T2NOW

• Research type

  Research Study

• Full title

  A 26 Week, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Parallel Group, Phase 3 Trial with a 26 Week Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 5 and 10 mg, and Saxagliptin 2.5 and 5 mg in Pediatric Patients with Type 2 Diabetes Mellitus who are between 10 and below 18 years of age

• IRAS ID

  209719

• Contact name

  Timothy Barrett

• Sponsor organisation

  AstraZeneca AB

• Eudract number

  2015-005042-66

• Duration of Study in the UK

  2 years, 7 months, 0 days

• Research summary

  Research Summary

  Diabetes Mellitus (DM) is a condition that causes a person's blood sugar level to become too high. There are two main types of DM: type 1 and type 2, with type 2 DM (T2DM) making up about 90% of all DM cases.
  DM is associated with severe side effects like vision loss and lower limb amputation. In 2012, DM was the direct cause of 1.5 million deaths.
  Until recently, T2DM was seen only in adults but it is now also occurring in children. Data from T2DM children for treatment are limited. Several oral blood sugar lowering medications are available for adults with T2DM, the only one approved for use in paediatric patients aged 10 and older is metformin.

  Saxagliptin and dapagliflozin have demonstrated, both individually and in combination with insulin or metformin, a favourable safety and tolerability profile in the adult development program.
  The purpose of this research study is to evaluate the effectiveness and safety of dapagliflozin and saxagliptin in patients with Type 2 Diabetes who are aged 10 to below 18 years old and are currently on diet and exercise and taking metformin, insulin, or both medicines.

  For this study, there will first be a screening phase of up to 6 weeks, followed by a 2 week lead in phase. Thereafter there will be a 26 week short-term treatment phase (week 1-week 26), and a 26 week long-term treatment phase (week 27-week 52). Following this there will be a follow-up telephone call on week 56 and a post study visit at week 104. (Please see below for more details).

  Approximately 243 participants between the ages of 10 and 18 years will be allowed to take part in the study.

  Summary of Results

  The purpose of this research study was to evaluate the effectiveness and safety of dapagliflozin and saxagliptin in participants with Type 2 Diabetes Mellitus (T2DM) aged 10 to below 18 years old and on a diet and exercise regime and taking metformin, insulin, or both medicines. A total of 245 participants from 21 countries were allowed to take part in the study. Participants were initially randomised in a 1:1:1 ratio to receive dapagliflozin 5 mg, saxagliptin 2.5 mg, or placebo (a pill that contains no medicine). 81 participants were radomised to the dapagliflozin group, 88 participants to the saxagliptin group, and 76 participants to the placebo group.

  For this study, there was a screening phase of up to 6 weeks, followed by a 2 week lead in phase. Then there was a 26 week short-term (ST) treatment phase (week 1-week 26), and a 26 week long-term (LT) treatment phase (week 27-week 52).The study medication was discontinued at Week 52, after which participant treatment was left to the Investigator's discretion. Following this there was a follow-up telephone call on week 56 and a post study visit at week 104.

  Of the randomised participants, 73 (90.1%), 82 (93.2%), and 66 (86.8%) participants in the dapagliflozin, saxagliptin, and placebo groups, respectively, completed study medication treatment throughout the 26-week double-blind (meaning neither investigators or participants knew which medication was given) ST period and 76 (93.8%), 83 (94.3%), and 68 (89.5%) participants, respectively, completed the ST period. All participants who completed the ST period entered the LT period. Of the randomised participants, 71 (87.7%), 75 (85.2%), and 56 (73.7%) participants in the dapagliflozin, saxagliptin, and placebo groups, respectively, completed study medication treatment throughout the LT period and 75 (92.6%), 79 (89.8%), and 61 (80.3%), respectively, completed the LT period.

  Sugar in the blood (glucose) can be measured through the haemoglobin A1c (HbA1c) test. Haemoglobin is the part of red blood cells that carry oxygen throughout the body. The higher the value, the more glucose in the blood.

  Add-on treatment with dapagliflozin resulted in a statistically significant and clinically meaningful improvement in glycaemic control in paediatric T2DM participants 10 to < 18 years of age who had haemaglobin A1c levels of 6.5% to 10.5% on diet and exercise and metformin, insulin, or metformin plus insulin at enrolment.

  Safety results were consistent with the overall well-established safety profile for dapagliflozin, and no new safety concerns were identified. Safety data indicates that dapagliflozin was well-tolerated in the treated paediatric participants.

  Add-on treatment with saxagliptin resulted in a numerical but not statistically significant improvement in glycaemic control compared with placebo in paediatric T2DM participants 10 to < 18 years of age who had HbA1c levels of 6.5% to 10.5% on diet and exercise and metformin, insulin, or metformin plus insulin at enrolment.

  Safety results were consistent with the overall well-established safety profile for saxagliptin in adults with T2DM, and no new safety concerns were identified. Safety data indicates that saxagliptin was well-tolerated in the treated paediatric participants.

  Overall, no new safety concerns were identified during the Week 104 non-treatment follow-up period in children with T2DM aged 10 to < 18 years of age who received up to 52 weeks of dapagliflozin or saxagliptin treatment.

• REC name

  West Midlands - Edgbaston Research Ethics Committee

• REC reference

  17/WM/0299

• Date of REC Opinion

  6 Oct 2017

• REC opinion

  Further Information Favourable Opinion