CIOMS FORM

SUSPECT ADVERSE REACTION REPORT

MFR. CONTROL No. : 2014-BI-14166BI(3)
I.REACTION INFORMATION
1.PATIENT INITIALS

RC
84 Kg
157 cm

1a.COUNTRY

2.DATE OF BIRTH
DA
MO

ZA

25

FEB

YR

2a. AGE
YRS

3. SEX

1951 63

4.-6. REACTION ONSET

DA
MO
YR

26

MAR

8.-12. CHECK ALL

APPROPRIATE
TO ADVERSE
2014
REACTION

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

PATIENT DIED

CHEST PAIN (Chest pain) [v.17.1] - Not Yet Recovered

CHEST PAIN (Chest pain) [v.17.1] - Not Yet Recovered
ABSCESS LEFT EYELID (Abscess of eyelid) [v.17.1] - Recovered
Case level outcome :Not Yet Recovered

LIFE THREATENING
XINVOLVED OR

PROLONGED INPATIENT
HOSPITALIZATION

Information was received from an investigator in South Africa concerning patient

number 62766, center number 76022, a 63 year old female patient who was enrolled
in clinical trial 1245.25, a Phase 3, multicenter, international, randomized,
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 patient's with increased cardiovascular risk. The patient's will be
administered BI 10773 10 mg, BI 10773 25 mg, or placebo.

INVOLVED PERSISTENCE OR
SIGNIFICANT DISABILITY
OR INCAPACITY

CONGENITAL ANOMALY
OTHER MEDICALLY IMPORTANT

The study medication was started on an unknown date and stopped on an unknown
date. The study medication was again started on 16Sep2014 at 0945.

CONDITION

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)

LASIX(FUROSEMIDE)(NR)(FUROSEMIDE)
DILATREND(CARVEDILOL)(NR)(CARVEDILOL)

14-JAN-2003 -

80 mg (40 mg,2 in 1
D)
12.5 mg (12.5 mg,1
in 1 D)

14-JAN-2003 -

Cont...

23. OTHER RELEVANT HISTORY

No Risk Factor Available

Past Disease:
CORONARY ARTERY BYPASS GRAFT (-Apr-2010 - )
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-14166BI(3)
Center no :76022
Log No :2014-BI-14166BI
Cont...
24c. DATE RECEIVED BY
MANUFACTURER

25-NOV-2014
DATE OF THIS REPORT

05-DEC-2014

24d. REPORT SOURCE

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

INITIAL

X FOLLOW UP

FINAL
Cont...

= Continuation attached sheet(s)

NA

Date : 05-DEC-2014
Page : 2 / 3

Boehringer Ingelheim
Global Pharmacovigilance
Binger Strasse 173
Ingelheim am Rhein55216
GERMANY

Continuation Sheet for CIOMS report

Mfr. Control No. : 2014-BI-14166BI(3)

Reaction Information ( Cont...)

Seq. No.
Reaction
Start Date
Duration
Event Location

:
:
:
:
:

1
CHEST PAIN (Chest pain) [v.17.1]
26-Mar-2014;10:00
Not yet subsided
Hospital

Seq. No.
Reaction
Start Date
Duration
Event Location

:
:
:
:
:

2
CHEST PAIN (Chest pain) [v.17.1]
18-Nov-2014
Not yet subsided
Hospital

Seq. No.
Reaction
Start Date
Stop Date
Duration
Event Location

:
:
:
:
:
:

3
ABSCESS LEFT EYELID (Abscess of eyelid) [v.17.1]
18-Nov-2014
22-Nov-2014
5 D
Hospital

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

On 26Mar2014 at 1000, the patient experienced moderate chest pain first episode which was considered serious
due to required hospitalization. It was reported that the patient had been experiencing retrosternal chest pain
since 26Mar2014 and was hospitalized for further investigation and treatment. Therapy for the event was not
reported. The patient had not yet recovered from chest pain.
On 18Nov2014, the patient developed severe chest pain second episode which was considered serious due to
prolonged hospitalization and severe abscess left eyelid which were considered serious due to required
hospitalization. The event chest pain was treated with Paracetamol 1g 8 hourly and Xefo 8mg twice daily (BD).
The patient was admitted by her ophthalmologist for an abscess of the eyelid and chest pain. The patient was
asked for to evaluate the chest pain. Clinically she complained of left chest pain sharp for one month. The
examination revealed left breast tenderness. The ultrasound and mammogram showed a suspicious lesion
1.84x1.35x1.47cm 4cm from the nipple at 6-7 o clock. On 18Nov2014, the event abscess of the left upper eyelid

was incised and drained by the ophthalmologist. On 21Nov2014, a fine needle aspiration biopsy was performed. On
22Nov2014, the patient recovered from the event abscess left eyelid and discharged from the hospital and was
awaiting for histology. The patient had not yet recovered from the event chest pain second episode.

The site had confirmed that the chest pain was not an outcome event. The chest pain was non cardiac and they
were waiting for the biopsy result to confirm the diagnosis.

The study medication was continued.

Concomitant medications included Lasix and Dilatrend both for ischaemic heart disease which started in Sep2002,
Aprovel for hypertension, Aspavor for ischaemic heart disease and hyperlipidemia and Ecotrin for ischaemic
heart disease and as an anticoagulant. Further concomitant diseases were not reported. Past diseases included
coronary artery bypass graft in April2010 and ischemic heart disease in Sep2002.
The investigator considers that there is not a causal relationship between the study medication and the events
chest pain first episode and abscess left eyelid.
The investigator considers that there is a causal relationship between the study medication and the event chest
pain second episode.
For regulatory reporting purposes, Boehringer Ingelheim has assessed
of a causal association between the events chest pain first episode,
medication.
For regulatory reporting purposes, Boehringer-Ingelheim has assessed
a causal association between the event chest pain second episode and

that there is not a reasonable possibility

abscess left eyelid and the study
that there is a reasonable possibility of
the study medication

Tracking of Changes:
19Nov2014: Follow up information was received. Updated event, suspect drug, causality, medication and
narrative.
25Nov2014: Follow up information received. Updated concomitant medication, event, causality, lab and case
narrative.
03Dec2014: Updated narrative.

Concomitant drugs(Cont...)
Seq. No.
Drug
Form of Admin.
Route of Admin.
Indication for use
Therapy Dates/Duration

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

Seq. No.

:
:
:
:
:
:

1
LASIX(FUROSEMIDE)(FUROSEMIDE)
1)NR
1)PO
1)ISCHAEMIC HEART DISEASE
1) cont.

:
:
:
:
:
:

2
DILATREND(CARVEDILOL)(CARVEDILOL)

1)NR
1)PO
1)ISCHAEMIC
HEART DISEASE

1) cont.

Date : 05-DEC-2014
Page : 3 / 3

Boehringer Ingelheim
Global Pharmacovigilance
Binger Strasse 173
Ingelheim am Rhein55216
GERMANY

Continuation Sheet for CIOMS report

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

:
:
:
:
:
:

Mfr. Control No. : 2014-BI-14166BI(3)

APROVEL(IRBESARTAN)(IRBESARTAN)
1)300 mg (300 mg,1 in 1 D)
1)NR
1)PO
1)HYPERTENSION
1) 25-APR-2000
- (cont. )

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use

:
:
:
:
:
:

Therapy Dates/Duration

Seq. No.
Drug
Daily Dose
Form of Admin.
Route of Admin.
Indication for use

:
:
:
:
:
:

Therapy Dates/Duration

4
ASPAVOR(ATORVASTATIN CALCIUM)(ATORVASTATIN CALCIUM)
1)40 mg (40 mg,1 in 1 D)
1)NR
1)PO
1)HYPERLIPIDEMIA
2)ISCHAEMIC HEART DISEASE
1) 15-JAN-2011
- (cont. )

5
ECOTRIN(ACETYLSALICYLIC ACID)(ACETYLSALICYLIC ACID)
1)81 mg (81 mg,1 in 1 D)
1)NR
1)PO
1)ANTICOAGULANT
2)ISCHAEMIC HEART DISEASE
1) 07-APR-2005
- (cont. )

Other relevant history (Cont...)

ISCHEMIC HEART DISEASE (-Sep-2002 - )
Concurrent Disease:
HYPERTENSION (Continuing: NR)
HYPERLIPIDEMIA (Continuing: NR)

Clinical Trial Identification ( Cont...)

Patient no
: 62766
Study identification for EUDRACT: 2009-016178-33

Additional information (continuation)

Lab Result :
Test name

BIOPSY
EXAMINATION
MAMMOGRAM
ULTRASOUND

Test date

21-Nov-2014

Test result

Normal value

Classification

result awaited
see narrative
see narrative
see narrative

Medical Evaluation
Listing of previously submitted cases to US IND, 102,145 and 108388 for the MedDRA PT chest pain, as of
01Dec2014 (this listing may also include cases where the patient received comparator rather than BI 10773):
include 2012-RD-00299EU.
Based on a review of the above case, the following was noted: The case involved a patient complaining of chest
pain, which was determined to be non-cardiac in origin with a downgrading of the case to not related.
In the curent case, a 63 year old female complained of left chest pain sharp for one month. The examination
revealed left breast tenderness. The ultrasound and mammogram showed a suspicious lesion 1.84x1.35x1.47cm 4cm
from the nipple at 6-7 o clock. Pathology results are pending.
Consideration of this report in light of the information currently provided does not change the current
understanding of the overall safety profile of BI 10773.