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

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03429543
Collaborator
(none)
175
Enrollment
83
Locations
3
Arms
62.2
Anticipated Duration (Months)
2.1
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 Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
175 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 4, 2022
Anticipated Study Completion Date :
May 26, 2023

Arms and Interventions

Arm Intervention/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

    Site City State Country Postal Code
    1 Phoenix Children's Hospital Phoenix Arizona United States 85016
    2 University of Arizona Tucson Arizona United States 85724
    3 CHOC Children's Hospital Orange California United States 92868
    4 Stanford University Medical Center Palo Alto California United States 94304
    5 Rady Children's Hospital - San Diego San Diego California United States 92123
    6 University of California San Francisco San Francisco California United States 94158
    7 Children's Hospital Colorado Aurora Colorado United States 80045
    8 Yale University School of Medicine New Haven Connecticut United States 06511
    9 Empire Clinical Research, LLC Miami Lakes Florida United States 33016
    10 Oceane7 Clinical Research Miami Florida United States 33144
    11 Pediatric and Adult Research Center Orlando Florida United States 32825
    12 Nemours Clinic Pensacola Florida United States 32514
    13 University of South Florida Tampa Florida United States 33612
    14 AdventHealth Medical Group, Pediatric Diabetes and Endocrinology at Winter Park Winter Park Florida United States 32789
    15 Children's Center for Advanced Pediatrics Atlanta Georgia United States 30329
    16 Atlanta Center Atlanta Georgia United States 30331
    17 Columbus Regional Research Institute Columbus Georgia United States 31904
    18 Rocky Mountain Diabetes and Osteoporosis Center Idaho Falls Idaho United States 83404
    19 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    20 Novak Center for Children's Health Louisville Kentucky United States 40202
    21 Johns Hopkins Hospital Baltimore Maryland United States 21287
    22 Boston Children's Hospital Boston Massachusetts United States 02115
    23 Joslin Diabetes Center Boston Massachusetts United States 02215
    24 Integrative Biosciences Center Detroit Michigan United States 48202
    25 University Of Mississippi Medical Center Jackson Mississippi United States 39216-4505
    26 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
    27 Advantage Clinical Trials Bronx New York United States 10468
    28 UBMD Pediatrics Buffalo New York United States 14203
    29 New York University Langone Medical Center New York New York United States 10016
    30 SUNY Upstate Medical University Syracuse New York United States 13210
    31 The University of North Carolina at Chapel Hill Chapel Hill North Carolina United States 27514
    32 University Hospitals of Cleveland Cleveland Ohio United States 44106
    33 University of Oklahoma Oklahoma City Oklahoma United States 73104
    34 University of Oklahoma Tulsa Oklahoma United States 74135
    35 Penn State College of Medicine Hershey Pennsylvania United States 17033
    36 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    37 Monument Health Rapid City Hospital, Inc. Rapid City South Dakota United States 57701
    38 LifeDoc Research, PLLC Memphis Tennessee United States 38119
    39 Vanderbilt University Medical Center Nashville Tennessee United States 37232
    40 Office of Amir A. Hassan, MD, P.A. Houston Texas United States 77089
    41 Saenz Medical Center La Joya Texas United States 78560
    42 Texas Diabetes Institute San Antonio Texas United States 78207
    43 University of Virginia Health System Charlottesville Virginia United States 22908
    44 Children's Hospital of Richmond at VCU Richmond Virginia United States 23219
    45 Sanatorio Allende S.A. Nueva Córdoba Argentina X5000JHQ
    46 Hospital de Clínicas Pte. Dr. Nicolás Avellaneda San Miguel de Tucumán Argentina 4000
    47 Instituto de Estudos e Pesquisas Clínicas IEP-CE Fortaleza Brazil 60160-230
    48 Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto Ribeirao Preto Brazil 14048-900
    49 University of Manitoba - Health Sciences Centre Winnipeg Manitoba Canada R3E 3P4
    50 The Hospital for Sick Children Toronto Ontario Canada M5G 1X8
    51 The First Hospital of Jilin University Changchun China 130021
    52 Zhengzhou Children'S Hospital Zhengzhou China 450017
    53 Centro de Diabetes Cardiovascular IPS Barranquilla Colombia 80020
    54 Dexa-Diab IPS Bogotá DC Colombia 110221
    55 Universitätsklinikum Freiburg Freiburg Germany 79106
    56 Soroka Univ. Medical Center Beer Sheva Israel 84101
    57 Rambam Medical Center Haifa Israel 31096
    58 The Chaim Sheba Medical Center Tel HaShomer Ramat-Gan Israel 5265601
    59 Severance Hospital Seoul Korea, Republic of 03722
    60 Asan Medical Center Seoul Korea, Republic of 05505
    61 Ajou University Hospital Suwon Korea, Republic of 16499
    62 Investigación en Salud y Metabolismo S.C. Chihuahua Mexico 31217
    63 CAIMED Investigacion en Salud, S.A. de C.V. Ciudad de México Mexico 06760
    64 Centro de Estudios de Investigación Metabólicos y Cardiovasculares, S.C. Ciudad Madero Mexico 89440
    65 Consultorio Medico Puebla Mexico 72190
    66 Investigacion Medica Sonora S.C. Sonora Mexico 83280
    67 Centro de Investigación Médica de Ocidente, S.C. Zapopan Mexico 45116
    68 San Juan Bautista School of Medicine Caguas Puerto Rico 00726
    69 Regional Clinical Hospital 'The Badge of Honor Order' Irkutsk Russian Federation 664049
    70 Ivanovo Reg.Clin.Hosp. Ivanovo Russian Federation 153040
    71 Rep.childrens clin.hosp. Izhevsk Russian Federation 426009
    72 State Medical University, Kazan Kazan Russian Federation 420012
    73 Munic. Instit. of HC "Kirov clin. hosp.#7 n.a.V.I.Urlova" Kirov Russian Federation 610014
    74 Endocrinology Scientific Center, MoH and Social Development Moscow Russian Federation 117036
    75 State Novosibirsk Regional Clinical Hospital Novosibirsk Russian Federation 630091
    76 Fed. State Budget Educational Instit. of Higher Education "Rostov State Med. Univ." of MoH of RF Rostov-on-Don Russian Federation 344022
    77 St. Petersburg State Pediatric University St. Petersburg Russian Federation 194100
    78 Siberian State Med.Uni,Faculty Therapy Dep.w/ Clin.Pharmacol Tomsk Russian Federation 634050
    79 Bahkir state med. Univ. of the Ministry Polyclinic Pediatric Ufa Russian Federation 450106
    80 Srinagarind Hospital Khon Kaen Thailand 40002
    81 Rajavithi Hospital Krung Thep Maha Nakhon Thailand 10400
    82 St George's Hospital London United Kingdom SW17 0QT
    83 Royal Berkshire Hospital Reading United Kingdom RG1 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:
    Aug 25, 2022
    Last Verified:
    Aug 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
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Empagliflozin
    Linagliptin

    Study Results

    No Results Posted as of Aug 25, 2022