Boehringer-Ingelheim POLO-AML-2 eResearchTechnology, Inc. (ERT) Centralized Digital 12-Lead ECG Services Toronto 23 February 2013 Investigator’s Meeting

ECG Recorded at site Transmitted to ERT for Analysis Results reported to the site via My Study Portal The ECG Process ECG to be checked by investigator for pathological results

General reminder When? Screening visit Before start EACH infusion of Volasertib/ Placebo Just before the end of EACH infusion of Volasertib/ Placebo EOT visit Remind: Before PK sampling or any blood sampling Recorded on ECG Machine delivered to your site by ERT Triplicate Checked locally immediately

Observations safety ECG ECG to be checked by investigator for pathological results Report any relevant change as an AE and possibly action taken related to study medication (please refer to protocol section) Print outs are signed and dated, filed as SD Once transmitted: centralized evaluation done by ERT  ECG reading report from ERT will be available on webportal Objective is evaluate relation between PK‘s and ECG‘s Record „exact“ time Use the same watch for the ECG and the PK (use the ECG clock time to document PK sampling time or make sure the watch used to document PK sampling time shows the same clock time as the ECG machine) to allow correlation of ECG and PK

Resting ECG Requirements  The subject has to be at rest in a supine position for at least 5 minutes  The subject should breathe normally  Please avoid talking to the subject during the relaxation phase  Subject should not be touched until the recording has finished  Any ambient noise should be kept to a minimum  Turn off any electrical devices which are not needed and which transforms electrical current

ERT MYSTUDYPORTAL website

 Ordering re supply (more ECG paper/electrodes) OR call or the helpdesk  View and or print ECG reports or tracings  Answering queries: site personnel receives alerting to a query => logon to the portal to resolve the query  Two Web-Based training courses available to the sites (optional): Training certificate to be printed  One is patient preparation  Second is the ELI 150 course My Study Portal – access site staff

Actions on Equipment Arrival  Check contents on arrival ELI 150 ECG machine Power Cable, Patient Cable, Telephone Cable Electrodes & ECG paper Laminated Quick Reference Guides Training CD  Plug machine in Confirm date and time (Very Important) Recommended to Power Cycle equipment on a monthly basis

 ERT recommends completing a test transmission  A test ECG will already be stored on each machine for this purpose  Sites should contact ERT customer care if Your Site  This procedure allows ERT to confirm successful ECG transmission from your site, and to assist with any issues prior to first ECG capture ERT Test Transmission – to be performed at SIV  ERT recommends completing a test transmission  A test ECG will already be stored on each machine for this purpose  Sites should contact ERT customer care if there are any problems transmitting the test ECG

Customer Care Your Primary Contact Point for ERT Questions  Machine Technical Support  Result Inquiries  Site Information Updates  Transmission Problems  Web Based Training Inquiries  Dial the toll free number for your country and press option 1 for cardiac safety assistance Dedicated Toll-Free Phone and Fax Numbers World-wide Available 24 hours a day, 7 days a week, 365 days a year Multilingual Support address:

Supplied Quick Guides

 Copies of the ERT Guides and Manuals are posted on My Study Portal  Any modified versions will also be posted here My Study Portal Quick Guides

SUBJECT NUMBER: (000001) DOB: (MM/DD/YYYY) AGE: (99) GENDER: (MALE/FEMALE) PERIOD: Cycle 1 VISIT: V1 TIMEPOINT: ECG 1 Press F6 (DONE) key after last entry Entering Patient Demographics Press F1 (ID) key to enter patient demography

 Check the LCD screen to ensure quality Recording ECGs

 Press AUTO key to record the ECG (one ECG at a time)  triplicate ECG needed  hit the auto key 3 times (interval of 2 to 3 minutes between each ECG, as per protocol ).  Press F6 (DONE) key after printing Recording ECGs

Review for Quality & Accuracy ECG Print out  Standard tracing with 10 second Lead II strip 2 copies of each ECG will print out Z-Fold Heat Sensitive Paper We recommend you take a photocopy for your permanent records or print a copy from My Study Portal Machine interpretation is given as a guide only Assessment by the investigator must be done to determine if volasertib/ placebo can be administrated or not and if relevant AE

The unit will ask “Save ECG?”  Press (F1) to Save  Press (F3) to Delete Save ECG? Save Delete Saving ECGs

 Plug the device into the phone line  Press the XMT key (Transmit key)  Press the (F1) key to Batch Transmit  Transmit everyday Transmitting ECGs

 Sites are able to respond to active queries online using My Study Portal  Access the “Electronic Query resolution” portlet  Click the pencil icon to access the query Responding to ERT Queries – My Study Portal

 The ECG Analysis Report will be provided to the investigator site via My Study Portal within 72 hours  This excludes weekends and holidays ECG Results Reporting My Study Portal ECG reports and waveforms

Site Supply Ordering  Sites can order study supplies online using My Study Portal  Click “Supply Ordering” in the Equipment and Supply Information portlet and click “New Order”  Enter the amount required and click “Continue”  To confirm the order click the checkbox, enter your login and password and click confirm order to submit the request to ERT Site Info Supplies Quantity

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