Protein Kinase C (PKC) Inhibitor-Diabetic Retinopathy Phase 3 Study
Sponsor
Chromaderm, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT00604383
Collaborator
(none)
685
1
2
51
13.4
Study Details
Study Description
Brief Summary
This study is to test whether or not 32 milligrams (mg) of ruboxistaurin a day over three years will reduce vision loss associated with diabetic retinopathy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
685 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
Phase 3, Multicenter,Parallel,Randomized Dbl-masked,Placebo-controlled Study of the Effects of 32 mg/dy Ruboxistaurin Vision Loss in Patients With Type 1 or Type 2 Diabetes Mellitus and an Early Treatment Diabetic Retinopathy Study Level Between 47A and 53E.
Study Start Date
:
Mar 1, 2001
Actual Primary Completion Date
:
Jun 1, 2005
Actual Study Completion Date
:
Jun 1, 2005
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ruboxistaurin
|
Drug: ruboxistaurin
32-mg tablet, orally, daily, up to 42 months
Other Names:
|
| Placebo Comparator: Placebo
|
Drug: placebo
1 tablet, orally, daily, up to 42 months
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Who Had Sustained Moderate Visual Loss (SMVL) as Defined as a Visual Acuity Loss of ≥15 Letters Measured Twice During a 6-month Period [Baseline through 36 months]
SMVL is defined as a ≥15-letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that the participant sustained during the last 6 months of study participation (Months 30-36). Participants who discontinued the study early may have had SMVL if there was a 6-month period of ≥15 letters lost in VA ending with the last visit at which VA was assessed. ETDRS visual acuity uses an eye chart with 5 letters per line. The scores range from 0 (no letters read correctly) to 100 (all letters read correctly). Percentage of participants = (number of participants who had SMVL) / (number of participants who were randomized) * 100.
Secondary Outcome Measures
- Percentage of Participants Who Developed Center Involved or Imminently Threatened Diabetic Macular Edema (DME) [Baseline through 36 months]
DME is the accumulation of extracellular fluid in the retinal tissue of the macular area, which can reduce the ability for fine visual discrimination. Percentage of participants = (number of participants who developed center involved or imminently threatened DME) / (number of participants who had no center involved or imminently threatened DME at baseline) * 100.
- Percentage of Participants Who Experienced the Development of Proliferative Diabetic Retinopathy (PDR) [Baseline through 36 months]
Percentage of participants = (number of participants who experienced the development of PDR) / (number of participants who were randomized) * 100.
- Change From Baseline up to 36 Months in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) [Baseline, up to 36 months]
NEI-VFQ-25 consisted of 25 questions and was used to measure the influence of visual disability and symptoms on general health of participants. The possible total score range for the NEI-VFQ-25 was from 0 (worst possible outcome) to 100 (best possible outcome).
- Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire [Baseline, up to 36 months]
SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions. There are 2 component scores, mental component score (MCS) and physical component score (PCS). MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. Both MCS and PCS have scores ranging from 0 to 100 with higher scores indicating better mental or physical health.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Type 1 or Type 2 diabetes mellitus
-
18 years or older
-
Meet specific requirements for diabetic retinopathy
-
Free of severe or chronically disabling conditions, except diabetes, diabetic retinopathy and diabetic macular edema
-
Hemoglobin A1c (HbA1C) ≤13.0%
Exclusion Criteria:
-
History of panretinal photocoagulation for diabetic retinopathy, conditions that might affect the progression of diabetic retinopathy, or unstable angina
-
Investigators, site personnel directly affiliated with the study and their families
-
Presence of eye disorders that may affect the progression of diabetic retinopathy or cause vision loss
-
Presence of medical disorder, cancer, or elevated laboratory measurements that could represent a safety risk during the study
-
Women who are pregnant, breastfeeding, intend to become pregnant, or who are sexually active without using an acceptable method of birth control
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern time (UTC/GMT -5 hours, EST) or speak with your personal physician. | Indianapolis | Indiana | United States |
Sponsors and Collaborators
- Chromaderm, Inc.
Investigators
- Study Director: Karl Beutner, Chromaderm, Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Chromaderm, Inc.
ClinicalTrials.gov Identifier:
NCT00604383
Other Study ID Numbers:
- 4743
- B7A-MC-MBCM
First Posted:
Jan 30, 2008
Last Update Posted:
Oct 6, 2016
Last Verified:
Aug 1, 2016
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | This study consisted of a 36-month treatment phase and a 0 to 6-month extended treatment phase. Completers are those who completed the 36-month treatment phase. |
| Arm/Group Title | Ruboxistaurin | Placebo |
|---|---|---|
| Arm/Group Description | One 32-milligram (mg) tablet, orally, daily, for up to 42 months | 1 tablet, orally, daily, for up to 42 months |
| Period Title: Overall Study | ||
| STARTED | 345 | 340 |
| Received at Least 1 Dose of Study Drug | 345 | 340 |
| Received Extended Treatment | 136 | 141 |
| COMPLETED | 258 | 256 |
| NOT COMPLETED | 87 | 84 |
Baseline Characteristics
| Arm/Group Title | Ruboxistaurin | Placebo | Total |
|---|---|---|---|
| Arm/Group Description | One 32-mg tablet, orally, daily, for up to 42 months | 1 tablet, orally, daily, for up to 42 months | Total of all reporting groups |
| Overall Participants | 345 | 340 | 685 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
59.48
(10.91)
|
59.18
(10.61)
|
59.33
(10.76)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
130
37.7%
|
122
35.9%
|
252
36.8%
|
| Male |
215
62.3%
|
218
64.1%
|
433
63.2%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| African Descent |
43
12.5%
|
27
7.9%
|
70
10.2%
|
| Caucasian |
259
75.1%
|
273
80.3%
|
532
77.7%
|
| East/Southeast Asian |
15
4.3%
|
12
3.5%
|
27
3.9%
|
| Hispanic |
18
5.2%
|
20
5.9%
|
38
5.5%
|
| Other |
9
2.6%
|
8
2.4%
|
17
2.5%
|
| Western Asian |
1
0.3%
|
0
0%
|
1
0.1%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
345
100%
|
340
100%
|
685
100%
|
Outcome Measures
| Title | Percentage of Participants Who Had Sustained Moderate Visual Loss (SMVL) as Defined as a Visual Acuity Loss of ≥15 Letters Measured Twice During a 6-month Period |
|---|---|
| Description | SMVL is defined as a ≥15-letter decrease from baseline in best-corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) that the participant sustained during the last 6 months of study participation (Months 30-36). Participants who discontinued the study early may have had SMVL if there was a 6-month period of ≥15 letters lost in VA ending with the last visit at which VA was assessed. ETDRS visual acuity uses an eye chart with 5 letters per line. The scores range from 0 (no letters read correctly) to 100 (all letters read correctly). Percentage of participants = (number of participants who had SMVL) / (number of participants who were randomized) * 100. |
| Time Frame | Baseline through 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | Ruboxistaurin | Placebo |
|---|---|---|
| Arm/Group Description | One 32-mg tablet, orally, daily, for 36 months | 1 tablet, orally, daily, for 36 months |
| Measure Participants | 345 | 340 |
| Number [percentage of participants] |
5.5
1.6%
|
9.1
2.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Ruboxistaurin, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.034 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Percentage of Participants Who Developed Center Involved or Imminently Threatened Diabetic Macular Edema (DME) |
|---|---|
| Description | DME is the accumulation of extracellular fluid in the retinal tissue of the macular area, which can reduce the ability for fine visual discrimination. Percentage of participants = (number of participants who developed center involved or imminently threatened DME) / (number of participants who had no center involved or imminently threatened DME at baseline) * 100. |
| Time Frame | Baseline through 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants who had no center involved or imminently threatened DME at baseline. |
| Arm/Group Title | Ruboxistaurin | Placebo |
|---|---|---|
| Arm/Group Description | One 32-mg tablet, orally, daily, for 36 months | 1 tablet, orally, daily, for 36 months |
| Measure Participants | 248 | 249 |
| Number [percentage of participants] |
44.4
12.9%
|
49.0
14.4%
|
| Title | Percentage of Participants Who Experienced the Development of Proliferative Diabetic Retinopathy (PDR) |
|---|---|
| Description | Percentage of participants = (number of participants who experienced the development of PDR) / (number of participants who were randomized) * 100. |
| Time Frame | Baseline through 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants. |
| Arm/Group Title | Ruboxistaurin | Placebo |
|---|---|---|
| Arm/Group Description | One 32-mg tablet, orally, daily, for 36 months | 1 tablet, orally, daily, for 36 months |
| Measure Participants | 345 | 340 |
| Number [percentage of participants] |
35.9
10.4%
|
36.5
10.7%
|
| Title | Change From Baseline up to 36 Months in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) |
|---|---|
| Description | NEI-VFQ-25 consisted of 25 questions and was used to measure the influence of visual disability and symptoms on general health of participants. The possible total score range for the NEI-VFQ-25 was from 0 (worst possible outcome) to 100 (best possible outcome). |
| Time Frame | Baseline, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with evaluable NEI-VFQ-25 total score. Last Observation Carried Forward (LOCF) was used to impute missing post-baseline values. |
| Arm/Group Title | Ruboxistaurin | Placebo |
|---|---|---|
| Arm/Group Description | One 32-mg tablet, orally, daily, for 36 months | 1 tablet, orally, daily, for 36 months |
| Measure Participants | 290 | 289 |
| Mean (Standard Deviation) [units on a scale] |
-3.82
(14.75)
|
-4.10
(13.45)
|
| Title | Change From Baseline up to 36 Months in Mental and Physical Components of the Medical Outcomes Study 36-Item Short Form (SF-36) Health Status Questionnaire |
|---|---|
| Description | SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions. There are 2 component scores, mental component score (MCS) and physical component score (PCS). MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. Both MCS and PCS have scores ranging from 0 to 100 with higher scores indicating better mental or physical health. |
| Time Frame | Baseline, up to 36 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized participants with evaluable SF-36 MCS and PCS. LOCF was used to impute missing post-baseline values |
| Arm/Group Title | Ruboxistaurin | Placebo |
|---|---|---|
| Arm/Group Description | One 32-mg tablet, orally, daily, for 36 months | 1 tablet, orally, daily, for 36 months |
| Measure Participants | 290 | 289 |
| MCS |
-12.21
(70.91)
|
-19.85
(70.05)
|
| PCS |
-30.63
(84.92)
|
-29.15
(79.41)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Ruboxistaurin | Placebo | ||
| Arm/Group Description | One 32-mg tablet, orally, daily, for up to 42 months | 1 tablet, orally, daily, for up to 42 months | ||
All Cause Mortality |
||||
| Ruboxistaurin | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Ruboxistaurin | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 145/345 (42%) | 157/340 (46.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 9/345 (2.6%) | 10 | 13/340 (3.8%) | 13 |
| Hypersplenism | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Idiopathic thrombocytopenic purpura | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Lymphadenopathy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Normochromic normocytic anaemia | 0/345 (0%) | 0 | 1/340 (0.3%) | 2 |
| Pancytopenia | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Thrombocytopenia | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 2/345 (0.6%) | 2 | 2/340 (0.6%) | 2 |
| Acute myocardial infarction | 5/345 (1.4%) | 5 | 6/340 (1.8%) | 6 |
| Angina pectoris | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Angina unstable | 5/345 (1.4%) | 6 | 4/340 (1.2%) | 4 |
| Aortic valve disease mixed | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Arrhythmia supraventricular | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Atrial fibrillation | 5/345 (1.4%) | 5 | 11/340 (3.2%) | 11 |
| Atrial flutter | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Atrioventricular block complete | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Atrioventricular block second degree | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Bradycardia | 3/345 (0.9%) | 3 | 1/340 (0.3%) | 1 |
| Cardiac arrest | 2/345 (0.6%) | 2 | 5/340 (1.5%) | 5 |
| Cardiac failure chronic | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Cardiac failure congestive | 25/345 (7.2%) | 38 | 19/340 (5.6%) | 26 |
| Cardio-respiratory arrest | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Cardiomyopathy | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Cor pulmonale chronic | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Coronary artery atherosclerosis | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 2 |
| Coronary artery disease | 30/345 (8.7%) | 38 | 30/340 (8.8%) | 33 |
| Coronary artery insufficiency | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Coronary artery occlusion | 1/345 (0.3%) | 1 | 3/340 (0.9%) | 3 |
| Hypertensive cardiomyopathy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Ischaemic cardiomyopathy | 1/345 (0.3%) | 1 | 2/340 (0.6%) | 2 |
| Mitral valve incompetence | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Myocardial infarction | 4/345 (1.2%) | 4 | 13/340 (3.8%) | 16 |
| Pericardial effusion | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Pericarditis | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Right ventricular failure | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Sick sinus syndrome | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Sinus bradycardia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Tachycardia | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Torsade de pointes | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Tricuspid valve incompetence | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Ventricular tachycardia | 2/345 (0.6%) | 3 | 2/340 (0.6%) | 2 |
| Ear and labyrinth disorders | ||||
| Hearing impaired | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Inner ear disorder | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Vestibular neuronitis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Endocrine disorders | ||||
| Hyperthyroidism | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Eye disorders | ||||
| Cataract | 0/345 (0%) | 0 | 1/340 (0.3%) | 2 |
| Endophthalmitis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Maculopathy | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Retinal artery occlusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 3 |
| Retinal detachment | 0/345 (0%) | 0 | 4/340 (1.2%) | 4 |
| Retinal neovascularisation | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Retinal tear | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Retinal vein occlusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Visual acuity reduced | 0/345 (0%) | 0 | 1/340 (0.3%) | 3 |
| Vitreous haemorrhage | 1/345 (0.3%) | 1 | 3/340 (0.9%) | 5 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Abdominal pain upper | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Abdominal strangulated hernia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Ascites | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Coeliac disease | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Colitis ischaemic | 0/345 (0%) | 0 | 2/340 (0.6%) | 3 |
| Colitis ulcerative | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 2 |
| Colonic haemorrhage | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Diabetic gastroparesis | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Diarrhoea | 0/345 (0%) | 0 | 4/340 (1.2%) | 4 |
| Duodenal ulcer haemorrhage | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Duodenitis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Dysphagia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Gastric ulcer haemorrhage | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Gastritis | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Gastritis erosive | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Gastrointestinal haemorrhage | 0/345 (0%) | 0 | 3/340 (0.9%) | 4 |
| Gastrointestinal inflammation | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Gastrooesophageal reflux disease | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Haematochezia | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Haemorrhoids | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hypoaesthesia oral | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Ileus | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Intestinal obstruction | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Lower gastrointestinal haemorrhage | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Mallory-weiss syndrome | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Nausea | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Oesophagitis | 1/345 (0.3%) | 1 | 2/340 (0.6%) | 2 |
| Pancreatitis | 3/345 (0.9%) | 3 | 2/340 (0.6%) | 2 |
| Pancreatitis acute | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Peptic ulcer | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Small intestinal obstruction | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Umbilical hernia | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Upper gastrointestinal haemorrhage | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Uvulitis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Vomiting | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| General disorders | ||||
| Asthenia | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Chest pain | 10/345 (2.9%) | 12 | 4/340 (1.2%) | 4 |
| Death | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Generalised oedema | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Impaired healing | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Multi-organ failure | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Non-cardiac chest pain | 4/345 (1.2%) | 4 | 5/340 (1.5%) | 6 |
| Pyrexia | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Sudden death | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Cholecystitis acute | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Cholecystitis chronic | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Cholelithiasis | 3/345 (0.9%) | 3 | 5/340 (1.5%) | 5 |
| Hepatic cirrhosis | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Hepatic failure | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hepatic steatosis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Portal hypertensive gastropathy | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Immune system disorders | ||||
| Allergy to arthropod sting | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Infections and infestations | ||||
| Abdominal abscess | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Abdominal infection | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Abscess | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Abscess limb | 2/345 (0.6%) | 2 | 3/340 (0.9%) | 3 |
| Abscess neck | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Acute tonsillitis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Appendicitis | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Bacteraemia | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Bronchitis | 1/345 (0.3%) | 1 | 2/340 (0.6%) | 2 |
| Bronchitis acute | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Cellulitis | 12/345 (3.5%) | 16 | 12/340 (3.5%) | 13 |
| Clostridium colitis | 4/345 (1.2%) | 4 | 2/340 (0.6%) | 2 |
| Cystitis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Diabetic foot infection | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Diarrhoea infectious | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Diverticulitis | 3/345 (0.9%) | 3 | 0/340 (0%) | 0 |
| Endocarditis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Enterococcal infection | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Fungal cystitis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Gangrene | 2/345 (0.6%) | 2 | 3/340 (0.9%) | 4 |
| Gastroenteritis | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Gastroenteritis viral | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Gastrointestinal infection | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Herpes zoster | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Influenza | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Localised infection | 2/345 (0.6%) | 2 | 2/340 (0.6%) | 2 |
| Mastoiditis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Meningitis viral | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Necrotising fasciitis | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Oesophageal candidiasis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Osteomyelitis | 8/345 (2.3%) | 9 | 6/340 (1.8%) | 9 |
| Otitis externa | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Paronychia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Parotitis | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Perirectal abscess | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Pneumonia | 14/345 (4.1%) | 15 | 13/340 (3.8%) | 15 |
| Post procedural cellulitis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Postoperative infection | 1/345 (0.3%) | 1 | 3/340 (0.9%) | 3 |
| Pseudomonas infection | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Pyelonephritis | 3/345 (0.9%) | 3 | 2/340 (0.6%) | 2 |
| Sepsis | 4/345 (1.2%) | 4 | 4/340 (1.2%) | 4 |
| Septic embolus | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Sinusitis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Staphylococcal bacteraemia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Staphylococcal infection | 2/345 (0.6%) | 2 | 2/340 (0.6%) | 3 |
| Staphylococcal sepsis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Streptococcal bacteraemia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Urinary tract infection | 2/345 (0.6%) | 2 | 5/340 (1.5%) | 5 |
| Urinary tract infection enterococcal | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Urosepsis | 1/345 (0.3%) | 1 | 4/340 (1.2%) | 5 |
| Wound infection | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Wound infection staphylococcal | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Ankle fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Brain contusion | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Chemical burn of skin | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Clavicle fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Closed head injury | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Contusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Dislocation of joint prosthesis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Drug toxicity | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Facial bones fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Fall | 6/345 (1.7%) | 6 | 5/340 (1.5%) | 5 |
| Femoral neck fracture | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Femur fracture | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Fibula fracture | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Foot fracture | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Forearm fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Haemothorax | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Head injury | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Hip fracture | 1/345 (0.3%) | 1 | 4/340 (1.2%) | 4 |
| Humerus fracture | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Joint dislocation | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Lower limb fracture | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Lung injury | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Meniscus lesion | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Patella fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Post procedural haematoma | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Post procedural haemorrhage | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Procedural hypertension | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Radius fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Rib fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Road traffic accident | 1/345 (0.3%) | 1 | 4/340 (1.2%) | 4 |
| Scapula fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Shunt occlusion | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Skin laceration | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Subdural haematoma | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Therapeutic agent toxicity | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Ulna fracture | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Vascular graft occlusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Wound dehiscence | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Investigations | ||||
| Blood glucose fluctuation | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Blood glucose increased | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Blood potassium increased | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Coagulation time abnormal | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Electrocardiogram qt prolonged | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Weight decreased | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Anorexia | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Dehydration | 2/345 (0.6%) | 3 | 7/340 (2.1%) | 9 |
| Diabetes mellitus inadequate control | 2/345 (0.6%) | 4 | 1/340 (0.3%) | 1 |
| Diabetic foot | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Diabetic ketoacidosis | 2/345 (0.6%) | 2 | 3/340 (0.9%) | 4 |
| Fluid overload | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Gout | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hypercalcaemia | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hyperglycaemia | 2/345 (0.6%) | 3 | 1/340 (0.3%) | 1 |
| Hyperkalaemia | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Hypoglycaemia | 4/345 (1.2%) | 4 | 3/340 (0.9%) | 3 |
| Hypovolaemia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Ketoacidosis | 1/345 (0.3%) | 3 | 0/340 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthritis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Arthropathy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Chest wall pain | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Intervertebral disc disorder | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Intervertebral disc protrusion | 2/345 (0.6%) | 2 | 2/340 (0.6%) | 2 |
| Lower limb deformity | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Lumbar spinal stenosis | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Monarthritis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Myositis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Neuropathic arthropathy | 2/345 (0.6%) | 3 | 2/340 (0.6%) | 2 |
| Osteoarthritis | 3/345 (0.9%) | 3 | 3/340 (0.9%) | 3 |
| Pain in extremity | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Pathological fracture | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Rotator cuff syndrome | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Spinal column stenosis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Spinal osteoarthritis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Tenosynovitis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Bladder cancer | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Bladder cancer recurrent | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Breast cancer in situ | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Colon cancer | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Endometrial cancer | 0/130 (0%) | 0 | 1/122 (0.8%) | 1 |
| Gastric cancer | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Malignant melanoma | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Malignant pleural effusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Metastases to bone | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Metastases to lymph nodes | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Metastases to pleura | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Metastatic malignant melanoma | 2/345 (0.6%) | 4 | 0/340 (0%) | 0 |
| Neoplasm malignant | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Non-small cell lung cancer | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Oesophageal adenocarcinoma metastatic | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Pancreatic carcinoma metastatic | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Prostate cancer | 0/215 (0%) | 0 | 1/218 (0.5%) | 1 |
| Renal cell carcinoma stage unspecified | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Spinal meningioma benign | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Squamous endometrial carcinoma | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Nervous system disorders | ||||
| Anoxic encephalopathy | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Carotid artery occlusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Carotid artery stenosis | 3/345 (0.9%) | 3 | 2/340 (0.6%) | 2 |
| Cerebellar haemorrhage | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Cerebral artery occlusion | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Cerebrovascular accident | 5/345 (1.4%) | 5 | 8/340 (2.4%) | 9 |
| Cognitive disorder | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Convulsion | 1/345 (0.3%) | 1 | 2/340 (0.6%) | 2 |
| Dementia | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Demyelinating polyneuropathy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Diabetic neuropathy | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Dizziness | 1/345 (0.3%) | 1 | 4/340 (1.2%) | 5 |
| Embolic stroke | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Encephalopathy | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Facial palsy | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Haemorrhage intracranial | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hemiparesis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hepatic encephalopathy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Intracranial aneurysm | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Intraventricular haemorrhage | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Loss of consciousness | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Migraine | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Neuropathy peripheral | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Paraesthesia | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Radiculopathy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Subarachnoid haemorrhage | 3/345 (0.9%) | 3 | 0/340 (0%) | 0 |
| Syncope | 4/345 (1.2%) | 5 | 7/340 (2.1%) | 8 |
| Syncope vasovagal | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Transient ischaemic attack | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Tremor | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Psychiatric disorders | ||||
| Confusional state | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Conversion disorder | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Delirium | 1/345 (0.3%) | 2 | 1/340 (0.3%) | 1 |
| Hallucination | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Major depression | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Mental status changes | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Psychotic disorder | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Renal and urinary disorders | ||||
| Azotaemia | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Bladder neck obstruction | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Nephrolithiasis | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Obstructive uropathy | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Renal artery stenosis | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Renal failure | 3/345 (0.9%) | 3 | 6/340 (1.8%) | 6 |
| Renal failure acute | 14/345 (4.1%) | 18 | 12/340 (3.5%) | 12 |
| Renal failure chronic | 9/345 (2.6%) | 12 | 5/340 (1.5%) | 6 |
| Renal tubular necrosis | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Urinary retention | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/215 (0.5%) | 1 | 0/218 (0%) | 0 |
| Priapism | 0/215 (0%) | 0 | 1/218 (0.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Acute respiratory failure | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Asthma | 2/345 (0.6%) | 3 | 1/340 (0.3%) | 1 |
| Chronic obstructive airways disease exacerbated | 0/345 (0%) | 0 | 2/340 (0.6%) | 3 |
| Chronic obstructive pulmonary disease | 3/345 (0.9%) | 3 | 2/340 (0.6%) | 2 |
| Dyspnoea | 3/345 (0.9%) | 3 | 2/340 (0.6%) | 2 |
| Hydrothorax | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hypercapnia | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hypoxia | 2/345 (0.6%) | 2 | 0/340 (0%) | 0 |
| Obstructive airways disorder | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Pleural effusion | 3/345 (0.9%) | 5 | 3/340 (0.9%) | 3 |
| Pneumonia aspiration | 0/345 (0%) | 0 | 2/340 (0.6%) | 2 |
| Pneumonitis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Pneumothorax | 0/345 (0%) | 0 | 1/340 (0.3%) | 2 |
| Pulmonary embolism | 2/345 (0.6%) | 2 | 4/340 (1.2%) | 4 |
| Pulmonary hypertension | 1/345 (0.3%) | 1 | 2/340 (0.6%) | 2 |
| Pulmonary oedema | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Respiratory arrest | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Respiratory distress | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Respiratory failure | 3/345 (0.9%) | 3 | 3/340 (0.9%) | 3 |
| Restrictive pulmonary disease | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Sleep apnoea syndrome | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Decubitus ulcer | 0/345 (0%) | 0 | 2/340 (0.6%) | 3 |
| Diabetic ulcer | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Skin ulcer | 2/345 (0.6%) | 3 | 7/340 (2.1%) | 7 |
| Surgical and medical procedures | ||||
| Cardiac pacemaker insertion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Carotid endarterectomy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Mastectomy | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Vascular disorders | ||||
| Aortic stenosis | 1/345 (0.3%) | 1 | 1/340 (0.3%) | 1 |
| Blood pressure inadequately controlled | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Deep vein thrombosis | 3/345 (0.9%) | 3 | 3/340 (0.9%) | 4 |
| Femoral artery occlusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Haematoma | 2/345 (0.6%) | 2 | 1/340 (0.3%) | 1 |
| Hypertension | 7/345 (2%) | 8 | 8/340 (2.4%) | 9 |
| Hypertensive emergency | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Hypoperfusion | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Hypotension | 4/345 (1.2%) | 4 | 2/340 (0.6%) | 2 |
| Orthostatic hypotension | 3/345 (0.9%) | 4 | 3/340 (0.9%) | 4 |
| Peripheral embolism | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Peripheral occlusive disease | 1/345 (0.3%) | 1 | 0/340 (0%) | 0 |
| Peripheral vascular disorder | 3/345 (0.9%) | 3 | 3/340 (0.9%) | 3 |
| Shock | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
| Subclavian vein thrombosis | 0/345 (0%) | 0 | 1/340 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Ruboxistaurin | Placebo | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 314/345 (91%) | 322/340 (94.7%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 30/345 (8.7%) | 33 | 36/340 (10.6%) | 37 |
| Eye disorders | ||||
| Dry eye | 17/345 (4.9%) | 19 | 19/340 (5.6%) | 21 |
| Eye pain | 22/345 (6.4%) | 30 | 18/340 (5.3%) | 28 |
| Maculopathy | 14/345 (4.1%) | 19 | 17/340 (5%) | 17 |
| Vision blurred | 18/345 (5.2%) | 22 | 19/340 (5.6%) | 26 |
| Visual disturbance | 19/345 (5.5%) | 26 | 20/340 (5.9%) | 26 |
| Vitreous floaters | 19/345 (5.5%) | 26 | 15/340 (4.4%) | 17 |
| Vitreous haemorrhage | 17/345 (4.9%) | 20 | 20/340 (5.9%) | 24 |
| Gastrointestinal disorders | ||||
| Constipation | 21/345 (6.1%) | 24 | 21/340 (6.2%) | 22 |
| Diarrhoea | 32/345 (9.3%) | 37 | 40/340 (11.8%) | 104 |
| Dyspepsia | 19/345 (5.5%) | 22 | 12/340 (3.5%) | 13 |
| Gastrooesophageal reflux disease | 27/345 (7.8%) | 27 | 21/340 (6.2%) | 21 |
| Nausea | 26/345 (7.5%) | 33 | 37/340 (10.9%) | 46 |
| Vomiting | 20/345 (5.8%) | 24 | 33/340 (9.7%) | 56 |
| General disorders | ||||
| Asthenia | 18/345 (5.2%) | 30 | 17/340 (5%) | 19 |
| Chest pain | 17/345 (4.9%) | 24 | 22/340 (6.5%) | 32 |
| Fatigue | 19/345 (5.5%) | 23 | 19/340 (5.6%) | 21 |
| Oedema peripheral | 61/345 (17.7%) | 73 | 67/340 (19.7%) | 99 |
| Pyrexia | 19/345 (5.5%) | 26 | 16/340 (4.7%) | 20 |
| Infections and infestations | ||||
| Bronchitis | 24/345 (7%) | 30 | 29/340 (8.5%) | 38 |
| Influenza | 44/345 (12.8%) | 55 | 45/340 (13.2%) | 49 |
| Localised infection | 21/345 (6.1%) | 29 | 22/340 (6.5%) | 29 |
| Nasopharyngitis | 59/345 (17.1%) | 91 | 67/340 (19.7%) | 112 |
| Onychomycosis | 18/345 (5.2%) | 19 | 18/340 (5.3%) | 19 |
| Pneumonia | 11/345 (3.2%) | 12 | 17/340 (5%) | 19 |
| Sinusitis | 25/345 (7.2%) | 38 | 32/340 (9.4%) | 43 |
| Upper respiratory tract infection | 23/345 (6.7%) | 29 | 35/340 (10.3%) | 51 |
| Urinary tract infection | 25/345 (7.2%) | 33 | 31/340 (9.1%) | 44 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 12/345 (3.5%) | 19 | 23/340 (6.8%) | 26 |
| Fall | 18/345 (5.2%) | 19 | 17/340 (5%) | 23 |
| Investigations | ||||
| Blood cholesterol increased | 25/345 (7.2%) | 25 | 16/340 (4.7%) | 16 |
| Cardiac murmur | 26/345 (7.5%) | 26 | 21/340 (6.2%) | 22 |
| Metabolism and nutrition disorders | ||||
| Hypercholesterolaemia | 30/345 (8.7%) | 30 | 28/340 (8.2%) | 28 |
| Obesity | 14/345 (4.1%) | 14 | 18/340 (5.3%) | 18 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 24/345 (7%) | 29 | 36/340 (10.6%) | 44 |
| Arthritis | 8/345 (2.3%) | 8 | 20/340 (5.9%) | 23 |
| Back pain | 32/345 (9.3%) | 36 | 27/340 (7.9%) | 34 |
| Joint swelling | 27/345 (7.8%) | 32 | 29/340 (8.5%) | 39 |
| Muscle spasms | 11/345 (3.2%) | 16 | 18/340 (5.3%) | 19 |
| Pain in extremity | 38/345 (11%) | 44 | 35/340 (10.3%) | 50 |
| Shoulder pain | 18/345 (5.2%) | 23 | 13/340 (3.8%) | 15 |
| Nervous system disorders | ||||
| Dizziness | 29/345 (8.4%) | 40 | 27/340 (7.9%) | 30 |
| Headache | 33/345 (9.6%) | 39 | 45/340 (13.2%) | 59 |
| Hypoaesthesia | 21/345 (6.1%) | 23 | 33/340 (9.7%) | 36 |
| Neuropathy peripheral | 19/345 (5.5%) | 21 | 15/340 (4.4%) | 15 |
| Psychiatric disorders | ||||
| Anxiety | 13/345 (3.8%) | 13 | 18/340 (5.3%) | 22 |
| Depression | 28/345 (8.1%) | 28 | 31/340 (9.1%) | 33 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 57/345 (16.5%) | 78 | 42/340 (12.4%) | 60 |
| Dyspnoea | 29/345 (8.4%) | 35 | 30/340 (8.8%) | 33 |
| Pharyngolaryngeal pain | 18/345 (5.2%) | 28 | 29/340 (8.5%) | 35 |
| Skin and subcutaneous tissue disorders | ||||
| Skin ulcer | 21/345 (6.1%) | 25 | 21/340 (6.2%) | 28 |
| Vascular disorders | ||||
| Hypertension | 58/345 (16.8%) | 58 | 50/340 (14.7%) | 50 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | info@chroma-derm.com |
|---|---|
| Organization | Chromaderm |
| Phone | |
| info@chroma-derm.com |
Responsible Party:
Chromaderm, Inc.
ClinicalTrials.gov Identifier:
NCT00604383
Other Study ID Numbers:
- 4743
- B7A-MC-MBCM
First Posted:
Jan 30, 2008
Last Update Posted:
Oct 6, 2016
Last Verified:
Aug 1, 2016