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

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ClinicalTrials.gov Identifier: NCT03429543
Recruitment Status : Recruiting
First Posted : February 12, 2018
Last Update Posted : June 13, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

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.

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
Diabetes Mellitus, Type 2 Drug: Linagliptin Drug: Empagliflozin Drug: Placebo Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 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 : March 20, 2018
Estimated Primary Completion Date : July 5, 2021
Estimated Study Completion Date : January 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Linagliptin
Linagliptin arm. Oral route. Linagliptin tablets administered once daily for 52 weeks
Drug: Linagliptin
Film Coated Tablet
Other Name: 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 Name: 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




Primary Outcome Measures :
  1. Change from baseline in HbA1c (%) [ Time Frame: 26 Weeks ]

Secondary Outcome Measures :
  1. Change from baseline in fasting plasma glucose (mg/dl) [ Time Frame: 26 Weeks ]
  2. Change from baseline in body weight (kg) [ Time Frame: 26 Weeks ]
  3. Change from baseline in systolic blood pressure (SBP) [ Time Frame: 26 Weeks ]
  4. Change from baseline in diastolic blood pressure (DBP) [ Time Frame: 26 Weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 for at least 12 weeks at Visit 1A
  • Insufficient glycaemic control (HbA1c ≥ 6.5% and ≤ 10.5%) as measured by the central laboratory at Visit 1A
  • Patients treated with

    • diet and exercise plus metformin at a stable dose for 8 weeks prior to Visit 2 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 Patients treated with diet and exercise only and 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) are also eligible in this trial.
  • 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

Exclusion Criteria:

  • Positive for islet cell antigen auto-antibodies (IA-2) and glutamic acid decarboxylase (GADA) auto antibodies as measured by the central laboratory at Visit 1A
  • Any history of ketoacidosis within 8 weeks prior to Visit 1A
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03429543


Contacts
Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
United States, Florida
Solutions Through Advanced Research, Inc. Recruiting
Jacksonville, Florida, United States, 32256
Contact: Thanh Nguyen    +001 (904) 619-8157    thanh.nguyen@jaxadvresearch.com   
Celen Medical Group Corp Recruiting
Miami, Florida, United States, 33135
Contact: Celia Padron    +001 (305) 587-2408    cpadronmd@celenmedical.com   
Global Health Clinical Trials, Corp Recruiting
Miami, Florida, United States, 33135
Contact: Rafael Cardenas    +001 (786) 409-5439    rcardenasmd@ghctrial.com   
Medical Research Center of Miami II Inc. Recruiting
Miami, Florida, United States, 33144
Contact: Yuneisy Garcia    +001 (305) 249-1183    yuneisy.garcia@medicalinvestigations.org   
Oceane7 Clinical Research Recruiting
Miami, Florida, United States, 33144
Contact: Edgar Gonzalez    +001 (305) 261-2738    e.gonzalez@oceane7.us   
Clinical Research Trials of Florida, Inc. Recruiting
Tampa, Florida, United States, 33607
Contact: Sady Alpizar    +001 (813) 873-8102    s.alpizar.md@gmail.com   
United States, Idaho
Rocky Mountain Diabetes and Osteoporosis Center Recruiting
Idaho Falls, Idaho, United States, 83404
Contact: Carl Vance    +001 (208) 523-1122    cdv-research@idahomed.com   
United States, New York
Advantage Clinical Trials Recruiting
Bronx, New York, United States, 10468
Contact: Giancarlo Guido    +001 (917) 962-0234    Gianguido2386@gmail.com   
Park Avenue Endocrinology and Nutrition Recruiting
New York, New York, United States, 10021
Contact: Dennis Gage    +001 (914) 906-7686    dgage68562@aol.com   
United States, Texas
Avant Research Associates LLC Recruiting
Beaumont, Texas, United States, 77702
Contact: Maria Blahey    +001 (409) 750-7262    blahey@avantresearch.com   
Research Institute of Dallas Recruiting
Dallas, Texas, United States, 75231
Contact: Stephen Aronoff    +001 (214) 265-2137    researcharonoff@yahoo.com   
Centex Studies, Inc. Recruiting
Houston, Texas, United States, 77058
Contact: Joe Pouzar    +001 (832) 457-2167    joepouzar@centexstudies.com   
Office of Amir A. Hassan, MD, P.A. Recruiting
Houston, Texas, United States, 77089
Contact: Amir Hassan    +001 (281) 944-3610    amir@clinicalrc.net   
Colombia
Centro de Diabetes Cardiovascular IPS Not yet recruiting
Barranquilla, Colombia, 80020
Contact: Jaime Ibarra Gomez    +57 315 7088373    glucosajoi@hotmail.com   
Dexa-Diab IPS Not yet recruiting
Bogotá DC, Colombia, 110221
Contact: Hernán Yupanqui Lozno    +57 1236 0710    h.yupanqui1@hotmail.com   
IPS Universitaria Servicio Salud - Universidad de Antioquia Not yet recruiting
Medellín, Colombia
Contact: Martín Toro Ramos    +57 3004229024    martoram1@gmail.com   
Korea, Republic of
Severance Hospital Recruiting
Seoul, Korea, Republic of, 03722
Contact: Ho-Seong Kim    82 2 2228 2069    kimho@yuhs.ac   
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 05505
Contact: Han-Wook Yoo    82 2 3010 3374    hwyoo@amc.seoul.kr   
Ajou University Hospital Recruiting
Suwon, Korea, Republic of, 16499
Contact: Jin Soon Hwang    82 31 219 5166    pedhwang@ajou.ac.kr   
Sponsors and Collaborators
Boehringer Ingelheim

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03429543     History of Changes
Other Study ID Numbers: 1218-0091
2016-000669-21 ( EudraCT Number )
First Posted: February 12, 2018    Key Record Dates
Last Update Posted: June 13, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2
Empagliflozin
Linagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action