Clinical trial NCT02268214: 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 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: 2014-10-20
Enrollment: 833
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 metformin and/or thiazolidinediones within 2 months prior to screening
* Taking any antidiabetic medication (other than insulin), 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
* 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 in HbA1c From Baseline at Week 24
timeFrame: From Baseline to Week 24
Secondary outcomes:
measure: Adjusted Mean Percent Change in Total Daily Insulin Dose From Baseline at Week 24
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Percent Change in Body Weight From Baseline at Week 24
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change in 24-hour Mean Continuous Glucose Monitoring Glucose From Baseline at Week 24
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change in 24-hour Continuous Glucose Monitoring MAGE From Baseline at Week 24
timeFrame: From Baseline to Week 24
measure: Adjusted Mean Change in Percent 24-hour Continuous Glucose Monitoring Glucose > 70 and <= 180 (mg/dL) From Baseline at Week 24
timeFrame: From Baseline to Week 24
measure: Subjects With HbA1c Reduction From Baseline to Week 24 (LOCF) >= 0.5% and Without Severe Hypoglycemia Events
timeFrame: From Baseline to Week 24
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Encino
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Tarzana
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Denver
country: United States
facility: Research Site
state: Colorado
city: Cooper City
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
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state: Florida
city: Port Orange
country: United States
facility: Research Site
state: Florida
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Des Moines
country: United States
facility: Research Site
state: Iowa
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Portland
country: United States
facility: Research Site
state: Maine
city: Hyattsville
country: United States
facility: Research Site
state: Maryland
city: Rockville
country: United States
facility: Research Site
state: Maryland
city: Kalamazoo
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Chesterfield
country: United States
facility: Research Site
state: Missouri
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Albany
country: United States
facility: Research Site
state: New York
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Asheville
country: United States
facility: Research Site
state: North Carolina
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Morehead City
country: United States
facility: Research Site
state: North Carolina
city: Langhorne
country: United States
facility: Research Site
state: Pennsylvania
city: Kingsport
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
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state: Tennessee
city: Amarillo
country: United States
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state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
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state: Texas
city: Salt Lake City
country: United States
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state: Utah
city: Olympia
country: United States
facility: Research Site
state: Washington
city: Concord
country: Australia
facility: Research Site
city: Daw Park
country: Australia
facility: Research Site
city: Fitzroy
country: Australia
facility: Research Site
city: Heidelberg West
country: Australia
facility: Research Site
city: Newcastle
country: Australia
facility: Research Site
city: Southport
country: Australia
facility: Research Site
city: Wollongong
country: Australia
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Saint Stefan/Stainz
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Bonheiden
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: London
country: Canada
facility: Research Site
state: Ontario
city: Laval
country: Canada
facility: Research Site
state: Quebec
city: Arhus C
country: Denmark
facility: Research Site
city: Esbjerg
country: Denmark
facility: Research Site
city: Odense
country: Denmark
facility: Research Site
city: Randers NØ
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Jyvaskyla
country: Finland
facility: Research Site
city: Kuopio
country: Finland
facility: Research Site
city: Oulu
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Besançon Cedex
country: France
facility: Research Site
city: Corbeil-Essonnes
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: SAINT HERBLAIN Cedex
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Aschaffenburg
country: Germany
facility: Research Site
city: Aßlar
country: Germany
facility: Research Site
city: Bad Oeynhausen
country: Germany
facility: Research Site
city: Falkensee
country: Germany
facility: Research Site
city: Munich
country: Germany
facility: Research Site
city: Munster
country: Germany
facility: Research Site
city: Neuwied
country: Germany
facility: Research Site
city: Oldenburg
country: Germany
facility: Research Site
city: Pohlheim
country: Germany
facility: Research Site
city: Schweinfurt
country: Germany
facility: Research Site
city: Sulzbach
country: Germany
facility: Research Site
city: Witten
country: Germany
facility: Research Site
city: Baja
country: Hungary
facility: Research Site
city: Balatonfured
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Létavértes
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Safed
country: Israel
facility: Research Site
city: Tel-Aviv
country: Israel
facility: Research Site
city: Tikva
country: Israel
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padowa
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Ravenna
country: Italy
facility: Research Site
city: Sesto San Giovanni
country: Italy
facility: Research Site
city: Siena
country: Italy
facility: Research Site
city: Aguascalientes
country: Mexico
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Cuernavaca
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Merida
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Monterrey
country: Mexico
facility: Research Site
city: Torreon
country: Mexico
facility: Research Site
city: Zapopan, Jalisco
country: Mexico
facility: Research Site
city: Zapopan
country: Mexico
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Dolj
country: Romania
facility: Research Site
city: Galati
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: A Coruña
country: Spain
facility: Research Site
city: Almeria
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Karlstad
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Belfast
country: United Kingdom
facility: Research Site
city: Chesterfield
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
city: Welwyn Garden City
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Anna Maria Langkilde
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: Dandona P, Mathieu C, Phillip M, Hansen L, Tschope D, Thoren F, Xu J, Langkilde AM; DEPICT-1 Investigators. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes: The DEPICT-1 52-Week Study. Diabetes Care. 2018 Dec;41(12):2552-2559. doi: 10.2337/dc18-1087. Epub 2018 Oct 23.
citation: Dandona P, Mathieu C, Phillip M, Hansen L, Griffen SC, Tschope D, Thoren F, Xu J, Langkilde AM; DEPICT-1 Investigators. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial. Lancet Diabetes Endocrinol. 2017 Nov;5(11):864-876. doi: 10.1016/S2213-8587(17)30308-X. Epub 2017 Sep 14.