Trial Outcomes & Findings for Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Background Metformin in Patient With Type 2 Diabetes (NCT NCT01778049)
NCT ID: NCT01778049
Last Updated: 2016-04-04
Results Overview
Change from baseline in Glycated haemoglobin (HbA1c) \[%\] after 24 weeks of treatment with double-blind trial medication, i.e. HbA1c change from baseline at Week 24. The term "baseline" was not used to refer to measurements prior to the administration of open-label medication. Such measurements were referred to as "pre-treatment". Analyses of change from pre-treatment used the last value before first administration of open-label medication as point of reference. Observed Case (OC): This method analyse only available data that were observed while patients were on treatment, i.e., excluding the missing data. All values measured after rescue medication taken were set to missing. Full Analysis Set (FAS): Includes all patients in the Treated set who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the double-blind part of the trial.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
708 participants
Primary outcome timeframe
Baseline and 24 weeks
Results posted on
2016-04-04
Participant Flow
Subjects randomised to 16 week(wk) open-label (OL) treatment with either empagliflozin (empa) 25 or empa 10 treatment, thereafter subjects entered to 1 wk open label placebo (Plc) add-on period in order to complete further eligibility evaluations before being randomised into 1 of the 24 wk double-blind treatment groups.
This was a randomised, double-blind, multi-national, parallel group trial. In this trial the treatment effects of linagliptin (lina) 5 compared with Plc were analysed as add-on to either empa 25 or empa 10. All trial treatments were administered in addition to metformin background treatment.
Participant milestones
| Measure |
Empa 10 mg OL
Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.
|
Empa 25 mg OL
Subjects were orally administered once daily empa 25 mg film-coated tablet for 16 week during OL treatment period, thereafter patients received once daily FDC Plc tablet matching to FDC empa 25 mg/lina 5 mg in addition to empa 25 mg for 1 wk during open label placebo add-on treatment period.
|
Lina5 (E10)
Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.
|
Plc (E10)
Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
Lina5 (E25)
Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.
|
Plc (E25)
Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
|---|---|---|---|---|---|---|
|
Open Label Treatment Period
STARTED
|
354
|
355
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
COMPLETED
|
256
|
226
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
NOT COMPLETED
|
98
|
129
|
0
|
0
|
0
|
0
|
|
Double Blind Treatment Period
STARTED
|
0
|
0
|
126
|
130
|
114
|
112
|
|
Double Blind Treatment Period
COMPLETED
|
0
|
0
|
111
|
118
|
102
|
105
|
|
Double Blind Treatment Period
NOT COMPLETED
|
0
|
0
|
15
|
12
|
12
|
7
|
Reasons for withdrawal
| Measure |
Empa 10 mg OL
Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.
|
Empa 25 mg OL
Subjects were orally administered once daily empa 25 mg film-coated tablet for 16 week during OL treatment period, thereafter patients received once daily FDC Plc tablet matching to FDC empa 25 mg/lina 5 mg in addition to empa 25 mg for 1 wk during open label placebo add-on treatment period.
|
Lina5 (E10)
Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.
|
Plc (E10)
Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
Lina5 (E25)
Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.
|
Plc (E25)
Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
|---|---|---|---|---|---|---|
|
Open Label Treatment Period
Adverse Event
|
5
|
15
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
Lack of Efficacy
|
1
|
1
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
Protocol Violation
|
5
|
5
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
Lost to Follow-up
|
4
|
3
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
Withdrawal by Subject
|
4
|
10
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
Not treated
|
2
|
1
|
0
|
0
|
0
|
0
|
|
Open Label Treatment Period
Other reason not defined above
|
77
|
94
|
0
|
0
|
0
|
0
|
|
Double Blind Treatment Period
Adverse Event
|
0
|
0
|
4
|
5
|
3
|
2
|
|
Double Blind Treatment Period
Lack of Efficacy
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Double Blind Treatment Period
Protocol Violation
|
0
|
0
|
2
|
0
|
0
|
0
|
|
Double Blind Treatment Period
Lost to Follow-up
|
0
|
0
|
4
|
1
|
5
|
2
|
|
Double Blind Treatment Period
Withdrawal by Subject
|
0
|
0
|
1
|
2
|
0
|
1
|
|
Double Blind Treatment Period
Not treated
|
0
|
0
|
0
|
2
|
2
|
0
|
|
Double Blind Treatment Period
Other reason not defined above
|
0
|
0
|
4
|
2
|
2
|
1
|
Baseline Characteristics
Linagliptin as Add on Therapy to Empagliflozin 10 mg or 25 mg With Background Metformin in Patient With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Empa 10 mg OL
n=352 Participants
Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.
|
Empa 25 mg OL
n=354 Participants
Subjects were orally administered once daily empa 25 mg film-coated tablet for 16 week during OL treatment period, thereafter patients received once daily FDC Plc tablet matching to FDC empa 25 mg/lina 5 mg in addition to empa 25 mg for 1 wk during open label placebo add-on treatment period.
|
Total
n=706 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.0 Years
STANDARD_DEVIATION 9.6 • n=5 Participants
|
56.7 Years
STANDARD_DEVIATION 9.9 • n=7 Participants
|
56.8 Years
STANDARD_DEVIATION 9.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
145 Participants
n=5 Participants
|
161 Participants
n=7 Participants
|
306 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
207 Participants
n=5 Participants
|
193 Participants
n=7 Participants
|
400 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 24 weeksPopulation: FAS (OC)
Change from baseline in Glycated haemoglobin (HbA1c) \[%\] after 24 weeks of treatment with double-blind trial medication, i.e. HbA1c change from baseline at Week 24. The term "baseline" was not used to refer to measurements prior to the administration of open-label medication. Such measurements were referred to as "pre-treatment". Analyses of change from pre-treatment used the last value before first administration of open-label medication as point of reference. Observed Case (OC): This method analyse only available data that were observed while patients were on treatment, i.e., excluding the missing data. All values measured after rescue medication taken were set to missing. Full Analysis Set (FAS): Includes all patients in the Treated set who had a baseline HbA1c assessment and at least 1 on-treatment HbA1c assessment during the double-blind part of the trial.
Outcome measures
| Measure |
Lina5 (E10)
n=111 Participants
Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.
|
Plc (E10)
n=110 Participants
Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
Lina5 (E25)
n=98 Participants
Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.
|
Plc (E25)
n=98 Participants
Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
|---|---|---|---|---|
|
Change From Baseline of HbA1c After 24 Weeks of Treatment.
|
-0.53 Percentage of HbA1c
Standard Error 0.07
|
-0.21 Percentage of HbA1c
Standard Error 0.07
|
-0.58 Percentage of HbA1c
Standard Error 0.07
|
-0.10 Percentage of HbA1c
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline and 24 weeksPopulation: FAS (OC)
Change from baseline FPG (mmol/L) after 24 weeks of treatment with double-blind trial medication, i.e. FPG change from baseline at Week 24.
Outcome measures
| Measure |
Lina5 (E10)
n=108 Participants
Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.
|
Plc (E10)
n=107 Participants
Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
Lina5 (E25)
n=93 Participants
Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.
|
Plc (E25)
n=94 Participants
Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
|---|---|---|---|---|
|
Fasting Plasma Glucose (FPG) Change From Baseline at 24 Weeks.
|
-0.44 mmol/L
Standard Error 0.18
|
0.21 mmol/L
Standard Error 0.18
|
-0.68 mmol/L
Standard Error 0.15
|
-0.24 mmol/L
Standard Error 0.15
|
Adverse Events
Empa 10 mg OL
Serious events: 12 serious events
Other events: 47 other events
Deaths: 0 deaths
Empa 25 mg OL
Serious events: 12 serious events
Other events: 38 other events
Deaths: 0 deaths
Lina5 (E10)
Serious events: 4 serious events
Other events: 22 other events
Deaths: 0 deaths
Plc (E10)
Serious events: 5 serious events
Other events: 10 other events
Deaths: 0 deaths
Lina5 (E25)
Serious events: 3 serious events
Other events: 18 other events
Deaths: 0 deaths
Plc (E25)
Serious events: 4 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Empa 10 mg OL
n=352 participants at risk
Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.
|
Empa 25 mg OL
n=354 participants at risk
Subjects were orally administered once daily empa 25 mg film-coated tablet for 16 week during OL treatment period, thereafter patients received once daily FDC Plc tablet matching to FDC empa 25 mg/lina 5 mg in addition to empa 25 mg for 1 wk during open label placebo add-on treatment period.
|
Lina5 (E10)
n=126 participants at risk
Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.
|
Plc (E10)
n=128 participants at risk
Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
Lina5 (E25)
n=112 participants at risk
Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.
|
Plc (E25)
n=112 participants at risk
Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Cardiac disorders
Angina unstable
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Cardiac disorders
Atrial fibrillation
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.78%
1/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Cardiac disorders
Myocardial infarction
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.78%
1/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Cardiac disorders
Myocardial ischaemia
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Gastrointestinal disorders
Intestinal polyp
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.57%
2/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.79%
1/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.79%
1/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
General disorders
Calcinosis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
General disorders
Chest pain
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
General disorders
Death
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
General disorders
General physical health deterioration
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.79%
1/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.57%
2/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Hepatobiliary disorders
Liver injury
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Abscess limb
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Bronchitis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Gangrene
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Infectious colitis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
1.8%
2/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Pneumonia
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.79%
1/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Upper respiratory tract infection
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.79%
1/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Injury, poisoning and procedural complications
Fall
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Injury, poisoning and procedural complications
Skull fractured base
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Investigations
Amylase increased
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.79%
1/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Musculoskeletal and connective tissue disorders
Haemarthrosis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.78%
1/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.79%
1/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.78%
1/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostatic adenoma
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Nervous system disorders
Cerebral haematoma
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.78%
1/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Nervous system disorders
Ischaemic stroke
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Reproductive system and breast disorders
Balanoposthitis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.78%
1/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Respiratory, thoracic and mediastinal disorders
Nasal turbinate hypertrophy
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.28%
1/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal lesion
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Skin and subcutaneous tissue disorders
Dermatitis bullous
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Skin and subcutaneous tissue disorders
Dyshidrotic eczema
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Vascular disorders
Extremity necrosis
|
0.00%
0/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.89%
1/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.28%
1/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.00%
0/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
Other adverse events
| Measure |
Empa 10 mg OL
n=352 participants at risk
Subjects were orally administered once daily empa 10 mg film-coated tablet for 16 wk during OL treatment period, thereafter patients received once daily fixed dose combination (FDC) placebo tablet matching to FDC empa 10 mg/lina 5 mg in addition to empa 10 mg for 1 week during open label placebo add-on treatment period.
|
Empa 25 mg OL
n=354 participants at risk
Subjects were orally administered once daily empa 25 mg film-coated tablet for 16 week during OL treatment period, thereafter patients received once daily FDC Plc tablet matching to FDC empa 25 mg/lina 5 mg in addition to empa 25 mg for 1 wk during open label placebo add-on treatment period.
|
Lina5 (E10)
n=126 participants at risk
Subjects were orally administered FDC empa 10 mg/lina 5 mg and placebo matching to empa 10 mg for 24 wk during the double-blind treatment period.
|
Plc (E10)
n=128 participants at risk
Subjects were orally administered empa 10 mg and matching placebo to FDC empa 10 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
Lina5 (E25)
n=112 participants at risk
Subjects were orally administered FDC empa 25 mg/lina 5 mg and placebo matching to empa 25 mg for 24 wk during the double-blind treatment period.
|
Plc (E25)
n=112 participants at risk
Subjects were orally administered empa 25 mg and matching placebo to FDC empa 25 mg/lina 5 mg for 24 wk during the double-blind treatment period.
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
4.8%
17/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
1.4%
5/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
6.3%
8/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
2.3%
3/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
1.8%
2/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
7.1%
8/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Infections and infestations
Urinary tract infection
|
4.5%
16/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
6.5%
23/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
7.9%
10/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
4.7%
6/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
9.8%
11/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
6.2%
7/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
|
Investigations
Lipase increased
|
4.3%
15/352 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
2.8%
10/354 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
3.2%
4/126 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
0.78%
1/128 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
6.2%
7/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
6.2%
7/112 • From first drug administration until 7 days after the last drug administration, up to 212 days (OL treatment period) and 205 days (double blind treatment period).
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER