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An Efficacy Study of Compound LY2624803 in the Treatment of Patients With Chronic Insomnia (SLUMBER)

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ClinicalTrials.gov Identifier: NCT00784875
Recruitment Status : Completed
First Posted : November 4, 2008
Results First Posted : February 29, 2012
Last Update Posted : February 29, 2012
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Primary Insomnia
Secondary Insomnia
Interventions Drug: LY2624803
Drug: Placebo
Drug: zolpidem
Enrollment 643
Recruitment Details LY2624803 was placed on clinical hold by Food and Drug Administration (FDA) on 18 December 2008. The FDA lifted the clinical hold effective 05 May 2009. For analysis purposes, participants who entered into study during 2008 were designated as Cohort 1, whereas participants who entered into study after 2008 were designated as Cohort 2.
Pre-assignment Details None of Cohort 1 participants completed the study and few progressed beyond Period B. The efficacy analyses were conducted using data from Cohort 2 participants only. Participant flow includes participants from both cohorts.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description Participants received LY2624803 1 mg in a 2-week treatment period. Participants received LY2624803 3 mg in a 2-week treatment period. Participants received Zolpidem 5 or 10 mg in a 2-week treatment period. Participants received placebo in a 2-week treatment period.
Period Title: Period A - Baseline
Started 0 0 0 643
Completed 0 0 0 461
Not Completed 0 0 0 182
Reason Not Completed
Entry Criteria Not Met             0             0             0             5
Adverse Event             0             0             0             8
Protocol Violation             0             0             0             25
Withdrawal by Subject             0             0             0             27
Physician Decision             0             0             0             2
Sponsor Decision             0             0             0             113
Lost to Follow-up             0             0             0             2
Period Title: Period B - Efficacy Endpoint
Started 114 113 117 117
Cohort 2 102 102 102 101
Completed 100 101 96 98
Not Completed 14 12 21 19
Reason Not Completed
Entry Criteria Not Met             0             0             2             1
Adverse Event             0             3             2             1
Protocol Violation             1             1             2             3
Lack of Efficacy             0             1             0             0
Withdrawal by Subject             4             1             1             2
Physician Decision             0             0             1             0
Sponsor Decision             9             6             12             12
Lost to Follow-up             0             0             1             0
Period Title: Period C
Started 103 97 97 98
Completed 96 91 84 91
Not Completed 7 6 13 7
Reason Not Completed
Adverse Event             1             0             4             2
Protocol Violation             0             0             1             2
Lack of Efficacy             0             0             1             0
Withdrawal by Subject             1             1             2             0
Physician Decision             0             0             1             1
Sponsor Decision             5             5             4             2
Period Title: Period D
Started 91 89 94 88
Completed 86 85 88 87
Not Completed 5 4 6 1
Reason Not Completed
Adverse Event             0             2             2             0
Protocol Violation             1             0             0             0
Withdrawal by Subject             2             0             2             0
Physician Decision             0             1             0             0
Sponsor Decision             1             1             1             0
Lost to Follow-up             1             0             1             1
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo Total
Hide Arm/Group Description Participants received LY2624803 1 mg in Period B (2-week treatment period). Participants received LY2624803 3 mg in Period B (2-week treatment period). Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period). Participants received placebo in Period B (2-week treatment period). Total of all reporting groups
Overall Number of Baseline Participants 102 102 102 101 407
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 102 participants 102 participants 102 participants 101 participants 407 participants
52.81  (14.07) 52.77  (14.73) 50.65  (15) 52.86  (13.66) 52.27  (14.35)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 102 participants 102 participants 102 participants 101 participants 407 participants
Female
66
  64.7%
52
  51.0%
61
  59.8%
61
  60.4%
240
  59.0%
Male
36
  35.3%
50
  49.0%
41
  40.2%
40
  39.6%
167
  41.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 102 participants 102 participants 102 participants 101 participants 407 participants
Caucasian 75 74 85 72 306
African 21 21 12 18 72
Hispanic 6 5 3 9 23
East Asian 0 2 1 2 5
Unknown or Not Reported 0 0 1 0 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 102 participants 102 participants 102 participants 101 participants 407 participants
102 102 102 101 407
1.Primary Outcome
Title Change From Baseline in Average Nightly Total Sleep Time at Week 4 (Week 2 of Period B) Endpoint
Hide Description Total Sleep Time is defined as time in bed minus total time awake. Minimum would be 0; no defined maximum (except if as defined as time in bed). The higher the number, the more time asleep. Calculated in minutes from participant-reported daily sleep questionnaire averaged across study Period B (2 weeks). Change score subtracts Period B average from Period A average (baseline). Analysis of covariance (ANCOVA) Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 102 102 102 101
Least Squares Mean (Standard Error)
Unit of Measure: minutes
30.16  (5.300) 37.33  (5.186) 50.63  (5.186) 22.79  (5.153)
2.Secondary Outcome
Title Change From Baseline in Unwanted Time Awake at Week 4 (Week 2 of Period B) Endpoint
Hide Description Unwanted time awake (minutes awake [MA] before sleep [between turning off the lights to first falling asleep], MA during sleep, MA after sleep before getting out of bed). Minimum would be 0; no defined maximum. The higher the number, the more the unwanted time awake. Calculated in minutes from participant-reported daily sleep questionnaire averaged (Avg.) across Period B. Change score subtracts Period B Avg. from Period A Avg. (baseline). ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group, and insomnia type.
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 102 102 102 101
Least Squares Mean (Standard Error)
Unit of Measure: minutes
Before Sleep (n= 101, 101, 101, 101) -7.08  (2.524) -6.45  (2.444) -20.48  (2.440) -1.46  (2.420)
During Sleep (n= 101, 102, 101, 101) -14.84  (2.881) -12.95  (2.812) -21.46  (2.819) -8.23  (2.794)
After Sleep (n= 100, 101, 99, 99) -9.07  (2.150) -8.31  (2.108) -4.91  (2.119) -5.05  (2.105)
3.Secondary Outcome
Title Change From Baseline in Number of Awakenings During Sleep at Week 4 (Week 2 of Period B) Endpoint
Hide Description Elicited from participant-reported daily sleep questionnaire averaged across study Period B (2 weeks). Change score subtracts Period B average from Period A average (baseline). ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 102 102 102 101
Least Squares Mean (Standard Error)
Unit of Measure: number of awakenings
-0.27  (0.066) -0.26  (0.065) -0.59  (0.065) -0.18  (0.065)
4.Secondary Outcome
Title Change From Baseline in Total Time Awake at Week 4 (Week 2 of Period B) Endpoint
Hide Description Calculated in minutes from participant-reported daily sleep questionnaire averaged across study Period B (2 weeks). Change score subtracts Period B average from Period A average (baseline). ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 102 102 102 101
Least Squares Mean (Standard Error)
Unit of Measure: minutes
-28.63  (4.678) -28.62  (4.591) -47.28  (4.579) -13.09  (4.547)
5.Secondary Outcome
Title Change From Baseline in Sleep Efficiency at Week 4 (Week 2 of Period B) Endpoint
Hide Description Calculated as (TIB-TTA)/TIB where TIB is time in bed and TTA is total unwanted time awake. Higher score indicates better sleep efficiency. ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 102 102 102 101
Least Squares Mean (Standard Error)
Unit of Measure: ratio
0.06  (0.009) 0.06  (0.009) 0.10  (0.009) 0.03  (0.009)
6.Secondary Outcome
Title Change From Baseline in Assessment of Sleep Quality at Week 4 (Week 2 of Period B) Endpoint
Hide Description Assessment of Sleep Quality (ASQ) scale is asked in the participant-reported daily sleep questionnaire; 8 items on 4 point Likert scale with a range of 0 to 24. Sleep experience score ranges from 0-9; awakening experience ranges from 0-15. The higher the score, the better the sleep. Scale is averaged across study Period B (2 weeks). Change score subtracts Period B average from Period A average (baseline). ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 102 102 102 101
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Total Score 0.17  (0.035) 0.17  (0.034) 0.25  (0.034) 0.13  (0.034)
Feeling upon Awakening Subscale 0.14  (0.034) 0.13  (0.033) 0.19  (0.033) 0.12  (0.033)
Sleep Experience Subscale 0.22  (0.042) 0.24  (0.042) 0.35  (0.042) 0.15  (0.041)
7.Secondary Outcome
Title Change From Baseline in Participants' Impression of Daytime Functioning Measured by Daily Consequences of Insomnia Questionnaire (DCIQ) at Week 4 (Week 2 of Period B) Endpoint
Hide Description DCIQ scale is asked in the participant-reported daily evening questionnaire; 5 point Likert scale with minimum of 0 and maximum of 44 (the higher the score, the more consequences of insomnia). Scale is averaged across study Period B (2 weeks). Change score subtracts Period B average from Period A average (baseline). ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 100 99 96 97
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.23  (0.395) -0.87  (0.385) -1.20  (0.394) -0.73  (0.386)
8.Secondary Outcome
Title Change From Baseline in the Insomnia Severity Index (ISI) at Week 4 (Week 2 of Period B) Endpoint
Hide Description The ISI is a brief self-report instrument that measures a participant’s perception of his or her insomnia. 7 questions on 5-point Likert scale with minimum of 0 and maximum of 28. The higher the score, the more severe the insomnia. It was collected at the bi-weekly office visits. ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 99 96 95 94
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.85  (0.587) -2.83  (0.578) -4.63  (0.582) -1.95  (0.574)
9.Secondary Outcome
Title Change From Baseline in Physical and Mental Component Scores as Measured by the Short Form 12 (SF-12) Version 2 at Week 4 (Week 2 of Period B) Endpoint
Hide Description The SF-12 is a subset of 12 items from the Medical Outcomes Study 36-Item Short Form Survey (SF-36) and was collected at the bi-weekly office visits. Each score ranges from 0-100. The components measure physical and mental health, respectively. Higher scores are indicative of better function. ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary)
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 97 95 94 92
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Physical Component Scores -2.32  (1.001) -0.28  (0.987) -0.82  (0.992) -1.84  (0.991)
Mental Component Scores 2.49  (1.198) 1.11  (1.181) 1.21  (1.191) 1.94  (1.184)
10.Secondary Outcome
Title Change From Baseline in Health-related Quality of Life as Measured by European Quality of Life (EuroQol) at Week 4 (Week 2 of Period B) Endpoint
Hide Description The EuroQoL Questionnaire–5 Dimension (EQ-5D) is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. The score ranges 0-100. The higher score indicates a better health state perceived by the participant. ANCOVA Model with dependent variable being change from baseline scores and independent variables being treatment, baseline, age group (<65 or ≥65), and insomnia type (primary vs. secondary).
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 98 95 94 93
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.06  (1.525) -2.56  (1.503) -1.71  (1.510) 0.23  (1.503)
11.Secondary Outcome
Title Treatment Satisfaction as Measured by the Participant Drug Preference Question
Hide Description After study Periods A, and B, participants were asked to rate their experience with the treatment they had just completed. Data are presented as percentage of participants preferring the treatment received in Period A (placebo) or treatment received in Period B.
Time Frame Baseline (Period A) and 2 weeks (Period B)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 99 96 95 94
Measure Type: Number
Unit of Measure: percentage of participants
Period A Treatment (placebo) 23.2 22.9 12.6 35.1
Period B Treatment 76.8 77.1 87.4 64.9
12.Secondary Outcome
Title Clinical Global Impression of Improvement (CGI-I) in Insomnia at Week 4 (Week 2 of Period B) Endpoint
Hide Description Measures clinician's perception of participant improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much improved) to 7 (very much worse). Data are presented as percentage of participants in each category.
Time Frame 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 102 102 102 99
Measure Type: Number
Unit of Measure: percentage of participants
1 - Very much improved 8.8 9.8 15.7 5.1
2 - Much improved 20.6 23.5 34.3 18.2
3 - Minimally improved 45.1 37.3 30.4 33.3
4 - No change 21.6 28.4 16.7 40.4
5 - Minimally Worse 2.0 0 1.0 3.0
6 - Much worse 2.0 1.0 2.0 0
7 - Very much worse 0 0 0 0
13.Secondary Outcome
Title Patient Global Impression of Improvement (PGI-I) in Insomnia at Week 4 (Week 2 of Period B) Endpoint
Hide Description A scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much improved) to 7 (very much worse). Data are presented as percentage of participants in each category.
Time Frame 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 99 96 95 94
Measure Type: Number
Unit of Measure: percentage of participants
1 - Very much improved 0 2.1 4.2 3.2
2 - Much improved 11.1 16.7 20.0 9.6
3 - Minimally improved 62.6 45.8 55.8 42.6
4 - No change 24.2 31.3 15.8 37.2
5 - Minimally worse 1.0 2.1 4.2 6.4
6 - Much worse 0 1.0 0 1.1
7 - Very much worse 1.0 1.0 0 0
14.Secondary Outcome
Title Change From Baseline in Total Sleep Time at Week 4 (Week 2 of Period B) Endpoint Based on Insomnia Type
Hide Description Total Sleep Time is defined as time in bed minus total time awake. Minimum would be 0; no defined maximum (except if as defined as time in bed). The higher the number, the more time asleep. Analyses were not performed by insomnia type (primary versus secondary) as originally planned because of insufficient number of secondary insomnia participants.
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were not performed by insomnia type because of insufficient number of secondary insomnia patients. Zero participants were analyzed.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
15.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Based on Insomnia Type
Hide Description Number of participants with AEs and SAEs. Analyses were not performed by insomnia type (primary versus secondary) as originally planned because of insufficient number of secondary insomnia participants.
Time Frame Baseline through 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were not performed by insomnia type because of insufficient number of secondary insomnia patients. Zero participants were analyzed.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Change From Baseline in Total Sleep Time at Week 4 (Week 2 of Period B) Endpoint Based on Age Group
Hide Description Total Sleep Time is defined as time in bed minus total time awake. Minimum would be 0; no defined maximum (except if as defined as time in bed). The higher the number, the more time asleep. Analyses were not performed by age group (under age 65 versus over age 65) as originally planned because of insufficient number of elderly participants.
Time Frame Baseline, 2 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were not performed by age group because of insufficient number of elderly patients. Zero participants were analyzed.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in Period B (2-week treatment period).
Participants received LY2624803 3 mg in Period B (2-week treatment period).
Participants received Zolpidem 5 or 10 mg in Period B (2-week treatment period).
Participants received placebo in Period B (2-week treatment period).
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Based on Age Group
Hide Description Number of participants with AEs and SAEs. Analyses were not performed by age group (under age 65 versus over age 65) as originally planned because of insufficient number of elderly participants.
Time Frame Baseline through 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were not performed by age group because of insufficient number of elderly patients. Zero participants were analyzed.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
18.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAE)
Hide Description Treatment Emergent Adverse Events (TEAEs) are defined as AEs that first occurred or worsened during the treatment period. TEAEs are summarized by study period and treatment group. TEAEs do not distinguish whether the events were deemed serious. A summary of non-serious AEs is located in the Reported Adverse Event module.
Time Frame Baseline through 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohorts 1 and 2 participants who received at least one dose of study drug.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Measure Type: Number
Unit of Measure: participants
Period B (n= 114, 113, 117, 117) 28 18 33 21
Period C (n= 103, 97, 97, 98) 26 34 42 22
Period D (n= 91, 89, 94, 88) 29 35 34 25
19.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAEs)
Hide Description SAEs do not distinguish whether the events are treatment-emergent. A summary of SAEs is located in the Reported Adverse Event module.
Time Frame Baseline through 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohorts 1 and 2 participants who received at least one dose of study drug.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Measure Type: Number
Unit of Measure: participants
1 1 2 2
20.Secondary Outcome
Title Change From Baseline in Blood Pressure (BP) at Each 2-Week Treatment Endpoint
Hide Description Change from baseline to the end of each of the 2-week treatment periods (Periods B, C, and D) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) are presented. Least Squares Mean (LSMean) values were adjusted for baseline and treatment.
Time Frame Baseline, 2 weeks of treatment over 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohorts 1 and 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Least Squares Mean (Standard Error)
Unit of Measure: mmHg
Period B: DBP (n= 112, 111, 117, 117) 0.15  (0.607) 0.21  (0.610) -0.45  (0.594) -0.41  (0.594)
Period B: SBP (n= 112, 111, 117, 117) 0.83  (0.908) 0.91  (0.912) -0.05  (0.888) -0.37  (0.888)
Period C: DBP (n= 102, 97, 97, 97) 0.35  (0.675) 1.11  (0.693) -0.68  (0.693) -0.51  (0.693)
Period C: SBP (n= 102, 97, 97, 97) 2.31  (0.932) 1.54  (0.960) 0.68  (0.957) 0.58  (0.958)
Period D: DBP (n= 91, 89, 93, 88) 0.33  (0.751) -0.31  (0.760) 0.37  (0.743) 0.75  (0.764)
Period D: SBP (n= 91, 89, 93, 88) 0.03  (1.097) 1.17  (1.109) 0.87  (1.085) 2.39  (1.118)
21.Secondary Outcome
Title Change From Baseline in Pulse Rate at Each 2-week Treatment Endpoint
Hide Description Change from baseline to the end of each of the 2-week treatment periods (Periods B, C, and D) for pulse rate are presented. Least Squares Mean (LSMean) values were adjusted for baseline and treatment.
Time Frame Baseline, 2 weeks of treatment over 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohorts 1 and 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute
Period B (n= 112, 111, 117, 117) 0.65  (0.664) 0.95  (0.669) 0.41  (0.653) 0.62  (0.649)
Period C (n= 102, 97, 97, 97) 0.42  (0.758) 0.94  (0.777) -0.64  (0.777) -0.02  (0.777)
Period D (n= 91, 89, 93, 88) 0.48  (0.813) -0.36  (0.820) 1.49  (0.803) 1.40  (0.826)
22.Secondary Outcome
Title Change From Baseline in Weight at Each 2-week Treatment Endpoint
Hide Description Change from baseline to the end of each of the 2-week treatment periods (Periods B, C, and D) for body weight are presented. Least Squares Mean (LSMean) values were adjusted for baseline and treatment.
Time Frame Baseline, 2 weeks of treatment over 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohorts 1 and 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Least Squares Mean (Standard Error)
Unit of Measure: kilogram
Period B (n= 111, 111, 115, 114) 0.13  (0.105) 0.27  (0.105) -0.08  (0.103) 0.06  (0.104)
Period C (n= 104, 100, 97, 96) 0.03  (0.129) 0.30  (0.132) -0.07  (0.135) 0.09  (0.134)
Period D (n=91, 90, 93, 88) 0.12  (0.164) 0.17  (0.165) 0.08  (0.162) 0.03  (0.166)
23.Secondary Outcome
Title Number of Participants With Abnormal Laboratory Analytes at Each 2-Week Treatment Endpoint
Hide Description Summary of number of participants with abnormal clinical chemistry, hematology and urinalysis laboratory results. A participant is included in the abnormal category if he/she experienced a result outside the normal reference ranges based on Lilly's reference range in the current period. All analytes have both lower and upper limits. The abnormal number includes both low (below normal range) and high (above normal range).
Time Frame 2 weeks of treatment over 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohorts 1 and 2 participants who received at least one dose of study drug, and had endpoint value. For LY2624803 1 mg, LY2624803 3 mg, Zolpidem 5 or 10 mg, and Placebo, the Number of Participants Analyzed were as follows: Period B: N=114, 113,117, 117; Period C: N=103, 97, 97, 98; and Period D: N=91, 89, 94, 88.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Measure Type: Number
Unit of Measure: participants
Period B: Alkaline Phosphatase 0 1 0 0
Period B: Alanine Transaminase 1 0 1 0
Period B: Aspartate Transaminase 1 1 0 0
Period B: Total Bilirubin 1 2 0 2
Period B: Creatine Phosphokinase 1 3 2 4
Period B: Creatinine 3 1 4 5
Period B: Glucose, Non-fasting or random 6 4 2 3
Period B: Blood Urea Nitrogen 2 1 2 2
Period B: Hemoglobin 2 1 0 1
Period B: Leukocyte Count 2 1 2 0
Period B: Platelet Count 1 1 1 0
Period C: Alkaline Phosphatase 0 0 0 0
Period C: Alanine Transaminase 0 0 2 1
Period C: Aspartate Transaminase 0 0 0 0
Period C: Total Bilirubin 1 1 2 1
Period C: Creatine Phosphokinase 3 2 0 2
Period C: Creatinine 3 0 4 3
Period C: Glucose, Non-fasting or random 4 5 1 5
Period C: Blood Urea Nitrogen 2 2 1 3
Period C: Hemoglobin 1 0 2 0
Period C: Leukocyte Count 2 3 0 1
Period C: Platelet Count 1 0 1 0
Period D: Alkaline Phosphatase 0 0 0 0
Period D: Alanine Transaminase 0 1 1 0
Period D: Aspartate Transaminase 2 1 1 1
Period D: Total Bilirubin 3 1 1 0
Period D: Creatine Phosphokinase 2 2 5 1
Period D: Creatinine 1 4 4 2
Period D: Glucose, Non-fasting or random 6 2 4 2
Period D: Blood Urea Nitrogen 0 2 0 1
Period D: Hemoglobin 0 1 0 2
Period D: Leukocyte Count 1 2 3 5
Period D: Platelet Count 0 3 0 1
24.Secondary Outcome
Title Change From Baseline in Heart Rate as Measured by Electrocardiogram (ECG) at Each 2-week Treatment Endpoint
Hide Description Change from baseline to the end of each of the 2-week treatment periods (Periods B, C, and D) for heart rate are presented. Least Squares Mean (LSMean) values were adjusted for baseline and treatment.
Time Frame Baseline, 2 weeks of treatment over 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 1 and 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute
Period B (n= 112, 110, 115, 112) 1.09  (0.689) 0.26  (0.695) 1.10  (0.681) 0.30  (0.688)
Period C (n= 99, 94, 96, 95) -0.59  (0.734) 0.31  (0.753) -0.02  (0.745) 1.14  (0.749)
Period D (n= 91,86, 93, 87) 1.71  (0.827) 1.71  (0.851) 1.43  (0.818) 0.86  (0.846)
25.Secondary Outcome
Title Change From Baseline in QT Interval Corrected Using Fridericia Formula (QTcF) as Measured by Electrocardiogram (ECG) at Each 2-week Treatment Endpoint
Hide Description QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTcF is the QT interval corrected for heart rate using Fridericia formula. Least Squares Mean (LSMean) values were adjusted for baseline and treatment.
Time Frame Baseline, 2 weeks of treatment over 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized Cohort 1 and 2 participants who received at least one dose of study drug, and had both baseline and endpoint values.
Arm/Group Title LY2624803 1 mg LY2624803 3 mg Zolpidem 5 or 10 mg Placebo
Hide Arm/Group Description:
Participants received LY2624803 1 mg in a 2-week treatment period.
Participants received LY2624803 3 mg in a 2-week treatment period.
Participants received Zolpidem 5 or 10 mg in a 2-week treatment period.
Participants received placebo in a 2-week treatment period.
Overall Number of Participants Analyzed 114 113 117 117
Least Squares Mean (Standard Error)
Unit of Measure: milliseconds
Period B (n= 112, 110, 115, 112) -0.04  (1.314) -2.62  (1.325) -1.02  (1.300) -1.43  (1.316)
Period C (n= 99, 94, 96, 95) -1.07  (1.335) -0.41  (1.373) -3.27  (1.356) -3.92  (1.370)
Period D (n= 91, 86, 93, 87) -2.00  (1.319) -2.99  (1.344) -3.59  (1.293) -1.68  (1.339)
Time Frame Adverse events are reported for periods B, C, and D. The number of participants at risk vary depending upon the period in which the AE occurred. Due to discontinuations, later periods had fewer participants.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Period B - LY2624803 1 mg Period B - LY2624803 3 mg Period B - Placebo Period B - Zolpidem 5 or 10 mg Period C - LY2624803 1 mg Period C - LY2624803 3 mg Period C - Placebo Period C - Zolpidem 5 or 10 mg Period D - LY2624803 1 mg Period D - LY2624803 3 mg Period D - Placebo Period D - Zolpidem 5 or 10 mg
Hide Arm/Group Description Patients received LY2624803 1 mg in Period B (2-week treatment period. Patients received LY2624803 3 mg in Period B (2-week treatment period). Patients received placebo in Period B (2-week treatment period). Patients received Zolpidem 5 or 10 mg in Period B (2-week treatment period). Patients received LY2624803 1 mg in Period C (2-week treatment period. Patients received LY2624803 3 mg in Period C (2-week treatment period). Patients received placebo in Period C (2-week treatment period). Patients received Zolpidem 5 or 10 mg in Period C (2-week treatment period). Patients received LY2624803 1 mg in Period D (2-week treatment period. Patients received LY2624803 3 mg in Period D (2-week treatment period). Patients received placebo in Period D (2-week treatment period). Patients received Zolpidem 5 or 10 mg in Period D (2-week treatment period).
All-Cause Mortality
Period B - LY2624803 1 mg Period B - LY2624803 3 mg Period B - Placebo Period B - Zolpidem 5 or 10 mg Period C - LY2624803 1 mg Period C - LY2624803 3 mg Period C - Placebo Period C - Zolpidem 5 or 10 mg Period D - LY2624803 1 mg Period D - LY2624803 3 mg Period D - Placebo Period D - Zolpidem 5 or 10 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Period B - LY2624803 1 mg Period B - LY2624803 3 mg Period B - Placebo Period B - Zolpidem 5 or 10 mg Period C - LY2624803 1 mg Period C - LY2624803 3 mg Period C - Placebo Period C - Zolpidem 5 or 10 mg Period D - LY2624803 1 mg Period D - LY2624803 3 mg Period D - Placebo Period D - Zolpidem 5 or 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/114 (0.88%)      1/113 (0.88%)      0/117 (0.00%)      1/117 (0.85%)      0/103 (0.00%)      0/97 (0.00%)      2/98 (2.04%)      1/97 (1.03%)      0/91 (0.00%)      0/89 (0.00%)      0/88 (0.00%)      0/94 (0.00%)    
Cardiac disorders                         
Atrial fibrillation  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Gastrointestinal disorders                         
Diverticulum  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Gastritis  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Infections and infestations                         
Appendicitis  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Injury, poisoning and procedural complications                         
Extradural haematoma  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Facial bones fracture  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Forearm fracture  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Hip fracture  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Period B - LY2624803 1 mg Period B - LY2624803 3 mg Period B - Placebo Period B - Zolpidem 5 or 10 mg Period C - LY2624803 1 mg Period C - LY2624803 3 mg Period C - Placebo Period C - Zolpidem 5 or 10 mg Period D - LY2624803 1 mg Period D - LY2624803 3 mg Period D - Placebo Period D - Zolpidem 5 or 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/114 (24.56%)      18/113 (15.93%)      21/117 (17.95%)      33/117 (28.21%)      26/103 (25.24%)      34/97 (35.05%)      22/98 (22.45%)      42/97 (43.30%)      29/91 (31.87%)      35/89 (39.33%)      25/88 (28.41%)      34/94 (36.17%)    
Blood and lymphatic system disorders                         
Anaemia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 1/88 (1.14%)  1 0/94 (0.00%)  0
Leukopenia  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Cardiac disorders                         
Palpitations  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Sinus bradycardia  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Ear and labyrinth disorders                         
Vertigo  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Eye disorders                         
Eye discharge  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Eye pain  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Gastrointestinal disorders                         
Diarrhoea  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 2/89 (2.25%)  2 0/88 (0.00%)  0 0/94 (0.00%)  0
Dry mouth  1  2/114 (1.75%)  2 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 1/103 (0.97%)  1 3/97 (3.09%)  3 0/98 (0.00%)  0 2/97 (2.06%)  2 0/91 (0.00%)  0 3/89 (3.37%)  3 2/88 (2.27%)  2 1/94 (1.06%)  1
Dyspepsia  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 1/94 (1.06%)  1
Flatulence  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Food poisoning  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Gastritis  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Gastrooesophageal reflux disease  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Nausea  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 1/97 (1.03%)  1 1/91 (1.10%)  1 1/89 (1.12%)  1 1/88 (1.14%)  1 1/94 (1.06%)  1
Stomach discomfort  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Toothache  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Vomiting  1  0/114 (0.00%)  0 0/113 (0.00%)  0 1/117 (0.85%)  1 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
General disorders                         
Fatigue  1  1/114 (0.88%)  1 1/113 (0.88%)  1 1/117 (0.85%)  1 1/117 (0.85%)  1 0/103 (0.00%)  0 2/97 (2.06%)  2 1/98 (1.02%)  1 3/97 (3.09%)  3 1/91 (1.10%)  1 1/89 (1.12%)  1 0/88 (0.00%)  0 1/94 (1.06%)  1
Feeling abnormal  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 1/97 (1.03%)  2 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Feeling jittery  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Irritability  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 2/117 (1.71%)  2 0/103 (0.00%)  0 0/97 (0.00%)  0 2/98 (2.04%)  2 2/97 (2.06%)  2 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 2/94 (2.13%)  2
Pain  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Sluggishness  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Suprapubic pain  1  0/114 (0.00%)  0 0/113 (0.00%)  0 1/117 (0.85%)  1 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Immune system disorders                         
Allergy to arthropod sting  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Drug hypersensitivity  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Hypersensitivity  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Seasonal allergy  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Infections and infestations                         
Cellulitis streptococcal  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Gastroenteritis  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Influenza  1  1/114 (0.88%)  1 0/113 (0.00%)  0 1/117 (0.85%)  1 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 2/94 (2.13%)  2
Lower respiratory tract infection  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Nasopharyngitis  1  0/114 (0.00%)  0 1/113 (0.88%)  1 2/117 (1.71%)  2 2/117 (1.71%)  2 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 2/97 (2.06%)  2 0/91 (0.00%)  0 2/89 (2.25%)  2 3/88 (3.41%)  3 1/94 (1.06%)  1
Oral herpes  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Otitis media  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Pharyngitis  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 2/97 (2.06%)  2 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Upper respiratory tract infection  1  1/114 (0.88%)  1 1/113 (0.88%)  1 1/117 (0.85%)  1 0/117 (0.00%)  0 2/103 (1.94%)  2 3/97 (3.09%)  3 1/98 (1.02%)  1 0/97 (0.00%)  0 4/91 (4.40%)  4 3/89 (3.37%)  3 0/88 (0.00%)  0 2/94 (2.13%)  2
Urinary tract infection  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 2/97 (2.06%)  2 0/98 (0.00%)  0 0/97 (0.00%)  0 1/91 (1.10%)  1 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Viral upper respiratory tract infection  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 1/103 (0.97%)  1 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Vulvovaginal mycotic infection  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Injury, poisoning and procedural complications                         
Back injury  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Contusion  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Hand fracture  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Joint sprain  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Limb injury  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Neck injury  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Overdose  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Poisoning  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Skin laceration  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Tooth fracture  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Upper limb fracture  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Investigations                         
Blood alkaline phosphatase increased  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Blood creatine phosphokinase increased  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Blood pressure increased  1  1/114 (0.88%)  1 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Blood sodium decreased  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Electrocardiogram t wave abnormal  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Heart rate increased  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 1/88 (1.14%)  1 0/94 (0.00%)  0
Liver function test abnormal  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Metabolism and nutrition disorders                         
Decreased appetite  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Hypercholesterolaemia  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Hypoglycaemia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Increased appetite  1  1/114 (0.88%)  1 2/113 (1.77%)  2 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 3/98 (3.06%)  3 0/97 (0.00%)  0 1/91 (1.10%)  1 1/89 (1.12%)  1 1/88 (1.14%)  1 1/94 (1.06%)  1
Musculoskeletal and connective tissue disorders                         
Arthralgia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 2/97 (2.06%)  2 2/91 (2.20%)  2 1/89 (1.12%)  1 0/88 (0.00%)  0 2/94 (2.13%)  2
Arthritis  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Arthropathy  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Back pain  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 2/89 (2.25%)  2 1/88 (1.14%)  1 0/94 (0.00%)  0
Bursitis  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Fibromyalgia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Intervertebral disc protrusion  1  0/114 (0.00%)  0 0/113 (0.00%)  0 1/117 (0.85%)  1 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 1/91 (1.10%)  1 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Muscle rigidity  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Muscle spasms  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Musculoskeletal pain  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 2/88 (2.27%)  2 0/94 (0.00%)  0
Musculoskeletal stiffness  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Myalgia  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Neck pain  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 1/97 (1.03%)  1 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 1/89 (1.12%)  1 1/88 (1.14%)  1 0/94 (0.00%)  0
Pain in extremity  1  1/114 (0.88%)  1 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 1/88 (1.14%)  1 0/94 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                         
Basal cell carcinoma  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Nervous system disorders                         
Amnesia  1  0/114 (0.00%)  0 1/113 (0.88%)  1 0/117 (0.00%)  0 1/117 (0.85%)  1 2/103 (1.94%)  2 0/97 (0.00%)  0 0/98 (0.00%)  0 2/97 (2.06%)  2 1/91 (1.10%)  1 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Ataxia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Coordination abnormal  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Depressed level of consciousness  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Dizziness  1  0/114 (0.00%)  0 1/113 (0.88%)  1 1/117 (0.85%)  1 4/117 (3.42%)  4 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 4/97 (4.12%)  4 2/91 (2.20%)  2 2/89 (2.25%)  2 1/88 (1.14%)  1 1/94 (1.06%)  1
Dizziness exertional  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Dysgeusia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 2/97 (2.06%)  2 1/91 (1.10%)  1 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Headache  1  4/114 (3.51%)  6 1/113 (0.88%)  1 3/117 (2.56%)  3 2/117 (1.71%)  3 3/103 (2.91%)  3 1/97 (1.03%)  1 2/98 (2.04%)  2 4/97 (4.12%)  4 0/91 (0.00%)  0 2/89 (2.25%)  2 2/88 (2.27%)  2 6/94 (6.38%)  6
Lethargy  1  0/114 (0.00%)  0 0/113 (0.00%)  0 1/117 (0.85%)  1 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Lumbar radiculopathy  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Memory impairment  1  0/114 (0.00%)  0 0/113 (0.00%)  0 1/117 (0.85%)  1 1/117 (0.85%)  1 1/103 (0.97%)  1 1/97 (1.03%)  1 1/98 (1.02%)  1 0/97 (0.00%)  0 2/91 (2.20%)  2 0/89 (0.00%)  0 0/88 (0.00%)  0 1/94 (1.06%)  1
Paraesthesia  1  1/114 (0.88%)  1 0/113 (0.00%)  0 2/117 (1.71%)  2 0/117 (0.00%)  0 2/103 (1.94%)  2 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Psychomotor hyperactivity  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Sciatica  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Sedation  1  1/114 (0.88%)  1 0/113 (0.00%)  0 2/117 (1.71%)  2 1/117 (0.85%)  1 0/103 (0.00%)  0 2/97 (2.06%)  2 1/98 (1.02%)  1 1/97 (1.03%)  1 3/91 (3.30%)  3 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Sleep paralysis  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Somnolence  1  2/114 (1.75%)  2 0/113 (0.00%)  0 2/117 (1.71%)  2 5/117 (4.27%)  5 4/103 (3.88%)  4 6/97 (6.19%)  6 3/98 (3.06%)  3 7/97 (7.22%)  7 7/91 (7.69%)  7 2/89 (2.25%)  2 3/88 (3.41%)  3 4/94 (4.26%)  4
Syncope vasovagal  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Tension headache  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Psychiatric disorders                         
Abnormal dreams  1  2/114 (1.75%)  2 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 2/97 (2.06%)  2 0/98 (0.00%)  0 2/97 (2.06%)  2 0/91 (0.00%)  0 2/89 (2.25%)  2 0/88 (0.00%)  0 2/94 (2.13%)  2
Agitation  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 1/117 (0.85%)  1 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Anxiety  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 2/97 (2.06%)  2 1/98 (1.02%)  1 1/97 (1.03%)  1 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 1/94 (1.06%)  1
Confusional state  1  0/114 (0.00%)  0 0/113 (0.00%)  0 1/117 (0.85%)  1 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Depression  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Hypervigilance  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 1/98 (1.02%)  1 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Initial insomnia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 1/89 (1.12%)  1 0/88 (0.00%)  0 0/94 (0.00%)  0
Insomnia  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 0/97 (0.00%)  0 0/91 (0.00%)  0 0/89 (0.00%)  0 1/88 (1.14%)  1 0/94 (0.00%)  0
Nervousness  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 0/103 (0.00%)  0 0/97 (0.00%)  0 0/98 (0.00%)  0 1/97 (1.03%)  1 0/91 (0.00%)  0 0/89 (0.00%)  0 0/88 (0.00%)  0 0/94 (0.00%)  0
Nightmare  1  0/114 (0.00%)  0 0/113 (0.00%)  0 0/117 (0.00%)  0 0/117 (0.00%)  0 1/103 (0.97%)  1 1/97 (1.03%)  1 0/98 (0.00%)  0 0/97 (0.00%)  0