Phase 3 Alogliptin Pediatric Study

Diabetes Mellitus, Type 2 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02856113
• Other study ID #: SYR-322_309
• Secondary ID: U1111-1174-19232
• Status: Completed
• Phase: Phase 3
• Start date: October 14, 2016
• Est. completion date: February 14, 2022

Study information

• Verified date: October 2022
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: February 14, 2022
• Est. primary completion date: August 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• Alogliptin Benzoate
Alogliptin benzoate tablets.
• Placebo
Alogliptin placebo-matching tablets.

Locations

Country	Name	City	State
Brazil	Hospital Universitario Joao de Barros Barreto	Belem	Para
Brazil	Instituto de Estudos e Pesquisas Clinicas do Ceara	Fortaleza	Ceara
Brazil	Instituto da Crianca com Diabetes	Porto Alegre	RIO Grande DO SUL
Brazil	Hospital Sirio Libanes	Sao Paulo
Israel	Hadassah University Hospital Mount Scopus	Jerusalem
Israel	The Chaim Sheba Medical Center	Ramat Gan	Tel Aviv
Israel	Clalit Medical Center	Tel Aviv
Italy	Ospedale Policlinico SS Annunziata	Chieti
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Ospedale Pediatrico Bambino Gesu	Roma
Mexico	Centro de Investigacion Cardiometabolica de Aguascalientes	Aguascalientes
Mexico	Ono Consultoria Medica Integral	Aguascalientes
Mexico	Centro de Atencion e Investigacion en Factores de Riesgo Cardiovascular Omega (Clinica Omega)	Ciudad de Mexico	Distrito Federal
Mexico	Desarrollo Etico en Investigacion Clinica	Guadalajara	Jalisco
Mexico	Endo Clinic	Guadalajara	Jalisco
Mexico	Instituto Nacional de Pediatria	Mexico	Distrito Federal
Mexico	Mentrials, SA de CV	Mexico	Distrito Federal
Mexico	IECSI-Centro Medico y de Investigacion Clinica	Monterrey	Nuevo LEON
Mexico	EL CIELO Medical Center	Puebla
Mexico	Centro Integral Medico Sjr	San Juan del Rio	Queretaro
Mexico	Investigacion Biomedica para el Desarrollo de Farmacos S.A. de C.V.	Zapopan	Jalisco
Poland	Twoja Przychodnia - Centrum Medyczne Nowa Sol	Nowa Sol	Lubuskie
Poland	MedPolonia	Poznan	Wielkopolskie
Poland	Sonomed	Szczecin	Zachodniopomorskie
Poland	Holmed	Warszawa	Mazowieckie
Poland	Specjalistyczna Praktyka Lekarska ASPIRO	Wroclaw	Dolnoslaskie
Russian Federation	Republican Children's Clinical Hospital-Izhevsk	Izhevsk	Udmurtia
Russian Federation	Kuzbass Regional Clinical Hospital n.a. S.V. Belyaev	Kemerovo
Russian Federation	Novosibirsk State Medical University	Novosibirsk
Russian Federation	Omsk Regional Children's Hospital	Omsk
Russian Federation	Saint Petersburg State Pediatric Medical Academy	Saint-Petersburg	Saint Petersburg
Russian Federation	Siberian State Medical University	Tomsk
United States	Pennington Biomedical Research Center	Baton Rouge	Louisiana
United States	University of Virginia	Charlottesville	Virginia
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Endocrine Consultants Research	Columbus	Georgia
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Florida	Gainesville	Florida
United States	Greenville Health System - Patewood	Greenville	South Carolina
United States	Gulfside Clinical Research	Gulfport	Mississippi
United States	Baylor College of Medicine Advanced Liver Therapies	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	Nemours Childrens Specialty Care - Jacksonville	Jacksonville	Florida
United States	Horizon View Medical Center	Las Vegas	Nevada
United States	University of Kentucky Health Care	Lexington	Kentucky
United States	Arkansas Children's Hospital Research Institute	Little Rock	Arkansas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	UT Le Bonheur Pediatric Specialists	Memphis	Tennessee
United States	Baptist Diabetes Associates Research	Miami	Florida
United States	University of Minnesota Masonic Children's Hospital - Pediatric Specialty Care Discovery Clinic	Minneapolis	Minnesota
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Ochsner Baptist Medical Center	New Orleans	Louisiana
United States	Endocrine Consultants Research - Oak Hill Court	Newnan	Georgia
United States	Sherif Khamis	Palmdale	California
United States	Lucile Packard Children's Hospital at Stanford University	Palo Alto	California
United States	Saint Joseph's Regional Medical Center - Paterson	Paterson	New Jersey
United States	Monument Health Clinical Research	Rapid City	South Dakota
United States	University of Rochester	Rochester	New York
United States	Saint Louis University	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington
United States	Multicare Health System Institute for Research and Innovation	Tacoma	Washington
United States	University of South Florida/USF Health	Tampa	Florida
United States	Touro University California	Vallejo	California
United States	Children's National Health System	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Takeda	Takeda Development Center Americas, Inc.

Countries where clinical trial is conducted

United States,  Brazil,  Israel,  Italy,  Mexico,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings		Week 26 and 52
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	Change From Baseline in CD26 (CD4+T Cells) Surface Antigen Levels at Weeks 26 and 52		Baseline, Weeks 26 and 52
Secondary	Change From Baseline in CD26 (CD8+T Cells) Surface Antigen Levels at Weeks 26 and 52		Baseline, Weeks 26 and 52