Clinical trial NCT02856113: Phase 3 Alogliptin Pediatric Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda Development Center Americas, Inc.
First posted: 2016-08-04
Enrollment: 152
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
timeFrame: Baseline and Week 26
Secondary outcomes:
measure: Change From Baseline in HbA1c at Weeks 12, 18, 39 and 52
timeFrame: Baseline and Weeks 12, 18, 39 and 52
measure: Percentage of Participants With Clinically Significant Physical Examination Findings
timeFrame: From Day 1 to end of treatment period (up to 52 weeks)
measure: Percentage of Participants With Abnormal Vital Signs Values
timeFrame: From Day 1 to end of treatment period (up to 52 weeks)
measure: Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings
timeFrame: Week 26 and 52
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAE)
timeFrame: From the study start up to end of the study (up to 54 weeks)
measure: Percentage of Participants With Total, Urinary and Respiratory Tract Infections and Hypersensitivity Reactions
timeFrame: From Day 1 to end of treatment period (up to 52 weeks)
measure: Percentage of Participants With Hypoglycemia
timeFrame: From Day 1 to end of treatment period (up to 52 weeks)
measure: Percentage of Participants With Abnormal Safety Laboratory Findings
timeFrame: From Day 1 to end of treatment period (up to 52 weeks)
measure: Change From Baseline in Biomarkers of Bone Turnover at Weeks 26 and 52
timeFrame: Baseline, Weeks 26 and 52
measure: Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52
timeFrame: Baseline, Weeks 26 and 52
measure: Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52
timeFrame: Baseline, Weeks 26 and 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital Research Institute
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Palmdale
country: United States
facility: Sherif Khamis
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital at Stanford University
state: California
city: Vallejo
country: United States
facility: Touro University California
state: California
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Nemours Childrens Specialty Care - Jacksonville
state: Florida
city: Miami
country: United States
facility: Baptist Diabetes Associates Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida/USF Health
state: Florida
city: Columbus
country: United States
facility: Endocrine Consultants Research
state: Georgia
city: Newnan
country: United States
facility: Endocrine Consultants Research - Oak Hill Court
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky Health Care
state: Kentucky
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Baptist Medical Center
state: Louisiana
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Children's Hospital - Pediatric Specialty Care Discovery Clinic
state: Minnesota
city: Gulfport
country: United States
facility: Gulfside Clinical Research
state: Mississippi
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Las Vegas
country: United States
facility: Horizon View Medical Center
state: Nevada
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center - Paterson
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Greenville
country: United States
facility: Greenville Health System - Patewood
state: South Carolina
city: Rapid City
country: United States
facility: Monument Health Clinical Research
state: South Dakota
city: Memphis
country: United States
facility: UT Le Bonheur Pediatric Specialists
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine Advanced Liver Therapies
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: Multicare Health System Institute for Research and Innovation
state: Washington
city: Fortaleza
country: Brazil
facility: Instituto de Estudos e Pesquisas Clinicas do Ceara
state: Ceara
city: Belem
country: Brazil
facility: Hospital Universitario Joao de Barros Barreto
state: Para
city: Porto Alegre
country: Brazil
facility: Instituto da Crianca com Diabetes
state: RIO Grande DO SUL
city: Sao Paulo
country: Brazil
facility: Hospital Sirio Libanes
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
state: Tel Aviv
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Mount Scopus
city: Tel Aviv
country: Israel
facility: Clalit Medical Center
city: Chieti
country: Italy
facility: Ospedale Policlinico SS Annunziata
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Palermo
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Ciudad de Mexico
country: Mexico
facility: Centro de Atencion e Investigacion en Factores de Riesgo Cardiovascular Omega (Clinica Omega)
state: Distrito Federal
city: Mexico
country: Mexico
facility: Instituto Nacional de Pediatria
state: Distrito Federal
city: Mexico
country: Mexico
facility: Mentrials, SA de CV
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Endo Clinic
state: Jalisco
city: Guadalajara
country: Mexico
facility: Desarrollo Etico en Investigacion Clinica
state: Jalisco
city: Zapopan
country: Mexico
facility: Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.
state: Jalisco
city: Monterrey
country: Mexico
facility: IECSI-Centro Medico y de Investigacion Clinica
state: Nuevo LEON
city: San Juan del Rio
country: Mexico
facility: Centro Integral Medico Sjr
state: Queretaro
city: Aguascalientes
country: Mexico
facility: Ono Consultoria Medica Integral
city: Aguascalientes
country: Mexico
facility: Centro de Investigacion Cardiometabolica de Aguascalientes
city: Puebla
country: Mexico
facility: EL CIELO Medical Center
city: Wroclaw
country: Poland
facility: Specjalistyczna Praktyka Lekarska ASPIRO
state: Dolnoslaskie
city: Nowa Sol
country: Poland
facility: Twoja Przychodnia - Centrum Medyczne Nowa Sol
state: Lubuskie
city: Warszawa
country: Poland
facility: Holmed
state: Mazowieckie
city: Poznan
country: Poland
facility: MedPolonia
state: Wielkopolskie
city: Szczecin
country: Poland
facility: Sonomed
state: Zachodniopomorskie
city: Saint-Petersburg
country: Russian Federation
facility: Saint Petersburg State Pediatric Medical Academy
state: Saint Petersburg
city: Izhevsk
country: Russian Federation
facility: Republican Children's Clinical Hospital-Izhevsk
state: Udmurtia
city: Kemerovo
country: Russian Federation
facility: Kuzbass Regional Clinical Hospital n.a. S.V. Belyaev
city: Novosibirsk
country: Russian Federation
facility: Novosibirsk State Medical University
city: Omsk
country: Russian Federation
facility: Omsk Regional Children's Hospital
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: