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Trial record 2 of 3 for:    herpes zoster oticus

CLARITY Extension Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00641537
Recruitment Status : Completed
First Posted : March 24, 2008
Results First Posted : December 2, 2013
Last Update Posted : February 7, 2014
Sponsor:
Information provided by (Responsible Party):
EMD Serono

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Interventions Drug: Cladribine
Drug: Placebo
Enrollment 867
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL) Placebo/No Treatment Cladribine 3.5 mg/kg/No Treatment Cladribine 5.25 mg/kg/No Treatment
Hide Arm/Group Description Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period).
Period Title: 96-week Period
Started 98 92 186 186 244 22 17 22
Completed 89 82 166 174 226 15 12 16
Not Completed 9 10 20 12 18 7 5 6
Reason Not Completed
Adverse Event             0             1             3             0             2             0             0             0
Lost to Follow-up             3             1             2             2             4             0             1             0
Protocol Violation             0             1             0             1             0             1             0             0
Death             2             0             1             0             0             0             0             0
Other             4             7             14             9             12             6             4             6
Period Title: 24-Week Supplemental Follow-up Period
Started 75 69 143 151 198 15 9 11
Completed 75 66 140 147 193 14 8 10
Not Completed 0 3 3 4 5 1 1 1
Reason Not Completed
Lost to Follow-up             0             1             1             3             2             1             0             0
Other             0             2             2             1             3             0             1             1
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL) Total
Hide Arm/Group Description Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Total of all reporting groups
Overall Number of Baseline Participants 98 92 186 186 244 806
Hide Baseline Analysis Population Description
Intention-to-treat (ITT) population included all participants who were randomized in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 98 participants 92 participants 186 participants 186 participants 244 participants 806 participants
40.7  (10.7) 40.8  (9.6) 40.6  (10.5) 41.4  (10.1) 41.6  (9.6) 41.1  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 98 participants 92 participants 186 participants 186 participants 244 participants 806 participants
Female
67
  68.4%
59
  64.1%
124
  66.7%
125
  67.2%
156
  63.9%
531
  65.9%
Male
31
  31.6%
33
  35.9%
62
  33.3%
61
  32.8%
88
  36.1%
275
  34.1%
1.Primary Outcome
Title Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 Lymphocyte Toxicity
Hide Description Lymphocyte toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). CTCAE grade for absolute lymphocyte counts included: Grade 1 = less than lower limit of normal; Grade 2 = less than 800 per cubic millimeter (/mm^3); Grade 3 = less than 500/mm^3; Grade 4 = less than 200/mm^3.
Time Frame Baseline up to Week 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data.
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL)
Hide Arm/Group Description:
Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Overall Number of Participants Analyzed 98 92 186 186 244
Measure Type: Number
Unit of Measure: percentage of participants
Grade 3 Lymphocyte toxicity 5.1 6.5 38.1 50.0 24.6
Grade 4 Lymphocyte toxicity 0 0 2.7 3.2 0.4
2.Primary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.
Time Frame Baseline up to week 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data.
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL)
Hide Arm/Group Description:
Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Overall Number of Participants Analyzed 98 92 186 186 244
Measure Type: Number
Unit of Measure: participants
AEs 74 71 149 149 194
SAEs 16 8 25 23 22
3.Primary Outcome
Title Median Time to Recovery From Grade 3 or 4 Lymphocyte Toxicity
Hide Description Lymphocyte toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). CTCAE grade for absolute lymphocyte counts included: Grade 1 = less than lower limit of normal; Grade 2 = less than 800 per cubic millimeter (/mm^3); Grade 3 = less than 500/mm^3; Grade 4 = less than 200/mm^3. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1 during the CLARITY Extension Study.
Time Frame Baseline up to Week 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data. 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL)
Hide Arm/Group Description:
Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Overall Number of Participants Analyzed 5 4 69 89 50
Median (Full Range)
Unit of Measure: days
21
(13 to 84)
30.5
(24.5 to 50)
211
(7 to 1183)
167
(6 to 798)
110.3
(4 to 700)
4.Primary Outcome
Title Number of Participants Who Developed Herpes Zoster Infections and Malignancies
Hide Description Herpes zoster infection is defined as having at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms herpes zoster, herpes zoster iridocyclitis, herpes zoster ophthalmic, herpes zoster multi-dermatomal, herpes zoster infection neurological, herpes zoster oticus. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre_specified grouping Malignant and unspecified tumors.
Time Frame Baseline up to Week 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all the randomized participants who had received at least 1 dose of study medication and had follow-up safety data.
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL)
Hide Arm/Group Description:
Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Overall Number of Participants Analyzed 98 92 186 186 244
Measure Type: Number
Unit of Measure: Participants
Herpes Zoster Infections 2 1 2 9 5
Malignancies 2 1 7 2 2
5.Secondary Outcome
Title Annualized Qualifying Relapse Rate
Hide Description A qualifying relapse was defined as an increase of 2 points in at least one functional system of the expanded disability status scale (EDSS) or an increase of 1 point in at least two functional systems (excluding changes in bowel or bladder function or cognition) in the absence of fever, lasting for at least 24 hours and to have been preceded by at least 30 days of clinical stability or improvement. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]) was calculated. The annualized relapse rate for each treatment group was calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat (ITT) population included all participants who were randomized in the study.
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL)
Hide Arm/Group Description:
Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Overall Number of Participants Analyzed 98 92 186 186 244
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per year
0.15
(0.08 to 0.22)
0.16
(0.09 to 0.23)
0.10
(0.06 to 0.14)
0.11
(0.07 to 0.15)
0.10
(0.07 to 0.13)
6.Secondary Outcome
Title Mean Number of Combined Unique (CU) Lesions
Hide Description Mean Number of CU lesions were measured by using magnetic resonance imaging (MRI) scans.
Time Frame Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized in the study.
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL)
Hide Arm/Group Description:
Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Overall Number of Participants Analyzed 98 92 186 186 244
Mean (Standard Deviation)
Unit of Measure: lesions
5.88  (15.31) 6.02  (9.22) 3.97  (7.18) 5.53  (14.79) 5.10  (9.08)
7.Secondary Outcome
Title Time to Disability Progression (Confirmed After 3 Months)
Hide Description Time to disability progression was defined as the time to a sustained increase in EDSS score of at least 1 point if baseline EDSS score between 0.5 and 4.5 inclusively, or at least 1.5 points if the baseline EDSS score was 0, or at least 0.5 point if the baseline EDSS score was at least 5, over a period of at least three months. Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. As few participants have reached EDSS progression, fourth Percentile of time to sustained increase in EDSS score was reported using Kaplan-Meier survival curve.
Time Frame Baseline up to Week 96
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Hide Analysis Population Description
ITT population included all participants who were randomized in the study.
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL)
Hide Arm/Group Description:
Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period.
Overall Number of Participants Analyzed 98 92 186 186 244
Measure Type: Number
Unit of Measure: months
5.6 5.5 8.2 5.5 5.4
Time Frame Adverse events collected from baseline up to Week 96 and 24-Week supplemental follow-up period.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL) Placebo/No Treatment Cladribine 3.5 mg/kg/No Treatment Cladribine 5.25 mg/kg/No Treatment Cladribine Low/Placebo (LLPP) (24-week Follow-up Period) Cladribine High Dose/Placebo (HLPP) (24-week Follow-up Period Cladribine Low/Low Dose (LLLL) (24-week Follow-up Period) Cladribine High/Low Dose (HLLL) (24-week Follow-up Period) Placebo/Cladribine Low Dose (PPLL) (24-week Follow-up Period) Placebo/No Treatment (24-week Follow-up Period) Cladribine 3.5 mg/kg/No Treatment (24-week Follow-up Period) Cladribine 5.25 mg/kg/No Treatment (24-week Follow-up Period)
Hide Arm/Group Description Participants who received cladribine 3.5 milligram/kilogram (mg/kg) in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received placebo matched to cladribine tablet 0.875 mg/kg orally over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and completed were re-randomized in this extension study and received Cladribine tablet orally as cumulative dose of 0.875 mg/kg over a course of 4 or 5 consecutive days of 28-day period at Week 1, 5, 48, and 52 resulting in total cladribine dose of 3.5 mg/kg during the treatment period of 96 weeks. Participants were followed up for 24 weeks in supplemental follow-up period. Participants who received placebo matched to cladribine in previous study 25643 (NCT00213135) and were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). Participants who received Cladribine 3.5 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). Participants who received Cladribine 5.25 mg/kg in previous study 25643 (NCT00213135) and completed were enrolled in this extension study and received no cladribine treatment and were followed up for safety assessment for 96 weeks (during the treatment period) and followed up for 24 weeks (during supplemental follow-up period). Participants who received placebo matched to cladribine tablet during the treatment period of 96 weeks were followed up for 24 weeks in supplemental follow-up period. Participants who received placebo matched to cladribine tablet during the treatment period of 96 weeks were followed up for 24 weeks in supplemental follow-up period. Participants who received cladribine 3.5 mg/kg during the treatment period of 96 weeks were followed up for 24 weeks in supplemental follow-up period. Participants who received cladribine 3.5 mg/kg during the treatment period of 96 weeks were followed up for 24 weeks in supplemental follow-up period. Participants who received cladribine 3.5 mg/kg during the treatment period of 96 weeks were followed up for 24 weeks in supplemental follow-up period. Participants who received no cladribine treatment during 96 weeks were followed up for 24-Week supplemental follow-up period. Participants who received no cladribine treatment during 96 weeks were followed up for 24 weeks in supplemental follow-up period. Participants who received no cladribine treatment during 96 weeks were followed up for 24 weeks in supplemental follow-up period.
All-Cause Mortality
Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL) Placebo/No Treatment Cladribine 3.5 mg/kg/No Treatment Cladribine 5.25 mg/kg/No Treatment Cladribine Low/Placebo (LLPP) (24-week Follow-up Period) Cladribine High Dose/Placebo (HLPP) (24-week Follow-up Period Cladribine Low/Low Dose (LLLL) (24-week Follow-up Period) Cladribine High/Low Dose (HLLL) (24-week Follow-up Period) Placebo/Cladribine Low Dose (PPLL) (24-week Follow-up Period) Placebo/No Treatment (24-week Follow-up Period) Cladribine 3.5 mg/kg/No Treatment (24-week Follow-up Period) Cladribine 5.25 mg/kg/No Treatment (24-week Follow-up Period)
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL) Placebo/No Treatment Cladribine 3.5 mg/kg/No Treatment Cladribine 5.25 mg/kg/No Treatment Cladribine Low/Placebo (LLPP) (24-week Follow-up Period) Cladribine High Dose/Placebo (HLPP) (24-week Follow-up Period Cladribine Low/Low Dose (LLLL) (24-week Follow-up Period) Cladribine High/Low Dose (HLLL) (24-week Follow-up Period) Placebo/Cladribine Low Dose (PPLL) (24-week Follow-up Period) Placebo/No Treatment (24-week Follow-up Period) Cladribine 3.5 mg/kg/No Treatment (24-week Follow-up Period) Cladribine 5.25 mg/kg/No Treatment (24-week Follow-up Period)
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/98 (14.29%)   7/92 (7.61%)   23/186 (12.37%)   21/186 (11.29%)   21/244 (8.61%)   1/22 (4.55%)   1/17 (5.88%)   3/22 (13.64%)   2/75 (2.67%)   0/69 (0.00%)   2/143 (1.40%)   1/151 (0.66%)   4/198 (2.02%)   0/15 (0.00%)   0/9 (0.00%)   0/11 (0.00%) 
Blood and lymphatic system disorders                                 
Lymphopenia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Iron deficiency anaemia * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Thrombocytopenia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  1/75 (1.33%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Cardiac disorders                                 
Adams-Stokes syndrome * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Atrial fibrillation * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Myocardial infarction * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Tachycardia * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Ear and labyrinth disorders                                 
Vertigo positional * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Endocrine disorders                                 
Basedow's disease * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Thyroiditis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Autoimmune thyroiditis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Eye disorders                                 
Iridocyclitis * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  1/75 (1.33%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Macular degeneration * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Gastrointestinal disorders                                 
Abdominal pain * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Colonic polyp * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Duodenal ulcer * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Duodenal ulcer perforation * 1  0/98 (0.00%)  1/92 (1.09%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Gastric haemorrhage * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Gastritis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Gastrooesophageal reflux disease * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Ileus paralytic * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Irritable bowel syndrome * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Peritonitis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Crohn's disease * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
General disorders                                 
Chest pain * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Death * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Drowning * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Influenza like illness * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Hepatobiliary disorders                                 
Cholelithiasis * 1  1/98 (1.02%)  0/92 (0.00%)  2/186 (1.08%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Cholecystitis * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Biliary colic * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Biliary tract disorder * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Immune system disorders                                 
Secondary immunodeficiency * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Infections and infestations                                 
Herpes zoster * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  2/186 (1.08%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pneumonia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  2/244 (0.82%)  0/22 (0.00%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Urinary tract infection * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Abscess oral * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Appendicitis * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Bacterial sepsis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Breast abscess * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Gastroenteritis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Infection * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Influenza * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pulmonary tuberculosis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pyelonephritis * 1  0/98 (0.00%)  1/92 (1.09%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pyelonephritis chronic * 1  0/98 (0.00%)  1/92 (1.09%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Urethral abscess * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Tuberculosis * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications                                 
Femoral neck fracture * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Humerus fracture * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Intentional overdose * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Limb injury * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Radius fracture * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  1/151 (0.66%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Road traffic accident * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Subdural haematoma * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Investigations                                 
Blood culture positive * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pregnancy test positive * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Tuberculin test positive * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Weight decreased * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Metabolism and nutrition disorders                                 
Diabetic ketoacidosis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Type 2 diabetes mellitus * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Hypokalaemia * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders                                 
Intervertebral disc protrusion * 1  1/98 (1.02%)  1/92 (1.09%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                 
Uterine leiomyoma * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  2/186 (1.08%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Lipoma * 1  0/98 (0.00%)  1/92 (1.09%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Malignant melanoma * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Adrenal adenoma * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Basal cell carcinoma * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  1/22 (4.55%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Bile duct cancer * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Breast cancer * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Breast fibroma * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Colorectal cancer metastatic * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Fibrous histiocytoma * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Haemangioma of liver * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Juvenile melanoma benign * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Lung neoplasm * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Melanocytic naevus * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Metastases to lung * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  1/143 (0.70%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Metastases to lymph nodes * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Neurilemmoma benign * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Prostatic adenoma * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Rectal cancer * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Renal cell carcinoma * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Seborrhoeic keratosis * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Skin papilloma * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Squamous cell carcinoma * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Thyroid adenoma * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Thyroid cancer * 1  0/98 (0.00%)  1/92 (1.09%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Ovarian cancer * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Nervous system disorders                                 
Brain injury * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Cauda equina syndrome * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Radicular syndrome * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Sciatica * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Status epilepticus * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pregnancy, puerperium and perinatal conditions                                 
Abortion missed * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  1/143 (0.70%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Abortion threatened * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Psychiatric disorders                                 
Mental disorder * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Suicidal ideation * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Suicide attempt * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Renal and urinary disorders                                 
Cystitis noninfective * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Renal failure acute * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Renal failure chronic * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Nephrolithiasis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Dysuria * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Reproductive system and breast disorders                                 
Menorrhagia * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Ovarian cyst * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Ovarian cyst ruptured * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders                                 
Asthma * 1  1/98 (1.02%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Bronchitis chronic * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pneumothorax * 1  0/98 (0.00%)  0/92 (0.00%)  1/186 (0.54%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Respiratory failure * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  1/244 (0.41%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Skin and subcutaneous tissue disorders                                 
Pain of skin * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  1/198 (0.51%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Surgical and medical procedures                                 
Abortion induced * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  1/186 (0.54%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Vascular disorders                                 
Varicose vein * 1  0/98 (0.00%)  1/92 (1.09%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
*
Indicates events were collected by non-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 5%
Cladribine Low/Placebo (LLPP) Cladribine High Dose/Placebo (HLPP) Cladribine Low/Low Dose (LLLL) Cladribine High/Low Dose (HLLL) Placebo/Cladribine Low Dose (PPLL) Placebo/No Treatment Cladribine 3.5 mg/kg/No Treatment Cladribine 5.25 mg/kg/No Treatment Cladribine Low/Placebo (LLPP) (24-week Follow-up Period) Cladribine High Dose/Placebo (HLPP) (24-week Follow-up Period Cladribine Low/Low Dose (LLLL) (24-week Follow-up Period) Cladribine High/Low Dose (HLLL) (24-week Follow-up Period) Placebo/Cladribine Low Dose (PPLL) (24-week Follow-up Period) Placebo/No Treatment (24-week Follow-up Period) Cladribine 3.5 mg/kg/No Treatment (24-week Follow-up Period) Cladribine 5.25 mg/kg/No Treatment (24-week Follow-up Period)
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   59/98 (60.20%)   53/92 (57.61%)   124/186 (66.67%)   123/186 (66.13%)   163/244 (66.80%)   15/22 (68.18%)   13/17 (76.47%)   18/22 (81.82%)   1/75 (1.33%)   3/69 (4.35%)   3/143 (2.10%)   9/151 (5.96%)   9/198 (4.55%)   7/15 (46.67%)   3/9 (33.33%)   6/11 (54.55%) 
Blood and lymphatic system disorders                                 
Lymphopenia * 1  9/98 (9.18%)  7/92 (7.61%)  68/186 (36.56%)  75/186 (40.32%)  69/244 (28.28%)  2/22 (9.09%)  2/17 (11.76%)  5/22 (22.73%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  1/15 (6.67%)  0/9 (0.00%)  0/11 (0.00%) 
Leukopenia * 1  1/98 (1.02%)  2/92 (2.17%)  19/186 (10.22%)  20/186 (10.75%)  12/244 (4.92%)  2/22 (9.09%)  0/17 (0.00%)  3/22 (13.64%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Neutropenia * 1  2/98 (2.04%)  2/92 (2.17%)  7/186 (3.76%)  10/186 (5.38%)  7/244 (2.87%)  1/22 (4.55%)  1/5 (20.00%)  5/22 (22.73%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Thrombocytopenia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  2/22 (9.09%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Anaemia of pregnancy * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Iron deficiency anaemia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Ear and labyrinth disorders                                 
Vertigo * 1  5/98 (5.10%)  1/92 (1.09%)  6/186 (3.23%)  5/186 (2.69%)  5/244 (2.05%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Ear pain * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Eye disorders                                 
Eye irritation * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Eye pruritus * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Gastrointestinal disorders                                 
Diarrhoea * 1  7/98 (7.14%)  6/92 (6.52%)  6/186 (3.23%)  9/186 (4.84%)  14/244 (5.74%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Nausea * 1  8/98 (8.16%)  4/92 (4.35%)  11/186 (5.91%)  7/186 (3.76%)  10/244 (4.10%)  0/22 (0.00%)  0/17 (0.00%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Toothache * 1  4/98 (4.08%)  6/92 (6.52%)  5/186 (2.69%)  3/186 (1.61%)  4/244 (1.64%)  0/22 (0.00%)  0/17 (0.00%)  3/22 (13.64%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Vomiting * 1  1/98 (1.02%)  5/92 (5.43%)  5/186 (2.69%)  0/186 (0.00%)  4/244 (1.64%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Tooth disorder * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  1/22 (4.55%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Faecal incontinence * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Gastrooesophageal reflux disease * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Mouth ulceration * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
General disorders                                 
Fatigue * 1  5/98 (5.10%)  5/92 (5.43%)  8/186 (4.30%)  10/186 (5.38%)  12/244 (4.92%)  1/22 (4.55%)  2/17 (11.76%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  1/9 (11.11%)  0/11 (0.00%) 
Influenza like illness * 1  5/98 (5.10%)  2/92 (2.17%)  14/186 (7.53%)  9/186 (4.84%)  10/244 (4.10%)  1/22 (4.55%)  2/17 (11.76%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Asthenia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  2/22 (9.09%)  0/17 (0.00%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Hyperthermia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  2/17 (11.76%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Immune system disorders                                 
Hypersensitivity * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Infections and infestations                                 
Nasopharyngitis * 1  19/98 (19.39%)  15/92 (16.30%)  22/186 (11.83%)  28/186 (15.05%)  45/244 (18.44%)  1/22 (4.55%)  0/17 (0.00%)  6/22 (27.27%)  1/75 (1.33%)  3/69 (4.35%)  3/143 (2.10%)  9/151 (5.96%)  9/198 (4.55%)  0/15 (0.00%)  0/9 (0.00%)  3/11 (27.27%) 
Influenza * 1  11/98 (11.22%)  10/92 (10.87%)  15/186 (8.06%)  23/186 (12.37%)  17/244 (6.97%)  4/22 (18.18%)  2/17 (11.76%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  2/15 (13.33%)  0/9 (0.00%)  0/11 (0.00%) 
Upper respiratory tract infection * 1  8/98 (8.16%)  9/92 (9.78%)  17/186 (9.14%)  20/186 (10.75%)  19/244 (7.79%)  1/22 (4.55%)  1/17 (5.88%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Urinary tract infection * 1  6/98 (6.12%)  4/92 (4.35%)  17/186 (9.14%)  16/186 (8.60%)  16/244 (6.56%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Bronchitis * 1  6/98 (6.12%)  7/92 (7.61%)  1/186 (0.54%)  12/186 (6.45%)  17/244 (6.97%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Respiratory tract infection viral * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  2/22 (9.09%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pneumonia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Sinusitis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Viral infection * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  1/22 (4.55%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Viral upper respiratory tract infection * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  1/22 (4.55%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Erythema infectiosum * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Herpes zoster * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  1/9 (11.11%)  0/11 (0.00%) 
Infected insect bite * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Injection site abscess * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Skin bacterial infection * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Furuncle * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  1/15 (6.67%)  0/9 (0.00%)  0/11 (0.00%) 
Hordeolum * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Oral herpes * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Injury, poisoning and procedural complications                                 
Contusion * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Joint sprain * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  1/22 (4.55%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Fall * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Investigations                                 
White blood cell count decreased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Alanine aminotransferase increased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  2/22 (9.09%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Blood creatine phosphokinase increased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Red blood cell burr cells present * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Liver function test abnormal * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Weight decreased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Blood potassium decreased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Blood urea increased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  1/15 (6.67%)  0/9 (0.00%)  0/11 (0.00%) 
Thyroid function test abnormal * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Weight increased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  1/15 (6.67%)  0/9 (0.00%)  0/11 (0.00%) 
White blood cell count increased * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders                                 
Back pain * 1  9/98 (9.18%)  9/92 (9.78%)  16/186 (8.60%)  18/186 (9.68%)  28/244 (11.48%)  1/22 (4.55%)  4/17 (23.53%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Pain in extremity * 1  8/98 (8.16%)  6/92 (6.52%)  10/186 (5.38%)  10/186 (5.38%)  11/244 (4.51%)  2/22 (9.09%)  1/17 (5.88%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  1/9 (11.11%)  0/11 (0.00%) 
Arthralgia * 1  5/98 (5.10%)  4/92 (4.35%)  5/186 (2.69%)  8/186 (4.30%)  13/244 (5.33%)  0/22 (0.00%)  1/17 (5.88%)  3/22 (13.64%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Musculoskeletal pain * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  2/22 (9.09%)  0/17 (0.00%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Joint swelling * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Sensation of heaviness * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Tendonitis * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  1/15 (6.67%)  0/9 (0.00%)  0/11 (0.00%) 
Nervous system disorders                                 
Headache * 1  20/98 (20.41%)  16/92 (17.39%)  21/186 (11.29%)  25/186 (13.44%)  38/244 (15.57%)  3/22 (13.64%)  1/17 (5.88%)  4/22 (18.18%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Dizziness * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  1/22 (4.55%)  1/17 (5.88%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Carpal tunnel syndrome * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Restless legs syndrome * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Syncope * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Paraesthesia * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  0/17 (0.00%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Pregnancy, puerperium and perinatal conditions                                 
Pregnancy * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Psychiatric disorders                                 
Depression * 1  6/98 (6.12%)  1/92 (1.09%)  6/186 (3.23%)  5/186 (2.69%)  9/244 (3.69%)  1/22 (4.55%)  1/17 (5.88%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Anxiety * 1  5/98 (5.10%)  2/92 (2.17%)  4/186 (2.15%)  5/186 (2.69%)  7/244 (2.87%)  0/22 (0.00%)  1/17 (5.88%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Depressed mood * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders                                 
Pharyngolaryngeal pain * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  2/22 (9.09%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
Cough * 1  0/98 (0.00%)  0/92 (0.00%)  0/186 (0.00%)  0/186 (0.00%)  0/244 (0.00%)  0/22 (0.00%)  1/17 (5.88%)  1/22 (4.55%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  1/11 (9.09%) 
Vascular disorders                                 
Hypertension * 1  4/98 (4.08%)  5/92 (5.43%)  5/186 (2.69%)  2/186 (1.08%)  7/244 (2.87%)  1/22 (4.55%)  1/17 (5.88%)  0/22 (0.00%)  0/75 (0.00%)  0/69 (0.00%)  0/143 (0.00%)  0/151 (0.00%)  0/198 (0.00%)  0/15 (0.00%)  0/9 (0.00%)  0/11 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Layout table for additonal information
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00641537     History of Changes
Other Study ID Numbers: 27820
First Submitted: March 13, 2008
First Posted: March 24, 2008
Results First Submitted: September 30, 2013
Results First Posted: December 2, 2013
Last Update Posted: February 7, 2014