Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO)TM

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03429543
Collaborator
(none)
186
Enrollment
92
Locations
3
Arms
62.3
Anticipated Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this research study is to evaluate the efficacy and safety of an empagliflozin dosing regimen and one dose of linagliptin in patients with type 2 diabetes who are aged 10 to below 18 years and are currently taking metformin, insulin or both drugs (DINAMO TM) or who are treatment naïve or not on active treatment after metformin withdrawal (DINAMO TM MONO) .

Empagliflozin and linagliptin are both approved for use in adult patients with type 2 diabetes. This study will assess how well empagliflozin and linagliptin work by finding out how these treatments affect blood glucose (sugar) levels compared to placebo (a pill that contains no active drug), in children and adolescents. Empagliflozin and linagliptin are considered investigational products in this study since while they have been approved for use in adults, they have not been approved for children and adolescents due to lack of clinical studies in this specific population.

Patients with type 2 diabetes have higher levels of blood glucose (sugar) than patients who do not have this disease. The high level of sugar in the blood can lead to serious short-term and long-term medical problems. The main goal of treating diabetic patients is to lower blood glucose to a normal level. Lowering and controlling blood glucose help prevent or delay complications of diabetes such as heart disease, kidney, eye and nerve diseases, and the possibility of amputation.

Empagliflozin is a drug that helps to reduce blood glucose (sugar) levels by causing glucose to be excreted in the urines.

Linagliptin works by increasing the production of insulin (a hormone that controls the level of blood glucose) after meals when blood glucose (sugar) levels are too high. This helps to lower blood sugar levels.

The subject will either receive one of the active study drugs or a placebo. This study will be double blind; this means that neither the subject, nor the study doctor will know which treatment the subject will receive.

Which treatment the subject receives is decided by a computer, purely by chance; this is called a "random assignment".

For this study, there will first be a screening visit, followed by a 2-week placebo run-in period (all subjects will take placebo once daily). This run-in period is designed to ensure subjects are able to take the study drugs as described in the study protocol. Thereafter there will be a 26-week treatment phase (week 1-week 26) and a 26-week safety extension period (week 27-week 52). Following this there will be a follow-up visit at week 55.

On Day 1 after the placebo run-in phase, the subject will be randomly assigned to receive one of the 3 treatments: empagliflozin 10 mg, linagliptin 5 mg or placebo in a blinded manner. This treatment will continue up to week 14. Then after week 14, the subject will be assigned to receive one of the following 4 treatments: empagliflozin 10 mg, empagliflozin 25 mg, linagliptin 5 mg or placebo in a blinded manner. The drugs assigned after week 14 will be the same drugs as on Day 1 but some subjects will receive a higher dose of empagliflozin.

After the completion of the 26-week treatment period, the subject will enter a 26-week safety extension period. The same active treatment that the subject had been assigned to at week 14 visit will be continued. Subjects assigned to placebo on Day 1 will be randomly assigned to receive one of the 3 active treatments: empagliflozin 10 mg, empagliflozin 25 mg or linagliptin 5 mg in a blinded manner. This safety extension period is primarily designed to provide additional information on how well empagliflozin and linagliptin are tolerated.

Following the treatment phases, there will be a follow-up visit at week 55

Intervention model description:

Eligible subjects with HbA1c of 6.5% to 10.5% at screening will be randomized in a 1:1:1 ratio to receive empagliflozin 10 mg, linagliptin 5 mg or placebo. HbA1c assessment will be performed at Week 12. All subjects with Week 12 HbA1c < 7% will remain on previously assigned randomized treatment. Subjects taking empagliflozin with Week 12 HbA1c >= 7% will be re-randomized in a 1:1 ratio to continue on the low dose treatment (empagliflozin 10 mg) or up-titrate to the high dose treatment (empagliflozin 25 mg). Subjects taking linagliptin or placebo with Week 12 HbA1c >= 7% will remain on previously assigned treatment. All subjects will get new medication kits dispensed at Week 14 to maintain the blinding.

At Week 26, all subjects previously assigned to placebo will be re-randomized in a 1:1:1:

ratio to receive one of the active treatments: empagliflozin 10 mg, empagliflozin 25 mg or linagliptin 5 mg. All subjects will get new medication kits dispensed at Week 14 to maintain the blinding.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
186 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Double-blind, Randomised, Placebo-controlled, Parallel Group Trial to Evaluate the Efficacy and Safety of Empagliflozin and Linagliptin Over 26 Weeks, With a Double-blind Active Treatment Safety Extension Period up to 52 Weeks, in Children and Adolescents With Type 2 Diabetes Mellitus
Actual Study Start Date :
Mar 20, 2018
Anticipated Primary Completion Date :
Nov 6, 2022
Anticipated Study Completion Date :
May 28, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Linagliptin

Linagliptin arm. Oral route. Linagliptin tablets administered once daily for 52 weeks

Drug: Linagliptin
Film Coated Tablet
Other Names:
  • ONDERO, TRAJENTA, TRAYENTA, TRAZENTA, TRADJENTA
  • Experimental: Empagliflozin

    Empagliflozin arm. Oral route. Start with a low dose of empagliflozin administered once daily and randomly up titrate to the high dose of empagliflozin administered once daily if HbA1c ≥ 7% at week 12

    Drug: Empagliflozin
    Film Coated Tablet
    Other Names:
  • JARDIANCE, JARDIANZ, GIBTULIO
  • Placebo Comparator: Placebo

    Placebo arm. Oral route. Placebo tablets administered once daily up to 26 weeks and then linagliptin or low dose of empagliflozin or high dose of empagliflozin administered once daily up to 52 weeks

    Drug: Placebo
    Film Coated Tablet

    Outcome Measures

    Primary Outcome Measures

    1. DINAMO TM: Change from baseline in HbA1c (%) [26 Weeks]

    2. DINAMO TM Mono: Occurrence of treatment failure up to or at Week 26 [Up to 26 Weeks]

    Secondary Outcome Measures

    1. DINAMO TM: Change from baseline in fasting plasma glucose (mg/dl) [26 Weeks]

    2. DINAMO TM: Change from baseline in body weight (kg) [26 Weeks]

    3. DINAMO TM: Change from baseline in systolic blood pressure (SBP) [26 Weeks]

    4. DINAMO TM: Change from baseline in diastolic blood pressure (DBP) [26 Weeks]

    5. DINAMO TM: Proportion of patients who achieve HbA1c < 6.5% [26 weeks]

    6. DINAMO TM: Proportion of patients who achieve HbA1c < 7.0% [26 Weeks]

    7. DINAMO TM Mono: Time to treatment failure [Up to 52 Weeks]

    8. DINAMO TM Mono: Change in HbA1c (%) from baseline [26 Weeks]

    9. DINAMO TM Mono: Change in FPG (mg/dL) from baseline [26 Weeks]

    10. DINAMO TM Mono: Change in body weight (kg) from baseline [26 Weeks]

    11. DINAMO TM Mono: Change in SBP (mmHg) from baseline [26 Weeks]

    12. DINAMO TM Mono: Change in DBP (mmHg) from baseline [26 Weeks]

    13. DINAMO TM Mono: Proportion of patients who achieve HbA1c < 6.5% [26 Weeks]

    14. DINAMO TM Mono :Proportion of patients who achieve HbA1c < 7.0% [26 Weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    10 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients aged 10 to 17 years (inclusive) at the time of randomisation (Visit 2)

    • Male and female patients

    • Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient's legal representative information sheet.

    • Signed and dated written informed consent provided by the patient's parent(s) (or legal guardian) and patient's assent in accordance with ICH-GCP and local legislation prior to admission to the trial (informed assent will be sought according to the patient's age, level of maturity, competence and capacity)

    • Documented diagnosis of T2DM at Visit 1A:

    • DINAMO TM: Documented diagnosis of T2DM for at least 8 weeks at Visit 1A

    • DINAMO TM Mono: Confirmation of T2DM at Visit 1A- Insufficient glycaemic control as measured by the central laboratory at Visit 1A:

    • DINAMO TM: HbA1c ≥ 6.5% and ≤ 10.5%

    • DINAMO TM Mono: HbA1c ≥ 6.5% and ≤ 9.0%

    • DINAMO TM: Patients treated with

    • diet and exercise plus metformin at a stable dose for 8 weeks prior to Visit 2 or not tolerating metformin (defined as patients who were on metformin treatment for at least 1 week and had to discontinue metformin due to metformin-related side effects as assessed by the investigator) AND/OR

    • diet and exercise plus stable basal or MDI insulin therapy,, defined as a weekly average variation of the basal insulin dose ≤ 0.1 IU/kg over 8 weeks prior to Visit 2. - DINAMOTM Mono: Drug-naïve patients or patients not on active treatment (including discontinuation of metformin due to intolerance [or previous discontinuation for other reasons] and/or discontinuation of insulin [insulin use must be 8 weeks or less] at investigator's discretion) prior to or at Visit 1A)

    • BMI ≥ 85th percentile for age and sex according to WHO references at Visit 1B

    • Non-fasting serum C-peptide levels ≥ 0.6 ng/ml as measured by the central laboratory at Visit 1A

    • Compliance with trial medication intake must be between 75% and 125% during the open-label placebo run-in period

    • Further inclusion criteria apply

    Exclusion Criteria:
    • Any history of acute metabolic decompensation such as diabetic ketoacidosis within 8 weeks prior to Visit 1A and up to randomisation (mild to moderate polyuria at the time of randomisation is acceptable)

    • Diagnosis of monogenic diabetes (e.g. MODY)

    • History of pancreatitis

    • Diagnosis of metabolic bone disease

    • Gastrointestinal disorders that might interfere with study drug absorption according to investigator assessment

    • Secondary obesity as part of a syndrome (e.g. Prader-Willi syndrome)

    • Any antidiabetic medication (with the exception of metformin and/or insulin background therapy) within 8 weeks prior to Visit 1A and until Visit 2

    • Treatment with weight reduction medications (including anti-obesity drugs) within 3 months prior to Visit 1A and until Visit 2

    • History of weight-loss surgery or current aggressive diet regimen (according to investigator assessment) at Visit 1A and until Visit 2

    • Treatment with systemic corticosteroids for > 1 week within 4 weeks prior to Visit 1A and up to Visit 2 Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary disease) is acceptable.

    • Change in dose of thyroid hormones within 6 weeks prior to Visit 1A or planned change or initiation of such therapy before Visit 2

    • Known hypersensitivity or allergy to the investigational products or their excipients

    • Impaired renal function defined as estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m² (according to Zappitelli formula) as measured by the central laboratory at Visit 1A

    • Indication of liver disease defined by serum level of either alanine transaminase (ALT), aspartate transaminase (AST) or alkaline phosphatase above 3 fold upper limit of normal (ULN) at Visit 1A as measured by the central laboratory at Visit 1A

    • History of belonephobia (needle phobia)

    • Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1A, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix

    • Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia)

    • Any other acute or chronic medical or psychiatric condition or laboratory abnormality that, based on investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome

    • Medical contraindications to metformin according to the local label (for patient on metformin background therapy)

    • Patient not able or cannot be supported by his/her parent(s) or legal guardian to understand and comply with study requirements based on investigator's judgement

    • Previous randomisation in this trial

    • Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s)

    • Chronic alcohol or drug abuse within 3 months prior to Visit 1A or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial

    • Female patients who are pregnant, nursing, or who plan to become pregnant in the trial

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Phoenix Children's HospitalPhoenixArizonaUnited States85016
    2University of ArizonaTucsonArizonaUnited States85724
    3CHOC Children's HospitalOrangeCaliforniaUnited States92868
    4Stanford University Medical CenterPalo AltoCaliforniaUnited States94304
    5Rady Children's Hospital - San DiegoSan DiegoCaliforniaUnited States92123
    6University of California San FranciscoSan FranciscoCaliforniaUnited States94158
    7Children's Hospital ColoradoAuroraColoradoUnited States80045
    8Yale University School of MedicineNew HavenConnecticutUnited States06511
    9Solutions Through Advanced Research, Inc.JacksonvilleFloridaUnited States32256
    10Empire Clinical Research, LLCMiami LakesFloridaUnited States33016
    11Oceane7 Clinical ResearchMiamiFloridaUnited States33144
    12Pediatric and Adult Research CenterOrlandoFloridaUnited States32825
    13Nemours ClinicPensacolaFloridaUnited States32514
    14University of South FloridaTampaFloridaUnited States33612
    15AdventHealth Medical Group, Pediatric Diabetes and Endocrinology at Winter ParkWinter ParkFloridaUnited States32789
    16Children's Center for Advanced PediatricsAtlantaGeorgiaUnited States30329
    17Atlanta CenterAtlantaGeorgiaUnited States30331
    18Columbus Regional Research InstituteColumbusGeorgiaUnited States31904
    19Rocky Mountain Diabetes and Osteoporosis CenterIdaho FallsIdahoUnited States83404
    20University of Iowa Hospitals and ClinicsIowa CityIowaUnited States52242
    21Novak Center for Children's HealthLouisvilleKentuckyUnited States40202
    22Johns Hopkins HospitalBaltimoreMarylandUnited States21287
    23Boston Children's HospitalBostonMassachusettsUnited States02115
    24Joslin Diabetes CenterBostonMassachusettsUnited States02215
    25Integrative Biosciences CenterDetroitMichiganUnited States48202
    26University Of Mississippi Medical CenterJacksonMississippiUnited States39216-4505
    27Children's Mercy Hospitals and ClinicsKansas CityMissouriUnited States64108
    28Montefiore Medical CenterBronxNew YorkUnited States10467
    29Advantage Clinical TrialsBronxNew YorkUnited States10468
    30UBMD PediatricsBuffaloNew YorkUnited States14203
    31New York University Langone Medical CenterNew YorkNew YorkUnited States10016
    32SUNY Upstate Medical UniversitySyracuseNew YorkUnited States13210
    33The University of North Carolina at Chapel HillChapel HillNorth CarolinaUnited States27514
    34University Hospitals of ClevelandClevelandOhioUnited States44106
    35University of OklahomaOklahoma CityOklahomaUnited States73104
    36University of OklahomaTulsaOklahomaUnited States74135
    37Penn State College of MedicineHersheyPennsylvaniaUnited States17033
    38Children's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUnited States19104
    39Monument Health Rapid City Hospital, Inc.Rapid CitySouth DakotaUnited States57701
    40LifeDoc Research, PLLCMemphisTennesseeUnited States38119
    41Vanderbilt University Medical CenterNashvilleTennesseeUnited States37232
    42Office of Amir A. Hassan, MD, P.A.HoustonTexasUnited States77089
    43Saenz Medical CenterLa JoyaTexasUnited States78560
    44Texas Diabetes InstituteSan AntonioTexasUnited States78207
    45Children's Hospital of Richmond at VCURichmondVirginiaUnited States23219
    46Sanatorio Allende S.A.Nueva CórdobaArgentinaX5000JHQ
    47Hospital de Clínicas Pte. Dr. Nicolás AvellanedaSan Miguel de TucumánArgentina4000
    48Scentryphar Pesquisa Clínica LtdaCampinasBrazil13020-431
    49Instituto de Estudos e Pesquisas Clínicas IEP-CEFortalezaBrazil60160-230
    50Fundação de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeir�o PretoRibeirão PretoBrazil14048-900
    51Dr. ConsultaSão PauloBrazil04254-020
    52University of Manitoba - Health Sciences CentreWinnipegManitobaCanadaR3E 3P4
    53The Hospital for Sick ChildrenTorontoOntarioCanadaM5G 1X8
    54First Hospital of Jilin UniversityChangchunChina130021
    55The Children's Hospital of Fudan UniversityShanghaiChina201102
    56Zhengzhou Children'S HospitalZhengzhouChina450017
    57Centro de Diabetes Cardiovascular IPSBarranquillaColombia80020
    58Dexa-Diab IPSBogotá DCColombia110221
    59IPS Universitaria Servicio Salud - Universidad de AntioquiaMedellínColombia050010
    60Universitätsklinikum FreiburgFreiburgGermany79106
    61Kinder- und Jugendkrankenhaus auf der BultHannoverGermany30173
    62Soroka Univ. Medical CenterBeer ShevaIsrael84101
    63Rambam Medical CenterHaifaIsrael31096
    64The Chaim Sheba Medical Center Tel HashomerRamat-GanIsrael5265601
    65Severance HospitalSeoulKorea, Republic of03722
    66Asan Medical CenterSeoulKorea, Republic of05505
    67Ajou University HospitalSuwonKorea, Republic of16499
    68Investigación en Salud y Metabolismo S.C.ChihuahuaMexico31217
    69CAIMED Investigacion en Salud, S.A. de C.V.Ciudad de MéxicoMexico06760
    70Centro de Estudios de Investigación Metabólicos y Cardiovasculares, S.C.Ciudad MaderoMexico89440
    71Consultorio MedicoPueblaMexico72190
    72Investigacion Medica Sonora S.C.SonoraMexico83280
    73Centro de Investigación Médica de Ocidente, S.C.ZapopanMexico45116
    74Sint Antonius Diabetes CentrumUtrechtNetherlands3543 AZ
    75APDP - Associação Protectora dos Diabéticos de PortugalLisboaPortugal1250-203
    76Centro Hospitalar Universitário São João,EPEPortoPortugal4202-451
    77San Juan Bautista School of MedicineCaguasPuerto Rico00726
    78Regional Clinical Hospital 'The Badge of Honor Order'IrkutskRussian Federation664049
    79Ivanovo Reg.Clin.Hosp.IvanovoRussian Federation153040
    80Rep.childrens clin.hosp.IzhevskRussian Federation426009
    81State Medical University, KazanKazanRussian Federation420012
    82Munic. Instit. of HC "Kirov clin. hosp.#7 n.a.V.I.Urlova"KirovRussian Federation610014
    83Endocrinology Scientific Center, MoH and Social DevelopmentMoscowRussian Federation117036
    84State Novosibirsk Regional Clinical HospitalNovosibirskRussian Federation630091
    85Fed. State Budget Educational Instit. of Higher Education "Rostov State Med. Univ." of MoH of RFRostov-on-DonRussian Federation344022
    86St. Petersburg State Pediatric UniversitySt. PetersburgRussian Federation194100
    87Siberian State Med.Uni,Faculty Therapy Dep.w/ Clin.PharmacolTomskRussian Federation634050
    88Bahkir state med. Univ. of the Ministry Polyclinic PediatricUfaRussian Federation450106
    89BMA Medical College & Vajira HospitalBangkokThailand10300
    90Rajavithi HospitalKrung Thep Maha NakhonThailand10400
    91St George's HospitalLondonUnited KingdomSW17 0QT
    92Royal Berkshire HospitalReadingUnited KingdomRG1 5AN

    Sponsors and Collaborators

    • Boehringer Ingelheim

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Boehringer Ingelheim
    ClinicalTrials.gov Identifier:
    NCT03429543
    Other Study ID Numbers:
    • 1218-0091
    • 2016-000669-21
    First Posted:
    Feb 12, 2018
    Last Update Posted:
    Oct 6, 2021
    Last Verified:
    Oct 1, 2021
    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
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 6, 2021