 |
| Ataxia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Balance disorder | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Carpal tunnel syndrome | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Cerebellar infarction | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Cerebellar microhaemorrhage | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Cerebellar syndrome | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Cerebral microhaemorrhage | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Corticobasal degeneration | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Dementia alzheimer's type | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Dizziness | 2/55 (3.6%) | 2 | 3/127 (2.4%) | 3 | 4/133 (3%) | 4 |
| Dizziness postural | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Dysgeusia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Essential tremor | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Extrapyramidal disorder | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Head discomfort | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Headache | 5/55 (9.1%) | 5 | 4/127 (3.1%) | 4 | 2/133 (1.5%) | 2 |
| Hypersomnia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hypogeusia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Lethargy | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Loss of consciousness | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Memory impairment | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Migraine | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Nervous system disorder | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Paraesthesia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Poor quality sleep | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Presyncope | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 2/133 (1.5%) | 2 |
| Somnolence | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Superficial siderosis of central nervous system | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Syncope | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Thalamic infarction | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Tremor | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 0/133 (0%) | 0 |
| Vertebral artery stenosis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Psychiatric disorders | ||||||
| Abnormal dreams | 0/55 (0%) | 0 | 3/127 (2.4%) | 4 | 2/133 (1.5%) | 2 |
| Affect lability | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Agitation | 1/55 (1.8%) | 2 | 1/127 (0.8%) | 1 | 3/133 (2.3%) | 3 |
| Anxiety | 3/55 (5.5%) | 3 | 4/127 (3.1%) | 4 | 0/133 (0%) | 0 |
| Confusional state | 3/55 (5.5%) | 4 | 3/127 (2.4%) | 3 | 1/133 (0.8%) | 1 |
| Delusion | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Depressed mood | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Depression | 2/55 (3.6%) | 2 | 3/127 (2.4%) | 3 | 3/133 (2.3%) | 4 |
| Disorientation | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 2 | 0/133 (0%) | 0 |
| Emotional distress | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Generalised anxiety disorder | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hallucination | 1/55 (1.8%) | 1 | 6/127 (4.7%) | 6 | 2/133 (1.5%) | 2 |
| Hallucination, auditory | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Hallucination, visual | 0/55 (0%) | 0 | 4/127 (3.1%) | 4 | 0/133 (0%) | 0 |
| Hypnopompic hallucination | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Insomnia | 3/55 (5.5%) | 3 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Mania | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Mental status changes | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Mood altered | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Mood swings | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Nightmare | 1/55 (1.8%) | 1 | 4/127 (3.1%) | 5 | 0/133 (0%) | 0 |
| Psychotic disorder | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Sleep disorder | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Suicidal ideation | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Tension | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Acute kidney injury | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Dysuria | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Haematuria | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Hypertonic bladder | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Lower urinary tract symptoms | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Nephrolithiasis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Pollakiuria | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 1/133 (0.8%) | 1 |
| Renal cyst | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Renal mass | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Benign prostatic hyperplasia | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Breast cyst | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Breast mass | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Breast pain | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Genital rash | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Atelectasis | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Cough | 6/55 (10.9%) | 6 | 5/127 (3.9%) | 5 | 2/133 (1.5%) | 3 |
| Dyspnoea | 2/55 (3.6%) | 2 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Dyspnoea exertional | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 2 |
| Lower respiratory tract congestion | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Nasal congestion | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Oropharyngeal pain | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Pleuritic pain | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Pneumothorax | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Rhinitis allergic | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Rhinorrhoea | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 0/133 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Actinic keratosis | 0/55 (0%) | 0 | 3/127 (2.4%) | 3 | 3/133 (2.3%) | 4 |
| Dermatitis | 0/55 (0%) | 0 | 1/127 (0.8%) | 2 | 1/133 (0.8%) | 1 |
| Dermatitis atopic | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Dermatitis contact | 5/55 (9.1%) | 5 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Dry skin | 1/55 (1.8%) | 1 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Eczema | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Eczema asteatotic | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Erythema | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hair colour changes | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hyperhidrosis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Idiopathic guttate hypomelanosis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Ingrowing nail | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Leukoderma | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Nail disorder | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Night sweats | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Pruritus | 0/55 (0%) | 0 | 1/127 (0.8%) | 2 | 1/133 (0.8%) | 3 |
| Psoriasis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Rash | 1/55 (1.8%) | 1 | 1/127 (0.8%) | 1 | 2/133 (1.5%) | 2 |
| Rash macular | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Rash papular | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Seborrhoeic dermatitis | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Skin hypopigmentation | 2/55 (3.6%) | 2 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Skin irritation | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Skin lesion | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 1 |
| Solar lentigo | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 1/133 (0.8%) | 3 |
| Splinter haemorrhages | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Telangiectasia | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Social circumstances | ||||||
| Orthosis user | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Walking aid user | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Blepharectomy | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Bursa removal | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Cataract operation | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 2/133 (1.5%) | 3 |
| Catheter placement | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Chest tube insertion | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Cochlea implant | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Coronary artery bypass | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Dental implantation | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Endodontic procedure | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Internal fixation of fracture | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Intraocular lens implant | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Knee arthroplasty | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Lens capsulotomy | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Medical device removal | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Micrographic skin surgery | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Nasal operation | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Open reduction of fracture | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Papilloma excision | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Skin neoplasm excision | 1/55 (1.8%) | 1 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Spinal fusion surgery | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Tooth extraction | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 1/133 (0.8%) | 1 |
| Transurethral prostatectomy | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Vertebroplasty | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Vascular disorders | ||||||
| Aortic disorder | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Arteriosclerosis | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Flushing | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 0/133 (0%) | 0 |
| Haematoma | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 2/133 (1.5%) | 2 |
| Hot flush | 0/55 (0%) | 0 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hypertension | 1/55 (1.8%) | 1 | 0/127 (0%) | 0 | 1/133 (0.8%) | 1 |
| Hypotension | 0/55 (0%) | 0 | 2/127 (1.6%) | 2 | 0/133 (0%) | 0 |
| Orthostatic hypertension | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
| Orthostatic hypotension | 1/55 (1.8%) | 1 | 5/127 (3.9%) | 5 | 1/133 (0.8%) | 1 |
| Supine hypertension | 0/55 (0%) | 0 | 1/127 (0.8%) | 1 | 0/133 (0%) | 0 |
Limitations/Caveats
Study was terminated due to low likelihood of identifying a statistically significant treatment effect.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can 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. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | Eli Lilly and Company |
| Phone | 800-545-5079 |
| Clinicaltrials.gov@lilly.com |
Responsible Party:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02791191
Other Study ID Numbers:
- 16223
- I7X-MC-LLCF
First Posted:
Jun 6, 2016
Last Update Posted:
Apr 19, 2021
Last Verified:
Mar 1, 2021