Phase 1 Study to Explore the Safety and Pharmacokinetics of DAPAglifozin in Adolescents and Adults With Type 1 Diabetes

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Dapagliflozin has been effective at lowering glucose and hemoglobin A1c (HbA1C) in subjects with tpye 2 diabetes (T2DM), when studied as monotherapy as well as in combination with insulin or oral anti-diabetic medications.This lead to investigations if this therapy would also be of benefit in type 1 diabetes as intensive insulin therapy is associated with glucose fluctuations, hypoglycemia, weight gain, and subsequent insulin resistance, all of which may reduce efficacy.

The purpose of the pilot study is to collect clinical data on the HbA1c-dependent effect of a single-dose of 10mg dapagliflozin on the insulin dose administered intravenously during a glucose-infusion and an oral mixed-meal for the ensuing 24 hours with blood glucose kept between 160 - 220 mg/dl.

The first objective is to investigate the degree of insulin dose reduction 24 hours after a single dose of 10mg dapagliflozin in patients with type 1 diabetes Further objectives are to investigate

• the effect on urinary glucose excretion

• if this effect is influenced by baseline glycemic control

• if dapagliflozin influences postprandial insulin need

• if dapagliflozin is associated with elevated ß-hydroxybutyrate levels

• PK after oral administration of 10mg dapagliflozin

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kinderkrankenhaus auf der Bult
• Treatments: Dapagliflozin

Criteria

Inclusion Criteria:

1. Provision of informed consent from participant and all legal representatives prior to any study specific procedures

2. Female and/or male aged 12 to 21years (both inclusive)

3. Subject must have type 1 diabetes (as diagnosed clinically) ≥ 12months

4. without completely inadequate glycemic control, defined as local laboratory A1c above 12.5% (subjects will be stratified according to glycemic control being in target (A1c 5.5 to 7.4%), slightly elevated (7.5 - 9.0%) or clearly elevated 9.1 - 12.5% ) obtained at the screening visit (Note: A one-time central laboratory re-test of the A1C is allowed)

5. Insulin use with an average daily dose between 0.6 - 2.0 U/kg, either continuous subcutaneous insulin infusion, (CSII) or multiple doses (at least 2x/day) of insulin

6. BMI 18.0 to 35.0 kg/m2 for adults or BMI between 10th and 99th age and gender related centile for pediatric patients

7. Minimum weight of 50 kg

8. Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study as judged by the investigator

9. WOCBP must have a negative urine pregnancy test at screening as well as at Visit 2 and Visit 4.

10. Women must not be breastfeeding

Exclusion Criteria:

1. History of T2DM, maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis

2. Any use of oral hypoglycemic agents within 12 months prior to the screening visit

3. History of diabetes ketoacidosis (DKA) within 12 weeks prior to prior to the screening visit

4. History of diabetes insipidus

5. History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 3 months prior to prior to the screening visit

6. Frequent episodes of hypoglycemia as defined by more than one episode requiring assistance, emergency care (paramedics or emergency room care) or glucagon therapy, or more than 2 unexplained episodes of symptomatic hypoglycemia within 3 months prior to the screening visit. An unexplained event is defined as an event that cannot be explained by circumstances such as dietary (e.g. missed meal), strenuous exercise, error in insulin dosing, etc.

7. Hypoglycemic unawareness

8. History of Addison's disease or chronic adrenal insufficiency

9. Prisoners or subjects who are involuntarily incarcerated

10. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness

11. Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for > 4 weeks within 3 months prior to Day -3 visit. NOTE: Topical or inhaled corticosteroids are allowed.

12. Any unstable endocrine, psychiatric, rheumatic disorders as judged by the Investigator.

13. Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data.

14. Subject with any condition which, in the judgment of the Investigator, may render the subject unable to complete the study or which may pose a significant risk to the subject.

15. Subject is currently abusing alcohol or other drugs or has done so within the last 6 months.

16. Subject is a participating investigator, study coordinator, employee of an investigator or immediate family member of any of the aforementioned.

17. Administration of any other investigational drug within 30 days of planned enrolment to this study.

18. No clinical conditions or clinically significant abnormalities, in any laboratory value(s) collected after screening and prior to randomization which, in the Investigator's judgment, should preclude entry into the treatment period