Type 1 Diabetes MellitusPhase 2NCT01498185
BMS - Safety, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Dapagliflozin in Type 1 Diabetes
A Phase 2 study testing Dapagliflozin in people with Type 1 Diabetes Mellitus, run by AstraZeneca at 12 sites in United States.
Trial summary
To obtain safety and tolerability information in patients with type 1 diabetes where Dapagliflozin is added on to Insulin (for 14 days) Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- 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
- 171 participants
- Where
- 12 sitesUnited States
- Study dates
- Feb 2012to Oct 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes with central lab Glycosylated hemoglobin (A1C) ≥ 7.0% and ≤ 10.0%
- Insulin use for at least 12 months and initiation immediately after diagnosis of diabetes
- Method of Insulin administration [multiple daily injections (MDI) or continuous subcutaneous Insulin infusion (CSII)] stable ≥ 3 months
- Stable basal Insulin dose ≥ 2 weeks
- Ages 18 to 65 years
- Central laboratory C-peptide value of < 0.7 ng/mL
- Body mass index (BMI) 18.5 to 35.0 kg/m2
Who cannot join
- History of type 2 diabetes mellitus (T2DM), maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
- Oral hypoglycemic agents
- History of diabetes ketoacidosis (DKA) within 24 weeks
- History of hospital admission for glycemic control within 6 months
- Frequent episodes of hypoglycemia (2 unexplained within 3 months) or hypoglycemic unawareness
- Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) or Serum total bilirubin > 2X Upper limit of normal (ULN)
Show all 9Show fewer
- Abnormal Free T4 [if screening Thyroid Stimulating Hormone (TSH) abnormal]
- Estimated glomerular filtration rate (eGFR) Modification of Diet in Renal Disease (MDRD) formula ≤ 60 mL/min/1.73m2
- Cardiovascular (CV)/Vascular Diseases within 6 months
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
United States12 sites
Profil Institute For Clinical Research, Inc.
Chula Vista, California, 91911
Dallas Diabetes & Endocrine Center
Dallas, Texas, 75230
Jasper Clinic, Inc.
Kalamazoo, Michigan, 49007
Kansas City University Of Medicine And Biosciences
Kansas City, Missouri, 64106
Central Kentucky Research Associates, Inc.
Lexington, Kentucky, 40509
Louisiana Research Associates, Inc.
New Orleans, Louisiana, 70114
Compass Research Phase 1, Llc
Orlando, Florida, 32806
Vince And Associates Clinical Research
Overland Park, Kansas, 66212
Progressive Medical Research
Port Orange, Florida, 32127
Regional Medical Clinic-Endocrinology
Rapid City, South Dakota, 57701
Va San Diego Healthcare System
San Diego, California, 92161
La Biomed Research Inst. At Harbor Ucla Med Ctr.
Torrance, California, 90502
About this study
Official title: A Randomized, Double-Blind, Placebo-controlled, Parallel Group, Phase 2 Trial to Explore the Safety, Pharmacokinetics and Pharmacodynamics of Dapagliflozin as an Add-on to Insulin Therapy in Subjects With Type 1 Diabetes Mellitus
To obtain safety and tolerability information in patients with type 1 diabetes where Dapagliflozin is added on to Insulin (for 14 days)
Read the detailed description
Study Classification : Safety, Pharmacokinetics and Pharmacodynamics
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Dapagliflozin, Placebo matching Dapagliflozin
- 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
Tablets, Oral, 1 mg, Once daily, 14 days
Placebo matching DapagliflozinDrug
Tablets, Oral, 0 mg, Once daily, 14 days
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Dapagliflozin (1 mg) | Experimental | Not described Receives: Drug: Dapagliflozin |
| Arm 2: Dapagliflozin (2.5 mg) | Experimental | Not described Receives: Drug: Dapagliflozin |
| Arm 3: Dapagliflozin (5 mg) | Experimental | Not described Receives: Drug: Dapagliflozin |
| Arm 4: Dapagliflozin (10 mg) | Experimental | Not described Receives: Drug: Dapagliflozin |
| Arm 5: Placebo matching Dapagliflozin | Experimental | Not described Receives: Drug: Placebo matching Dapagliflozin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in 7-Point Glucose Monitoring (7-PGM) at Day 7
7-PGM was measured as milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the assessment on Day -1, prior to the start date and time of the first dose of the double-blind study medication. 7-PGM included the average of all available glucose values before and 2-hour (hr) after each meal (breakfast, lunch, dinner) as well as bedtime. Measurements were on Day -1, and Day 7 in the double-blind period.
Measured: From Baseline to Day 7
Secondary outcomes (7)
Dapagliflozin Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax)
Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Cmax was recorded directly from experimental observations.
Measured: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax)
Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Tmax was recorded directly from experimental observations.
Measured: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The concentrations below the lower limit of quantitation (<LLOQ) were set as "missing" for the calculation of PK parameters as well as summary statistics. AUC[TAU], was calculated by a mixture of logand linear-trapezoidal summations.
Measured: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax)
Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Cmax was recorded directly from experimental observations.
Measured: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax)
Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The Tmax was recorded directly from experimental observations.
Measured: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The concentrations below the lower limit of quantitation (<LLOQ) were set as "missing" for the calculation of PK parameters as well as summary statistics. AUC[TAU], was calculated by a mixture of logand linear-trapezoidal summations.
Measured: Day 7 (0 hr to 24 hr post dose)
Pharmacokinetic Parameters on Day 7 - Ratio of Metabolite (RM) to Parent AUC[TAU]
Serial blood samples were collected predose 0 hr, and hr 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 in the double-blind period. Individual subject PK parameter values were derived by non-compartmental methods by a validated PK analysis program, Kinetica®. Actual sampling times were used for PK calculations and nominal times were used for generation of mean plasma concentration-time plots and summaries. Pre-dose sample collection times were changed from negative numbers (based on elapsed time to dose) to zero for the purpose of calculating PK parameters. The concentrations below the lower limit of quantitation (<LLOQ) were set as "missing" for the calculation of PK parameters as well as summary statistics. MR was calculated as the ratio of metabolite to parent AUC(TAU), corrected for molecular weights of dapagliflozin and dapagliflozin 3-O-glucuronide (408.82 and 584.99, respectively).
Measured: Day 7 (0 hr to 24 hr post dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2011 (estimated)
- Study startFeb 2012
- Primary completionOct 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Astra Zeneca, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01498185
- Sponsor's protocol ID
- MB102-072
- Status last verified
- Dec 2016
- First submitted
- 21 Dec 2011
- Last updated
- 10 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Melin J, Tang W, Rekic D, Hamren B, Penland RC, Boulton DW, Parkinson J. Dapagliflozin Pharmacokinetics Is Similar in Adults With Type 1 and Type 2 Diabetes Mellitus. J Clin Pharmacol. 2022 Oct;62(10):1227-1235. doi: 10.1002/jcph.2062. Epub 2022 May 2.
PubMed 35403243Henry RR, Rosenstock J, Edelman S, Mudaliar S, Chalamandaris AG, Kasichayanula S, Bogle A, Iqbal N, List J, Griffen SC. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2015 Mar;38(3):412-9. doi: 10.2337/dc13-2955. Epub 2014 Sep 30.
PubMed 25271207
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-controlled, Parallel Group, Phase 2 Trial to Explore the Safety, Pharmacokinetics and Pharmacodynamics of Dapagliflozin as an Add-on to Insulin Therapy in Subjects With Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01498185
- Acronym / sponsor ID
- MB102-072
- Conditions
- Type 1 Diabetes Mellitus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 171 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Astra Zeneca, Bristol-Myers Squibb
- Study start
- Feb 2012
- Primary completion
- Oct 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 23 Dec 2011 (estimated)
- Results
- Posted 10 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To obtain safety and tolerability information in patients with type 1 diabetes where Dapagliflozin is added on to Insulin (for 14 days)
Detailed description
Study Classification : Safety, Pharmacokinetics and Pharmacodynamics
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Dapagliflozin (1 mg) | Experimental | Drug: Dapagliflozin |
| Arm 2: Dapagliflozin (2.5 mg) | Experimental | Drug: Dapagliflozin |
| Arm 3: Dapagliflozin (5 mg) | Experimental | Drug: Dapagliflozin |
| Arm 4: Dapagliflozin (10 mg) | Experimental | Drug: Dapagliflozin |
| Arm 5: Placebo matching Dapagliflozin | Experimental | Drug: Placebo matching Dapagliflozin |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Type 1 diabetes with central lab Glycosylated hemoglobin (A1C) ≥ 7.0% and ≤ 10.0%
- Insulin use for at least 12 months and initiation immediately after diagnosis of diabetes
- Method of Insulin administration [multiple daily injections (MDI) or continuous subcutaneous Insulin infusion (CSII)] stable ≥ 3 months
- Stable basal Insulin dose ≥ 2 weeks
- Ages 18 to 65 years
Key exclusion criteria (9 listed)
- History of type 2 diabetes mellitus (T2DM), maturity onset diabetes of young (MODY), pancreatic surgery or chronic pancreatitis
- Oral hypoglycemic agents
- History of diabetes ketoacidosis (DKA) within 24 weeks
- History of hospital admission for glycemic control within 6 months
- Frequent episodes of hypoglycemia (2 unexplained within 3 months) or hypoglycemic unawareness
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 |
|---|---|---|
| DapagliflozinTablets, Oral, 1 mg, Once daily, 14 days | Drug | Arm 1: Dapagliflozin (1 mg), Arm 2: Dapagliflozin (2.5 mg), Arm 3: Dapagliflozin (5 mg), Arm 4: Dapagliflozin (10 mg) |
| Placebo matching DapagliflozinTablets, Oral, 0 mg, Once daily, 14 days | Drug | Arm 5: Placebo matching Dapagliflozin |
Primary outcome
Mean Change From Baseline in 7-Point Glucose Monitoring (7-PGM) at Day 7
Time frame: From Baseline to Day 7
7-PGM was measured as milligrams per deciliter (mg/dL) by a central laboratory. Baseline was defined as the assessment on Day -1, prior to the start date and time of the first dose of the double-blind study medication. 7-PGM included the average of all available glucose values before and 2-hour (hr) after each meal (breakfast, lunch, dinner) as well as bedtime. Measurements were on Day -1, and Day 7 in the double-blind period.
7 secondary outcomes
Dapagliflozin Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
Time frame: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Time of Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 7 (0 hr to 24 hr post dose)
Dapagliflozin 3-O-glucuronide Pharmacokinetic Parameters on Day 7 - Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
Time frame: Day 7 (0 hr to 24 hr post dose)
Pharmacokinetic Parameters on Day 7 - Ratio of Metabolite (RM) to Parent AUC[TAU]
Time frame: Day 7 (0 hr to 24 hr post dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35403243Melin J, Tang W, Rekic D, Hamren B, Penland RC, Boulton DW, Parkinson J. Dapagliflozin Pharmacokinetics Is Similar in Adults With Type 1 and Type 2 Diabetes Mellitus. J Clin Pharmacol. 2022 Oct;62(10):1227-1235. doi: 10.1002/jcph.2062. Epub 2022 May 2.
- Derived from this study: PubMed 25271207Henry RR, Rosenstock J, Edelman S, Mudaliar S, Chalamandaris AG, Kasichayanula S, Bogle A, Iqbal N, List J, Griffen SC. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care. 2015 Mar;38(3):412-9. doi: 10.2337/dc13-2955. Epub 2014 Sep 30.
- MB102072\_Clinical\_Study\_ProtocolLink provided by the sponsor.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin in people with Type 1 Diabetes Mellitus, run by AstraZeneca at 12 sites in United States.
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 7 inclusion and 9 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 10 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Change From Baseline in 7-Point Glucose Monitoring (7-PGM) at Day 7 (time frame: From Baseline to Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01498185, which also lists 2 linked publications.
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 10 Feb 2017.