1. StrokeNet NCC Central Pharmacy
University of Cincinnati
Holmes Hospital Room 1209
200 Albert Sabin Way ML 0405
Cincinnati, OH
Phone:
Fax:
Zachariah Durant PharmD
Lindsay Vandergriff CPhT II
Brittany Gebelt CPhT II
Hours of Operation: Monday-Friday 8:30am-5:00pm

2. Table of Contents MOST Study Update Shipping Study Drug Request
Receipt
Temperature Monitoring
Drug Accountability
Kit components
Compounding/Dispensing
Expiration/Destruction

3. MOST Study Updates Original Design Updated Design Double-blinded
Blinded kits
3 kits with 3 identical blinded premade vials
Separate vials for bolus (vial 1), 0-2 hour infusion (vial 2), and 2-12 hour infusion (vial 3)
No compounding required
Drug vials pre-labeled for study
All 3 arms titrated
Single-blinded (Subject only)
Unblinded kits
3 kits with unblinded manufacturer products
Infusion 1 (100 mL vial) used for bolus & 0-2 hour infusion & Infusion 2 (250 mL bag) for hour infusion
Argatroban kit requires compounding
CPS required to label infusion 1 & 2 for blinding
Only argatroban arm titrated

4. Study Drug Shipping Uploading Institutional Pharmacy License in WebDCU™
WebDCU™>Regulatory Documents>Site Reg Doc Submission

5. Study Drug Shipping Adding Drug Shipping Address into WebDCU™
Institutional pharmacy license address and drug shipping address must match.
If the addresses do not match, please notify the StrokeNet NCC Project Manager, Dana Acklin Winfrey, or the StrokeNet NCC Central Pharmacy

6. Study Drug Shipping
No shipments will take place, unless absolutely necessary, for receipt on Saturday, Sunday or holidays
StrokeNet NCC Central Pharmacy Hours: M-F 8:30 am – 5:00 pm EST.
UPS® will send an with a tracking number to the CPS to track shipments.
CPSs can add a group pharmacy to receive UPS® tracking s by ing the StrokeNet NCC Central Pharmacy
UPS® tracking website:
Study drug will be shipped with a USB temperature logger, cold packs, and enough insulation to maintain a temperature range of 2-8°C ( °F) for at least 24 hours.

7. Study Drug Packaging and Packing Slip
Study Drug Kit Box
Insulated Shipping Container .

8. Study Drug Requests
WebDCU™ study drug shipment requests will automatically be sent to the StrokeNet NCC Central Pharmacy when:
Sites that are released to enroll
Subjects are randomized
Study drug is damaged/expired
Drug Request will be sent to the NCC Central Pharmacy 14 days prior to kit expiration
CPSs will have 3 study drug kits in stock initially
CPSs will have 1 kit for each study arm
CPS inventory may increase due to site enrollment during the trial

9. Study Drug Receipt
Upon receipt of the drug shipment, the CPS will verify the receipt of the study drug kit(s) against the packing slip
The CPS will review the temperature data from the logger and confirm that the study drug did not experience any temperature excursions in transit
See slide 12 & 13 for how to use the USB temperature data logger
If NO temperature excursions or discrepancies are identified, the CPS will confirm receipt of all study drug kits in WebDCU™
Drug Tracking>Drug Receiving
If there is a temperature excursion or discrepancy please contact the LTC, Iris Deeds at

10. Study Drug Receipt
Study drug kits are unavailable for dispensing until received into WebDCU™
Kits will have an unique verification code on the kit label used to receive inventory into WebDCU
If study drug kit(s) are not received into WebDCU™ within 2 days of shipment, the CPS will receive an automated notification prompting them to receive the study drug kit(s) in WebDCU™

11. Study Drug Receipt

12. Study Drug Receipt USB Temperature Data Logger
Upon arrival of the shipment, the CPS will review the temperature data from the logger and confirm that the study drug did not experience any temperature excursions in transit
If a temperature excursion is documented by the temperature data logger contact the Lead Trial Coordinator, Iris Deeds, before receiving inventory in WebDCU™
If the data logger shows a red flashing LED prior to the CPS stopping the data logger, an alarm has been triggered which may indicate a potential temperature excursion in transit

13. Study Drug Receipt USB Temperature Data Logger
The CPS will print and store the temperature data log in the CPS’s MOST trial binder where it will be reviewed during monitoring visits.
Once the data has been retrieved from the logger and the temperature curve is printed, the temperature logger can be disposed of per the institution’s policy.

14. Storage Temperature Monitoring
Study drug kits should be stored refrigerated between 2-8°C ( °F)
Eptifibatide is required to be stored under USP refrigeration guidelines
Argatroban and sodium chloride 0.9% can be stored refrigerated per USP <659>
Study drug should be protected from excessive exposure to light.
Storage areas must have a temperature monitoring system
CPSs may use their own institution-specific temperature monitoring log to document temperature readings if such temperature log is deemed equivalent to the MOST Temperature Accountability Log
Sample temperature monitoring logs will be provided and available in WebDCU™
Toolbox>Project Documents

15. Temperature Excursions
A temperature excursion can occur during daily monitoring of the study drug storage area or during transit of the study drug
Any study drug exposed to a temperature excursion should be quarantined in the appropriate storage temperature
Any known temperature excursions should be reported to the LTC, Iris Deeds at
Submit the following documents to the LTC for temperature excursions
The Temperature Excursion Report Form (TERF) - available in WebDCU™
Toolbox>Project Documents – submit for both storage and in transit excursions
Temperature data log from USB logger for excursions in transit only

16. Temperature Excursions During Transit and Daily Monitoring
In Transit
Drug Storage
Do NOT receive the inventory into WebDCU™ and quarantine study drug at the appropriate storage temperature (2- 8°C)
Enrollment may continue because the kits are not in CPS inventory for randomization
Complete and submit the Temperature Excursion Report Form (TERF) and temperature data log from the USB data logger to the LTC
The LTC will review the forms and contact the CPS with instructions
If the study drug is deemed fit for use, the CPS should receive the kits in WebDCU™
If the study drug is deemed not fit for use, the CPS will need to receive the kits and immediately mark them as damaged in WebDCU™
Note in the comments “temperature excursion in transit damaged per LTC”
Quarantine study drug at the appropriate storage temperature (2-8°C)
Study enrollment must cease until LTC reviews the temperature excursion
Complete and submit the Drug Temperature Excursion Report Form (TERF) to the LTC
The LTC will review the forms and contact the CPS with instructions
If the study drug is deemed fit for use, the CPS can restart enrollment
If the study drug is deemed not fit for use, the CPS will mark the affected kits as damaged in in WebDCU™
Note in the comments “temperature excursion in storage damaged per LTC”

17. Study Drug Temperature Excursion Report (TERF)Form Appendix B

18. Study Drug Accountability
Each CPS is required to maintain study drug accountability records
This can be using physical paper logs (examples found in WebDCU™ Toolbox>Project Document) or via institution’s electronic inventory system
Additional internal recordkeeping documenting drug receipt and distribution of study drug may be required per CPS institutional policy

19. Study Drug Accountability Logs
Appendix D
SAMPLE Study Drug Inventory and Dispensing Log
Appendix E
SAMPLE Study Subject Drug Dispensing Log

20. Study Drug & Drug Kits
Each CPS will receive 3 study drug kits initially
Kits must be stored refrigerated between 2-8°C ( °F)
Eptifibatide requires refrigerated storage
Argatroban and placebo can be stored refrigerated per USP <659>
Kits will arrive unblinded to the CPS pharmacy.
Generally, a maximum of 3 kits will be kept at each CPS
Based on enrollment the maximum number of kits at a CPS may increase
The kits will be labeled and tamper evident sealed
It is recommended not to break the tamper evident seal until the kit is dispensed
If the CPS has a policy to open kits, have a local SOP document available that ensures integrity of the kit and kit components for monitoring visits .

21. Study Drug Kit Labels
Each kit label will identify the treatment arm and components of each kit
Argatroban Kit
Eptifibatide Kit
Placebo Kit

22. Study Drug Kits & Kit Components
Each study drug kit box will be 8”x 8”x 3” by size containing the following kit components:
Components inside of the kit will have barcode labels specific to inventory management from the StrokeNet Central Pharmacy.
Argatroban Kit
2- argatroban 250mg/2.5mL vial
1- sodium chloride 0.9% 100mL glass vial
1- sodium chloride 0.9% 250mL bag
1- vial hanger for 100mL glass vial
1- argatroban compounding card
Eptifibatide Kit
1- eptifibatide 75mg/100mL with attached vial hanger
1- sodium chloride 0.9% 250mL bag
Placebo Kit
1- sodium chloride 0.9% 100mL glass vial
1- sodium chloride 0.9% 250mL bag
1- vial hanger for 100mL glass vial .

23. Study Drug Kit Components
The MOST study will use commercially available marketed product.
Manufacturers of all drug kit components will change throughout the trial based on market availability
Regardless of the manufacturer the following will remain the same
Drug Concentration
Vial and Bag Volumes

24. Study Drug Kit Components
Please note that the Argatroban arm will require compounding which is covered on slides 25-30

25. Argatroban Compounding Procedures
All CPS specific protocols and local, state, and federal laws must followed while compounding study drug
Argatroban kits will contain the following:
2- argatroban 250mg/2.5mL vials
1- sodium chloride 0.9% 100mL glass vial
1- sodium chloride 0.9% 250mL bag
1- 100mL glass vial hanger
1- argatroban compounding direction card
Note: Bolus dose should be given within 60 minutes of the subjects tPA bolus

26. Argatroban Compounding Procedures
Confirm proper kit selection using the Study Drug Kit ID on the MOST Randomization Verification Form
Retrieve 1 vial of 250mg/2.5 mL argatroban and the 100 mL normal saline glass vial

27. Argatroban Compounding Procedures
Following all hospital specific protocols and applicable laws aseptically prepare argatroban Infusion 1 (bolus and 0-2 hour infusion)
a) Remove the cap from each vial and swab septum with an isopropyl alcohol swab
b) Withdraw 1 mL (100 mg) from the 250mg/2.5mL argatroban and inject it into the 100mL normal saline glass vial
c) Label the resultant vial with a subject-specific study label that covers the entirety of the manufacturer’s original label and all exposed glass should be covered as much as possible
2” x 3” label

28. Argatroban Compounding Procedures
Verify product and label then dispense immediately
This vial will be used for the bolus and the 0-2 hour infusion (Infusion 1)
Study drug bolus should be administered within 60 minutes of tPA bolus dose
Follow individual CPS standard operating procedures when dispensing and administering the study drug bolus dose.
CPS pharmacy or qualified MOST staff can draw the weight based bolus dose or bolus can be administered via the IV pump
Within 1 hour of dispensing the initial infusion, please prepare and dispense infusion 2
If time allows, Infusion 1 and 2 can be compounded and dispensed simultaneously

29. Argatroban Compounding Procedures
Following all hospital specific protocols and applicable laws aseptically prepare argatroban Infusion 2 (2-12 hour infusion)
a) Retrieve the second 250mg/2.5mL argatroban vial and 250 mL 0.9% sodium chloride bag
b) Remove the cap from the argatroban vial and swab septum with an isopropyl alcohol swab
c) Swab the 250 mL 0.9% sodium chloride bag port using an isopropyl alcohol swab
d) Aseptically withdraw 2.5 mL (250 mg) from the 250mg/2.5mL argatroban vial and inject it into the 250mL normal saline bag
Label Infusion 2 with a subject-specific study label (example on next slide)
The label for infusion 2 does not have to cover the entire manufacturer’s label
All arms of the study will use a similar 250mL normal saline bag as a base for infusion 2

30. Argatroban Compounding Procedures
Verify product and label then dispense Infusion 2 immediately
Infusion 2 must be at the subject’s bedside within 2 hours from the time study drug bolus is administered to avoid treatment gaps 
Time permitting, Infusion 1 and 2 may be compounded simultaneously
Front
Back

31. Eptifibatide and Placebo Kit Components
Eptifibatide kits will contain the following:
1- eptifibatide 75mg/100mL (manufacturers supply an attach vial hanger)
1- sodium chloride 0.9% 250mL bag
Placebo kits will contain the following:
1- sodium chloride 0.9% 100mL glass vial
1- 100mL glass vial hanger
Note: Bolus dose should be given within 60 minutes of the subjects tPA bolus .

32. Eptifibatide and Placebo Kit Components
Confirm proper kit selection using the Study Drug Kit ID on the MOST Randomization Verification Form
Retrieve 75 mg/100 mL eptifibatide or 0.9% sodium chloride 100 mL glass vial and label with a subject- specific study label that covers the entirety of the manufacturer’s original label and as much of the exposed glass as possible
The manufacturers label must be completely covered and all exposed glass should be covered as much as possible (example in argatroban directions)
This vial will be used for the bolus and the 0-2 hour infusion (infusion 1)
Please follow individual CPS standard operating procedures for dispensing and administering the bolus dose

33. Eptifibatide and Placebo Kit Components
Verify product and label then dispense immediately
Study Drug bolus should be administered within 60 minutes of tPA bolus dose
Within 1 hour obtain the normal saline 250mL bag for the hour infusion (Infusion 2) and label it with a subject- specific study label
The label for Infusion 2 does not have to cover the entire manufacturer’s label
All arms of the study will use an identical 250mL normal saline bag as the base for infusion 2
Verify product and label then dispense the normal saline bag
Time permitting, Infusion 1 and 2 may be dispensed simultaneously
Infusion 2 must be at the subjects bedside within 2 hours of study drug bolus administration to avoid treatment gaps

34. Study Drug Kit Expiration
Study drug kit expiration is determined by the individual kit components
WebDCU™ automatically generates the kit expiration to correspond to the earliest expiration of the kit components
Study drug kit expiration dates are available in 2 locations:
MOST study drug packing slip
WebDCU™ (Drug Tracking Tab>Drug Removing from Inventory)
Will NOT be on study drug kit labels

35. Study Drug Kit Expiration

36. Study Drug Destruction & Return
CPSs should follow their institutional policy regarding drug destruction protocol
The StrokeNet NCC Central pharmacy can accept returns for destruction if a CPSs institutional policy requires returning the damage or expired drug kits
Follow the steps below to return study drug to the StrokeNet NCC Central Pharmacy
Study Drug Return Form must be completed and returned with the shipment
Returns should be addressed and shipped to the StrokeNet NCC Central Pharmacy via the CPSs preferred postal carrier
Return cost will be at the expense of the CPS
Package tracking information must be provided to StrokeNet NCC Central Pharmacy via
Temperature monitoring is NOT required for returns
Subject identifiers must be removed from returns

37. Available on WebDCU™ - Toolbox>Project Documents
Study Drug Return Form
Available on WebDCU™ - Toolbox>Project Documents

38. Questions Please visit WebDCU™ for a copy of the MOST Pharmacy Manual
Toolbox>Project Documents