CIOMS FORM

SUSPECT ADVERSE REACTION REPORT

MFR. CONTROL No. : 2014-BI-58743BI(0)
I.REACTION INFORMATION
1.PATIENT INITIALS

PRIVACY
95 Kg
168.5 cm

1a.COUNTRY

2.DATE OF BIRTH
DA
MO

BR

09

AUG

YR

2a. AGE
YRS

3. SEX

1952 62

4.-6. REACTION ONSET

DA
MO
YR

15

NOV

8.-12. CHECK ALL

APPROPRIATE
TO ADVERSE
2014
REACTION

7.+13. DESCRIBE REACTION(S) (include relevant test/lab data)

PATIENT DIED

CONGESTIVE HEART FAILURE (Cardiac failure congestive) [v.17.1] - Not Yet

Recovered
Case level outcome :Not Yet Recovered

LIFE THREATENING
INVOLVED OR

Information was received from an investigator in Brazil concerning patient number

61796, center number 55016, a 62 year-old male patient with type 2 diabetes
mellitus who was enrolled in the clinical trial 1245.25, a Phase 3, multicentre,
international, randomised, parallel group, double blind cardiovascular safety
study of BI 10773 (10 mg and 25 mg administered orally once daily) compared to
usual care in type 2 diabetes mellitus patients with increased cardiovascular
risk. Patients will be administered BI 10773 10 mg, BI 10773 25 mg, or placebo.
The study medication was started on 18Oct2012 at 0900 hours.

PROLONGED INPATIENT
HOSPITALIZATION

INVOLVED PERSISTENCE OR
SIGNIFICANT DISABILITY
OR INCAPACITY

CONGENITAL ANOMALY
XOTHER MEDICALLY IMPORTANT
CONDITION

On 15Nov2014, the patient had mild congestive heart failure. The event was

medically significant
Cont...

II.SUSPECT DRUG(S) INFORMATION

14. SUSPECT DRUG(S) (include generic name)

Subject Unblinded :Yes

20.DID EVENT ABATE

AFTER STOPPING DRUG?

Blinded

YES
15. DAILY DOSE

16. ROUTE OF ADMINISTRATION

NO

NA

21.DID EVENT
REAPPEAR AFTER
REINTRODUCTION?

17. INDICATIONS FOR USE

YES
18. THERAPY DATES(From/To)

NO

19. THERAPY DURATION

III.CONCOMITANT DRUGS AND HISTORY

22.CONCOMITANT DRUGS AND DATES OF ADMINISTRATION (Exclude those used to treat event)

INSULIN HUMAN(INSULIN
HUMAN)(see text)(INSULIN
HUMAN)

-Feb-2013 -

formulation-injectable, dose per app

40+40 (see text)

Cont...

23. OTHER RELEVANT HISTORY

No Risk Factor Available

Concurrent Disease:
CORONARY ARTERY DISEASE (--2007 - ) (Continuing: NR)
Cont...
IV.

MANUFACTURER

24a. NAME AND ADDRESS OF MANUFACTURER

Boehringer Ingelheim

Global Pharmacovigilance

Binger Strasse 173

Ingelheim am Rhein 55216 GERMANY

EUDRACT no:2009-016178-33
24b. MFR. CONTROL NO.
Study no :1245.25
2014-BI-58743BI(0)
Center no :55016
Log No :2014-BI-58743BI
Cont...
24c. DATE RECEIVED BY
MANUFACTURER

03-DEC-2014
DATE OF THIS REPORT

15-DEC-2014

24d. REPORT SOURCE

X STUDY
LITERATURE
AUTHORITY
X HEALTH PROFESSIONAL OTHER
25a. REPORT TYPE

XINITIAL

FOLLOW UP

FINAL
Cont...

= Continuation attached sheet(s)

NA

Date : 15-DEC-2014
Page : 2 / 4

Boehringer Ingelheim
Global Pharmacovigilance
Binger Strasse 173
Ingelheim am Rhein55216
GERMANY

Continuation Sheet for CIOMS report

Mfr. Control No. : 2014-BI-58743BI(0)

Reaction Information ( Cont...)

Seq. No.
Reaction
Start Date
Duration
Event Location

:
:
:
:
:

1
CONGESTIVE HEART FAILURE (Cardiac failure congestive) [v.17.1]
15-Nov-2014
Not yet subsided
Not Reported

Describe Reaction(s)(Include relevant test/lab data) ( Cont...)

considered serious as it was medically significant. It was reported that the patient arrived on a scheduled
visit 18 (v18) in the center and informed edema on the lower limbs since 15Nov2014 which was still present.

Physical examination revealed crackles with lung bass which was a signal of the congestive heart failure. So
the patient was prescribed for the exchange of hydrochlorothiazide to furosemide 40 mg on 03Dec2014.
The patient had not yet recovered from the event congestive heart failure.
The study medication was continued.

Concomitant medications included Insulin human, Insulin regular and metformin, all three for diabetes type II
which had started since 1997, Enalapril and hydrochlorothiazide, both for hypertension which had started since
2002, Acetyl salicylic acid for prevention of ischemic heart disease, Omeprazol for epigastric pain, metoprolol
tartarate, Isosorbide and Propactinitrate, all three for ischemic heart disease, clopidogrel for worsens of

ischemic cardiopathy, ciprofibrate and Rosuvastatin, both for dyslipidemia which had started since 2000,

Fluoxetin for depression which had started since 2004. Further concomitant diseases included coronary artery
disease since 2007, peripheral artery occlusive disease since 2007 and obesity since 1980.

The investigator considers that there is a possible causal relationship between the study medication and the
event congestive heart failure.
For regulatory reporting purposes, Boehringer Ingelheim has assessed that there is a reasonable possibility of
a causal association between the event congestive heart failure and the study medication.
The following BI case ID is linked to this patient: 2012-BP-27081BP.

Concomitant drugs(Cont...)

Seq. No.
Drug
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:

1
INSULIN HUMAN(INSULIN HUMAN)(INSULIN HUMAN)
1)see text
1)SC
1)DIABETES TYPE II
1) ongoing

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

2
INSULIN REGULAR(INSULIN BOVINE)(INSULIN BOVINE)
1)formulation-injectable, dose per app 18+18, daily dose 36 (see text)
1)see text
1)SC
1)DIABETES TYPE II
1) 27-JUN-2014
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

3
ENALOPRIL(ENALAPRIL)(ENALAPRIL)
1)Dose per app: 10 and daily dose 20 (see text,2 in 1 D)
1)TA
1)PO
1)HYPERTENSION
1) --2004
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

4
ACETYL SALICYLIC ACID(ACETYLSALICYLIC ACID)(ACETYLSALICYLIC ACID)
1)Dose per app: 100 and daily dose 100 (see text,1 in 1 D)
1)TA
1)PO
1)PREVENTION ISCHEMIC HEART DISEASE
1) --2004
- (ongoing )

:
:
:
:
:
:
:

5
HYDROCHLOROTHIAZIDE(HYDROCHLOROTHIAZIDE)(HYDROCHLOROTHIAZIDE)

1)Dose per app: 25 and daily dose 25 (see text,1 in 1 D)

1)TA

1)PO
1)HYPERTENSION
1) --2004
- (ongoing

:
:

6
OMEPRAZOL(OMEPRAZOLE)(OMEPRAZOLE)

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

Seq. No.
Drug

Date : 15-DEC-2014
Page : 3 / 4

Boehringer Ingelheim
Global Pharmacovigilance
Binger Strasse 173
Ingelheim am Rhein55216
GERMANY

Continuation Sheet for CIOMS report

Mfr. Control No. : 2014-BI-58743BI(0)

Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:

1)Dose per app: 40 and daily dose 40 (see text,1 in 1 D)

1)TA
1)PO
1)EPIGASTIC PAIN
1) 15-AUG-2012
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

7
METOPROLOL TARTRATE(METOPROLOL TARTRATE)(METOPROLOL TARTRATE)
1)Dose per app: 100 and daily dose 200 (see text,2 in 1 D)
1)TA
1)PO
1)ISCHEMIC HEART DISEASE
1) 27-OCT-2012
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

8
CLOPIDOGREL(CLOPIDOGREL)(CLOPIDOGREL)
1)Dose per app: 75 and daily dose 75 (see text,1 in 1 D)
1)TA
1)PO
1)WORSENS OF ISCHEMIC CARDIOPATHY
1) 27-OCT-2012
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

9
METFORMIN(METFORMIN)(METFORMIN)
1)Dose per app: 500 and daily dose 1500 (see text,3 in 1 D)
1)TA
1)PO
1)DIABELATE TYPE II
1) 08-NOV-2012
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

10
ISOSORBIDE(ISOSORBIDE DINITRATE)(ISOSORBIDE DINITRATE)
1)Dose per app: 5 and daily dose 5 (see text,1 in 1 D)
1)TA
1)SL
1)ISCHEMIC HEART DISEASE
1) 26-OCT-2012
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

11
CIPROFIBRATE(CIPROFIBRATE)(CIPROFIBRATE)
1)Dose per app: 100 and daily dose 100 (see text,1 in 1 D)
1)TA
1)PO
1)DYSLIPIDEMIA
1) 15-MAR-2014
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

12
FLUOXETIN(FLUOXETINE HYDROCHLORIDE)(FLUOXETINE HYDROCHLORIDE)
1)Dose per app: 20 and daily dose 20 (see text,1 in 1 D)
1)TA
1)PO
1)DEPRESSION
1) 27-OCT-2014
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

13
PROPACTINITRATE(PROPATYLNITRATE)(PROPATYLNITRATE)
1)Dose per app: 30 and daily dose 90 (see text,3 in 1 D)
1)TA
1)PO
1)ISCHEMIC HEART DISEASE
1) 27-JUN-2014
- (ongoing )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

:
:
:
:
:
:
:

14
ROSUVASTATINE(ROSUVASTATIN CALCIUM)(ROSUVASTATIN CALCIUM)
1)Dose
per app: 20 and daily dose 20 (see text,1 in 1 D)
1)TA
1)PO
1)DYSLIPIDEMIA
1) 27-JUN-2014
-

Date : 15-DEC-2014
Page : 4 / 4

Boehringer Ingelheim
Global Pharmacovigilance
Binger Strasse 173
Ingelheim am Rhein55216
GERMANY

Continuation Sheet for CIOMS report

Mfr. Control No. : 2014-BI-58743BI(0)

Other relevant history (Cont...)

PERIPHERAL ARTERY OCCLUSIVE DISEASE (--2007 - ) (Continuing: NR)
HYPERTENSION (--2002 - ) (Continuing: NR)
DYSLIPIDEMIA (--2000 - ) (Continuing: NR)
OBESITY (--1980 - ) (Continuing: NR)
DEPRESSION (--2004 - ) (Continuing: NR)
EPIGASTRIC PAIN (Continuing: NR)
ISCHEMIC HEART DISEASE (Continuing: NR)
WORSENS OF ISCHEMIC CARDIOPATHY (Continuing: NR)

Clinical Trial Identification ( Cont...)

Patient no
: 61796
Study identification for EUDRACT: 2009-016178-33

Additional information (continuation)

Lab Result :
Test name

Test date

PHYSICAL EXAMINATION

Test result

Normal value

Classification

see narrative

Medical Evaluation
Listing of previously submitted cases to US IND, 102,145 and 108388 for the MedDra PT, cardiac failure
congestive, as of 09Dec2014 (this listing may also include cases where the patient received comparator
rather
than BI 10773): 2010-RU-00006BP, 2014-BI-32991BI.
Based on a review of the above cases, the following common features were noted: In one case a 56 year old
female was hospitalized for CHF and was found to have anemia. The case was complicated by the concomitant
medical conditions of diabetes mellitus, arterial hypertension, pulmonary hypertension, chornic kidney
disease stage IV, diabetic nephropathy, diabetic neuropathy, and cerebrovascular disease. The second case of a
64 year old female was also complicated by worsening chronic anaemia which started in Oct2011, hypertension, a
history of congestive cardiac failure, ,atrial fibrillation and angina pectoris, all of which startedsince
2007.
In the current case, a 62 year old male patient had an episode of mild congestive heart failure after 755 days
on study medication. The patient was not hospoitalized. The case is also complicated by the concomitant
medical conditions of Diabetes melliitus, hypertension, coronary artery disease since 2007, peripheral artery
occlusive disease since 2007 and obesity since 1980.
Consideration of this report in light of the review of the previous reports does not change the current
understanding of the overall safety profile of BI 10773.