Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO)TM
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

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.
    


Intervention name(s): Linagliptin; Empagliflozin; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Film Coated Tablet; Film Coated Tablet; Film Coated Tablet
Other intervention name(s): ONDERO, TRAJENTA, TRAYENTA, TRAZENTA, TRADJENTA; JARDIANCE, JARDIANZ, GIBTULIO
Intervention MeSH terms: Empagliflozin; Linagliptin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment