A Study for Treatment of Pain in Patients With Diabetic Neuropathy.
This study has been completed.
Sponsor:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00785577
First received: November 3, 2008
Last updated: April 30, 2012
Last verified: April 2012
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Results First Received: August 25, 2011
| Study Type: | Interventional |
|---|---|
| Study Design: | Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment |
| Condition: |
Diabetic Neuropathy, Painful |
| Interventions: |
Drug: Placebo Drug: Pregabalin Drug: LY545694 21 mg Drug: LY545694 49 mg Drug: LY545694 105 mg |
Participant Flow
Recruitment Details
| Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
|---|
| No text entered. |
Pre-Assignment Details
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
|---|
| Study Period 1 was an up to 5-week screening phase when participants stopped use of excluded medications (525 participants entered; 252 discontinued ). Study Period 2 was a 5-week, double-blind therapy period when randomization and dispensing of study drug occurred. Study Period 3 was a 1-week washout phase when all study medication was stopped. |
Reporting Groups
| Description | |
|---|---|
| Placebo | LY545694 placebo twice daily (BID) oral (po) for 5 weeks and pregabalin placebo capsules three times daily (TID) po for 6 weeks. |
| Pregabalin | Pregabalin thrice daily TID po for 6 weeks: 50 mg TID po for Week 1, 100 mg TID po for Weeks 2 - 5, and 50 mg TID po taper for Week 6. |
| LY545694 21 mg | LY545694 21 milligrams (mg) BID po for 1 week. |
| LY545694 49 mg | LY545694 escalated to 49 mg BID po during Week 2; possible titration down to 21 mg BID po within 1 week of escalation for remainder of study treatment. |
| LY545694 105 mg | LY545694 escalated to 105 mg BID po during Week 3 through Week 5; possible titration down to 49 mg BID po within 1 week of escalation for the remainder of study treatment. |
Participant Flow for 2 periods
Period 1: Study Period 2: Therapy Phase
| Placebo | Pregabalin | LY545694 21 mg | LY545694 49 mg | LY545694 105 mg | |
|---|---|---|---|---|---|
| STARTED | 89 | 45 | 43 | 49 | 47 |
| COMPLETED | 78 | 36 | 25 | 36 | 27 |
| NOT COMPLETED | 11 | 9 | 18 | 13 | 20 |
| Adverse Event | 5 | 7 | 14 | 10 | 17 |
| Lack of Efficacy | 0 | 0 | 0 | 0 | 1 |
| Lost to Follow-up | 0 | 0 | 0 | 1 | 0 |
| Physician Decision | 1 | 0 | 0 | 0 | 0 |
| Protocol Violation | 1 | 1 | 1 | 0 | 1 |
| Withdrawal by Subject | 2 | 1 | 1 | 0 | 1 |
| Entry Criteria Exclusion | 1 | 0 | 1 | 1 | 0 |
| Sponsor Decision | 1 | 0 | 1 | 1 | 0 |
Period 2: Study Period 3: 1-Week Washout Phase
| Placebo | Pregabalin | LY545694 21 mg | LY545694 49 mg | LY545694 105 mg | |
|---|---|---|---|---|---|
| STARTED | 78 | 36 | 25 | 36 | 27 |
| COMPLETED | 78 | 36 | 25 | 35 | 26 |
| NOT COMPLETED | 0 | 0 | 0 | 1 | 1 |
| Adverse Event | 0 | 0 | 0 | 1 | 0 |
| Death | 0 | 0 | 0 | 0 | 1 |
Baseline Characteristics
Reporting Groups
| Description | |
|---|---|
| Placebo | LY545694 placebo twice daily (BID) oral (po) for 5 weeks and pregabalin placebo capsules three times daily (TID) po for 6 weeks. |
| Pregabalin | Pregabalin thrice daily TID po for 6 weeks: 50 mg TID po for Week 1, 100 mg TID po for Weeks 2 - 5, and 50 mg TID po taper for Week 6. |
| LY545694 21 mg | LY545694 21 milligrams (mg) BID po for 1 week. |
| LY545694 49 mg | LY545694 escalated to 49 mg BID po during Week 2; possible titration down to 21 mg BID po within 1 week of escalation for remainder of study treatment. |
| LY545694 105 mg | LY545694 escalated to 105 mg BID po during Week 3 through Week 5; possible titration down to 49 mg BID po within 1 week of escalation for the remainder of study treatment. |
| Total | Total of all reporting groups |
Baseline Measures
| Placebo | Pregabalin | LY545694 21 mg | LY545694 49 mg | LY545694 105 mg | Total | |
|---|---|---|---|---|---|---|
|
Number of Participants
[units: participants] |
89 | 45 | 43 | 49 | 47 | 273 |
|
Age
[units: years] Mean ± Standard Deviation |
55.32 ± 10.00 | 56.89 ± 8.19 | 56.95 ± 8.35 | 58.59 ± 7.71 | 56.47 ± 7.77 | 56.62 ± 8.71 |
|
Gender
[units: participants] |
||||||
| Female | 37 | 17 | 20 | 25 | 19 | 118 |
| Male | 52 | 28 | 23 | 24 | 28 | 155 |
|
Race/Ethnicity, Customized
[units: participants] |
||||||
| American Indian or Alaskan Native | 7 | 4 | 2 | 4 | 2 | 19 |
| Asian | 0 | 0 | 1 | 0 | 1 | 2 |
| Black or African American | 10 | 6 | 9 | 4 | 8 | 37 |
| Multiple | 1 | 0 | 1 | 1 | 1 | 4 |
| White | 71 | 35 | 30 | 40 | 35 | 211 |
|
Region of Enrollment
[units: participants] |
||||||
| United States | 57 | 29 | 28 | 29 | 28 | 171 |
| Mexico | 26 | 13 | 12 | 16 | 16 | 83 |
| Puerto Rico | 6 | 3 | 3 | 4 | 3 | 19 |
Outcome Measures
| 1. Primary: | Change From Baseline in Weekly Mean 24-hour Average Pain Severity (APS) Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 2. Secondary: | Change From Baseline in Weekly Mean Night Pain Severity Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 3. Secondary: | Change From Baseline in Weekly Mean Worst Daily Pain Severity Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 4. Secondary: | Number of Participants With 30% Reduction in Weekly Mean 24-hour Average Pain Severity (APS) Score [ Time Frame: Baseline through 5 weeks ] |
| 5. Secondary: | Change From Baseline in Average Brief Pain Inventory - Interference (BPI-I) Subscale Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 6. Secondary: | Change From Baseline in Brief Pain Inventory - Severity (BPI-S) Subscale Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 7. Secondary: | Change From Baseline in Clinical Global Impression of Severity (CGI-S) Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 8. Secondary: | Patient Global Impression of Improvement (PGI-I) Score at 5 Weeks [ Time Frame: Week 5 ] |
| 9. Secondary: | Change From Baseline in Short-form McGill Pain Questionnaire (SF-MPQ) Sensory Subscale Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 10. Secondary: | Change From Baseline in Assessment of Sleep Questionnaire (ASQ) Total Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 11. Secondary: | Change From Baseline in Neuropathy-Specific Quality of Life (NeuroQoL) Questionnaire Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 12. Secondary: | Change From Baseline in Short Form-36 (SF-36) Health Survey Bodily Pain Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 13. Secondary: | Change From Baseline of European Quality of Life Scale - 5 Dimensions (EQ-5D) at 5 Weeks: United States Population Based Index Score [ Time Frame: Baseline, 5 weeks ] |
| 14. Secondary: | Change From Baseline in Sheehan Disability Scale (SDS) Global Impairment Score at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 15. Secondary: | Number of Participants Who Discontinued Due to Adverse Events (AEs) During the Therapy (Double-blind) Phase and 1-Week Washout (Follow-up) Phase [ Time Frame: Baseline through 6 weeks ] |
| 16. Secondary: | Number of Participants With Serious Treatment Emergent Abnormal High or Low Laboratory Values [ Time Frame: Baseline through 5 weeks ] |
| 17. Secondary: | Change From Baseline in Vital Signs: Systolic Blood Pressure and Diastolic Blood Pressure at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 18. Secondary: | Change From Baseline in Vital Signs: Pulse Rate at 5 Weeks [ Time Frame: Baseline, 5 weeks ] |
| 19. Secondary: | Number of Participants With Electrocardiogram Change in Heart Rate Using Bazett's (QTcB) and Fridericia's (QTcF) Formulas [ Time Frame: Baseline through 5 weeks ] |
| 20. Secondary: | Percentage of Participants With Reported Hypoglycemic Events [ Time Frame: Baseline through 5 weeks ] |
| 21. Secondary: | Change From Baseline in Overall Total Quick Inventory of Depressive Symptomatology (QIDS) Score [ Time Frame: Baseline, 5 weeks ] |
| 22. Secondary: | Number of Participants With Suicidal Behaviors and Ideations [ Time Frame: Baseline through week 5 ] |
| 23. Secondary: | Number of Participants Reporting Blurry or Hazy Vision Using the Subjective Vision Inventory (SVI) Question 1 (Q1) at 5 Weeks [ Time Frame: Week 5 ] |
| 24. Secondary: | Pharmacokinetic (PK) Parameter: Clearance of LY545694 (CLp) and Compound 645838 (CLm) [ Time Frame: Baseline through 5 weeks ] |
| 25. Secondary: | Time to Response [ Time Frame: Baseline through 5 weeks ] |
| 26. Secondary: | Number of Participants With Neurological Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Baseline through 5 weeks ] |
Serious Adverse Events Other Adverse Events
| Time Frame | No text entered. |
|---|---|
| Additional Description | No text entered. |
Frequency Threshold
| Threshold above which other adverse events are reported | 1% |
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Reporting Groups
| Description | |
|---|---|
| Placebo | LY545694 placebo twice daily (BID) oral (po) for 5 weeks and pregabalin placebo capsules three times daily (TID) po for 6 weeks |
| LY545694 21 mg | LY545694 21 milligrams (mg) twice daily (BID) oral (po) for 1 week |
| LY545694 49 mg | LY545694 escalated to 49 mg twice daily (BID) oral (po) during Week 2; possible titration down to 21 mg BID po within 1 week of escalation for remainder of study treatment. |
| LY545694 105 mg | LY545694 escalated to 105 mg twice daily (BID) oral (po) during Week 3 through Week 5; possible titration down to 49 mg BID po within 1 week of escalation for the remainder of study treatment. |
| Pregabalin | Pregabalin thrice daily (TID) oral (po) for 6 weeks: 50 mg TID po for Week 1, 100 mg TID po for Weeks 2 - 5, and 50 mg TID po taper for Week 6 |
| Placebo Washout | A one-week washout period in which no placebo was taken. |
| LY545694 21 mg Washout | A one-week washout period in which no LY545694 21 mg was taken. |
| LY545694 49 mg Washout | A one-week washout period in which no LY545694 49 mg was taken. |
| LY545694 105 mg Washout | A one-week washout period in which no LY545694 105 mg was taken. |
| Pregabalin Washout | A one-week washout period in which no pregabalin was taken. |
Other Adverse Events
| Placebo | LY545694 21 mg | LY545694 49 mg | LY545694 105 mg | Pregabalin | Placebo Washout | LY545694 21 mg Washout | LY545694 49 mg Washout | LY545694 105 mg Washout | Pregabalin Washout | |
|---|---|---|---|---|---|---|---|---|---|---|
| Total, other (not including serious) adverse events | ||||||||||
| # participants affected / at risk | 53/89 | 33/43 | 43/49 | 40/47 | 31/45 | 15/89 | 4/43 | 7/49 | 7/47 | 6/45 |
| Blood and lymphatic system disorders | ||||||||||
| Leukopenia † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Thrombocytosis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cardiac disorders | ||||||||||
| Bundle branch block left † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) |
| # events | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Left ventricular hypertrophy † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Nodal rhythm † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Palpitations † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 2/43 (4.65%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Sinus tachycardia † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Ear and labyrinth disorders | ||||||||||
| Hyperacusis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hypoacusis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Tinnitus † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Vertigo † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 1/43 (2.33%) | 2/49 (4.08%) | 3/47 (6.38%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 1 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Eye disorders | ||||||||||
| Blepharitis † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blepharospasm † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Conjunctival haemorrhage † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Diabetic retinopathy † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dry eye † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Lacrimation increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Macular oedema † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Ocular hyperaemia † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Phosphenes † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Photophobia † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Retinal exudates † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) |
| # events | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Retinopathy † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Uveitis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Vision blurred † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 4/43 (9.30%) | 2/49 (4.08%) | 4/47 (8.51%) | 3/45 (6.67%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 2 | 4 | 2 | 4 | 3 | 0 | 0 | 0 | 0 | 0 |
| Visual impairment † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Gastrointestinal disorders | ||||||||||
| Abdominal distension † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Abdominal pain † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 1/43 (2.33%) | 1/49 (2.04%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 3 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Abdominal pain upper † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Constipation † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 2/43 (4.65%) | 2/49 (4.08%) | 1/47 (2.13%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) |
| # events | 1 | 2 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 1 |
| Diarrhoea † 1 | ||||||||||
| # participants affected / at risk | 7/89 (7.87%) | 3/43 (6.98%) | 4/49 (8.16%) | 2/47 (4.26%) | 2/45 (4.44%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 8 | 3 | 4 | 2 | 3 | 1 | 0 | 0 | 0 | 0 |
| Dry mouth † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Dyspepsia † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Faecal incontinence † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Flatulence † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Gastritis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 3/49 (6.12%) | 2/47 (4.26%) | 2/45 (4.44%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 3 | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
| Gastrointestinal disorder † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 1/49 (2.04%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Gastrointestinal haemorrhage † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Gastrooesophageal reflux disease † 1 | ||||||||||
| # participants affected / at risk | 3/89 (3.37%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hiatus hernia † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Lip disorder † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Nausea † 1 | ||||||||||
| # participants affected / at risk | 11/89 (12.36%) | 12/43 (27.91%) | 15/49 (30.61%) | 12/47 (25.53%) | 2/45 (4.44%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) |
| # events | 12 | 14 | 17 | 14 | 2 | 0 | 0 | 0 | 1 | 0 |
| Paraesthesia oral † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Toothache † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Vomiting † 1 | ||||||||||
| # participants affected / at risk | 4/89 (4.49%) | 6/43 (13.95%) | 12/49 (24.49%) | 8/47 (17.02%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 1/49 (2.04%) | 1/47 (2.13%) | 0/45 (0.00%) |
| # events | 4 | 7 | 13 | 11 | 0 | 1 | 0 | 1 | 1 | 0 |
| General disorders | ||||||||||
| Asthenia † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 3/49 (6.12%) | 2/47 (4.26%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 5 | 4 | 1 | 0 | 0 | 0 | 0 | 0 |
| Chills † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 1/43 (2.33%) | 1/49 (2.04%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Fatigue † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 1/43 (2.33%) | 3/49 (6.12%) | 2/47 (4.26%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 2 | 1 | 3 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Feeling cold † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Feeling jittery † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 1/47 (2.13%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Gait disturbance † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 1/43 (2.33%) | 1/49 (2.04%) | 3/47 (6.38%) | 1/45 (2.22%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) |
| # events | 1 | 1 | 1 | 3 | 1 | 1 | 0 | 0 | 1 | 0 |
| Irritability † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Malaise † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Oedema peripheral † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 6/45 (13.33%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 1 | 0 | 6 | 0 | 0 | 0 | 0 | 0 |
| Pain † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 1/43 (2.33%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Temperature intolerance † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hepatobiliary disorders | ||||||||||
| Liver disorder † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Immune system disorders | ||||||||||
| Drug hypersensitivity † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Food allergy † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Infections and infestations | ||||||||||
| Bronchitis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cystitis † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Gastroenteritis bacterial † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Herpes simplex † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Influenza † 1 | ||||||||||
| # participants affected / at risk | 3/89 (3.37%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 3 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Localised infection † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 2/47 (4.26%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Nasopharyngitis † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Pharyngitis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Respiratory tract infection † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Sinusitis † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Tinea cruris † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Tooth abscess † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Upper respiratory tract infection † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 1/49 (2.04%) | 2/47 (4.26%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| Urinary tract infection † 1 | ||||||||||
| # participants affected / at risk | 3/89 (3.37%) | 0/43 (0.00%) | 1/49 (2.04%) | 1/47 (2.13%) | 1/45 (2.22%) | 2/89 (2.25%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 3 | 0 | 1 | 1 | 1 | 2 | 0 | 1 | 0 | 0 |
| Viral infection † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Wound infection † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Ankle fracture † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Contusion † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Excoriation † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Fall † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 1/49 (2.04%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Ligament sprain † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Limb injury † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Meniscus lesion † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Muscle strain † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Post-traumatic pain † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) |
| # events | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Rib fracture † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Tooth fracture † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Investigations | ||||||||||
| Blood bicarbonate abnormal † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood bicarbonate increased † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood bilirubin increased † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood calcium increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood creatine phosphokinase increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 2/47 (4.26%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 1 | 0 | 0 |
| Blood creatinine increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Blood glucose decreased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Blood glucose increased † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 2/43 (4.65%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood pressure diastolic decreased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Blood pressure increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 2/47 (4.26%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood pressure systolic decreased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Blood urea increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Electrocardiogram poor r-wave progression † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Electrocardiogram qrs complex prolonged † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Electrocardiogram t wave abnormal † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Gamma-glutamyltransferase increased † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glucose urine present † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Grip strength decreased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Haemoglobin decreased † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Heart rate increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hepatic enzyme increased † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Liver function test abnormal † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Low density lipoprotein increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Monofilament pressure perception test abnormal † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Neurological examination abnormal † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Qrs axis abnormal † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Red blood cell sedimentation rate increased † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Rheumatoid factor increased † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Weight decreased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Weight increased † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 1/47 (2.13%) | 4/45 (8.89%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 1 | 4 | 0 | 0 | 0 | 0 | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 4/43 (9.30%) | 9/49 (18.37%) | 2/47 (4.26%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 2 | 4 | 9 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dyslipidaemia † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Fluid retention † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Food intolerance † 1 | ||||||||||
| # participants affected / at risk | 0/89 (0.00%) | 1/43 (2.33%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hyperglycaemia † 1 | ||||||||||
| # participants affected / at risk | 3/89 (3.37%) | 2/43 (4.65%) | 5/49 (10.20%) | 3/47 (6.38%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 3 | 2 | 5 | 3 | 1 | 0 | 0 | 0 | 0 | 0 |
| Hyperkalaemia † 1 | ||||||||||
| # participants affected / at risk | 1/89 (1.12%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) | 0/89 (0.00%) | 0/43 (0.00%) | 0/49 (0.00%) | 0/47 (0.00%) | 0/45 (0.00%) |
| # events | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hypertriglyceridaemia † 1 | ||||||||||
| # participants affected / at risk | 2/89 (2.25%) | 0/43 (0.00%) | 1/49 (2.04%) | 0/47 (0.00%) | 1/45 (2.22%) | 0/89 (0.00%) | 0/43 (0.00%) |