Phase 3 Alogliptin Pediatric Study

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

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).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Alogliptin Benzoate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 01308-050
    • Hospital Sirio Libanes
  • Ceara
    • Fortaleza, Ceara, Brazil, 60160-230
      • Instituto de Estudos E Pesquisas Clinicas Do Ceara
  • Para
    • Belem, Para, Brazil, 66073-005
      • Hospital Universitário João de Barros Barreto
  • RIO Grande DO SUL
    • Porto Alegre, RIO Grande DO SUL, Brazil, 91350-250
      • Instituto da Crianca com Diabetes
• Israel
  • Jerusalem, Israel, 9765422
    • Hadassah University Hospital Mount Scopus
  • Tel Aviv, Israel, 6203854
    • Clalit Medical Center
  • Tel Aviv
    • Ramat Gan, Tel Aviv, Israel, 52621
      • The Chaim Sheba Medical Center
• Italy
  • Chieti, Italy, 66100
    • Ospedale Policlinico SS Annunziata
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria Federico II
  • Palermo, Italy
    • Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
  • Roma, Italy, 146
    • Ospedale Pediatrico Bambino Gesù
• Mexico
  • Aguascalientes, Mexico, 20129
    • Ono Consultoria Medica Integral
  • Aguascalientes, Mexico
    • Centro de Investigación Cardiometabólica de Aguascalientes
  • Puebla, Mexico, 72160
    • El Cielo Medical Center
  • Distrito Federal
    • Ciudad de Mexico, Distrito Federal, Mexico, 6700
      • Centro de Atencion e Investigacion en Factores de Riesgo Cardiovascular Omega (Clinica Omega)
    • Mexico, Distrito Federal, Mexico, 14530
      • Instituto Nacional de Pediatría
    • Mexico, Distrito Federal, Mexico, 6400
      • Mentrials, SA de CV
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44500
      • Desarrollo Etico en Investigacion Clinica
    • Guadalajara, Jalisco, Mexico, 44130
      • Endo Clinic
    • Zapopan, Jalisco, Mexico, 45030
      • Investigación Biomédica para el Desarrollo de Fármacos S.A. de C.V.
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64310
      • IECSI-Centro Medico y de Investigacion Clinica
  • Queretaro
    • San Juan del Rio, Queretaro, Mexico, 76800
      • Centro Integral Medico Sjr
• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-341
      • Specjalistyczna Praktyka Lekarska Aspiro
  • Lubuskie
    • Nowa Sol, Lubuskie, Poland, 67-100
      • Twoja Przychodnia - Centrum Medyczne Nowa Sol
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-494
      • Holmed
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-693
      • MedPolonia
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 71-685
      • SONOMED
• Russian Federation
  • Kemerovo, Russian Federation, 650066
    • Kuzbass Regional Clinical Hospital n.a. S.V. Belyaev
  • Novosibirsk, Russian Federation, 630087
    • Novosibirsk State Medical University
  • Omsk, Russian Federation, 644001
    • Omsk Regional Children's Hospital
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University
  • Saint Petersburg
    • Saint-Petersburg, Saint Petersburg, Russian Federation, 194100
      • Saint Petersburg State Pediatric Medical Academy
  • Udmurtia
    • Izhevsk, Udmurtia, Russian Federation, 426009
      • Republican Children's Clinical Hospital-Izhevsk
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital Research Institute
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Palmdale, California, United States, 93550
      • Sherif Khamis
    • Palo Alto, California, United States, 94304
      • Lucile Packard Children's Hospital at Stanford University
    • Vallejo, California, United States, 94592
      • Touro University California
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale New Haven Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Childrens Specialty Care - Jacksonville
    • Miami, Florida, United States, 33156
      • Baptist Diabetes Associates Research
    • Tampa, Florida, United States, 33612
      • University of South Florida/USF Health
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Endocrine Consultants Research
    • Newnan, Georgia, United States, 30265
      • Endocrine Consultants Research - Oak Hill Court
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • University of Kentucky Health Care
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
    • New Orleans, Louisiana, United States, 70115
      • Ochsner Baptist Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • University of Minnesota Masonic Children's Hospital - Pediatric Specialty Care Discovery Clinic
  • Mississippi
    • Gulfport, Mississippi, United States, 39501
      • Gulfside Clinical Research
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • Nevada
    • Las Vegas, Nevada, United States, 89149
      • Horizon View Medical Center
  • New Jersey
    • Paterson, New Jersey, United States, 07503
      • Saint Joseph's Regional Medical Center - Paterson
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System - Patewood
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Monument Health Clinical Research
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • UT Le Bonheur Pediatric Specialists
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Advanced Liver Therapies
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98003
      • Seattle Children's Hospital
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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.
2. 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:

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 gram per deciliter (g/dL) (<110 gram per liter [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 milliliter per minute (mL/min) based on calculation by central lab using the Schwartz formula for estimated glomerular filtration rate (eGFR) 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 (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:

1. 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.
2. The participant must not have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to randomization.
3. Must not have received an antidiabetic agent other than metformin or insulin within the 12 weeks prior to randomization.
4. 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.
5. 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).
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 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; Alogliptin placebo-matching tablets.
Experimental: Alogliptin 25 mg; 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; Alogliptin benzoate tablets.; Other Names: SYR-322; Nesina; Vipidia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Takeda
• Collaborators: Takeda Development Center Americas, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2016
• Primary Completion (Actual): August 6, 2021
• Study Completion (Actual): February 14, 2022

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 2, 2016
• First Posted (Estimate): August 4, 2016

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Alogliptin
• Other Study ID Numbers: SYR-322_309; U1111-1174-1923 (Registry Identifier: WHO); 2015-000208-25 (EudraCT Number); 173300410A0019 (Registry Identifier: NREC); MOH_2017-12-26_000698 (Other Identifier: CRS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect Participant privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No