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



Status:Recruiting
Conditions:Diabetes, Diabetes
Therapuetic Areas:Endocrinology
Healthy:No
Age Range:10 - 17
Updated:4/4/2019
Start Date:March 20, 2018
End Date:January 31, 2022
Contact:Boehringer Ingelheim
Email:clintriage.rdg@boehringer-ingelheim.com
Phone:1-800-243-0127

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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

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.


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
We found this trial at
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Orlando, Florida 32825
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1211 Medical Center Dr
Nashville, Tennessee 37232
(615) 322-5000
Phone: +001 (615) 343-8116
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4202 E Fowler Ave
Tampa, Florida 33620
(813) 974-2011
Phone: +001 (813) 974-5529
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Anchorage, Alaska 99508
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Atlanta, Georgia 30331
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Bronx, New York 10468
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Buffalo, New York 14203
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11100 Euclid Ave
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Houston, Texas 77062
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922 Southwest 82nd Avenue
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Miami Lakes, Florida
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1428 Madison Ave
New York, New York 10029
(212) 241-6500
Phone: +001 (212) 241-6936
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1919 E Thomas Rd
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2713 West Virginia Avenue
Tampa, Florida 33607
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