WHAT

ABOUT

THE IM

P?

IMP

HANDLING F

OR THE T

RIAL S

ITE P

HARMACY

CONTENTS

Study outline and objectivesWhat are the IMPs?How are they being used?Where do they come from?How do we get them?What do we do with them? Advice to participants?What about unblinding?What questions do you have?

STUDY OUTLINE AND OBJECTIVES

OUTLINE:

PHASE 3, RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED 2X2 FACTORIAL TRIAL

PRIMARY OBJECTIVE

To determine whether the naturally-occurring omega -3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) prevents colorectal adenomas, either alone or in combination with aspirin

SECONDARY OBJECTIVE

To assess the tolerability and safety of EPA in the free fatty acid form (EPA-FFA) alone, and in combination with aspirin, in elderly (60-73) years participants

1o endpoint – number of patients with a polyp(s) at one year

2o endpoints – polyp number, ‘advanced’ lesions, location, AEs

STUDY OUTLINE AND OBJECTIVES

INCLUSION:

60-73 Yrs BCSP Patients

Classified as High Risk following a Single Clearance Colonoscopy within past 4 weeks

nb high risk = 5 or more small adenomas or 3 or more adenomas with at least one being ≥10mm diameter

STUDY OUTLINE AND OBJECTIVESEXCLUSION CRITERIA: main ones listed here (see protocol for extensive list)

Need for a repeat colonoscopy of flexible sigmoidoscopy within a 3 month windowMalignant change in an adenoma requiring colorectal cancer MDT managementRegular (>3 doses/week) prescribed or OTC aspirin or prescribed or OTC non-aspirin NSAID useAspirin intolerance, hypersensitivity including aspirin-sensitive asthmaActive peptic ulcer disease within past 3 months or any previous peptic ulcer (not on PPI therapy)Fish or seafood allergyCurrent or planned regular(>3 doses/week) use of fish oil supplementsKnown clinical diagnosis or gene carrier of a hereditary CRC predisposition,(Familial Adenomatous Polyposis) or Hereditary Non Polyposis Colorectal CancerPrevious or newly diagnosed Inflammatory Bowel Disease or colorectal resectionKnown bleeding diathesis or concomitant warfarin therapy or any other anti-coagulant or anti-platelet therapySevere liver impairmentSevere renal failure (creatinine clearance <10ml/min)Current Methotrexate use at a weekly dose of 15 mg or moreInvolved in another interventional clinical trialFailure to give Informed Consent

WHAT ARE THE IMPS?Eicosapentaenoic acid in free fatty acid form (EPA-FFA) • a Fish Oil• naturally-occurring, ω-3 PUFA • provided in gastro-resistant capsules of 500mg designed to release

the contents of the capsules in the small intestine to reduce GI side effects and enable improved absorption• principal undesirable effects are expressed through the

gastrointestinal tract with diarrhoea, abdominal pain, nausea and vomiting• These are normally relatively mild in severity and can be minimised

or removed by dosing with food or dose reduction to 1g daily• EPA-FFA has not yet received marketing approval

EPA-FFA placebo consists of gastro-resistant capsules of capric and capryllic acid triglycerides

WHAT ARE THE IMPS?

Aspirin (acetylsalicylic acid) • supplied as enteric-coated 300mg tablets • see aspirin SPC in Pharmacy File for additional information • Aspirin EC 300mg tablets have marketing approval in the

EU

Aspirin placebo consists of the same excipients as in the active formulation of the drug minus the active ingredient.

HOW ARE THEY BEING USED? - DOSES

Two 500mg gastro-resistant capsules of EPA-FFA (or placebo) will be taken orally twice daily with food giving a total daily dose of 2g.

One 300mg enteric-coated aspirin tablet (or placebo) will be taken orally once a day with food.

The Trial treatment is taken daily from the date randomisation to the day before the surveillance colonoscopy, between 350-360 days.

The Trial treatment will not be available to the patients via the seAFOod Polyp Prevention Trial team when they have finished the Trial.

 

HOW ARE THEY BEING USED - DOSE MODIFICATIONS

Doses of EPA-FFA can be modified if side-effects occur which the Investigator suspects to be related to EPA-FFA• Dose modifications of EPA-FFA are advised by the SSP during

clinic or telephone visits following a defined flow chart• Dose modification are be recorded by the SSP in the medical

notes and adverse event section of the CRF • Dose modification of EPA-FFA does not alter the number of

capsules dispensed for a trial participant

Aspirin dose cannot be modified

WHERE DO THEY COME FROM?

Gastro-resistant Eicosapentaenoic Acid in free fatty acid form (EPA-FFA) 500mg capsules and matching placebo are supplied in bulk by SLA Pharma AG.

Aspirin 300mg E/C tablets and matching placebo are supplied in bulk by Bayer-Schering Pharma AG.

Packaging, labelling and release of blinded trial treatment containers, is carried out by Stockport Pharmaceuticals, Stepping Hill Hospital.

Supplies are delivered to the study sites from Stockport Pharmaceuticals, Stepping Hill Hospital.

HOW DO WE GET THEM?

Initial supply and resupply from Stockport Pharmaceuticals is at the request of the Trial Manager.

IMPs are supplied in outer boxes of 32 containers consisting of:

20 cartons of 150 x capsules EPA-FFA 500mg or placebo and 12 bottles of 62 Aspirin 300mg E/C or placebo tablets.

 IMPs deliveries must be booked into the on-line stock control system without delay

https://ctu4.nottingham.ac.uk/0921_stock/login.asp

Issues concerning stock levels should be reported to the Trial Manager as soon as possible.

WHAT DO WE DO WITH THEM?

Storage

below 25oC

report temperature excursions to the co-ordinating centre as soon as possible

Documentation

Complete

IMP Inventories and

Participant IMP Accountability Document

PRESCRIBING AND DISPENSING

• Prescription is generated from the web-based randomisation system and completed by the prescribing physicianNote: EPA-FFA is a fish oil and allergy to fish oil is part of the

exclusion criteria.• It defines which container numbers should be dispensed

for the participant.• The container numbers specified will have been

delivered to your hospital

• Confirm local logistics regarding prescribing and dispensing

Dispensing is at week 0 and week 25Each participant has 5 packs of these at each dispensing(EPA-FFA 500mg or Placebo capsules 150 capsules per container)

And 3 packs of theseat each dispensing(Aspirin 300mg E/C or Placebo 62 tablets per container)

Container Number

Complete these boxes:

Participant IDVisit Number

Dispensing DateParticipant Name

The IMP Label looks like this:

ADVICE TO PARTICIPANTS?

It would be helpful if Pharmacy could remind the participants to:

•Complete one pack before starting the next• Take both the capsules and the tablets with food•Do not take aspirin containing products•Do not take Fish oil/omega 3 supplements

RETURNS

There is no requirement for Pharmacy to count returns except for destruction

Participant returns are counted in Clinic and recorded on the CRF

Returns should be collected in Pharmacy and

• date returned recorded on Participant IMP Accountability Log• stored until authorised to destroy by Sponsor

WHAT ABOUT UNBLINDING?

“For the majority of cases, unblinding will not be required because there is no antidote to the investigational treatments, and the medical care and usually the management of the patient would not be any different even if the treatment group assignment of the patient were known.”

  Protocol

UNBLINDING PROCEDURE

• Local pharmacy contact(s) will have access to the emergency unblinding web-based system during office hours should it be required in a Medical Emergencyhttps://ctu4.nottingham.ac.uk/0921_unblind/login.asp

• Leeds Pharmacy are providing emergency blind breaks outside office hours• Contact details are in the pharmacy file

If it not a medical emergency refer the person requesting unblinding to the local PI

 

PHARMACY FILE

Your Pharmacy file contains further information

and

Contact details

Please complete the site specific information on the contact details in section 1.

WHAT QUESTIONS DO YOU HAVE?