Type 1 DiabetesPhase 1DAPA-IIT1NCT02325206
Phase 1 Study to Explore the Safety and Pharmacokinetics of DAPAglifozin in Adolescents and Adults With Type 1 Diabetes
A Phase 1 study testing dapagliflozin in people with Type 1 Diabetes, run by Kinderkrankenhaus auf der Bult at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 21 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- dapagliflozin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2014to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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.
Show all 18Show fewer
- 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.
- Subject is a participating investigator, study coordinator, employee of an investigator or immediate family member of any of the aforementioned.
- Administration of any other investigational drug within 30 days of planned enrolment to this study.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Double-blind, Placebo-controlled, Single-center Phase 1 Study to Explore the Safety and Pharmacokinetics of DAPAglifozin as Add-on to Intravenous Insulin-infusion in Adolescents and Adults With Type 1 Diabetes
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.
Read more
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.
- Conditions
- Type 1 Diabetes
- Being tested
- dapagliflozin, Placebo
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dapagliflozinDrug
Also called Forxiga
one administration in the morning
PlaceboDrug
Also called Control
one administration in the morning
| Study group | Role | What they receive |
|---|---|---|
| dapafliflozin | Experimental | one administration of 10mg dapagliflozin as tablet Receives: Drug: dapagliflozin |
| placebo | Placebo comparator | one administration as tablet identical to the experimental drug Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 24hours
Secondary outcomes (2)
HbA1c effect
effect of baseline HbA1c on insulin-dose lowering effect of 10mg dapagliflozin
Measured: 24hours
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
Measured: 24hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kinderkrankenhaus auf der Bult
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Thomas Danne, Kinderkrankenhaus auf der Bult
- Investigators
- Thomas Danne, MD, Principal investigator, Kinderkrankenhaus auf der Butl
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02325206
- Sponsor's protocol ID
- ESR-14-10179
- Acronym
- DAPA-IIT1
- Status last verified
- Feb 2016
- First submitted
- 19 Dec 2014
- Last updated
- 19 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Placebo-controlled, Single-center Phase 1 Study to Explore the Safety and Pharmacokinetics of DAPAglifozin as Add-on to Intravenous Insulin-infusion in Adolescents and Adults With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02325206
- Acronym / sponsor ID
- DAPA-IIT1 / ESR-14-10179
- Conditions
- Type 1 Diabetes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Kinderkrankenhaus auf der BultUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 24 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dapafliflozin | Experimental | Drug: dapagliflozinone administration of 10mg dapagliflozin as tablet |
| placebo | Placebo comparator | Drug: Placeboone administration as tablet identical to the experimental drug |
Who may qualify
- Ages
- 12 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dapagliflozinAlso: Forxigaone administration in the morning | Drug | dapafliflozin |
| PlaceboAlso: Controlone administration in the morning | Drug | placebo |
Primary outcome
reduction of intravenous insulin dose
Time frame: 24hours
reduction of intravenous insulin dose with glucose kept between 160 - 240 mg/dl 24 hours after oral administration of 10mg dapagliflozin
2 secondary outcomes
HbA1c effect
Time frame: 24hours
urinary glucose excretion
Time frame: 24hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2016.
- Individual participant dataSharing planned: No
Related trials for Type 1 Diabetes
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Danne, MD principal investigator
Kinderkrankenhaus auf der Butl
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing dapagliflozin in people with Type 1 Diabetes, run by Kinderkrankenhaus auf der Bult at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
reduction of intravenous insulin dose (time frame: 24hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2016.