Phase 3 Alogliptin Pediatric Study

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy of alogliptin 25 milligram (mg) once daily compared to placebo when administered as monotherapy, or when added onto a background of metformin alone, insulin alone, or a combination of metformin and insulin, as measured by the glycosylated hemoglobin (HbA1c) change from Baseline at Week 26 in pediatric participants with type 2 diabetes mellitus (T2DM).

Detailed Description
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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 T2DM and are experiencing inadequate glycemic control. This study will look at HbA1c fluctuations in children who take alogliptin in addition to their background antidiabetic therapy. The study will enroll approximately 150 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant 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 25 mg but has no active ingredient (that is, 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.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Alogliptin Compared With Placebo in Pediatric Subjects With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Alogliptin Benzoate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a confirmed diagnosis of T2DM using American Diabetes Association (ADA) and World Health Organization (WHO) criteria (laboratory determinations of fasting plasma glucose [FPG] greater than or equal to [>=] 126 mg/dL, random glucose >=200 mg/dL [>=11.10 mmol/L], HbA1c >=6.5 percent (%), or 2-hour oral glucose tolerance test [OGTT] glucose >=200 mg/dL), documented in the participants' medical record. The participant and/or his/her legal representative (that is, 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: Has a history of hypersensitivity or allergy to alogliptin, other dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, insulin or related compounds. Has a confirmed diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY). Has a hemoglobin level <11.0 gram per deciliter (g/dL) (<110 gram per liter [g/L]) for males and <10.0 g/dL (<100 g/L) for females. Has a history of any hemoglobinopathy that may affect determination of HbA1c levels. Has a history of bariatric surgery. Has a history of proliferative diabetic retinopathy within the 6 months prior to Screening. Has had more than 1 episode of diabetic ketoacidosis (DKA) at any time after diagnosis of T2DM. Has a history of more than 1 episode of pancreatitis. Has serum creatinine >=1.5 mg/dL for male participants or >=1.4 mg/dL for female participants, or creatinine clearance <60 milliliter per minute (mL/min) based on calculation by central lab using the Schwartz formula for estimated glomerular filtration rate (eGFR) at screening Visit. Has a documented history of infection with human immunodeficiency virus or chronic active viral hepatitis. The participant and/or his/her legal representative (that is, 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: For participants who have had the diagnosis of T2DM for less than 1 year and/or who are taking insulin at Screening, additional criteria will need to be met prior to randomization: Must have an HbA1c level of >=6.5% to <11.0% if the participant is treatment naïve or on metformin alone or >=7.0% to <11.0% if the participant is on insulin alone or in combination with metformin. The participant must not have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to randomization. Must not have received an antidiabetic agent other than metformin or insulin within the 12 weeks prior to randomization. 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. Has a systolic blood pressure <160 millimeter of mercury (mmHg) and a diastolic pressure <100 mm Hg. (Antihypertensive medications will be allowed during the study). 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).7. Does not plan to leave the geographic area within 1 calendar year following randomization. For participants who have had the diagnosis of T2DM for less than 1 year and/or who are taking insulin prior to randomization, the following criteria must also be met: 8. Must have a fasting C-peptide concentration>=0.6 nanogram per milliliter (ng/mL) (>=0.20 nanomole per liter [nmol/L]) (drawn at least 1 week after treatment for ketosis or acidosis, if applicable). 9. No presence of autoantibodies as documented by glutamic acid decarboxylase [GAD] 65 and islet antigen [IA]-2 antibodies below the upper limit of the normal reference ranges at randomization. 10. Have a body mass index (BMI) greater than (>) 85th percentile, documented at randomization.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Alogliptin matching-placebo tablets, orally, once daily (QD) for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period. | Drug: Placebo<br>* Alogliptin placebo-matching tablets.<br>|
| Experimental: Alogliptin 25 mg<br>Alogliptin 25 mg tablets, orally, QD for 52 weeks and background antidiabetic therapy (metformin and/or insulin), if applicable, maintained at the same dose throughout the first 26 weeks of the treatment period. | Drug: Alogliptin Benzoate<br>* Alogliptin benzoate tablets.<br>* Other names: Vipidia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Week 26 relative to Baseline. Mixed model for repeated measures (MMRM) was used for the analysis. | Baseline and Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 | Change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was collected at Weeks 12, 18, 39 and 52 relative to Baseline. MMRM was used for the analysis. | Baseline and Weeks 12, 18, 39 and 52 | 
| Percentage of Participants With Clinically Significant Physical Examination Findings | Physical examination included examination of the following body systems: (1) respiratory system; (2) cardiovascular system; (3) nervous system (4) dermatologic system; and (5) gastrointestinal system. A summarized data for the above body systems was reported for participants with clinically significant findings. | From Day 1 to end of treatment period (up to 52 weeks) | 
| Percentage of Participants With Abnormal Vital Signs Values | Vital signs included body temperature (oral or tympanic measurement), respiratory rate, blood pressure [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] resting more than 5 minutes, and pulse (beats per minute). Data for participants with abnormal vital signs was reported. The percentage of participants are calculated based on the participants with non-missing data at that time-point. | From Day 1 to end of treatment period (up to 52 weeks) | 
| Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings |  | Week 26 and 52 | 
| Percentage of Participants With Treatment-emergent Adverse Events (TEAE) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. | From the study start up to end of the study (up to 54 weeks) | 
| Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions | The percentage of participants are calculated based on the participants with non-missing data at that time-point. | From Day 1 to end of treatment period (up to 52 weeks) | 
| Percentage of Participants With Hypoglycemia | Mild to moderate hypoglycemia (abnormal low blood sugar) was defined as blood glucose less than (<) 60 milligram per deciliter (mg/dL) (3.33 millimole per liter [mmol/L]) in the presence of symptoms, or blood glucose <50 mg/dL (2.78 mmol/L) with or without symptoms. Severe hypoglycemia was defined as any episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, associated with a documented blood glucose <60 mg/dL (3.33 mmol/L) (unless the clinical situation makes obtaining a blood glucose difficult [example, it involves coma or seizure]). | From Day 1 to end of treatment period (up to 52 weeks) | 
| Percentage of Participants With Abnormal Safety Laboratory Findings | The percentage of participants with any abnormal standard safety laboratory values (hematology, serum chemistry, and urinalysis) were collected throughout study. Abnormal values for hematology included hematocrit (percentage of hematocrit [%]), hemoglobin (grams per liter [g/L]), erythrocyte mean corpuscular volume (MCV)(femtoliter [fL]), erythrocytes (10^12/L), and leukocytes (10^9/L). Abnormal values for serum chemistry included for alanine aminotransferase (units per liter [U/L]), aspartate aminotransferase (U/L), cholesterol (millimoles per liter [mmol/L]), gamma glutamyl transferase (U/L), glucose (mmol/L): < 2.8 mmol/L, potassium (mmol/L), sodium (mmol/L), and triglycerides (mmol/L). ULN is upper limit of normal and LLN is lower limit of normal. | From Day 1 to end of treatment period (up to 52 weeks) | 
| Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 | Biomarkers of bone turnover are bone-specific alkaline phosphatase to assess changes in bone formation and C-terminal telopeptide (CTX) to assess changes in bone resorption. | Baseline, Weeks 26 and 52 | 
| Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52 |  | Baseline, Weeks 26 and 52 | 
| Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52 |  | Baseline, Weeks 26 and 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy