Phase 3 Alogliptin Pediatric Study

The drug being tested in this study is called alogliptin. Alogliptin is being tested to treat
children 10 to 17 years of age who have type 2 diabetes mellitus (T2DM) and are experiencing
inadequate glycemic control. This study will look at glycosylated hemoglobin (HbA1c)
fluctuations in children who take alogliptin in addition to their background antidiabetic
therapy.

The study will enroll approximately 200 patients. Participants will be randomly assigned (by
chance, like flipping a coin) to one of the two treatment groups—which will remain
undisclosed to the patient and study doctor during the study (unless there is an urgent
medical need):

- Alogliptin 25 mg

- Placebo (dummy inactive pill) - this is a tablet that looks like the tablet containing
alogliptin 25mg but has no active ingredient (i.e. has no alogliptin)

All participants will be asked to take one tablet at the same time each day throughout the
study in addition to their current background antidiabetic therapy (metformin and/or insulin)
if applicable.

This multi-center trial will be conducted worldwide. The overall time to participate in this
study is approximately 56 weeks. Participants will make multiple visits to the clinic, and
will be contacted by telephone 2 weeks after the last dose of study drug for a follow-up
assessment.

Inclusion Criteria:

1. Has a confirmed diagnosis of type 2 diabetes mellitus (T2DM) using American Diabetes
Association (ADA) and World Health Organization (WHO) criteria (laboratory
determinations of fasting plasma glucose (FPG) ≥126 mg/dL, random glucose ≥200 mg/dL
[≥11.10 mmol/L], glycosylated hemoglobin (HbA1c) ≥6.5%, or 2-hour oral glucose
tolerance test [OGTT] glucose ≥200 mg/dL), documented in the participants' medical
record.

2. Documented fasting C-peptide concentration ≥0.6 ng/mL (≥0.20 nmol/L) (drawn at least 1
week after treatment for ketosis or acidosis, if applicable).

3. Documented glutamic acid decarboxylase [GAD] 65 and islet cell antigen [ICA] 512
antibodies below the upper limit of the normal reference ranges.

4. Has body mass index (BMI) ≥85th percentile, documented at Screening.

5. Is thought to be able to swallow the tablet containing the study medication.

6. The participant and/or his/her legal representative (ie, parents or legal guardians)
are able and willing to monitor their own blood glucose concentrations with a home
glucose monitor and complete participant diaries.

Exclusion Criteria:

1. Has a history of hypersensitivity or allergy to alogliptin, other dipeptidyl
peptidase-4 (DPP-4) inhibitors, metformin, insulin or related compounds.

2. Has a confirmed diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of
the young (MODY).

3. Has a hemoglobin level <11.0 g/dL (<110 g/L) for males and <10.0 g/dL (<100 g/L) for
females.

4. Has a history of any hemoglobinopathy that may affect determination of HbA1c levels.

5. Has a history of bariatric surgery.

6. Has a history of proliferative diabetic retinopathy within the 6 months prior to
Screening.

7. Has had more than 1 episode of diabetic ketoacidosis (DKA) at any time after diagnosis
of T2DM.

8. Has a history of more than 1 episode of pancreatitis.

9. Has serum creatinine ≥1.5 mg/dL for male participants or ≥1.4 mg/dL for female
participants, or creatinine clearance <60 mL/min based on calculation by central lab
using the Cockcroft-Gault approximation at Screening Visit.

10. Has a documented history of infection with human immunodeficiency virus or chronic
active viral hepatitis.

11. The participant and/or his/her legal representative (ie, parents or legal guardians)
is unable to understand verbal or written English, or any other language for which a
certified translation of the approved informed consent/assent is available.

Additional Criteria That Must be Met Prior to Randomization:

1. Must have an HbA1c level of ≥6.5% to <11.0%.

2. Must not have received an antidiabetic agent other than metformin or insulin within
the 12 weeks prior to randomization.

3. Must not have received oral or parenteral steroids for more than 3 weeks
(cumulatively) within the 6 months prior to randomization or have received a course of
oral or parenteral steroids within the 2 months prior to randomization.

4. Has a systolic blood pressure <160 mmHg and a diastolic pressure <100 mmHg.
(Antihypertensive medications will be allowed during the study).

5. Has an alanine aminotransferase (ALT) level <3 × upper limit of normal (ULN) or an ALT
level <5 × ULN with a confirmed diagnosis of nonalcoholic fatty liver disease (NAFLD).

6. Does not plan to leave the geographic area within 1 calendar year following
randomization.