Trial Outcomes & Findings for Diabetic Retinopathy Candesartan Trials (NCT NCT00252733)

NCT ID: NCT00252733

Last Updated: 2014-05-14

Results Overview

Two steps were defined as either a 1-step change in each eye or as a 2-step change in one eye only. ETDRS is a scale with 11 steps (1-11, where a score of 1 represents no retinopathy and a score of 11 represents proliferative retinopathy). A generalized log-rank test was used to test difference between treatments.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 5238 participants
• Primary outcome timeframe: From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.
• Results posted on: 2014-05-14

Participant Flow

First subject enrolled in the DIRECT Programme 8 June 2001 and last subject completed the DIRECT Programme 16 April 2008 mainly in hospital based clinics. 4514 patients type 1 diabetes were enrolled of whom 1421 proceeded to randomization, 711 to the candesartan arm and 710 to the placebo arm.

The most common reason for not being randomized was that all eligibility criteria were not fulfilled, followed by withdrawn informed consent.

Participant milestones

Measure	Candesartan Candesartan cilexetil 32 mg once daily	Placebo Placebo Comparator
Overall Study STARTED	711	710
Overall Study COMPLETED	605	618
Overall Study NOT COMPLETED	106	92

Reasons for withdrawal

Measure	Candesartan Candesartan cilexetil 32 mg once daily	Placebo Placebo Comparator
Overall Study Withdrawal by Subject	73	67
Overall Study Death	7	5
Overall Study Lost to Follow-up	12	6
Overall Study Multiple Reasons	14	14

Baseline Characteristics

Diabetic Retinopathy Candesartan Trials

Baseline characteristics by cohort

Measure	Candesartan n=711 Participants Candesartan cilexetil 32 mg once daily	Placebo n=710 Participants Placebo Comparator	Total n=1421 Participants Total of all reporting groups
Age, Continuous	29.60 years STANDARD_DEVIATION 8.0 • n=5 Participants	29.90 years STANDARD_DEVIATION 8.1 • n=7 Participants	29.75 years STANDARD_DEVIATION 8.05 • n=5 Participants
Sex: Female, Male Female	298 Participants n=5 Participants	318 Participants n=7 Participants	616 Participants n=5 Participants
Sex: Female, Male Male	413 Participants n=5 Participants	392 Participants n=7 Participants	805 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to end of study, i.e. 5 years, with visits after a half year, one year and thereafter one visit per year.

Population: The population was the Intention To Treat population which includes all randomized patients with any post-randomization data.

Two steps were defined as either a 1-step change in each eye or as a 2-step change in one eye only. ETDRS is a scale with 11 steps (1-11, where a score of 1 represents no retinopathy and a score of 11 represents proliferative retinopathy). A generalized log-rank test was used to test difference between treatments.

Outcome measures

Measure	Candesartan n=711 Participants Candesartan cilexetil 32 mg once daily	Placebo n=710 Participants Placebo Comparator
Number of Participants With a 2-step or Greater Increase in Early Treatment Diabetic Retinopathy Study (ETDRS) Severity Scale.	178 Participants 0.071	217 Participants 0.086

SECONDARY outcome

Timeframe: From baseline to end of study, i.e. 5 years.

Population: The population was the Intention To Treat population which includes all randomized patients with any post-randomization data.

An estimate of the slope from fitting a linear regression of log(UAER) over time for each patient.

Outcome measures

Measure	Candesartan n=711 Participants Candesartan cilexetil 32 mg once daily	Placebo n=710 Participants Placebo Comparator
Rate of Change in Urinary Albumin Excretion Rate (UAER).	0.510 log (µg/min)/year Interval 0.487 to 0.534	0.543 log (µg/min)/year Interval 0.52 to 0.566

Adverse Events

Candesartan

Serious events: 102 serious events

Other events: 85 other events

Deaths: 0 deaths

Placebo

Serious events: 112 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Measure	Candesartan n=710 participants at risk Candesartan cilexetil 32 mg once daily	Placebo n=710 participants at risk Placebo Comparator
Blood and lymphatic system disorders Anaemia	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Blood and lymphatic system disorders Bicytopenia	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Blood and lymphatic system disorders Iron Deficiency Anaemia	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Blood and lymphatic system disorders Lymphoid Tissue Hyperplasia	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Myocardial Infarction	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.56% 4/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Acute Coronary Syndrome	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Angina Pectoris	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Atrial Flutter	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Cardiac Failure Acute	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Coronary Artery Disease	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Palpitations	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Pericardial Disease	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Pericardial Effusion	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Cardiac disorders Pericarditis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Congenital, familial and genetic disorders Phimosis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Endocrine disorders Basedow's Disease	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Endocrine disorders Hyperthyroidism	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Eye disorders Diplopia	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Dyspepsia	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Gastritis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Inguinal Hernia	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Abdominal Pain	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Appendicitis Perforated	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Coeliac Disease	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Colitis Ulcerative	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Enteritis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Gastric Ulcer	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Haemorrhoidal Haemorrhage	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Hiatus Hernia	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Ileus	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Intestinal Obstruction	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Mallory-Weiss Syndrome	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Pancreatitis Chronic	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Gastrointestinal disorders Tooth Disorder	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
General disorders Chest Pain	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
General disorders Generalised Oedema	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Hepatobiliary disorders Cholecystitis Acute	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Hepatobiliary disorders Hepatitis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Immune system disorders Hypersensitivity	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Immune system disorders Sarcoidosis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Gastroenteritis	1.3% 9/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Appendicitis	0.56% 4/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.42% 3/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Pneumonia	0.42% 3/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Anogenital Warts	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Bronchitis	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Gastroenteritis Viral	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Pharyngitis	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Pilonidal Cyst	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Pulmonary Tuberculosis	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Pyelonephritis	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Acute Sinusitis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Cat Scratch Disease	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Cellulitis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Cystitis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Gangrene	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Hepatitis B	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Hepatitis Viral	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Pyelonephritis Chronic	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Sinusitis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Tooth Abscess	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Toxoplasmosis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Urinary Tract Infection	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Viral Labyrinthitis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Ankle Fracture	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.42% 3/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Facial Bones Fracture	0.42% 3/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Head Injury	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Multiple Injuries	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Contusion	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Foot Fracture	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Foreign Body In Eye	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Joint Dislocation	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Joint Injury	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Limb Crushing Injury	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Limb Injury	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Lumbar Vertebral Fracture	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Overdose	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Road Traffic Accident	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Spinal Fracture	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Tendon Rupture	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Injury, poisoning and procedural complications Traumatic Amputation	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Investigations Blood Creatine Phosphokinase Increased	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Investigations HIV Test Positive	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Investigations International Normalised Ratio Increased	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Diabetic Ketoacidosis	1.7% 12/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	2.4% 17/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Hypoglycaemia	2.4% 17/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	2.3% 16/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.85% 6/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Ketoacidosis	0.42% 3/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.70% 5/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Hyperglycaemia	0.42% 3/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.56% 4/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Dehydration	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Hypoglycaemic Seizure	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Metabolism and nutrition disorders Shock Hypoglycaemic	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Vascular disorders Arthralgia	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Compartment Syndrome	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Periarthritis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acrochordon	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign Neoplasm Of Thyroid Gland	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix Carcinoma	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Retroperitoneal Neoplasm	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin Papilloma	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Teratoma Benign	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid Cancer	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Convulsion	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Hypoglycaemic Coma	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Carpal Tunnel Syndrome	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Cerebral Infarction	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Cerebrovascular Accident	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Diabetic Autonomic Neuropathy	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Epilepsy	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Guillain-Barre Syndrome	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Hydrocephalus	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Leukoencephalomyelitis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Multiple Sclerosis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Nervous system disorders Radiculitis Brachial	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Pregnancy, puerperium and perinatal conditions Abortion Spontaneous	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Pregnancy, puerperium and perinatal conditions Abortion	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Pregnancy, puerperium and perinatal conditions Intra-Uterine Death	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Psychiatric disorders Depression	0.42% 3/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Psychiatric disorders Completed Suicide	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Psychiatric disorders Confusional State	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Psychiatric disorders Suicide Attempt	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Renal and urinary disorders Haematuria	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Renal and urinary disorders Ureteric Obstruction	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Reproductive system and breast disorders Menorrhagia	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.28% 2/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Reproductive system and breast disorders Bartholin's Cyst	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Reproductive system and breast disorders Endometriosis	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Reproductive system and breast disorders Menstruation Irregular	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Reproductive system and breast disorders Ovarian Cyst	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Reproductive system and breast disorders Vaginal Haemorrhage	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Respiratory, thoracic and mediastinal disorders Asthma	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Respiratory, thoracic and mediastinal disorders Nasal Polyps	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Respiratory, thoracic and mediastinal disorders Sleep Apnoea Syndrome	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Skin and subcutaneous tissue disorders Rash	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Skin and subcutaneous tissue disorders Skin Ulcer	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.
Vascular disorders Deep Vein Thrombosis	0.00% 0/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	0.14% 1/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.

Other adverse events

Measure	Candesartan n=710 participants at risk Candesartan cilexetil 32 mg once daily	Placebo n=710 participants at risk Placebo Comparator
Vascular disorders Hypotension	12.0% 85/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.	6.1% 43/710 • During treatment, up to 5 years. The population used was the safety population which includes all patients who received at least 1 dose of randomized study drug and for whom any post-randomization data were available.

Additional Information

Niklas Berglind, GPS Atacand

AstraZeneca

Phone: +46 31 7766310

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place