Phase 3 Alogliptin Pediatric Study
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 |
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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):
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Alogliptin 25 mg
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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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
- 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
- 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.
- Percentage of Participants with Abnormal Physical Examination Findings [From Day 1 to end of treatment period (up to 52 weeks)]
- 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).
- Percentage of Participants with Abnormal 12-lead Electrocardiogram (ECG) Findings [From Day 1 to end of treatment period (up to 52 weeks)]
- 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.
- 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.
- 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]).
- 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.
- 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.
- 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
Inclusion Criteria:
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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.
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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:
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Has a history of hypersensitivity or allergy to alogliptin, other dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, insulin or related compounds.
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Has a confirmed diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young (MODY).
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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.
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Has a history of any hemoglobinopathy that may affect determination of HbA1c levels.
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Has a history of bariatric surgery.
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Has a history of proliferative diabetic retinopathy within the 6 months prior to Screening.
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Has had more than 1 episode of diabetic ketoacidosis (DKA) at any time after diagnosis of T2DM.
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Has a history of more than 1 episode of pancreatitis.
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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.
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Has a documented history of infection with human immunodeficiency virus or chronic active viral hepatitis.
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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:
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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.
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The participant must not have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to randomization.
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Must not have received an antidiabetic agent other than metformin or insulin within the 12 weeks prior to randomization.
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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.
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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).
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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:
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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).
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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.
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Have a body mass index (BMI) greater than (>) 85th percentile, documented at randomization.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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.- SYR-322_309
- U1111-1174-1923
- 2015-000208-25
- 173300410A0019
- MOH_2017-12-26_000698