Clinical trial NCT02460978: Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes
Official title: A Multicenter, Randomized, Double-Blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Dapagliflozin as an Add-on to Insulin Therapy in Subjects With Type 1 Diabetes Mellitus - Study Two
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Keywords: Dapagliflozin
Efficacy
Safety
Add on to insulin
Oral Antidiabetic
Type 1 diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2015-06-03
Enrollment: 815
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if adding dapagliflozin to insulin is a safe and effective therapy to improve glycemic control in patients with type 1 diabetes.

Detailed description: Study Classification: Safety, Efficacy and Pharmacokinetics/dynamics

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Type 1 Diabetes mellitus (T1DM)
* Central laboratory C-peptide \< 0.7 ng/ml (0.23 nmol/L)
* Insulin use for at least 12 months per patient reported or medical records
* Method of insulin administration (MDI or CSII) must have been unchanged for at least 3 months prior to screening
* Subjects must be on a total insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to screening
* If on MDI insulin administration, subject must be on ≥ 3x injections per day
* Screening Visit: Central laboratory HbA1c ≥ 7.7% and ≤ 11.0%
* Body mass index (BMI) ≥ 18.5 kg/m2

Exclusion Criteria:

* History of Type 2 Diabetes mellitus (T2DM) or maturity onset diabetes of the young (MODY), pancreatic surgery, or chronic pancreatitis that could result in decreased beta cell capacity
* Taking any non-insulin antihyperglicemic agent within 1 month prior to screening
* Taking GLP-1 receptor agonist within 2 months prior to screening for once weekly administration and within 1 month prior to screening for once or twice daily administration
* Taking metformin and/or thiazolidinediones within 2 months prior to screening
* History of diabetes ketoacidosis requiring medical intervention within 1 month prior to screening
* History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 1 month prior to screening
* Frequent episodes of severe hypoglycemia (more than one episode requiring medical assistance, emergency care), and/or glucagon therapy administered by a third-party individual within 1 month prior to screening
* History of Addison's disease

Primary outcomes:
measure: Adjusted Mean Change From Baseline in HbA1c at Week 24
timeFrame: Baseline and 24 weeks
Secondary outcomes:
measure: Adjusted Mean Percentage Change From Baseline in Total Daily Insulin Dose at Week 24
timeFrame: Baseline and 24 weeks
measure: Adjusted Mean Percentage Change From Baseline in Body Weight at Week 24
timeFrame: Baseline and 24 weeks
measure: Adjusted Mean Change From Baseline in 24-hour Continuous Glucose Monitoring (CGM) Mean Value at Week 24
timeFrame: Baseline and 24 weeks
measure: Adjusted Mean Change From Baseline in 24-hour CGM Mean Amplitude of Glycemic Excursion (MAGE) Value at Week 24
timeFrame: Baseline and 24 weeks
measure: Change From Baseline in the Percent of 24-hour Glucose Readings Obtained From CGM That Falls Within the Target Range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24
timeFrame: Baseline and 24 weeks
measure: Percentage of Subjects With HbA1c Reduction From Baseline to Week 24 Last Observation Carried Forward (LOCF) >= 0.5% and Without Severe Hypoglycemia Events at Week 24
timeFrame: Baseline and 24 weeks
Other outcomes:
Locations:
city: Concord
country: United States
facility: Research Site
state: California
city: Fresno
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Mateo
country: United States
facility: Research Site
state: California
city: San Ramon
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Golden
country: United States
facility: Research Site
state: Colorado
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Bradenton
country: United States
facility: Research Site
state: Florida
city: Clearwater
country: United States
facility: Research Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami Springs
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
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state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Roswell
country: United States
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state: Georgia
city: Chicago
country: United States
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state: Illinois
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Lexington
country: United States
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state: Kentucky
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Edina
country: United States
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state: Minnesota
city: Jefferson City
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
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state: Missouri
city: Reno
country: United States
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state: Nevada
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Albany
country: United States
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state: New York
city: Flushing
country: United States
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state: New York
city: Mineola
country: United States
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state: New York
city: New Hyde Park
country: United States
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state: New York
city: New York
country: United States
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state: New York
city: Philadelphia
country: United States
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state: Pennsylvania
city: Amarillo
country: United States
facility: Research Site
state: Texas
city: Austin
country: United States
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state: Texas
city: Dallas
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state: Texas
city: Edinburg
country: United States
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state: Texas
city: Mesquite
country: United States
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state: Texas
city: San Antonio
country: United States
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state: Texas
city: San Antonio
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state: Texas
city: Bennington
country: United States
facility: Research Site
state: Vermont
city: Federal Way
country: United States
facility: Research Site
state: Washington
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Cordoba
country: Argentina
facility: Research Site
city: Corrientes
country: Argentina
facility: Research Site
city: Mar del Plata
country: Argentina
facility: Research Site
city: Ramos Mejía
country: Argentina
facility: Research Site
city: Brussels (Uccle)
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Cambridge
country: Canada
facility: Research Site
state: Ontario
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Smiths Falls
country: Canada
facility: Research Site
state: Ontario
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Falkensee
country: Germany
facility: Research Site
city: Freiburg im Breisgau
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Pohlheim
country: Germany
facility: Research Site
city: Saarlouis
country: Germany
facility: Research Site
city: Sulzbach-Rosenberg
country: Germany
facility: Research Site
city: Wangen
country: Germany
facility: Research Site
city: Aki-gun
country: Japan
facility: Research Site
city: Amagasaki-shi
country: Japan
facility: Research Site
city: Chitose-shi
country: Japan
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Fukuyama-shi
country: Japan
facility: Research Site
city: Higashiosaka-shi
country: Japan
facility: Research Site
city: Ibusuki-shi
country: Japan
facility: Research Site
city: Kagoshima-shi
country: Japan
facility: Research Site
city: Kamakura-shi
country: Japan
facility: Research Site
city: Kashiwara-shi
country: Japan
facility: Research Site
city: Kitakyushu-shi
country: Japan
facility: Research Site
city: Koriyama-shi
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Miura-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Obihiro-shi
country: Japan
facility: Research Site
city: Oita-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Oyama-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Shibuya-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shizuoka-shi
country: Japan
facility: Research Site
city: Tsukuba-shi
country: Japan
facility: Research Site
city: Ushiku-shi
country: Japan
facility: Research Site
city: Uwajima-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Hoogeveen
country: Netherlands
facility: Research Site
city: Maastricht
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: St.Petersburg
country: Russian Federation
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Helsingborg
country: Sweden
facility: Research Site
city: Linkoping
country: Sweden
facility: Research Site
city: Uddevalla
country: Sweden
facility: Research Site
city: Olten
country: Switzerland
facility: Research Site
city: St. Gallen
country: Switzerland
facility: Research Site
city: Zollikerberg
country: Switzerland
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Northampton
country: United Kingdom
facility: Research Site
city: Oldham
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
city: Wakefield
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Anna Maria Langkilde, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Groop PH, Dandona P, Phillip M, Gillard P, Edelman S, Jendle J, Xu J, Scheerer MF, Thoren F, Iqbal N, Repetto E, Mathieu C. Effect of dapagliflozin as an adjunct to insulin over 52 weeks in individuals with type 1 diabetes: post-hoc renal analysis of the DEPICT randomised controlled trials. Lancet Diabetes Endocrinol. 2020 Oct;8(10):845-854. doi: 10.1016/S2213-8587(20)30280-1.
citation: Mathieu C, Dandona P, Birkenfeld AL, Hansen TK, Iqbal N, Xu J, Repetto E, Scheerer MF, Thoren F, Phillip M. Benefit/risk profile of dapagliflozin 5 mg in the DEPICT-1 and -2 trials in individuals with type 1 diabetes and body mass index >/=27 kg/m2. Diabetes Obes Metab. 2020 Nov;22(11):2151-2160. doi: 10.1111/dom.14144. Epub 2020 Aug 20.
citation: Parkinson J, Tang W, Astrand M, Melin J, Ekholm E, Hamren B, Boulton DW. Model-based characterization of the relationship between dapagliflozin systemic exposure and HbA1c response in patients with type 1 diabetes mellitus. Diabetes Obes Metab. 2019 Jun;21(6):1381-1387. doi: 10.1111/dom.13664. Epub 2019 Mar 14.
citation: Mathieu C, Dandona P, Gillard P, Senior P, Hasslacher C, Araki E, Lind M, Bain SC, Jabbour S, Arya N, Hansen L, Thoren F, Langkilde AM; DEPICT-2 Investigators. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care. 2018 Sep;41(9):1938-1946. doi: 10.2337/dc18-0623. Epub 2018 Jul 19.