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CANVAS-R: A Study of the Effects of Canagliflozin (JNJ-28431754) on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT01989754
Collaborator
The George Institute for Global Health, Australia (Other)
5,813
Enrollment
354
Locations
2
Arms
37.3
Actual Duration (Months)
16.4
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effect of canagliflozin compared to placebo on progression of albuminuria in participants with Type 2 Diabetes Mellitus receiving standard care but with inadequate glycemic control and at elevated risk of cardiovascular events.

Condition or Disease Intervention/Treatment Phase
  • Drug: Placebo
  • Drug: Canagliflozin, 100 mg
  • Drug: Canagliflozin, 300 mg
 Phase 4

Detailed Description

The study will be conducted in adult participants with Type 2 Diabetes Mellitus (T2DM), receiving standard of care for hyperglycemia and cardiovascular (CV) risk factors, who have either a history of a prior CV event or 2 or more risk factors for a CV event. Participants will be randomly assigned in a 1:1 ratio to canagliflozin or matching placebo to be taken once daily. Canagliflozin will be provided at a dose of 100 mg/day through Week 13 and then increased at the discretion of the investigator to a dose of 300 mg/day, if the participant requires additional glycemic control and is tolerating the 100 mg dose.

The study consists of a 2-week screening period and a double-blind treatment period lasting between 78 and 156 weeks; study completion is targeted for when the last subject randomized has approximately 78 weeks of follow-up or when 688 major adverse cardiovascular events are accumulated between CANVAS and CANVAS-R. A total of 5,700 participants are targeted to be recruited into the study. Participants can be either drug naïve to antihyperglycemic agents, using monotherapy, or using combination of antihyperglycemic therapy for the control of blood glucose levels.

The completion target was reached in February 2017.

Study Design

Study Type:
Interventional
Actual Enrollment :
5813 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus
Actual Study Start Date :
Jan 16, 2014
Actual Primary Completion Date :
Feb 23, 2017
Actual Study Completion Date :
Feb 23, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Canagliflozin (JNJ-28431754)

Each patient will receive canagliflozin (JNJ-28431754) 100 mg once daily during the first 13 weeks, then the dose may be increased to 300 mg once daily.

Drug: Canagliflozin, 100 mg
One 100 mg capsule taken orally (by mouth) once daily

Drug: Canagliflozin, 300 mg
One 300 mg capsule taken orally (by mouth) once daily
Placebo Comparator: Placebo

Each patient will receive placebo (inactive medication) once daily.

Drug: Placebo
One placebo capsule taken orally (by mouth) once daily for 156 weeks

Outcome Measures

Primary Outcome Measures

  1. Progression of Albuminuria [Up to 3 years]

    Progression defined as the development of micro-albuminuria (Urine Albumin Creatinine Ratio [UACR] 30 to 300 milligram per gram [mg/g]) or macroalbuminuria (Albumin/creatinine ratio [ACR] of greater than [>] 300 mg/g) in a participant with baseline normoalbuminuria (ACR less than [<] 30 mg/g) or the development of macro-albuminuria in a participant with baseline microalbuminuria with an ACR increase greater than or equal to (>=) 30 percent from baseline. Participants with macroalbuminuria at baseline (ACR>300 mg/g) were excluded from the analysis. Event rate was estimated based on the time to the first occurrence of the event.

Secondary Outcome Measures

  1. Composite of Cardiovascular (CV) Death Events or Hospitalization for Heart Failure [Approximately 3 years]

    Analyses were using adjudicated events, that is (i.e.) CV death events or hospitalization due to heart failure, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event.

  2. Cardiovascular (CV) Death [Approximately 3 years]

    Analyses were using adjudicated events, i.e. CV death events, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event.

Eligibility Criteria

Criteria

Ages Eligible for Study:
30 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Must have a diagnosis of type 2 diabetes mellitus

  • Must have inadequate diabetes control (as defined by glycosylated hemoglobin level

=7.0% to <=10.5% at screening)

  • Greater than or equal to (>=) 30 yrs old with history of cardiovascular (CV) event, or

= 50 yrs old with high risk of CV events

  • Must be either not on antihyperglycemic agents (AHA) therapy, or on AHA monotherapy, or combination AHA therapy with any approved agent for the control of blood glucose levels.

Exclusion Criteria

  • History of diabetic ketoacidosis, type 1 diabetes mellitus, pancreas or beta-cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy

  • History of one or more severe hypoglycemic episode within 6 months before screening

  • History of hereditary glucose-galactose malabsorption or primary renal glucosuria

  • Ongoing, inadequately controlled thyroid disorder

  • Renal disease that required treatment with immunosuppressive therapy or a history of chronic dialysis or renal transplant

  • Myocardial infarction, unstable angina, revascularization procedure, or cerebrovascular accident within 3 months before screening.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Little Rock Arkansas United States
2 Carmichael California United States
3 Concord California United States
4 Pismo Beach California United States
5 Roseville California United States
6 Thousand Oaks California United States
7 Denver Colorado United States
8 Hollywood Florida United States
9 Jacksonville Florida United States
10 Miami Florida United States
11 New Port Richey Florida United States
12 Opa-locka Florida United States
13 Orlando Florida United States
14 Palm Harbor Florida United States
15 Tampa Florida United States
16 Meridian Idaho United States
17 Chicago Illinois United States
18 Valparaiso Indiana United States
19 Topeka Kansas United States
20 Louisville Kentucky United States
21 Mandeville Louisiana United States
22 Metairie Louisiana United States
23 Elkridge Maryland United States
24 Flint Michigan United States
25 Picayune Mississippi United States
26 Kansas City Missouri United States
27 Saint Louis Missouri United States
28 Washington Missouri United States
29 Omaha Nebraska United States
30 Las Vegas Nevada United States
31 Cornelius North Carolina United States
32 Hickory North Carolina United States
33 Mooresville North Carolina United States
34 Canal Fulton Ohio United States
35 Franklin Ohio United States
36 Mason Ohio United States
37 Oklahoma City Oklahoma United States
38 Beaver Pennsylvania United States
39 Levittown Pennsylvania United States
40 Norristown Pennsylvania United States
41 Pittsburgh Pennsylvania United States
42 Tipton Pennsylvania United States
43 Greer South Carolina United States
44 Jefferson City Tennessee United States
45 Austin Texas United States
46 Pearland Texas United States
47 Bountiful Utah United States
48 Draper Utah United States
49 Salt Lake City Utah United States
50 West Jordan Utah United States
51 South Burlington Vermont United States
52 Falls Church Virginia United States
53 Norfolk Virginia United States
54 Virginia Beach Virginia United States
55 Spokane Washington United States
56 Milwaukee Wisconsin United States
57 Wauwatosa Wisconsin United States
58 Buenos Aires Argentina
59 Ciudad Autonoma De Buenos Aires Argentina
60 Ciudad De Buenos Aires Argentina
61 Cordoba Argentina
62 Mar Del Plata Argentina
63 Moron Argentina
64 Rosario Argentina
65 Zarate, Buenos Aires Argentina
66 Box Hill Australia
67 Cairns Australia
68 Daw Park Australia
69 Freemantle Australia
70 Liverpool Australia
71 Melbourne Australia
72 Newcastle Australia
73 Sherwood Australia
74 Sydney Australia
75 Tasmania Australia
76 Woden Australia
77 Woolloongabba Australia
78 Bonheiden Belgium
79 Brugge Belgium
80 Edegem Belgium
81 Gent Belgium
82 La Louvière Belgium
83 Leuven Belgium
84 Liege Belgium
85 Liÿge Belgium
86 Merksem Belgium
87 Ransart Belgium
88 Roeselare Belgium
89 Tessenderlo Belgium
90 Belem Brazil
91 Belo Horizonte Brazil
92 Campinas Brazil
93 Caxias Do Sul Brazil
94 Curitiba Brazil
95 Fortaleza Brazil
96 Mogi Das Cruzes Brazil
97 Passo Fundo Brazil
98 Porto Alegre Brazil
99 Rio De Janeiro Brazil
100 Sao Paulo Brazil
101 São José Do Rio Preto Brazil
102 São Paulo Brazil
103 Coquitlam British Columbia Canada
104 Winnipeg Manitoba Canada
105 Halifax Nova Scotia Canada
106 Guelph Ontario Canada
107 Mississauga Ontario Canada
108 Oshawa Ontario Canada
109 Sarnia Ontario Canada
110 Thornhill Ontario Canada
111 Toronto Ontario Canada
112 Laval Quebec Canada
113 Lévis Quebec Canada
114 Quebec City Quebec Canada
115 Saint Marc Des Carriéres Quebec Canada
116 Sherbrooke Quebec Canada
117 Westmont Quebec Canada
118 Saskatoon Saskatchewan Canada
119 Baotou China
120 Beijing China
121 Hangzhou China
122 Jinan China
123 Shenyang China
124 Wuxi China
125 Beroun Czechia
126 Ostrava Czechia
127 Plzen Czechia
128 Praha 10 Czechia
129 Praha 1 Czechia
130 Praha 4 Czechia
131 Praha 8 Czechia
132 Znojmo Czechia
133 Amiens France
134 Bois Guillaume France
135 Bordeaux France
136 Dijon France
137 Grenoble France
138 La Rochelle Cedex 1 France
139 Le Creusot France
140 Narbonne Cedex France
141 Paris France
142 Poitiers France
143 Aschaffenburg Germany
144 Aßlar Germany
145 Bad Oeynhausen Germany
146 Dortmund Germany
147 Dresden Germany
148 Freiburg Germany
149 Hannover Germany
150 Kassel Germany
151 Mainz Germany
152 Neuwied Germany
153 Saarbrücken Germany
154 Villingen-Schwenningen Germany
155 Balatonfured Hungary
156 Budapest Hungary
157 Dunaújváros Hungary
158 Eger Hungary
159 Kecskemét Hungary
160 Nagykanizsa Hungary
161 Pecs Hungary
162 Szekesfehervar Hungary
163 Szikszó Hungary
164 Szombathely Hungary
165 Zalaegerszeg Hungary
166 *Osenza* Italy
167 Arenzano Italy
168 Bologna Italy
169 Catanzaro Italy
170 Chieri (Torino) Italy
171 Firenze Italy
172 Messina Italy
173 Milano Italy
174 Napoli Italy
175 Ravenna Italy
176 Roma N/A Italy
177 Roma Italy
178 Sesto San Giovanni (Milano) Italy
179 Verona Italy
180 Ansan Korea, Republic of
181 Bucheon Korea, Republic of
182 Busan Korea, Republic of
183 Changwon Korea, Republic of
184 Cheongju Korea, Republic of
185 Daegu Korea, Republic of
186 Gyeonggi-Do Korea, Republic of
187 Iksan Korea, Republic of
188 Incheon Korea, Republic of
189 Jeonju Korea, Republic of
190 Seongnam-Si Korea, Republic of
191 Seoul Korea, Republic of
192 Suwon Korea, Republic of
193 Ulsan Korea, Republic of
194 Wonju-Si Korea, Republic of
195 Batu Caves Malaysia
196 Georgetown Malaysia
197 Ipoh Malaysia
198 Kelantan Malaysia
199 Kota Bharu Malaysia
200 Kuala Lumpur Malaysia
201 Kuching Malaysia
202 Aguascalientes Mexico
203 Celaya Mexico
204 Cuernavaca Mexico
205 Culiacan Mexico
206 Guadalajara Mexico
207 Mexico Mexico
208 Pachuca De Soto Mexico
209 Queretaro Mexico
210 San Luis Potosi Mexico
211 Tampico Mexico
212 Almelo Netherlands
213 Almere Netherlands
214 Amersfoort Netherlands
215 Amsterdam Netherlands
216 Dordrecht Netherlands
217 Eindhoven Netherlands
218 Groningen Netherlands
219 Hardenberg Netherlands
220 Hoogeveen Netherlands
221 Hoogezand Netherlands
222 Kloosterhaar Netherlands
223 Leiden Netherlands
224 Meppel Netherlands
225 Poortvliet Netherlands
226 Rotterdam Netherlands
227 Utrecht Netherlands
228 Velp Netherlands
229 Waalwijk Netherlands
230 Wamel Netherlands
231 Zoetermeer Netherlands
232 Zwijndrecht Netherlands
233 Auckland New Zealand
234 Christchurch New Zealand
235 Newtown New Zealand
236 Palmerston North New Zealand
237 Rotorua New Zealand
238 Tauranga New Zealand
239 Wellington New Zealand
240 Bialystok Poland
241 Bydgoszcz Poland
242 Chrzanow Poland
243 Gdansk Poland
244 Grodzisk Mazowiecki Poland
245 Katowice Poland
246 Krakow Poland
247 Lublin Poland
248 Oswiecim Poland
249 Torun Poland
250 Tychy Poland
251 Warszawa Poland
252 Wroclaw Poland
253 Ponce Pr Puerto Rico
254 Trujillo Alto Puerto Rico
255 Arkhangelsk Russian Federation
256 Barnaul Russian Federation
257 Chelyabinsk Russian Federation
258 Kemerovo Russian Federation
259 Nizhny Novgorod Russian Federation
260 Penza Russian Federation
261 Rostov-On-Don Russian Federation
262 Saint Petersburg Russian Federation
263 Saint-Petersburg Russian Federation
264 Samara Russian Federation
265 Saratov Russian Federation
266 Smolensk Russian Federation
267 St Petersburg Russian Federation
268 St-Petersburg Russian Federation
269 Syktyvkar Russian Federation
270 Tyumen Russian Federation
271 Vsevolzhsk Russian Federation
272 Yaroslavl Russian Federation
273 A Coruna Spain
274 Alcalá De Henares Spain
275 Alicante Spain
276 Almeria Spain
277 Alzira Spain
278 Barcelona Spain
279 Ciudad Real Spain
280 Cordoba Spain
281 Ferrol Spain
282 Figueres Spain
283 Galdakao Spain
284 Madrid Spain
285 Malaga Spain
286 Móstoles Spain
287 Palma De Mallorca Spain
288 Sabadell Spain
289 San Sebastian De Los Reyes Spain
290 Sant Joan D'Alacant Spain
291 Santa Cruz De Tenerife Spain
292 Santiago De Compostela Spain
293 Segovia Spain
294 Sevilla N/A Spain
295 Sevilla Spain
296 Valencia Spain
297 Viladecans Spain
298 Borås Sweden
299 Goteborg Sweden
300 Helsingborg Sweden
301 Karlstad Sweden
302 Linköping Sweden
303 Lund Sweden
304 Malmo Sweden
305 Stockholm Sweden
306 Uddevalla Sweden
307 Uppsala Sweden
308 Vallingby Sweden
309 Västra Frölunda Sweden
310 Kaohsiung County Taiwan
311 Taichung Taiwan
312 Tainan Taiwan
313 Taipei Taiwan
314 Tiachung Taiwan
315 Xindian Taiwan
316 Cherkasy Ukraine
317 Chernivtsy Ukraine
318 Dnipropetrovsk Ukraine
319 Ivan-Frankivsk Ukraine
320 Ivano-Frankovsk Ukraine
321 Kharkiv Ukraine
322 Kharkov Ukraine
323 Kiev Ukraine
324 Kyiv Ukraine
325 Lviv Ukraine
326 Odesa Ukraine
327 Odessa Ukraine
328 Poltava Ukraine
329 Sumy Ukraine
330 Ternopil Ukraine
331 Uzhgorod Ukraine
332 Vinnitsa Ukraine
333 Vinnytsya Ukraine
334 Zaporizhzhia Ukraine
335 Zaporizhzhya Ukraine
336 Addlestone United Kingdom
337 Belfast United Kingdom
338 Birmingham United Kingdom
339 Blackburn United Kingdom
340 Bristol United Kingdom
341 Bury St Edmunds United Kingdom
342 Chesterfield United Kingdom
343 Derby United Kingdom
344 Doncaster United Kingdom
345 Ipswich United Kingdom
346 Leicester United Kingdom
347 Liverpool United Kingdom
348 Manchester United Kingdom
349 Salford United Kingdom
350 Taunton United Kingdom
351 Torquay United Kingdom
352 Truro United Kingdom
353 Wellingborough United Kingdom
354 Welwyn Garden City United Kingdom

Sponsors and Collaborators

  • Janssen Research & Development, LLC
  • The George Institute for Global Health, Australia

Investigators

  • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01989754
Other Study ID Numbers:
  • CR102647
  • 2013-003050-25
  • 28431754DIA4003
First Posted:
Nov 21, 2013
Last Update Posted:
Dec 11, 2018
Last Verified:
Nov 1, 2018
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Janssen Research & Development, LLC
Albuminuria
Canagliflozin
Cardiovascular outcomes
Type 2 Diabetes Mellitus
T2DM
JNJ-28431754
Antihyperglycemic Agent
Additional relevant MeSH terms:
Albuminuria
Diabetes Mellitus
Diabetes Mellitus, Type 2
Canagliflozin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail A total of 5,813 participants were randomized. However, 1 participant was randomized twice and only the first randomization was included in the Intent-to-treat (ITT) analysis set. Thus 2,905 and 2,907 participants were randomly assigned to the placebo and canagliflozin groups in the ITT analysis set, respectively.
Arm/Group Title Placebo (Placebo) Canagliflozin (Experimental)
Arm/Group Description Participants received one capsule of matching placebo orally once daily for the duration of the study or until early discontinuation from treatment. Participants received canagliflozin (JNJ-28431754) 100 milligram (mg) once daily during the first 13 weeks, then the dose was increased to 300 mg once daily (if the participant required additional glycemic control, provided the 100-mg dose was well tolerated).
Period Title: Overall Study
STARTED 2905 2907
Treated 2903 2904
COMPLETED 2866 2872
NOT COMPLETED 39 35

Baseline Characteristics

Arm/Group Title Placebo (Placebo) Canagliflozin (Experimental) Total
Arm/Group Description Participants received one capsule of matching placebo orally once daily for the duration of the study or until early discontinuation from treatment. Participants received canagliflozin (JNJ-28431754) 100 milligram (mg) once daily during the first 13 weeks, then the dose was increased to 300 mg once daily (if the participant required additional glycemic control, provided the 100-mg dose was well tolerated). Total of all reporting groups
Overall Participants 2905 2907 5812
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
64
(8.28)
63.9
(8.42)
64
(8.35)
Sex: Female, Male (Count of Participants)
Female
1111
38.2%
1053
36.2%
2164
37.2%
Male
1794
61.8%
1854
63.8%
3648
62.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
586
20.2%
604
20.8%
1190
20.5%
Not Hispanic or Latino
2303
79.3%
2290
78.8%
4593
79%
Unknown or Not Reported
16
0.6%
13
0.4%
29
0.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
19
0.7%
14
0.5%
33
0.6%
Asian
245
8.4%
244
8.4%
489
8.4%
Native Hawaiian or Other Pacific Islander
09
0.3%
08
0.3%
17
0.3%
Black or African American
125
4.3%
106
3.6%
231
4%
White
2372
81.7%
2393
82.3%
4765
82%
More than one race
10
0.3%
09
0.3%
19
0.3%
Unknown or Not Reported
125
4.3%
133
4.6%
258
4.4%
Race/Ethnicity, Customized (Count of Participants)
Asian
245
8.4%
244
8.4%
489
8.4%
Black or African American
125
4.3%
106
3.6%
231
4%
Hispanic or Latino
407
14%
437
15%
844
14.5%
Other
174
6%
172
5.9%
346
6%
White Non-Hispanic
1954
67.3%
1948
67%
3902
67.1%
Region of Enrollment (Count of Participants)
ARGENTINA
146
5%
159
5.5%
305
5.2%
AUSTRALIA
58
2%
51
1.8%
109
1.9%
BELGIUM
86
3%
66
2.3%
152
2.6%
BRAZIL
277
9.5%
272
9.4%
549
9.4%
CANADA
136
4.7%
146
5%
282
4.9%
CHINA
46
1.6%
46
1.6%
92
1.6%
CZECH REPUBLIC
67
2.3%
72
2.5%
139
2.4%
FRANCE
69
2.4%
55
1.9%
124
2.1%
GERMANY
46
1.6%
55
1.9%
101
1.7%
HUNGARY
82
2.8%
97
3.3%
179
3.1%
ITALY
49
1.7%
49
1.7%
98
1.7%
MALAYSIA
50
1.7%
42
1.4%
92
1.6%
MEXICO
118
4.1%
110
3.8%
228
3.9%
NETHERLANDS
117
4%
132
4.5%
249
4.3%
NEW ZEALAND
49
1.7%
56
1.9%
105
1.8%
POLAND
186
6.4%
177
6.1%
363
6.2%
RUSSIAN FEDERATION
213
7.3%
199
6.8%
412
7.1%
SOUTH KOREA
73
2.5%
94
3.2%
167
2.9%
SPAIN
247
8.5%
249
8.6%
496
8.5%
SWEDEN
118
4.1%
103
3.5%
221
3.8%
TAIWAN
44
1.5%
32
1.1%
76
1.3%
UKRAINE
213
7.3%
236
8.1%
449
7.7%
UNITED KINGDOM
78
2.7%
73
2.5%
151
2.6%
UNITED STATES
337
11.6%
336
11.6%
673
11.6%

Outcome Measures

1. Primary Outcome
Title Progression of Albuminuria
Description Progression defined as the development of micro-albuminuria (Urine Albumin Creatinine Ratio [UACR] 30 to 300 milligram per gram [mg/g]) or macroalbuminuria (Albumin/creatinine ratio [ACR] of greater than [>] 300 mg/g) in a participant with baseline normoalbuminuria (ACR less than [<] 30 mg/g) or the development of macro-albuminuria in a participant with baseline microalbuminuria with an ACR increase greater than or equal to (>=) 30 percent from baseline. Participants with macroalbuminuria at baseline (ACR>300 mg/g) were excluded from the analysis. Event rate was estimated based on the time to the first occurrence of the event.
Time Frame Up to 3 years

Outcome Measure Data

Analysis Population Description
The intent to treat (ITT) population included all participants who were randomized. Here 'N' signifies number of participants who were evaluable for this endpoint.
Arm/Group Title Placebo Canagliflozin (Experimental)
Arm/Group Description Participants received one capsule of matching placebo orally once daily for the duration of the study or until early discontinuation from treatment. Participants received canagliflozin (JNJ-28431754) 100 milligram (mg) once daily during the first 13 weeks, then the dose was increased to 300 mg once daily (if the participant required additional glycemic control, provided the 100-mg dose was well tolerated).
Measure Participants 2905 2907
Number [Events per 1000 patient-year]
153.01
99.80
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin (Experimental)
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value <.0001
Comments
Method Cox proportional hazard method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.57 to 0.73
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Composite of Cardiovascular (CV) Death Events or Hospitalization for Heart Failure
Description Analyses were using adjudicated events, that is (i.e.) CV death events or hospitalization due to heart failure, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event.
Time Frame Approximately 3 years

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo Canagliflozin (Experimental)
Arm/Group Description Participants received one capsule of matching placebo orally once daily for the duration of the study or until early discontinuation from treatment. Participants received canagliflozin (JNJ-28431754) 100 milligram (mg) once daily during the first 13 weeks, then the dose was increased to 300 mg once daily (if the participant required additional glycemic control, provided the 100-mg dose was well tolerated).
Measure Participants 2905 2907
Number [Events per 1000 patient-years]
21.91
15.85
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin (Experimental)
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.0148
Comments
Method Stratified Cox proportional hazard
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.55 to 0.94
Parameter Dispersion Type:
Value:
Estimation Comments
3. Secondary Outcome
Title Cardiovascular (CV) Death
Description Analyses were using adjudicated events, i.e. CV death events, and adjudication of these outcomes by the Endpoint Adjudication Committee (EAC) were done in a blinded fashion. Event rate was estimated based on the time to the first occurrence of the event.
Time Frame Approximately 3 years

Outcome Measure Data

Analysis Population Description
ITT population included all participants who were randomized.
Arm/Group Title Placebo Canagliflozin (Experimental)
Arm/Group Description Participants received one capsule of matching placebo orally once daily for the duration of the study or until early discontinuation from treatment. Participants received canagliflozin (JNJ-28431754) 100 milligram (mg) once daily during the first 13 weeks, then the dose was increased to 300 mg once daily (if the participant required additional glycemic control, provided the 100-mg dose was well tolerated).
Measure Participants 2905 2907
Number [Events per 1000 patient-years]
11.60
10.06
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Canagliflozin (Experimental)
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.4067
Comments
Method Stratified Cox proportional hazard
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.61 to 1.22
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame Approximately 3 years
Adverse Event Reporting Description On-treatment analysis set included all randomized participants who were treated and received at least 1 dose of study drug. The number of deaths (all causes) reported here is adjudicated death that occurred within 30 days of the last dose of the study drug.
Arm/Group Title Placebo (Placebo) Canagliflozin (Experimental)
Arm/Group Description Participants received one capsule of matching placebo orally once daily for the duration of the study or until early discontinuation from treatment. Participants received canagliflozin (JNJ-28431754) 100 milligram (mg) once daily during the first 13 weeks, then the dose was increased to 300 mg once daily (if the participant required additional glycemic control, provided the 100-mg dose was well tolerated).
All Cause Mortality
Placebo (Placebo) Canagliflozin (Experimental)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 71/2903 (2.4%) 68/2904 (2.3%)
Serious Adverse Events
Placebo (Placebo) Canagliflozin (Experimental)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 775/2903 (26.7%) 714/2904 (24.6%)
Blood and lymphatic system disorders
Anaemia 6/2903 (0.2%) 10/2904 (0.3%)
Febrile Neutropenia 1/2903 (0%) 0/2904 (0%)
Iron Deficiency Anaemia 2/2903 (0.1%) 1/2904 (0%)
Polycythaemia 0/2903 (0%) 1/2904 (0%)
Thrombocytopenia 1/2903 (0%) 0/2904 (0%)
Cardiac disorders
Acute Coronary Syndrome 11/2903 (0.4%) 4/2904 (0.1%)
Acute Left Ventricular Failure 1/2903 (0%) 1/2904 (0%)
Acute Myocardial Infarction 26/2903 (0.9%) 32/2904 (1.1%)
Adams-Stokes Syndrome 0/2903 (0%) 1/2904 (0%)
Angina Pectoris 33/2903 (1.1%) 22/2904 (0.8%)
Angina Unstable 42/2903 (1.4%) 42/2904 (1.4%)
Aortic Valve Disease 1/2903 (0%) 0/2904 (0%)
Aortic Valve Incompetence 1/2903 (0%) 0/2904 (0%)
Arrhythmia 1/2903 (0%) 2/2904 (0.1%)
Arteriosclerosis Coronary Artery 5/2903 (0.2%) 3/2904 (0.1%)
Atrial Fibrillation 18/2903 (0.6%) 14/2904 (0.5%)
Atrial Flutter 7/2903 (0.2%) 5/2904 (0.2%)
Atrial Tachycardia 0/2903 (0%) 1/2904 (0%)
Atrioventricular Block Complete 1/2903 (0%) 3/2904 (0.1%)
Atrioventricular Block Second Degree 1/2903 (0%) 2/2904 (0.1%)
Bradycardia 1/2903 (0%) 2/2904 (0.1%)
Cardiac Arrest 9/2903 (0.3%) 5/2904 (0.2%)
Cardiac Disorder 0/2903 (0%) 1/2904 (0%)
Cardiac Failure 41/2903 (1.4%) 19/2904 (0.7%)
Cardiac Failure Acute 3/2903 (0.1%) 2/2904 (0.1%)
Cardiac Failure Chronic 3/2903 (0.1%) 4/2904 (0.1%)
Cardiac Failure Congestive 18/2903 (0.6%) 11/2904 (0.4%)
Cardiac Valve Disease 2/2903 (0.1%) 0/2904 (0%)
Cardio-Respiratory Arrest 1/2903 (0%) 1/2904 (0%)
Cardiogenic Shock 2/2903 (0.1%) 0/2904 (0%)
Cardiopulmonary Failure 0/2903 (0%) 1/2904 (0%)
Conduction Disorder 2/2903 (0.1%) 0/2904 (0%)
Congestive Cardiomyopathy 1/2903 (0%) 0/2904 (0%)
Coronary Artery Disease 29/2903 (1%) 34/2904 (1.2%)
Coronary Artery Insufficiency 0/2903 (0%) 1/2904 (0%)
Coronary Artery Occlusion 3/2903 (0.1%) 4/2904 (0.1%)
Coronary Artery Stenosis 8/2903 (0.3%) 5/2904 (0.2%)
Diabetic Cardiomyopathy 1/2903 (0%) 0/2904 (0%)
Ischaemic Cardiomyopathy 4/2903 (0.1%) 1/2904 (0%)
Left Ventricular Dysfunction 1/2903 (0%) 0/2904 (0%)
Left Ventricular Failure 1/2903 (0%) 1/2904 (0%)
Mitral Valve Stenosis 0/2903 (0%) 1/2904 (0%)
Myocardial Fibrosis 0/2903 (0%) 1/2904 (0%)
Myocardial Infarction 24/2903 (0.8%) 31/2904 (1.1%)
Myocardial Ischaemia 9/2903 (0.3%) 7/2904 (0.2%)
Pericardial Effusion 0/2903 (0%) 2/2904 (0.1%)
Pericarditis 3/2903 (0.1%) 0/2904 (0%)
Prinzmetal Angina 1/2903 (0%) 0/2904 (0%)
Right Ventricular Failure 2/2903 (0.1%) 0/2904 (0%)
Sinus Bradycardia 1/2903 (0%) 0/2904 (0%)
Sinus Node Dysfunction 4/2903 (0.1%) 0/2904 (0%)
Supraventricular Tachycardia 1/2903 (0%) 1/2904 (0%)
Tachycardia 1/2903 (0%) 0/2904 (0%)
Tricuspid Valve Incompetence 0/2903 (0%) 1/2904 (0%)
Ventricular Arrhythmia 1/2903 (0%) 0/2904 (0%)
Ventricular Asystole 1/2903 (0%) 0/2904 (0%)
Ventricular Extrasystoles 1/2903 (0%) 1/2904 (0%)
Ventricular Fibrillation 0/2903 (0%) 2/2904 (0.1%)
Ventricular Tachycardia 2/2903 (0.1%) 1/2904 (0%)
Ear and labyrinth disorders
Haematotympanum 0/2903 (0%) 1/2904 (0%)
Hypoacusis 1/2903 (0%) 0/2904 (0%)
Vertigo 2/2903 (0.1%) 1/2904 (0%)
Endocrine disorders
Basedow's Disease 0/2903 (0%) 1/2904 (0%)
Hyperparathyroidism 2/2903 (0.1%) 0/2904 (0%)
Hyperparathyroidism Primary 0/2903 (0%) 1/2904 (0%)
Hyperthyroidism 1/2903 (0%) 0/2904 (0%)
Eye disorders
Amaurosis Fugax 0/2903 (0%) 1/2904 (0%)
Cataract 3/2903 (0.1%) 10/2904 (0.3%)
Diabetic Retinopathy 0/2903 (0%) 1/2904 (0%)
Diplopia 1/2903 (0%) 2/2904 (0.1%)
Eye Haemorrhage 1/2903 (0%) 0/2904 (0%)
Eye Pain 1/2903 (0%) 0/2904 (0%)
Eyelid Ptosis 0/2903 (0%) 1/2904 (0%)
Glaucoma 1/2903 (0%) 0/2904 (0%)
Macular Fibrosis 0/2903 (0%) 1/2904 (0%)
Retinal Artery Occlusion 1/2903 (0%) 0/2904 (0%)
Retinal Detachment 0/2903 (0%) 1/2904 (0%)
Retinopathy 1/2903 (0%) 0/2904 (0%)
Gastrointestinal disorders
Abdominal Hernia 3/2903 (0.1%) 0/2904 (0%)
Abdominal Pain 5/2903 (0.2%) 2/2904 (0.1%)
Abdominal Pain Lower 0/2903 (0%) 1/2904 (0%)
Abdominal Pain Upper 2/2903 (0.1%) 0/2904 (0%)
Anal Fistula 0/2903 (0%) 1/2904 (0%)
Ascites 1/2903 (0%) 1/2904 (0%)
Barrett's Oesophagus 1/2903 (0%) 0/2904 (0%)
Bowel Movement Irregularity 1/2903 (0%) 0/2904 (0%)
Colitis 0/2903 (0%) 1/2904 (0%)
Colitis Ischaemic 0/2903 (0%) 1/2904 (0%)
Colitis Microscopic 1/2903 (0%) 0/2904 (0%)
Colitis Ulcerative 0/2903 (0%) 1/2904 (0%)
Colonic Pseudo-Obstruction 1/2903 (0%) 0/2904 (0%)
Constipation 1/2903 (0%) 1/2904 (0%)
Diarrhoea 4/2903 (0.1%) 1/2904 (0%)
Diverticular Perforation 0/2903 (0%) 1/2904 (0%)
Diverticulum 0/2903 (0%) 2/2904 (0.1%)
Diverticulum Intestinal 1/2903 (0%) 0/2904 (0%)
Duodenal Ulcer 1/2903 (0%) 1/2904 (0%)
Duodenal Ulcer Haemorrhage 2/2903 (0.1%) 0/2904 (0%)
Duodenal Ulcer Perforation 1/2903 (0%) 0/2904 (0%)
Enterocolitis 1/2903 (0%) 0/2904 (0%)
Food Poisoning 0/2903 (0%) 1/2904 (0%)
Gastric Polyps 1/2903 (0%) 0/2904 (0%)
Gastroduodenitis 0/2903 (0%) 1/2904 (0%)
Gastrointestinal Haemorrhage 3/2903 (0.1%) 3/2904 (0.1%)
Haematemesis 1/2903 (0%) 0/2904 (0%)
Ileus 1/2903 (0%) 0/2904 (0%)
Impaired Gastric Emptying 1/2903 (0%) 0/2904 (0%)
Inguinal Hernia 4/2903 (0.1%) 2/2904 (0.1%)
Intestinal Haemorrhage 2/2903 (0.1%) 0/2904 (0%)
Intestinal Ischaemia 3/2903 (0.1%) 0/2904 (0%)
Intestinal Obstruction 1/2903 (0%) 0/2904 (0%)
Intestinal Ulcer Perforation 1/2903 (0%) 0/2904 (0%)
Large Intestine Perforation 0/2903 (0%) 1/2904 (0%)
Lower Gastrointestinal Haemorrhage 1/2903 (0%) 1/2904 (0%)
Melaena 0/2903 (0%) 2/2904 (0.1%)
Mesenteric Arterial Occlusion 0/2903 (0%) 1/2904 (0%)
Mesenteric Vein Thrombosis 2/2903 (0.1%) 0/2904 (0%)
Oesophageal Obstruction 1/2903 (0%) 0/2904 (0%)
Pancreatitis 1/2903 (0%) 0/2904 (0%)
Pancreatitis Acute 2/2903 (0.1%) 3/2904 (0.1%)
Peptic Ulcer 1/2903 (0%) 2/2904 (0.1%)
Pneumoperitoneum 1/2903 (0%) 0/2904 (0%)
Rectal Tenesmus 1/2903 (0%) 0/2904 (0%)
Salivary Gland Calculus 0/2903 (0%) 1/2904 (0%)
Salivary Gland Fistula 1/2903 (0%) 0/2904 (0%)
Small Intestinal Obstruction 0/2903 (0%) 2/2904 (0.1%)
Swollen Tongue 1/2903 (0%) 0/2904 (0%)
Tooth Disorder 1/2903 (0%) 0/2904 (0%)
Umbilical Hernia 1/2903 (0%) 6/2904 (0.2%)
Upper Gastrointestinal Haemorrhage 2/2903 (0.1%) 3/2904 (0.1%)
Volvulus 1/2903 (0%) 0/2904 (0%)
General disorders
Adverse Drug Reaction 1/2903 (0%) 1/2904 (0%)
Cardiac Death 1/2903 (0%) 0/2904 (0%)
Chest Discomfort 2/2903 (0.1%) 0/2904 (0%)
Chest Pain 17/2903 (0.6%) 22/2904 (0.8%)
Complication Associated with Device 0/2903 (0%) 1/2904 (0%)
Cyst 1/2903 (0%) 0/2904 (0%)
Death 7/2903 (0.2%) 5/2904 (0.2%)
Drug Intolerance 0/2903 (0%) 1/2904 (0%)
Gait Disturbance 0/2903 (0%) 1/2904 (0%)
Generalised Oedema 1/2903 (0%) 0/2904 (0%)
Impaired Healing 0/2903 (0%) 1/2904 (0%)
Malaise 1/2903 (0%) 1/2904 (0%)
Non-Cardiac Chest Pain 7/2903 (0.2%) 9/2904 (0.3%)
Oedema Peripheral 2/2903 (0.1%) 0/2904 (0%)
Peripheral Swelling 1/2903 (0%) 0/2904 (0%)
Pyrexia 3/2903 (0.1%) 2/2904 (0.1%)
Sudden Cardiac Death 1/2903 (0%) 0/2904 (0%)
Sudden Death 6/2903 (0.2%) 6/2904 (0.2%)
Vascular Stent Restenosis 0/2903 (0%) 1/2904 (0%)
Vascular Stent Thrombosis 1/2903 (0%) 0/2904 (0%)
Hepatobiliary disorders
Bile Duct Stone 2/2903 (0.1%) 0/2904 (0%)
Biliary Colic 1/2903 (0%) 1/2904 (0%)
Cholangitis 0/2903 (0%) 2/2904 (0.1%)
Cholangitis Acute 1/2903 (0%) 0/2904 (0%)
Cholecystitis 3/2903 (0.1%) 3/2904 (0.1%)
Cholecystitis Acute 1/2903 (0%) 2/2904 (0.1%)
Cholelithiasis 7/2903 (0.2%) 5/2904 (0.2%)
Cholelithiasis Obstructive 0/2903 (0%) 1/2904 (0%)
Gallbladder Polyp 0/2903 (0%) 1/2904 (0%)
Haemobilia 0/2903 (0%) 1/2904 (0%)
Hepatic Cirrhosis 0/2903 (0%) 1/2904 (0%)
Hepatic Lesion 1/2903 (0%) 0/2904 (0%)
Hydrocholecystis 0/2903 (0%) 1/2904 (0%)
Jaundice Cholestatic 1/2903 (0%) 0/2904 (0%)
Liver Injury 0/2903 (0%) 1/2904 (0%)
Non-Alcoholic Steatohepatitis 1/2903 (0%) 0/2904 (0%)
Immune system disorders
Anaphylactic Reaction 2/2903 (0.1%) 0/2904 (0%)
Drug Hypersensitivity 0/2903 (0%) 1/2904 (0%)
Sarcoidosis 1/2903 (0%) 1/2904 (0%)
Infections and infestations
Abscess 1/2903 (0%) 0/2904 (0%)
Abscess Limb 2/2903 (0.1%) 1/2904 (0%)
Abscess Neck 0/2903 (0%) 1/2904 (0%)
Appendicitis 2/2903 (0.1%) 6/2904 (0.2%)
Arthritis Bacterial 1/2903 (0%) 1/2904 (0%)
Bronchitis 3/2903 (0.1%) 0/2904 (0%)
Campylobacter Gastroenteritis 1/2903 (0%) 0/2904 (0%)
Carbuncle 1/2903 (0%) 0/2904 (0%)
Cellulitis 11/2903 (0.4%) 9/2904 (0.3%)
Cellulitis Staphylococcal 0/2903 (0%) 1/2904 (0%)
Cellulitis Streptococcal 0/2903 (0%) 1/2904 (0%)
Cholecystitis Infective 1/2903 (0%) 1/2904 (0%)
Colonic Abscess 0/2903 (0%) 1/2904 (0%)
Device Related Infection 1/2903 (0%) 2/2904 (0.1%)
Diabetic Foot Infection 4/2903 (0.1%) 3/2904 (0.1%)
Diabetic Gangrene 2/2903 (0.1%) 0/2904 (0%)
Diverticulitis 3/2903 (0.1%) 3/2904 (0.1%)
Ear Infection 1/2903 (0%) 0/2904 (0%)
Empyema 0/2903 (0%) 1/2904 (0%)
Endocarditis 0/2903 (0%) 2/2904 (0.1%)
Epididymitis 1/2903 (0%) 0/2904 (0%)
Erysipelas 5/2903 (0.2%) 0/2904 (0%)
Escherichia Infection 1/2903 (0%) 0/2904 (0%)
Escherichia Sepsis 0/2903 (0%) 1/2904 (0%)
Escherichia Urinary Tract Infection 1/2903 (0%) 2/2904 (0.1%)
Eye Infection 1/2903 (0%) 0/2904 (0%)
Gangrene 2/2903 (0.1%) 5/2904 (0.2%)
Gastroenteritis 9/2903 (0.3%) 8/2904 (0.3%)
Gastroenteritis Viral 1/2903 (0%) 2/2904 (0.1%)
Genital Infection Fungal 0/2903 (0%) 1/2904 (0%)
Hepatitis B 1/2903 (0%) 0/2904 (0%)
Herpes Zoster 1/2903 (0%) 0/2904 (0%)
Hiv Infection 1/2903 (0%) 0/2904 (0%)
Infected Dermal Cyst 1/2903 (0%) 0/2904 (0%)
Infected Skin Ulcer 1/2903 (0%) 3/2904 (0.1%)
Infection 1/2903 (0%) 1/2904 (0%)
Infective Exacerbation of Chronic Obstructive Airways Disease 2/2903 (0.1%) 1/2904 (0%)
Influenza 1/2903 (0%) 5/2904 (0.2%)
Intervertebral Discitis 0/2903 (0%) 1/2904 (0%)
Laryngitis 0/2903 (0%) 2/2904 (0.1%)
Localised Infection 6/2903 (0.2%) 5/2904 (0.2%)
Lower Respiratory Tract Infection 6/2903 (0.2%) 1/2904 (0%)
Lung Abscess 0/2903 (0%) 1/2904 (0%)
Mastoiditis 0/2903 (0%) 1/2904 (0%)
Orchitis 2/2903 (0.1%) 0/2904 (0%)
Osteomyelitis 5/2903 (0.2%) 6/2904 (0.2%)
Osteomyelitis Chronic 0/2903 (0%) 1/2904 (0%)
Otitis Media Acute 1/2903 (0%) 0/2904 (0%)
Parasitic Gastroenteritis 1/2903 (0%) 0/2904 (0%)
Paronychia 0/2903 (0%) 1/2904 (0%)
Pelvic Abscess 1/2903 (0%) 0/2904 (0%)
Penile Abscess 0/2903 (0%) 1/2904 (0%)
Perinephric Abscess 0/2903 (0%) 1/2904 (0%)
Peritonsillar Abscess 1/2903 (0%) 0/2904 (0%)
Pharyngotonsillitis 0/2903 (0%) 1/2904 (0%)
Pneumococcal Sepsis 0/2903 (0%) 1/2904 (0%)
Pneumonia 31/2903 (1.1%) 26/2904 (0.9%)
Pneumonia Legionella 1/2903 (0%) 0/2904 (0%)
Pneumonia Pneumococcal 2/2903 (0.1%) 0/2904 (0%)
Post Procedural Infection 0/2903 (0%) 1/2904 (0%)
Post Procedural Sepsis 0/2903 (0%) 1/2904 (0%)
Postoperative Wound Infection 0/2903 (0%) 1/2904 (0%)
Pulmonary Sepsis 1/2903 (0%) 0/2904 (0%)
Pulmonary Tuberculosis 0/2903 (0%) 1/2904 (0%)
Pyelonephritis 2/2903 (0.1%) 5/2904 (0.2%)
Pyelonephritis Acute 3/2903 (0.1%) 1/2904 (0%)
Respiratory Tract Infection 13/2903 (0.4%) 5/2904 (0.2%)
Scrotal Abscess 0/2903 (0%) 1/2904 (0%)
Scrotal Infection 0/2903 (0%) 1/2904 (0%)
Sepsis 9/2903 (0.3%) 4/2904 (0.1%)
Septic Shock 6/2903 (0.2%) 4/2904 (0.1%)
Sinusitis 1/2903 (0%) 0/2904 (0%)
Soft Tissue Infection 0/2903 (0%) 2/2904 (0.1%)
Staphylococcal Infection 2/2903 (0.1%) 0/2904 (0%)
Staphylococcal Sepsis 0/2903 (0%) 1/2904 (0%)
Stenotrophomonas Infection 0/2903 (0%) 1/2904 (0%)
Subcutaneous Abscess 2/2903 (0.1%) 0/2904 (0%)
Tooth Abscess 0/2903 (0%) 1/2904 (0%)
Tooth Infection 1/2903 (0%) 0/2904 (0%)
Tracheobronchitis 0/2903 (0%) 1/2904 (0%)
Upper Respiratory Tract Infection 2/2903 (0.1%) 2/2904 (0.1%)
Urinary Tract Infection 13/2903 (0.4%) 11/2904 (0.4%)
Urinary Tract Infection Enterococcal 0/2903 (0%) 1/2904 (0%)
Urosepsis 1/2903 (0%) 1/2904 (0%)
Wound Infection 1/2903 (0%) 0/2904 (0%)
Injury, poisoning and procedural complications
Ankle Fracture 2/2903 (0.1%) 0/2904 (0%)
Arterial Bypass Stenosis 0/2903 (0%) 1/2904 (0%)
Carotid Artery Restenosis 0/2903 (0%) 2/2904 (0.1%)
Cataract Operation Complication 1/2903 (0%) 0/2904 (0%)
Clavicle Fracture 0/2903 (0%) 1/2904 (0%)
Concussion 0/2903 (0%) 1/2904 (0%)
Contusion 3/2903 (0.1%) 1/2904 (0%)
Craniocerebral Injury 0/2903 (0%) 2/2904 (0.1%)
Epiphyseal Fracture 0/2903 (0%) 1/2904 (0%)
Eye Injury 1/2903 (0%) 0/2904 (0%)
Facial Bones Fracture 1/2903 (0%) 3/2904 (0.1%)
Fall 4/2903 (0.1%) 5/2904 (0.2%)
Femoral Neck Fracture 2/2903 (0.1%) 0/2904 (0%)
Femur Fracture 6/2903 (0.2%) 4/2904 (0.1%)
Fibula Fracture 1/2903 (0%) 2/2904 (0.1%)
Foot Fracture 1/2903 (0%) 1/2904 (0%)
Fractured Coccyx 0/2903 (0%) 1/2904 (0%)
Hand Fracture 1/2903 (0%) 2/2904 (0.1%)
Head Injury 2/2903 (0.1%) 0/2904 (0%)
Hip Fracture 5/2903 (0.2%) 3/2904 (0.1%)
Humerus Fracture 2/2903 (0.1%) 3/2904 (0.1%)
Jaw Fracture 0/2903 (0%) 1/2904 (0%)
Joint Dislocation 0/2903 (0%) 1/2904 (0%)
Laceration 0/2903 (0%) 2/2904 (0.1%)
Ligament Sprain 2/2903 (0.1%) 0/2904 (0%)
Limb Crushing Injury 0/2903 (0%) 1/2904 (0%)
Limb Injury 2/2903 (0.1%) 5/2904 (0.2%)
Lumbar Vertebral Fracture 1/2903 (0%) 1/2904 (0%)
Meniscus Injury 0/2903 (0%) 2/2904 (0.1%)
Patella Fracture 2/2903 (0.1%) 1/2904 (0%)
Pneumocephalus 1/2903 (0%) 0/2904 (0%)
Post Laminectomy Syndrome 0/2903 (0%) 1/2904 (0%)
Post Procedural Haematoma 0/2903 (0%) 1/2904 (0%)
Post Procedural Haematuria 0/2903 (0%) 2/2904 (0.1%)
Post Procedural Haemorrhage 1/2903 (0%) 2/2904 (0.1%)
Postoperative Hernia 1/2903 (0%) 0/2904 (0%)
Postoperative Respiratory Failure 0/2903 (0%) 1/2904 (0%)
Procedural Headache 0/2903 (0%) 1/2904 (0%)
Procedural Pain 0/2903 (0%) 1/2904 (0%)
Pubis Fracture 0/2903 (0%) 1/2904 (0%)
Radius Fracture 0/2903 (0%) 1/2904 (0%)
Rib Fracture 4/2903 (0.1%) 4/2904 (0.1%)
Road Traffic Accident 0/2903 (0%) 2/2904 (0.1%)
Spinal Fracture 0/2903 (0%) 2/2904 (0.1%)
Subarachnoid Haemorrhage 2/2903 (0.1%) 0/2904 (0%)
Subdural Haematoma 1/2903 (0%) 1/2904 (0%)
Suture Related Complication 0/2903 (0%) 1/2904 (0%)
Tendon Injury 1/2903 (0%) 0/2904 (0%)
Tendon Rupture 2/2903 (0.1%) 0/2904 (0%)
Thermal Burn 1/2903 (0%) 2/2904 (0.1%)
Thoracic Vertebral Fracture 1/2903 (0%) 0/2904 (0%)
Tibia Fracture 1/2903 (0%) 4/2904 (0.1%)
Toxicity to Various Agents 1/2903 (0%) 0/2904 (0%)
Traumatic Fracture 0/2903 (0%) 2/2904 (0.1%)
Traumatic Ulcer 1/2903 (0%) 0/2904 (0%)
Ulna Fracture 1/2903 (0%) 2/2904 (0.1%)
Upper Limb Fracture 2/2903 (0.1%) 1/2904 (0%)
Vascular Graft Stenosis 1/2903 (0%) 0/2904 (0%)
Wound 1/2903 (0%) 0/2904 (0%)
Wound Dehiscence 1/2903 (0%) 1/2904 (0%)
Wound Necrosis 0/2903 (0%) 1/2904 (0%)
Wrist Fracture 1/2903 (0%) 0/2904 (0%)
Investigations
Arteriogram Coronary 2/2903 (0.1%) 0/2904 (0%)
Blood Creatinine Increased 0/2903 (0%) 1/2904 (0%)
Blood Glucose Increased 3/2903 (0.1%) 0/2904 (0%)
Ejection Fraction Decreased 1/2903 (0%) 0/2904 (0%)
Electrocardiogram QT Prolonged 1/2903 (0%) 0/2904 (0%)
Electrocardiogram St-T Change 0/2903 (0%) 1/2904 (0%)
Electrocardiogram T Wave Inversion 0/2903 (0%) 1/2904 (0%)
International Normalised Ratio Increased 1/2903 (0%) 0/2904 (0%)
Liver Function Test Increased 0/2903 (0%) 1/2904 (0%)
Platelet Count Decreased 1/2903 (0%) 0/2904 (0%)
White Blood Cell Count Decreased 0/2903 (0%) 1/2904 (0%)
Metabolism and nutrition disorders
Acidosis 0/2903 (0%) 1/2904 (0%)
Cachexia 1/2903 (0%) 1/2904 (0%)
Dehydration 2/2903 (0.1%) 3/2904 (0.1%)
Diabetes Mellitus 18/2903 (0.6%) 5/2904 (0.2%)
Diabetes Mellitus Inadequate Control 12/2903 (0.4%) 6/2904 (0.2%)
Diabetic Complication 1/2903 (0%) 0/2904 (0%)
Diabetic Ketoacidosis 2/2903 (0.1%) 5/2904 (0.2%)
Electrolyte Imbalance 1/2903 (0%) 0/2904 (0%)
Fluid Overload 2/2903 (0.1%) 1/2904 (0%)
Gout 1/2903 (0%) 1/2904 (0%)
Hyperglycaemia 11/2903 (0.4%) 5/2904 (0.2%)
Hyperkalaemia 5/2903 (0.2%) 2/2904 (0.1%)
Hyperosmolar Hyperglycaemic State 1/2903 (0%) 0/2904 (0%)
Hypertriglyceridaemia 0/2903 (0%) 1/2904 (0%)
Hypoglycaemia 9/2903 (0.3%) 6/2904 (0.2%)
Hypokalaemia 1/2903 (0%) 0/2904 (0%)
Hyponatraemia 4/2903 (0.1%) 3/2904 (0.1%)
Hypovolaemia 2/2903 (0.1%) 1/2904 (0%)
Lactic Acidosis 0/2903 (0%) 2/2904 (0.1%)
Metabolic Acidosis 1/2903 (0%) 1/2904 (0%)
Obesity 3/2903 (0.1%) 2/2904 (0.1%)
Type 2 Diabetes Mellitus 1/2903 (0%) 1/2904 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia 3/2903 (0.1%) 4/2904 (0.1%)
Arthritis 2/2903 (0.1%) 2/2904 (0.1%)
Arthropathy 1/2903 (0%) 0/2904 (0%)
Back Pain 11/2903 (0.4%) 2/2904 (0.1%)
Bursitis 1/2903 (0%) 0/2904 (0%)
Cervical Spinal Stenosis 0/2903 (0%) 1/2904 (0%)
Costochondritis 1/2903 (0%) 0/2904 (0%)
Dactylitis 0/2903 (0%) 1/2904 (0%)
Dupuytren's Contracture 0/2903 (0%) 1/2904 (0%)
Extremity Contracture 0/2903 (0%) 1/2904 (0%)
Foot Deformity 0/2903 (0%) 2/2904 (0.1%)
Intervertebral Disc Compression 1/2903 (0%) 0/2904 (0%)
Intervertebral Disc Disorder 1/2903 (0%) 1/2904 (0%)
Intervertebral Disc Protrusion 5/2903 (0.2%) 7/2904 (0.2%)
Knee Deformity 0/2903 (0%) 1/2904 (0%)
Lumbar Spinal Stenosis 4/2903 (0.1%) 1/2904 (0%)
Muscular Weakness 2/2903 (0.1%) 2/2904 (0.1%)
Musculoskeletal Chest Pain 2/2903 (0.1%) 2/2904 (0.1%)
Musculoskeletal Pain 2/2903 (0.1%) 2/2904 (0.1%)
Osteitis 1/2903 (0%) 2/2904 (0.1%)
Osteoarthritis 16/2903 (0.6%) 13/2904 (0.4%)
Osteonecrosis 0/2903 (0%) 1/2904 (0%)
Pathological Fracture 0/2903 (0%) 1/2904 (0%)
Plantar Fasciitis 1/2903 (0%) 0/2904 (0%)
Polymyalgia Rheumatica 0/2903 (0%) 1/2904 (0%)
Rhabdomyolysis 1/2903 (0%) 0/2904 (0%)
Rotator Cuff Syndrome 1/2903 (0%) 4/2904 (0.1%)
Sacroiliitis 0/2903 (0%) 1/2904 (0%)
Spinal Column Stenosis 1/2903 (0%) 1/2904 (0%)
Spinal Osteoarthritis 4/2903 (0.1%) 1/2904 (0%)
Spinal Pain 3/2903 (0.1%) 3/2904 (0.1%)
Spondylolisthesis 0/2903 (0%) 1/2904 (0%)
Synovial Cyst 1/2903 (0%) 0/2904 (0%)
Tendonitis 1/2903 (0%) 0/2904 (0%)
Tenosynovitis 0/2903 (0%) 1/2904 (0%)
Tenosynovitis Stenosans 1/2903 (0%) 0/2904 (0%)
Trigger Finger 0/2903 (0%) 1/2904 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute Myeloid Leukaemia 1/2903 (0%) 0/2904 (0%)
Adenocarcinoma Gastric 0/2903 (0%) 1/2904 (0%)
Adenocarcinoma of Colon 3/2903 (0.1%) 1/2904 (0%)
Adenosquamous Cell Lung Cancer 1/2903 (0%) 0/2904 (0%)
B-Cell Lymphoma 2/2903 (0.1%) 0/2904 (0%)
Basal Cell Carcinoma 2/2903 (0.1%) 2/2904 (0.1%)
Benign Lung Neoplasm 0/2903 (0%) 1/2904 (0%)
Benign Neoplasm 0/2903 (0%) 1/2904 (0%)
Benign Neoplasm of Thyroid Gland 1/2903 (0%) 0/2904 (0%)
Bile Duct Cancer 0/2903 (0%) 1/2904 (0%)
Bladder Cancer 4/2903 (0.1%) 4/2904 (0.1%)
Bladder Cancer Recurrent 0/2903 (0%) 1/2904 (0%)
Bladder Transitional Cell Carcinoma 2/2903 (0.1%) 1/2904 (0%)
Bowen's Disease 1/2903 (0%) 0/2904 (0%)
Breast Adenoma 0/2903 (0%) 1/2904 (0%)
Breast Cancer 2/2903 (0.1%) 3/2904 (0.1%)
Breast Cancer Metastatic 0/2903 (0%) 1/2904 (0%)
Breast Cancer Stage Ii 0/2903 (0%) 1/2904 (0%)
Breast Cancer Stage Iii 0/2903 (0%) 1/2904 (0%)
Cerebral Hygroma 1/2903 (0%) 0/2904 (0%)
Cholangiocarcinoma 2/2903 (0.1%) 1/2904 (0%)
Chronic Myeloid Leukaemia 1/2903 (0%) 0/2904 (0%)
Colon Adenoma 0/2903 (0%) 1/2904 (0%)
Colon Cancer 0/2903 (0%) 4/2904 (0.1%)
Colon Cancer Metastatic 0/2903 (0%) 1/2904 (0%)
Colorectal Adenocarcinoma 1/2903 (0%) 0/2904 (0%)
Colorectal Cancer 0/2903 (0%) 1/2904 (0%)
Diffuse Large B-Cell Lymphoma 1/2903 (0%) 0/2904 (0%)
Gastric Cancer 1/2903 (0%) 2/2904 (0.1%)
Glioblastoma 0/2903 (0%) 1/2904 (0%)
Hodgkin's Disease 1/2903 (0%) 0/2904 (0%)
Invasive Ductal Breast Carcinoma 2/2903 (0.1%) 0/2904 (0%)
Large Cell Lung Cancer 0/2903 (0%) 1/2904 (0%)
Laryngeal Cancer 1/2903 (0%) 1/2904 (0%)
Lipoma 2/2903 (0.1%) 0/2904 (0%)
Lung Adenocarcinoma 2/2903 (0.1%) 4/2904 (0.1%)
Lung Adenocarcinoma Metastatic 0/2903 (0%) 1/2904 (0%)
Lung Cancer Metastatic 1/2903 (0%) 1/2904 (0%)
Lung Neoplasm Malignant 6/2903 (0.2%) 6/2904 (0.2%)
Lymphoma 1/2903 (0%) 0/2904 (0%)
Malignant Melanoma 0/2903 (0%) 3/2904 (0.1%)
Malignant Melanoma in Situ 0/2903 (0%) 1/2904 (0%)
Malignant Neoplasm of Unknown Primary Site 0/2903 (0%) 1/2904 (0%)
Mediastinum Neoplasm 1/2903 (0%) 0/2904 (0%)
Meningioma Benign 1/2903 (0%) 0/2904 (0%)
Metastases to Central Nervous System 0/2903 (0%) 2/2904 (0.1%)
Metastases to Liver 1/2903 (0%) 1/2904 (0%)
Neuroendocrine Carcinoma Metastatic 1/2903 (0%) 1/2904 (0%)
Neuroendocrine Tumour 0/2903 (0%) 1/2904 (0%)
Non-Hodgkin's Lymphoma 0/2903 (0%) 1/2904 (0%)
Non-Small Cell Lung Cancer 1/2903 (0%) 0/2904 (0%)
Oesophageal Squamous Cell Carcinoma 0/2903 (0%) 1/2904 (0%)
Ovarian Cancer Metastatic 1/2903 (0%) 0/2904 (0%)
Pancreatic Carcinoma 6/2903 (0.2%) 1/2904 (0%)
Papillary Cystadenoma Lymphomatosum 1/2903 (0%) 0/2904 (0%)
Papillary Thyroid Cancer 0/2903 (0%) 1/2904 (0%)
Plasma Cell Myeloma 1/2903 (0%) 0/2904 (0%)
Prostate Cancer 8/2903 (0.3%) 0/2904 (0%)
Prostate Cancer Metastatic 0/2903 (0%) 1/2904 (0%)
Rectal Cancer 3/2903 (0.1%) 0/2904 (0%)
Renal Cancer 0/2903 (0%) 1/2904 (0%)
Schwannoma 1/2903 (0%) 0/2904 (0%)
Serous Cystadenocarcinoma of Pancreas 1/2903 (0%) 0/2904 (0%)
Small Cell Lung Cancer Metastatic 1/2903 (0%) 0/2904 (0%)
Squamous Cell Carcinoma 1/2903 (0%) 1/2904 (0%)
Squamous Cell Carcinoma of Lung 1/2903 (0%) 0/2904 (0%)
Squamous Cell Carcinoma of Skin 0/2903 (0%) 1/2904 (0%)
Squamous Cell Carcinoma of the Oral Cavity 0/2903 (0%) 1/2904 (0%)
Squamous Cell Carcinoma of the Tongue 1/2903 (0%) 0/2904 (0%)
Tongue Neoplasm Malignant Stage Unspecified 0/2903 (0%) 1/2904 (0%)
Ureteric Cancer 1/2903 (0%) 0/2904 (0%)
Uterine Cancer 2/2903 (0.1%) 1/2904 (0%)
Uterine Leiomyoma 1/2903 (0%) 1/2904 (0%)
Nervous system disorders
Basilar Artery Occlusion 0/2903 (0%) 1/2904 (0%)
Brain Injury 0/2903 (0%) 1/2904 (0%)
Brain Stem Infarction 0/2903 (0%) 1/2904 (0%)
Brain Stem Stroke 0/2903 (0%) 2/2904 (0.1%)
Carotid Arteriosclerosis 2/2903 (0.1%) 0/2904 (0%)
Carotid Artery Occlusion 1/2903 (0%) 0/2904 (0%)
Carotid Artery Stenosis 7/2903 (0.2%) 9/2904 (0.3%)
Carpal Tunnel Syndrome 1/2903 (0%) 1/2904 (0%)
Cerebellar Infarction 1/2903 (0%) 1/2904 (0%)
Cerebral Haematoma 0/2903 (0%) 1/2904 (0%)
Cerebral Haemorrhage 1/2903 (0%) 3/2904 (0.1%)
Cerebral Infarction 5/2903 (0.2%) 4/2904 (0.1%)
Cerebral Ischaemia 1/2903 (0%) 1/2904 (0%)
Cerebrovascular Accident 37/2903 (1.3%) 15/2904 (0.5%)
Cervicobrachial Syndrome 1/2903 (0%) 1/2904 (0%)
Cognitive Disorder 1/2903 (0%) 0/2904 (0%)
Diabetic Mononeuropathy 1/2903 (0%) 0/2904 (0%)
Diabetic Neuropathy 1/2903 (0%) 2/2904 (0.1%)
Dizziness Postural 2/2903 (0.1%) 2/2904 (0.1%)
Embolic Stroke 1/2903 (0%) 0/2904 (0%)
Epilepsy 1/2903 (0%) 2/2904 (0.1%)
Facial Nerve Disorder 1/2903 (0%) 0/2904 (0%)
Generalised Tonic-Clonic Seizure 1/2903 (0%) 0/2904 (0%)
Haemorrhagic Stroke 4/2903 (0.1%) 2/2904 (0.1%)
Headache 1/2903 (0%) 2/2904 (0.1%)
Hemiparesis 0/2903 (0%) 2/2904 (0.1%)
Hydrocephalus 1/2903 (0%) 2/2904 (0.1%)
Hypertensive Encephalopathy 1/2903 (0%) 0/2904 (0%)
Hypoxic-Ischaemic Encephalopathy 1/2903 (0%) 0/2904 (0%)
Intraventricular Haemorrhage 0/2903 (0%) 1/2904 (0%)
Ischaemic Cerebral Infarction 0/2903 (0%) 1/2904 (0%)
Ischaemic Stroke 12/2903 (0.4%) 20/2904 (0.7%)
Lacunar Infarction 2/2903 (0.1%) 2/2904 (0.1%)
Lacunar Stroke 1/2903 (0%) 0/2904 (0%)
Lethargy 0/2903 (0%) 1/2904 (0%)
Loss of Consciousness 0/2903 (0%) 2/2904 (0.1%)
Lumbar Radiculopathy 0/2903 (0%) 1/2904 (0%)
Metabolic Encephalopathy 1/2903 (0%) 0/2904 (0%)
Migraine 0/2903 (0%) 1/2904 (0%)
Myasthenia Gravis 1/2903 (0%) 0/2904 (0%)
Myasthenia Gravis Crisis 0/2903 (0%) 1/2904 (0%)
Nerve Compression 0/2903 (0%) 1/2904 (0%)
Neuralgia 0/2903 (0%) 1/2904 (0%)
Paraesthesia 1/2903 (0%) 0/2904 (0%)
Peripheral Nerve Paresis 0/2903 (0%) 1/2904 (0%)
Presyncope 1/2903 (0%) 3/2904 (0.1%)
Radiculopathy 1/2903 (0%) 0/2904 (0%)
Sciatica 2/2903 (0.1%) 0/2904 (0%)
Seizure 2/2903 (0.1%) 0/2904 (0%)
Sensory Loss 1/2903 (0%) 0/2904 (0%)
Spinal Cord Compression 1/2903 (0%) 0/2904 (0%)
Syncope 8/2903 (0.3%) 10/2904 (0.3%)
Thalamic Infarction 0/2903 (0%) 1/2904 (0%)
Toxic Encephalopathy 0/2903 (0%) 1/2904 (0%)
Transient Ischaemic Attack 10/2903 (0.3%) 8/2904 (0.3%)
Tremor 0/2903 (0%) 1/2904 (0%)
Trigeminal Neuralgia 0/2903 (0%) 1/2904 (0%)
Vascular Encephalopathy 0/2903 (0%) 1/2904 (0%)
Vascular Headache 1/2903 (0%) 0/2904 (0%)
Vertebral Artery Occlusion 1/2903 (0%) 0/2904 (0%)
Vertebrobasilar Insufficiency 1/2903 (0%) 2/2904 (0.1%)
Vocal Cord Paralysis 0/2903 (0%) 1/2904 (0%)
Product Issues
Device Breakage 1/2903 (0%) 0/2904 (0%)
Device Loosening 0/2903 (0%) 1/2904 (0%)
Device Malfunction 2/2903 (0.1%) 0/2904 (0%)
Patient-Device Incompatibility 0/2903 (0%) 1/2904 (0%)
Psychiatric disorders
Bipolar Disorder 2/2903 (0.1%) 0/2904 (0%)
Completed Suicide 0/2903 (0%) 1/2904 (0%)
Confusional State 2/2903 (0.1%) 1/2904 (0%)
Delirium 2/2903 (0.1%) 0/2904 (0%)
Depression 1/2903 (0%) 0/2904 (0%)
Depression Suicidal 0/2903 (0%) 1/2904 (0%)
Emotional Disorder 1/2903 (0%) 0/2904 (0%)
Major Depression 1/2903 (0%) 0/2904 (0%)
Psychotic Disorder 0/2903 (0%) 1/2904 (0%)
Suicidal Ideation 1/2903 (0%) 0/2904 (0%)
Suicide Attempt 0/2903 (0%) 1/2904 (0%)
Renal and urinary disorders
Acute Kidney Injury 15/2903 (0.5%) 7/2904 (0.2%)
Bladder Obstruction 0/2903 (0%) 1/2904 (0%)
Chronic Kidney Disease 2/2903 (0.1%) 3/2904 (0.1%)
Diabetic Nephropathy 1/2903 (0%) 1/2904 (0%)
Haematuria 1/2903 (0%) 3/2904 (0.1%)
Hydronephrosis 1/2903 (0%) 0/2904 (0%)
Ketonuria 0/2903 (0%) 1/2904 (0%)
Nephrolithiasis 2/2903 (0.1%) 8/2904 (0.3%)
Nephropathy 1/2903 (0%) 0/2904 (0%)
Nephropathy Toxic 0/2903 (0%) 1/2904 (0%)
Nephrotic Syndrome 1/2903 (0%) 0/2904 (0%)
Pelvi-Ureteric Obstruction 1/2903 (0%) 0/2904 (0%)
Pollakiuria 0/2903 (0%) 1/2904 (0%)
Proteinuria 1/2903 (0%) 0/2904 (0%)
Renal Colic 0/2903 (0%) 2/2904 (0.1%)
Renal Failure 2/2903 (0.1%) 2/2904 (0.1%)
Renal Haematoma 0/2903 (0%) 1/2904 (0%)
Renal Impairment 2/2903 (0.1%) 1/2904 (0%)
Renal Injury 3/2903 (0.1%) 0/2904 (0%)
Stress Urinary Incontinence 1/2903 (0%) 0/2904 (0%)
Tubulointerstitial Nephritis 1/2903 (0%) 0/2904 (0%)
Ureterolithiasis 1/2903 (0%) 1/2904 (0%)
Urethral Stenosis 0/2903 (0%) 1/2904 (0%)
Urinary Incontinence 0/2903 (0%) 1/2904 (0%)
Urinary Retention 2/2903 (0.1%) 1/2904 (0%)
Reproductive system and breast disorders
Balanoposthitis 0/2903 (0%) 1/2904 (0%)
Benign Prostatic Hyperplasia 5/2903 (0.2%) 4/2904 (0.1%)
Endometrial Hyperplasia 0/2903 (0%) 1/2904 (0%)
Endometrial Hypertrophy 1/2903 (0%) 0/2904 (0%)
Epididymal Disorder 0/2903 (0%) 1/2904 (0%)
Erectile Dysfunction 0/2903 (0%) 1/2904 (0%)
Fallopian Tube Cyst 1/2903 (0%) 0/2904 (0%)
Metrorrhagia 0/2903 (0%) 1/2904 (0%)
Peyronie's Disease 1/2903 (0%) 0/2904 (0%)
Prostatitis 3/2903 (0.1%) 1/2904 (0%)
Prostatomegaly 0/2903 (0%) 1/2904 (0%)
Uterine Polyp 0/2903 (0%) 1/2904 (0%)
Uterine Prolapse 0/2903 (0%) 1/2904 (0%)
Respiratory, thoracic and mediastinal disorders
Acute Pulmonary Oedema 5/2903 (0.2%) 0/2904 (0%)
Acute Respiratory Distress Syndrome 1/2903 (0%) 0/2904 (0%)
Acute Respiratory Failure 3/2903 (0.1%) 1/2904 (0%)
Asthma 2/2903 (0.1%) 3/2904 (0.1%)
Asthmatic Crisis 1/2903 (0%) 0/2904 (0%)
Atelectasis 1/2903 (0%) 0/2904 (0%)
Bronchitis Chronic 1/2903 (0%) 0/2904 (0%)
Bronchospasm 2/2903 (0.1%) 1/2904 (0%)
Chronic Obstructive Pulmonary Disease 11/2903 (0.4%) 2/2904 (0.1%)
Cough 1/2903 (0%) 1/2904 (0%)
Dyspnoea 8/2903 (0.3%) 8/2904 (0.3%)
Epistaxis 0/2903 (0%) 3/2904 (0.1%)
Haemoptysis 2/2903 (0.1%) 0/2904 (0%)
Haemothorax 1/2903 (0%) 0/2904 (0%)
Hypoventilation 1/2903 (0%) 0/2904 (0%)
Mediastinal Effusion 0/2903 (0%) 1/2904 (0%)
Nasal Obstruction 1/2903 (0%) 0/2904 (0%)
Pleural Effusion 5/2903 (0.2%) 2/2904 (0.1%)
Pneumonia Aspiration 2/2903 (0.1%) 0/2904 (0%)
Pneumothorax 0/2903 (0%) 1/2904 (0%)
Pulmonary Embolism 5/2903 (0.2%) 6/2904 (0.2%)
Pulmonary Fibrosis 0/2903 (0%) 1/2904 (0%)
Pulmonary Mass 0/2903 (0%) 1/2904 (0%)
Pulmonary Oedema 6/2903 (0.2%) 0/2904 (0%)
Pulmonary Sarcoidosis 0/2903 (0%) 1/2904 (0%)
Respiratory Acidosis 1/2903 (0%) 1/2904 (0%)
Respiratory Alkalosis 1/2903 (0%) 0/2904 (0%)
Respiratory Failure 3/2903 (0.1%) 1/2904 (0%)
Sleep Apnoea Syndrome 1/2903 (0%) 1/2904 (0%)
Vocal Cord Leukoplakia 0/2903 (0%) 1/2904 (0%)
Skin and subcutaneous tissue disorders
Angioedema 1/2903 (0%) 0/2904 (0%)
Dermatitis Allergic 1/2903 (0%) 0/2904 (0%)
Diabetic Foot 9/2903 (0.3%) 10/2904 (0.3%)
Diabetic Ulcer 1/2903 (0%) 1/2904 (0%)
Skin Fissures 1/2903 (0%) 0/2904 (0%)
Skin Necrosis 0/2903 (0%) 2/2904 (0.1%)
Skin Ulcer 5/2903 (0.2%) 7/2904 (0.2%)
Urticaria 1/2903 (0%) 0/2904 (0%)
Social circumstances
Penile Prosthesis User 1/2903 (0%) 0/2904 (0%)
Victim of Homicide 0/2903 (0%) 1/2904 (0%)
Surgical and medical procedures
Coronary Arterial Stent Insertion 0/2903 (0%) 1/2904 (0%)
Hospitalisation 0/2903 (0%) 1/2904 (0%)
Stent Placement 0/2903 (0%) 1/2904 (0%)
Vascular disorders
Aortic Aneurysm 1/2903 (0%) 0/2904 (0%)
Aortic Arteriosclerosis 1/2903 (0%) 0/2904 (0%)
Aortic Stenosis 4/2903 (0.1%) 5/2904 (0.2%)
Arterial Thrombosis 1/2903 (0%) 0/2904 (0%)
Arteriosclerosis 2/2903 (0.1%) 2/2904 (0.1%)
Circulatory Collapse 1/2903 (0%) 1/2904 (0%)
Deep Vein Thrombosis 2/2903 (0.1%) 1/2904 (0%)
Diabetic Vascular Disorder 1/2903 (0%) 0/2904 (0%)
Extremity Necrosis 5/2903 (0.2%) 3/2904 (0.1%)
Haematoma 1/2903 (0%) 1/2904 (0%)
Hypertension 4/2903 (0.1%) 1/2904 (0%)
Hypertensive Crisis 6/2903 (0.2%) 1/2904 (0%)
Hypotension 3/2903 (0.1%) 0/2904 (0%)
Hypovolaemic Shock 0/2903 (0%) 1/2904 (0%)
Iliac Artery Occlusion 0/2903 (0%) 1/2904 (0%)
Intermittent Claudication 3/2903 (0.1%) 4/2904 (0.1%)
Orthostatic Hypotension 4/2903 (0.1%) 1/2904 (0%)
Peripheral Arterial Occlusive Disease 9/2903 (0.3%) 9/2904 (0.3%)
Peripheral Artery Occlusion 1/2903 (0%) 4/2904 (0.1%)
Peripheral Artery Stenosis 2/2903 (0.1%) 8/2904 (0.3%)
Peripheral Artery Thrombosis 1/2903 (0%) 0/2904 (0%)
Peripheral Embolism 1/2903 (0%) 1/2904 (0%)
Peripheral Ischaemia 5/2903 (0.2%) 7/2904 (0.2%)
Peripheral Vascular Disorder 4/2903 (0.1%) 9/2904 (0.3%)
Peripheral Venous Disease 0/2903 (0%) 1/2904 (0%)
Poor Peripheral Circulation 0/2903 (0%) 1/2904 (0%)
Post Thrombotic Syndrome 0/2903 (0%) 1/2904 (0%)
Vascular Insufficiency 0/2903 (0%) 1/2904 (0%)
Other (Not Including Serious) Adverse Events
Placebo (Placebo) Canagliflozin (Experimental)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 25/2903 (0.9%) 94/2904 (3.2%)
Reproductive system and breast disorders
Balanoposthitis 25/2903 (0.9%) 94/2904 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.

Results Point of Contact

Name/Title Director Clinical Development
Organization Janssen Research & Development, LLC
Phone 844-434-4210
Email ClinicalTrialDisclosure@its.jnj.com
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01989754
Other Study ID Numbers:
  • CR102647
  • 2013-003050-25
  • 28431754DIA4003
First Posted:
Nov 21, 2013
Last Update Posted:
Dec 11, 2018
Last Verified:
Nov 1, 2018