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

NCT02325206 | Completed Phase 1 DMC

• 1 other identifier: ESR-14-10179
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Type 1 Diabetes

Outcome Measures

Primary Outcomes (1)

• reduction of intravenous insulin dose

  reduction of intravenous insulin dose with glucose kept between 160 - 240 mg/dl 24 hours after oral administration of 10mg dapagliflozin

  24hours

Secondary Outcomes (2)

• HbA1c effect

  24hours

• urinary glucose excretion

  24hours

Study Arms (2)

dapafliflozin

EXPERIMENTAL

one administration of 10mg dapagliflozin as tablet

Drug: dapagliflozin

placebo

PLACEBO COMPARATOR

one administration as tablet identical to the experimental drug

Drug: Placebo

Interventions

dapagliflozin DRUG

one administration in the morning

Also known as: Forxiga

dapafliflozin

Placebo DRUG

one administration in the morning

Also known as: Control

placebo

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Provision of informed consent from participant and all legal representatives prior to any study specific procedures
• Female and/or male aged 12 to 21years (both inclusive)
• Subject must have type 1 diabetes (as diagnosed clinically) ≥ 12months
• 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)
• 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
• BMI 18.0 to 35.0 kg/m2 for adults or BMI between 10th and 99th age and gender related centile for pediatric patients
• Minimum weight of 50 kg
• 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
• WOCBP must have a negative urine pregnancy test at screening as well as at Visit 2 and Visit 4.
• Women must not be breastfeeding

You may not qualify if:

• History of T2DM, maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
• Any use of oral hypoglycemic agents within 12 months prior to the screening visit
• History of diabetes ketoacidosis (DKA) within 12 weeks prior to prior to the screening visit
• History of diabetes insipidus
• History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 3 months prior to prior to the screening visit
• 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.
• Hypoglycemic unawareness
• History of Addison's disease or chronic adrenal insufficiency
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness
• 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.
• Any unstable endocrine, psychiatric, rheumatic disorders as judged by the Investigator.
• 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.
• 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.
• Subject is currently abusing alcohol or other drugs or has done so within the last 6 months.

Sponsors & Collaborators

• Kinderkrankenhaus auf der Bult: lead

Study Sites (1)

Kinder - und Jugendkrankenhaus AUF DER BULT

Hanover, 30173, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Thomas Danne, MD

  Kinderkrankenhaus auf der Butl

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: December 24, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 19, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)