STAKT - Drug supply

1. 18th March 2013 Investigator Meeting STAKT - Drug supply

2. Clinical Trial Supplies

3. Clinical Trial Supplies for STAKT

4. Kit Design: IWRS Stage 1 • Kit design – 480mg / placebo twice daily dosing for 4.5 days Patient takes 6 capsules in the morning and 6 capsules in the evening = 2 bottles per patient for the 4.5 days (6 capsules overage per patient) 30 x 80mg / placebo Bottles are labelled with a 2 panel label consisting of main body of text plus a peel off portion to be attached to the CRF. Bottle size: 75cc

5. Kit Distribution – Stage 1 • 4 bottles sent to each of the 15 sites expected to recruit in Stage 1 (as always need both treatment arms available for next pt to be recruited) • Each time bottles are dispensed it will automatically be replaced by the IWR system • As treatment allocation is unpredictable at sites (e.g. a site may only ever recruit one patient), some bottles may never get used • There are no re-supplies required for these patients, therefore new bottles shipped are for new patients.

6. Kit design – 360mg / 240mg / placebo twice daily dosing for 4.5 days Kit design: IWRS Stage 2 Patient takes 5 capsules in the morning (1 capsule from each bottle) and 5 capsules in the evening (1 capsule from each bottle) for 4.5 days (2 caps overage per bottle): Bottle 1 10 x 80mg / placebo Bottle 2 10 x 80mg / placebo Bottle 3 10 x 80mg / placebo Bottle 4 10 x 80mg / placebo Bottle 5 10 x 40mg / placebo Regardless of the dose level the patient has been allocated to, to maintain the blind, all patients will take 10 capsules per day, they may be all active, all placebo or a combination of both.

7. Kit design – 360mg / 240mg / placebo twice daily dosing for 4.5 days Kit design: IWRS Stage 2 • Each patient kit will contain 5 bottles to cover the 4.5 days of dosing required: Bottle 1 – white label Bottle 2 – White label Bottle 4 – While label Bottle 3 – White label Bottle 5 – purple label Labelled and sealed kit Bottles are labelled with a single panel label and the carton label is a 2 panel label consisting of main body of text plus a peel off portion to be attached to the CRF Card, cell filler Kit Size: 150x105x90mm

8. IWRS Kit distribution: Stage 2 Upon site activation 3 kits will be shipped to a site Each time a patient kit is dispensed it will automatically be replaced by the IWR system (single kit shipments) As treatment allocation is unpredictable at sites (e.g. a site may only ever recruit one or two patients), some kits may never get used.

9. Site and user Spreadsheet: • Prior to Go-Live of the system, a site and user spreadsheet will need to be filled out. This document can be updated on an on going basis through the life of the study, it contains information relating to the sites and users for the study. • Each user for that site will receive an email with there account details • 7-digit account number • A separate email will be sent containing password information • Temporary password – which will need to be changed the first time you log in to the system. • Passwords expiry every 90 days Upon site activation the following documents will be sent out to the site: • Site user guide • This document contains information on how to use the system along with helpdesk contact numbers for the study. IWRS – provided by Cenduit

10. General IWRS information: C.I.R.T. = Cenduit Interactive Response Technology for Clinical Trials I.W.R.S. = Interactive Web Response System that provides the C.I.R.T. interface via the internet. C.I.R.T Functionality Subject Management • Randomisation and un-blinding Drug Supply Tracking • Site inventory and resupply Reporting • Patient, Inventory and End User details

11. Account Set Up www.cenduitsolutions.com Remember: Do not share your log in details After 3 incorrect entries, you will be required to reset your password on the fourth attempt 7-digit Account Number 8-digit Password Temporary Password New Password

12. C.I.R.T Main menu • Select the Protocol Number from the “Studies” menu option. • Select a Form from the “Forms” menu option. • Forms for Site Users • Site Shipment Confirmation • Patient Randomisation • Discontinuation/Completion • Patient Un-blinding by Site

13. General IWRS information: Sites will be activated by the lead site once all approvals and contracts are in place Site activation to be performed through the IWRS Once a site is activated an IMP order will be automatically raised and shipped to site within 5 working days. On receipt of a shipment, the site must update the IWRS confirming receipt before the IMP can be dispensed to patients. Once a patient has been randomised they will not require any further dispensing visits in the IWRS however once the patient has completed treatment or is discontinued prior to completion they must be discontinued in the IWRS.

14. General IWRS information cont: Once all patients have entered into Stage 1, the IWRS will need to switch off Stage 1 and switch stage 2 on for recruitment. Un-blinding will be carried out by Peter Fox and his team, this will be done through the IWR system Un-blinding should only be carried out for a medical emergency If you have issues using the system please contact the Cenduit helpdesk on: • Toll-free helpdesk 00800 1012 1960 • Email address: global.helpdesk@cenduit.com • Website: WWW.cenduitsolutions.com • Or contact Kerry Tingley on 01403 212623 – during office hours • Email address: kerry.tingley@thermofisher.com

15. Randomisation • Patient randomisation: • A site user randomises a patient through the IWRS using the randomisation form. • The following information will need to be inputted into the system to create the randomisation: • Select site number • Patient initials (3 digits required e.g. JAC or J-C) • Patients DOB • A randomisation response will be generated providing the patient number and kit number to be dispensed, sites must keep confirmations as source documentation. • Patient number will consist of: 3 letter site code followed by 3 digit system generated number, sequential by site e.g. ABC001

16. Patient Discontinuation/Completion • Once a patient has completed their treatment cycle, site users will need to access the IRT and discontinue/complete the patient in the system. • Required Information: • Site Number • Patient Number • Patient’s Date of Birth • Patient Status? • Early Discontinuation • Completion of Study • Early Discontinuation or Completion Date

17. Destruction of IP and accountability Sites are to destroy expired and unused medication for both Stage 1 and Stage 2 The lead site will confirm to each site when destruction can be carried out At the end of the trial a full accountability of drug products must be carried out and certificates of delivery and returns must be signed and copies retained in the investigator files.

18. Any Questions:

19. Thank you