Phase 3 Alogliptin Pediatric Study

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT02856113
Collaborator
Takeda Development Center Americas, Inc. (Industry)
151
55
2
62.6
2.7
0

Study Details

Study Description

Brief Summary

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).

Condition or Disease Intervention/Treatment Phase
  • Drug: Alogliptin Benzoate
  • Drug: Placebo
Phase 3

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 in the United States, Brazil, Germany, Italy, Poland, Russia, Israel and Mexico. 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 Design

Study Type:
Interventional
Actual Enrollment :
151 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Nov 28, 2016
Actual Primary Completion Date :
Aug 6, 2021
Actual Study Completion Date :
Feb 14, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alogliptin 25 mg

Alogliptin 25 mg tablets, orally, once daily 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
  • Placebo Comparator: Placebo

    Alogliptin placebo-matching tablets, orally, once daily 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.

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in HbA1c at Week 26 [Baseline and Week 26]

      The change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 26 relative to Baseline.

    Secondary Outcome Measures

    1. Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52 [Baseline and Weeks 12, 18, 39 and 52]

      The change in the value of HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Weeks 12, 18, 39 and 52 relative to Baseline.

    2. Percentage of Participants with Abnormal Physical Examination Findings [From Day 1 to end of treatment period (up to 52 weeks)]

    3. Percentage of Participants With Abnormal Vital Signs Values [From Day 1 to end of treatment period (up to 52 weeks)]

      Vital signs will include body temperature (oral or tympanic measurement), respiratory rate, blood pressure (resting more than 5 minutes), and pulse (beats per minute).

    4. Percentage of Participants with Abnormal 12-lead Electrocardiogram (ECG) Findings [From Day 1 to end of treatment period (up to 52 weeks)]

    5. Percentage of Participants with Treatment-emergent Adverse Events (TEAE) [From Day 1 to end of the study (up to 54 weeks)]

      An AE is 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.

    6. Percentage of Participants with Infections and Hypersensitivity Reactions [From Day 1 to end of treatment period (up to 52 weeks)]

      Percentage of participants with infections (total) and urinary tract infections (UTIs) and respiratory tract infection (RTI) will be reported.

    7. Percentage of Participants with Hypoglycemia [From Day 1 to end of treatment period (up to 52 weeks)]

      Mild to moderate hypoglycemia (abnormal low blood sugar) is 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 is 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]).

    8. Percentage of Participants with Abnormal Safety Laboratory Findings [From Day 1 to end of treatment period (up to 52 weeks)]

      The percentage of participants with any abnormal standard safety laboratory values (hematology, serum chemistry, and urinalysis) will be collected throughout study.

    9. Change from Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52 [Baseline, 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.

    10. Change from Baseline in CD26 Surface Antigen Levels at Weeks 26 and 52 [Baseline, Weeks 26 and 52]

      The change in the value of CD26 surface antigen collected at Week 26 and Week 52 relative to Baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    10 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    1. 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).

    2. 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.

    3. Have a body mass index (BMI) greater than (>) 85th percentile, documented at randomization.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Arkansas Children's Hospital Research Institute Little Rock Arkansas United States 72202
    2 Sherif Khamis Palmdale California United States 93550
    3 Lucile Packard Children's Hospital at Stanford University Palo Alto California United States 94304
    4 Touro University California Vallejo California United States 94592
    5 Yale New Haven Hospital New Haven Connecticut United States 6511
    6 University of Florida Gainesville Florida United States 32610
    7 Nemours Childrens Specialty Care - Jacksonville Jacksonville Florida United States 32207
    8 Baptist Diabetes Associates Research Miami Florida United States 33156
    9 University of South Florida Tampa Florida United States 33612
    10 Endocrine Consultants Research Columbus Georgia United States 31904-4501
    11 Indiana University Indianapolis Indiana United States 46202
    12 University of Iowa Iowa City Iowa United States 52242
    13 University of Kentucky Lexington Kentucky United States 40536
    14 Pennington Biomedical Research Center Baton Rouge Louisiana United States 70808-4124
    15 Ochsner Baptist Medical Center New Orleans Louisiana United States 70115
    16 University of Minnesota Masonic Children's Hospital - Pediatric Specialty Care Discovery Clinic Minneapolis Minnesota United States 55454
    17 SSM Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
    18 Horizon View Medical Center Las Vegas Nevada United States 89149
    19 Saint Joseph's Regional Medical Center - Paterson Paterson New Jersey United States 7503
    20 University of Rochester Rochester New York United States 14642
    21 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    22 Greenville Health System - Patewood Greenville South Carolina United States 29615
    23 Regional Medical Clinic Rapid City South Dakota United States 57701
    24 UT Le Bonheur Pediatric Specialists Memphis Tennessee United States 38103
    25 University of Texas Southwestern Medical Center Dallas Texas United States
    26 Baylor College of Medicine Houston Texas United States 77030
    27 University of Virginia Charlottesville Virginia United States 22908
    28 Seattle Children's Hospital Seattle Washington United States 98003
    29 Multicare Health System Institute for Research and Innovation Tacoma Washington United States 98405
    30 Instituto de Estudos e Pesquisas Clinicas IEP-CE Fortaleza Ceara Brazil 60160-230
    31 Hospital Universitario Joao de Barros Barreto Belem Para Brazil 66073-000
    32 Centro de Pesquisas em Diabetes - CPD Porto Alegre Rio Grande Do Sul Brazil 90035-170
    33 Hospital Nossa Senhora da Conceicao - Instituto da Crianca com Diabetes Porto Alegre Rio Grande Do Sul Brazil 91350-250
    34 Hospital Sirio Libanes Sao Paulo Brazil 01308-050
    35 Pfutzner Science & Health Institute GmbH Mainz Rheinland-Pfalz Germany 55116
    36 Chaim Sheba Medical Center Ramat Gan Tel Aviv Israel 52621
    37 Hadassah Medical Center Jerusalem Israel 91120
    38 Clalit Medical Center Tel Aviv Israel 6203854
    39 Istituto G Gaslini Ospedale Pediatrico IRCCS Genova Liguria Italy 16147
    40 Azienda Ospedaliero Universitaria Di Modena Policlinico Modena Piacenza Italy 41124
    41 Arcispedale Santa Maria Nuova Parma Italy 43126
    42 Ospedale Pediatrico Bambino Gesu Roma Italy 00165
    43 Mentrials, SA de CV Ciudad De Mexico Distrito Federal Mexico 06700
    44 Centro de Atencion e Investigacion en Factores de Riesgo Cardiovascular Omega (Clinica Omega) Ciudad De Mexico Distrito Federal Mexico 14000
    45 Desarrollo Etico en Investigacion Clinica Guadalajara Jalisco Mexico 44500
    46 Endo Clinic Guadalajara Jalisco Mexico 44680
    47 iBiomed Investigacion Biomedica Guadalajara Zapopan Jalisco Mexico 45030
    48 Centro Integral Medico Sjr San Juan del Rio Queretaro Mexico 76800
    49 Ono Consultoria Medica Integral Aguascalientes Mexico 20129
    50 Centro de Investigacion Cardiometabolica de Aguascalientes Aguascalientes Mexico 20230
    51 Medical University of Silesia Katowice Slaskie Poland 40-75
    52 Med-Polonia Sp. z o.o. Poznan Wielkopolskie Poland 60-693
    53 Samodzielny Publiczny Szpital Kliniczny nr 1 Pomorskiego UM im. prof. Tadeusza Sokolowskiego Szczecin Zachodniopomorskie Poland 71-252
    54 Twoja Przychodnia - Centrum Medyczne Nowa Sol Szczecin Zachodniopomorskie Poland 71-270
    55 Sonomed Szczecin Zachodniopomorskie Poland 71-685

    Sponsors and Collaborators

    • Takeda
    • Takeda Development Center Americas, Inc.

    Investigators

    • Study Director: Medical Director Clinical Science, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Takeda
    ClinicalTrials.gov Identifier:
    NCT02856113
    Other Study ID Numbers:
    • SYR-322_309
    • U1111-1174-1923
    • 2015-000208-25
    • 173300410A0019
    • MOH_2017-12-26_000698
    First Posted:
    Aug 4, 2016
    Last Update Posted:
    Mar 16, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Takeda
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 16, 2022