Pilot Study to Explore the Efficacy of DAPAglifozin as add-on to Closed-loop Control in Patients With Type 1 Diabetes

NCT02987738 | Completed Phase 1 DMC

• 1 other identifier: ESR-15-11453
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Dapagliflozin has a unique mechanism of action that does not directly affect either insulin resistance or insulin secretion, but rather improves glycemia by reduction of glucose re-absorption from proximal renal tubules. Dapagliflozin is expected to reduce mean daily glucose, improve glycemic control and reduce overall insulin requirements. Improved glycemic control with reduced variability may also lead to reduced frequency of hypoglycemia. In youth with T1D, Dapagliflozin led to a significant reduction of insulin needed to achieve target glucose irrespective of preexisting HbA1c levels. In this pilot study data will be collected to investigate the effect on glucose of two doses of 10mg (each) dapagliflozin within range for the ensuing 24 hours during the DreaMed automated insulin delivery in patients with type 1 diabetes dosing with dapagliflozin in an in-patient setting combined with an automated sensor based CE marked insulin delivery system to data if dapagliflozin is a suitable add-on therapy. This will provide optimal monitoring of subject safety and assessment of the effects of dapagliflozin in a structured setting. If this inpatient study shows evidence that Dapagliflozin is a suitable add on therapy and leads to an increase of time within the target glucose range when using a sensor based insulin pump therapy (closed-loop) further outpatient studies are planned to be conducted.

Conditions

Type1diabetes

Outcome Measures

Primary Outcomes (1)

• Time in Range 70-180%

  Collection of clinical data regarding the treatment of two doses of 10mg dapagliflozin as add-on to night and day closed-loop control using the DreaMed Algorithm and the time within glucose range 70-180 mg/dl (3.9-10mmol/l) \[%\]

  24 hours

Secondary Outcomes (4)

• urinary glucose excretion

  24 hours

• postprandial insulin need

  24 hours

• ß-hydroxybutyrate

  24 hours

• Reduction of Insulin dose

  24 hours

Study Arms (2)

dapagliflozin

EXPERIMENTAL

two administrations of 10 mg dapagliflozin as tablet

Drug: Dapagliflozin

Placebo Oral Tablets

PLACEBO COMPARATOR

two administrations identical to the experimental drug

Drug: Placebo Oral Tablet

Interventions

Dapagliflozin DRUG

two administrations in the evening and 12 hours later

Also known as: Forxiga

dapagliflozin

Placebo Oral Tablet DRUG

two administrations in the evening and 12 hours later

Also known as: Control

Placebo Oral Tablets

Eligibility Criteria

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

You may qualify if:

• Male or female aged 12-21 years (both inclusive)
• Type 1 diabetes mellitus (as diagnosed clinically) ≥ 12 months
• No DKA 12 weeks prior to the study
• On CSII (insulin pump therapy) since at least 3 months
• Average daily dose of Insulin between 0.6 - 2.0 U/kg
• Body mass index 18 to 35 kg/m2 or the 10th to 99th centile for BMI according to age and gender with a minimum weight of 50kg
• A1c range 6,5% - 11% (inclusive)

You may not qualify if:

• History of drug or alcohol abuse within the last five years prior to screening
• Anamnestic history of hypersensitivity to the study drugs (or any component of the study drug) or to drugs with similar chemical structures
• History of severe or multiple allergies
• Treatment with any other investigational drug within 3 months prior to screening
• Progressive fatal disease
• History of significant cardiovascular, respiratory, gastrointestinal, hepatic (ALAT and/or ASAT \> 3 times the normal reference range), renal (creatinine \> 1.1 mg/dl in women and \> 1.5 mg/dl in men), neurological, psychiatric and/or hematological disease as judged by the investigator
• Pregnant or lactating women
• Sexually active women of childbearing potential not consistently and correctly practicing birth control by implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner
• Lack of compliance or other similar reason that, according to investigator, precludes satisfactory participation in the study
• History of Type 2 diabetes, 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.

Sponsors & Collaborators

• Kinderkrankenhaus auf der Bult: lead
• AstraZeneca: collaborator
• Alcedis GmbH: collaborator

Study Sites (1)

Kinder - und Jugendkrankenhaus AUF DER BULT

Hanover, 30173, Germany

Location

MeSH Terms

Interventions

dapagliflozin

Study Officials

• Thomas Danne, MD

  Kinder- und Jugendkrankenhaus AUF DER BULT

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2016
• First Posted: December 9, 2016
• Study Start: February 9, 2017
• Primary Completion: December 19, 2017
• Study Completion: December 19, 2017
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)