1 US Investigator Meeting DIAS-4, Chicago, July 2011

DIAS 3&4Investigational Medicinal Products (IMP)

2US Investigator Meeting DIAS-4, Chicago, July 2011

Agenda

IMP formulation IMP shipment and storageDose Reconstitution of IMP IMP Accountability

3US Investigator Meeting DIAS-4, Chicago, July 2011

IMP Formulation

Supplied in vials containing white lyophilised powder for solution for injection

Contains either 9 mg desmoteplase or placebo

Reconstituted with 10 ml of WFI

Each patient will receive:90 μg/kg desmoteplase or placeboSingle IV bolus injection over 1-2 minutes

4US Investigator Meeting DIAS-4, Chicago, July 2011

This is how IMP looks!

•The initial supply of medication will consist of 2 packs.

•Don’t break the silver seal until it is used

150 x 113 x 58 mm

5US Investigator Meeting DIAS-4, Chicago, July 2011

IMP Storage

IMP must be stored at 2-8℃

Temperature must be monitored at least every working day and documented.

In case of temperature excursion CRA need to be notified immediately

Temperature will be monitored during transportation as well

6US Investigator Meeting DIAS-4, Chicago, July 2011

IMP Shipment

Cold Chain Shipment

Upon receipt:Check if the temperature during the transportation

was within 2-8 ℃

Acknowledge the IMP receipt by making a medication arrival call in IVRS/IWRS

7US Investigator Meeting DIAS-4, Chicago, July 2011

How to read TempTale

1. Hold down the stop button until the stop icon appears

2. No bell icon: IMP delivered within temperature rangeBell icon present: IMP did not arrive within accepted temperature limits. Wait for confirmation from Lundbeck CSC

TempTale needs to be returned to courier immediately!

8US Investigator Meeting DIAS-4, Chicago, July 2011

Randomisation

The IV/IWRS will be used for randomisation. - Screening number

- Subject’s Date Of Birth

- Subject’s NIHSS Score

- Date of Stroke Onset

- Time of Stroke Onset (24 hour clock format)

- Subject’s weight (in Kilograms)

The IV/IWRS will instruct the site in an e-mail and/or fax: - The IMP number to use

- The volume of mediciation to be administred

9US Investigator Meeting DIAS-4, Chicago, July 2011

2. Reconstitute lyophilized powder with 10 ml Water For Injection

Agitate gently until all particles of the study medication are dissolved

Reconstitution of IMP

1. Choose assigned IMP number

Check IMP number on IV/IWRS- Randomisation confirmation

Check vial and remove blue cap

Water

For Injection

10 ml

10US Investigator Meeting DIAS-4, Chicago, July 2011

Reconstitution of IMP

3. Prepare a syringe (accuracy 0,2ml) with volume of IMP as given by the IV/IWRS Randomisation confirmation

RANDOMIZATION FAX

Patient XXX

Volume: X,y ml

accuracy of 0,2 ml

4. Please flush i.v. line with 10 ml WFI or Normal Saline before and after IMP administration to avoid any interaction with infusion contents!

X,y ml

11US Investigator Meeting DIAS-4, Chicago, July 2011

IMP Inventory Form

12US Investigator Meeting DIAS-4, Chicago, July 2011

IMP Inventory Log

13US Investigator Meeting DIAS-4, Chicago, July 2011

IMP re-supply

Randomisation will trigger the IMP re-supply

After the 1st patient: 2 IMPs will be sent

After the 2nd patient: 1 IMP will be sent

14US Investigator Meeting DIAS-4, Chicago, July 2011

IMP return

Used IMP must be stored in refrigerator at 2-8 ℃ on site until the patient has had the Day 90 visit

After the patient has completed the study the IMP can be kept at ambient storage condition until it is returned

CRA to check accountability before IMP return

IMP to be returned to depot

Please contact CRA when you return IMP

15US Investigator Meeting DIAS-4, Chicago, July 2011

Thank you