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CompletedNCT02325206DAPA-IIT1Updated Feb 19, 2016

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

A Phase 1 interventional study of dapagliflozin and Placebo in Type 1 Diabetes, sponsored by Kinderkrankenhaus auf der Bult. Completed at 1 site in Germany. Open to participants aged 12 Years to 21 Years. Per ClinicalTrials.gov, last updated 2016-02-19.

Sponsored by Kinderkrankenhaus auf der Bult · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
36
Allocation
Randomized
Ages
12 Years to 21 Years
Sex
All
01

Study 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
Read the detailed description

The purpose of the study is to evaluate the safety profile and tolerability, particularly with regard to hypoglycemia and ketone development, following once daily oral dose of 10 mg of dapagliflozin administered in subjects with type 1 diabetes (T1DM) as a single dose as well as pharmacokinetics (PK) for 18 hours of treatment.

The study aimed to patients who have different degrees of inadequate glycemic control despite insulin use. Approximately 36 subjects will be screened in order to randomize 10 patients in each different HbA1C category.

The trial will consist of six visits: a screening visit (Visit 1), two dosing visits (Visit 2 and Visit 4), two phone visits (Visit 3 and Visit 5) and a follow-up visit (Visit 6). Furthermore, an information visit will take place prior to the screening visit in order to obtain patient's informed consent. Screening will take place 2-21 days prior to Visit 2 and the follow-up visit will take place 5-21 days after the end of Visit 4. The dosing visits will be separated by a wash-out period (5-30 days between the end of Visit 2 and begin of Visit 4) during which the subjects will resume their normal insulin treatment. Each phone visit (Visit 3 and Visit 5) will take place 3-5 days after the end of dosing Visits 2 and 4. The planned total duration of the trial is 18-78 days per subject (rescheduled visits excluded). Each subject will be randomised to a treatment sequence consisting of two treatment periods in which the subjects will receive dapagliflozin and placebo on two separate dosing visits.

Subjects metabolic control will be achieved by a variable i.v. infusion of human insulin by an infusion pump. The procedure will be used in order to aim and maintain blood glucose levels between 160 and 220 mg/dl thereby being in the range of the urinary threshold of glucose.

The fluid infusion and insulin dosing scheme will depend on body weight (BW) and blood glucose (BG) levels.

Two standardized mixed-meals will be given 6 hours and 12 hours after dosing. Blood glucose measurements will be performed every 15min for 120min after the mixed-meal.

Blood samples for determination of dapagliflozin concentration in serum will be taken 18times in 24hours as well as every urine sample will be collected for 24 hours after dosing for the determination of 24hour urinary glucose and creatinine for efficacy measurement.

After conclusion of the trial the documented insulin doses over time will be summed up for calculation of the total insulin dose and the insulin dose per kg body weight per 24 hours. Separate calculations will be done for the overnight period pre-dosing, six hours after dosing, two hours prior and after the first and second Standard Meal and until the end of the visit.

02

Conditions studied

  • Type 1 Diabetes
03

In context

Diabetes Mellitus, Type 1

3,614 studies on the registry are indexed under Diabetes Mellitus, Type 1; 586 are open to participants now.

This study's enrollment of 36 is close to the median of 40 across 2,718 interventional studies indexed under Diabetes Mellitus, Type 1.

Browse Diabetes Mellitus, Type 1 studies →

Lead sponsor

Kinderkrankenhaus auf der Bult is the lead sponsor of 14 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
36 participants (actual)

Study arms

  • Experimental
    dapafliflozin

    one administration of 10mg dapagliflozin as tablet

    Drug: dapagliflozin

  • Placebo comparator
    placebo

    one administration as tablet identical to the experimental drug

    Drug: Placebo

Interventions

  • one administration in the morning

    Also known as: Forxiga

  • DrugPlacebo

    one administration in the morning

    Also known as: Control

06

What researchers measure

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

    Time frame: 24hours

Secondary outcomes

  1. HbA1c effect

    effect of baseline HbA1c on insulin-dose lowering effect of 10mg dapagliflozin

    Time frame: 24hours

  2. urinary glucose excretion

    increase of urinary glucose excretion with blood glucose kept between 160 - 220 mg/dl 24 hours after oral administration of 10mg dapagliflozin

    Time frame: 24hours

07

Study locations

1 site
  • Kinder - und Jugendkrankenhaus AUF DER BULT
    Hanover, 30173, Germany
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Dec 2014, a primary completion of Dec 2015 and a completion of Dec 2015. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 19, 2014
First posted
Dec 24, 2014
Start
Dec 2014
Primary completionActual
Dec 2015
CompletionActual
Dec 2015
Last update
Feb 19, 2016
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 19, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02325206
Lead sponsor
Kinderkrankenhaus auf der Bult
Responsible party
Thomas Danne (Prof. Dr. med., Kinderkrankenhaus auf der Bult) — Principal investigator
First posted
Dec 24, 2014
Start date
Dec 2014
Primary completion
Dec 2015
Completion
Dec 2015
Last update
Feb 19, 2016

Study contacts

Thomas Danne, MD
principal investigator · Kinderkrankenhaus auf der Butl

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Dapagliflozin

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