27 April 2010 Jane Fendl

Version: Final 14-Apr-2010 1

27 April 2010

Jane Fendl

MODULE G A Comparative Trial between Sun Rise Gum and Sun Set

Gum in Healthy Gum Chewing Subjects

NOTE: this presentation is just for demonstration & may not be consistent or accurate.


AGENDAPart IStudy TeamTrial TimelinesOverview of Protocol Review

Trial ProductsInclusion / Exclusion CriteriaVisit ProceduresAEs, SAEs,

Questions

Part IIInvestigational drugMonitoringQuestions


STUDY TEAM Clinician

Associate Director

Project Manager

Data Manager

Statistician

Primary Clinical Research Associate

Project Associate

Dr. Doublemint

Dr. Juicey Fruit

Jane Fendl

Dr. Jot It Down

Dr. Clinical Significance

John “Omissions” Doe

Jenny “Organized” Jones


TIMELINES

Screening: 14 Apr 2010 – 30 Apr 2010

FPFV: 01 May 2010

FPFT to LPLT: 12 weeks

LPLV: 24 Jul 2010

DBL: 08 Sep 2010

Clinical Trial Report: 07 Nov 2010


OVERVIEW OF CHEWING GUM

Sun Rise is the new formulation of the ultra long lasting gum

Sun Set is the current formulation of the ultra long lasting gum

Sun Rise◦ offers longer lasting flavor ◦ has predictable steady flavor profile that is

expected to result in a reduced rate of buying


BACKGROUND

As of today: 10 clinical trials have been conducted for Sun Rise and

Sun Set gum Includes 9 Phase 1 trials and 2 Phase 2 exploratory

trials 1000 subjects have chewed Sun Rise or Sun Set gum Data from Previous trials have shown

In single chew studies, peak flavor concentrations were observed at ~10 hours post initial chew

Elimination half-life (t½) of approximately 20 hours Generally well enjoyed (most frequently reported AEs

in the trials were headache, a common side effect in prolonged chewing and hunger )


RATIONALEThe Sun Rise formulation will be compared to the

Sun Set formulation. Both have identical formulations but the ingredients are from different campaigns as the manufacturing process has been optimized.

The current trial will test for taste equivalence between the two formulations Sun Rise (SR) and Sun Set (SS).

Achievement of taste equivalence between the two formulations will imply that the taste and chewability information obtained with Sun Rise (SR) thus far can be assumed to be identical to that with Sun Set (SS).


PROTOCOL OVERVIEW

Randomized, Single-centre, Double-blind, Two-period cross-

over trial in healthy gum chewing subjects


GENERAL TRIAL INFORMATION

Trial PopulationMales and females Age 18-55 (inclusive)Number of subjects planned to screen: Up to 100Planned number of subjects to be randomized: 80Planned number of subjects to complete the trial: 60*

VisitsScreening (-14 to -3 days)Visits 2 & 3 (13-21 days between V2 & V3)Visit 4 (7-21 days from V3)

*Replacement of dropouts and withdrawals will take place in order to ensure that 60 subjects complete the trial.


Primary objective: to test for taste equivalence between two

formulations of Sun Rise and Sunset based on AUCsr,0-10h,SD, Cmax,sr,SD, AUCss,0-10h,SD and Cmax,ss,SD.

OBJECTIVES

Secondary objectives:to compare the taste of the two

formulationsto evaluate the long term taste and

chewability of the two formulations


PRIMARY ENDPOINTS

The onset of flavor AUCsr,0-10h,SD, area under the flavor concentration-time curve from 0 to 10 hours after single strip of gum

ENDPOINTS

The onset of flavor AUCss,0-10h,SD, area under the flavor concentration-time curve from 0 to 10 hours after single strip of gum


TRIAL DESIGN Randomized, single–centre, double-blind, two period

cross over trial in healthy gum chewing subjects. Dose administration will occur at Visit 2,

randomization):Dose level of Sun Rise and Sun Set will be 1 strip of

gum Trial product will be administered as a single strip

placed into the mouth of the subject.Subjects will remain in the clinic until 12 hours

after dose administration.


TRIAL DESIGN con’t Subjects will return to the clinic at 18 hours, 24

hours, and 36 hours after dose administration for analysis.

Subjects will have a wash out period of 13-21 days before returning to the clinic for the second treatment period (Visit 3).

Second treatment period is identical to the first treatment period.

Subjects will return to the clinic for a follow-up visit 7-21 days after dosing on Visit 3.


TRIAL PRODUCTS

Sun Rise a pack of 5 strips

Sun Set a pack of 5 strips


Key Inclusion Criteria

Male or female aged 18 - 55 years (both inclusive)

Considered generally healthy upon completion of medical history, physical examination, vital signs and ECG, as judged by the Investigator

Able to chew gum for long hours and without swallowing it


Key Exclusion Criteria History of 1st degree relatives that can’t chew gum

and walk Subject who has donated any blood or plasma in

the past month or more than 500 mL within 3 months prior to screening

Use of any competing gum within 3 weeks prior to screening

Use of any nicotine gum or weight reduction gum 3 weeks prior to screening

Smoker


Withdrawal Criteria

The subject may be withdrawn from the trial at the discretion of the Investigator or the sponsor due to a safety concern of if judged non-compliant with trial procedures.

A subject must be withdrawn if the following applies: Pregnancy or intent to become pregnant Protocol deviation: If a protocol deviation or

concurrent illness occurs, which, in the clinical judgment of the Investigator, may invalidate the study by interfering with the comparability of the study, the subject will be withdrawn by the Investigator

Withdrawal of consent Blood donation during the course of the trial


Assessments for Safety Physical Exams:

Complete/Full PE: Visits 1, 2, 3 and 4Vital signs: All visits ECG: Visits 1 and 4 (with rhythm strip)

Laboratory Assessments (biochemistry, hematology, urinalysis): Visits 1 and 4;

Pregnancy Testing: serum ß-HCG at Visits 1 and 4; urine test is acceptable for all other visits

Adverse event monitoring: All visits


Laboratory Assessments

Local Laboratory: Hematology, Biochemistry, Urinalysis, Serum

Pregnancy Test


Laboratory Assessment con’t

4Serum ß-hCG test (at screening and follow-up): urine stick test (at the dosing visits)

Screen Treatment

Follow-up Visit Visit 1 Visit 2 or 3 Visit 4 Day (within the visit for Visits 2 or 3)

-14 to -3 1 2, 3 4-6 21 to 43 Hematology/biochemistry and lipids X

X X

Pregnancy test (females only)4 X X X Urinalysis X X PK sampling6 X X X


CONCOMITANT ILLNESS & MEDICATION

Concomitant Illness: Present at the start of the trial (e.g., first visit)

Concomitant Medication: Medication other than the trial products, taken during the trial, including screening and run-in periods


Randomization & Blinding

At screening the subject must be assigned the lowest available subject number.

At randomization, the subject must always be assigned the visit box with the lowest available 6 digit number.

The subject will only have one box containing two visit boxes each containing two packages of gum.

Subject box 1 will be dispensed to the subject at Visit 2. The second visit box will remain in the subject box until Visit 3.

A replacement subject must be allocated to the same treatment sequence as the subject he replaces.


Trial Supplies Trial Supplies Trial Products:

Sun Rise (SR) 1 strip of gum in a 5 strip packSun Set (SS) 1 strip of gum in a 5 strip pack

Packaging and Distribution:Double-blind1 subject box with two visit boxes

two visit boxes per subject box (Visit 2 and Visit 3)

each visit box with will have 2 packs of gumSubject box, visit box and gum pack will have

same number


Delivery and Receipt Trial products will be shipped directly from vendor When dispatched, site will receive a Shipment

Notification Upon receipt, all products will be kept in secure,

limited access area. Check the materials against the shipping receipts (i.e.

quantity, numbers, etc.) Check that all materials are received in good

condition


Trial Product Accountability

Trial Product accountability forms will be reviewed regularly

Trial product(s) will be stored in their recommended storage conditions

Any storage deviations will be reported immediately to the un-blinded CRA (this may result in quarantine of affected trial product)

Returned trial product will be accounted for by the CRA and destroyed onsite


Monitoring

Case Report Forms (CRFs)

2 part NCR paper CRFs

Enter data into CRFs from source documentation

Corrections to CRFs

Affirmation Statement


Monitoring con’t First MV within 2 weeks after the 1st subject is

screened

100% SDV (source data verification)

2-3 week intervals or more frequently, as required, depending on enrollment

Review Investigator Trial File (ITF) binders

Review regulatory documents

Collect CRFs and IRB documents

CRA to perform trial product accountability on a regular basis


Questions?

27 April 2010 Jane Fendl

Documents

rise gum

lasting gum

healthy gum

set gum data

rise formulation

rise sr

set formulation

comparative trial