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CompletedNCT02551874Updated Dec 11, 2018Results posted

A 24-week Open-Label, Phase 3b Trial With a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects withType 2 Diabetes Who Have Glycemic Control on Metformin

A Phase 3 interventional study of Saxagliptin, Onglyza and Dapagliflozin, Farxiga in Type 2 Diabetes Mellitus, sponsored by AstraZeneca. Completed at 40 sites in 10 countries. Open to participants aged 18 Years to 120 Years. Per ClinicalTrials.gov, last updated 2018-12-11.

Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
650
Allocation
Randomized
Ages
18 Years to 120 Years
Sex
All
01

Study summary

This research study of subjects with inadequately controlled type 2 diabetes mellitus (T2DM) will compare the glycemic control (measured by HbA1c) in subjects co-administered saxagliptin and dapagliflozin, in addition to metformin with or without sulfonylurea, to subjects receiving insulin glargine, in addition to metformin with or without sulfonylurea, over a treatment period of 52 weeks.

Read the detailed description

CV181-369; A 24 Week International, Open-Label Trial With a 28 Week Extension to Evaluate the Efficacy of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects With Type 2 Diabetes on Metformin With or Without Sulfonylurea Therapy

02

Conditions studied

  • Type 2 Diabetes Mellitus
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 650 is above the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

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

04

Who can participate

Ages eligible
18 Years to 120 Years
Sexes eligible
All
Accepts healthy volunteers
No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion criteria

Inclusion Criteria:

  • At least 18 years of age at screening
  • HbA1c ≥ 8% and ≤ 12% at screening
  • Fasting plasma glucose (FPG) ≤ 270 mg/dL (15mmol/L)
  • Stable dose metformin ≥ 1500 mg per day with or without a stable dose of sulfonylurea (defined as at least 50% maximal dose per local label) for at least 8 weeks
  • estimated glomerular filtration rate (eGFR) \< 60 ml/ml/1.73m2
  • Body Mass Index ≤ 45.0 kg/m2

Exclusion criteria

Exclusion Criteria:

  • Clinical diagnosis of Type 1 diabetes
  • History of ketoacidosis
  • Renal, hepatic or pancreatic disease
  • Impairment of renal function (defined as creatinine clearance [CrCl] \< 60 mL/min
  • Cardiovascular or vascular diseases identified within 3 months of participationImpairment of renal function (defined as creatinine clearance [CrCl] \< 60 mL/min
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
650 participants (actual)

Study arms

  • Experimental
    Saxagliptin/Dapagliflozin/Metformin

    Oral route. Saxagliptin/Dapa adminsitered once daily for 24 weeks at a dose of 5 mg Saxagliptin and 10 mg Dapagliflozin

    Drug: Saxagliptin, Onglyza · Drug: Dapagliflozin, Farxiga · Drug: Metformin

  • Active comparator
    Insulin Glargine, Lantos/Metformin

    Insulin glargine administered once a day with starting dose of 0.2 Unit per kg or 10 units.

    Drug: Glargine insulin

Interventions

  • DrugSaxagliptin, Onglyza

    Tablets, Oral, 5mg , Once daily, 24 weeks

    Also known as: Onglyza

  • DrugDapagliflozin, Farxiga

    Tablets, Oral, 10mg , Once daily, 24 weeks

    Also known as: BMS-512148

  • DrugGlargine insulin

    100 Units/ml solution for injection in a prefilled SoloStar pen

    Also known as: Lantus

  • DrugMetformin

    Tablets, Oral, ≥ 1500mg/≤ 2500mg, Once daily, 24 weeks

    Also known as: Glucophage

06

What researchers measure

Primary outcomes

  1. Mean Change From Baseline in HbA1c at Week 24

    To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 0.3%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

    Time frame: Baseline and Week 24

Secondary outcomes

  1. Mean Change From Baseline in Total Body Weight at Week 24

    To compare the mean change from baseline in total body weight with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment

    Time frame: Baseline and Week 24

  2. Percentage of Subjects With Confirmed Hypoglycaemia at Week 24

    Hypoglycemia defined as plasma glucose ≤70 mg/dL (3.9 mmol/L)

    Time frame: Baseline and Week 24

  3. Percentage of Subjects Achieving a Therapeutic Glycemic Response, Without Hypoglycaemia, at Week 24

    To compare the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, without any reported hypoglycemia, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

    Time frame: Baseline and Week 24

  4. Percentage of Subjects Achieving a Therapeutic Glycemic Response at Week 24

    To examine whether the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 10%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

    Time frame: Baseline and Week 24

  5. Change From Baseline in the Mean Value of 24-hour Glucose at Week 2

    Change from baseline in the mean value of 24-hour glucose readings measured by Continuous Glucose Monitoring with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior to titrated insulin glargine plus metformin with or without SU after 2 weeks of open-label treatment.

    Time frame: Baseline and Week 2

07

Results

Posted Sep 18, 2018

Participant flow

This study was conducted at 112 centers in 11 countries from 20 Oct 2015 to 10 Nov 2017. There were 2 data cut-offs for this study: 8 May 2017 for analyses of the short-term study period (after 24 weeks of open-label treatment) and 10 Nov 2017 for analyses of the short-term plus long-term study period (after 52 weeks of open-label treatment).

Participant flow — Overall Study
MilestoneDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Started324326
Received treatment in short-term study324319
Entered long-term study306294
Received treatment in long-term study295284
Completed296287
Not completed2839
Withdrew: Lost to follow-up02
Withdrew: Pregnancy01
Withdrew: Reason not reported104
Withdrew: Did not receive randomized treatment07
Withdrew: Did not enter long-term study1825

Outcome measures

PrimaryMean Change From Baseline in HbA1c at Week 24

To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 0.3%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

Time frame:
Baseline and Week 24
Reported as:
Least squares mean · % HbA1c
Mean Change From Baseline in HbA1c at Week 24
% HbA1cDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Mean Change From Baseline in HbA1c at Week 24-1.67 (-1.79 to -1.55)-1.54 (-1.66 to -1.42)
Statistical analysis
  • Dapagliflozin + Saxagliptin + Metformin vs Titrated Insulin + Metformin · Mixed Models Analysis · p = 0.118 (Superiority) · Mean difference (final values): -0.13 · 95% CI -0.30 to 0.03Adjusted for treatment, baseline HbA1c, randomization stratification factor, visit, treatment-by-visit, and baseline HbA1c-by-visit.
SecondaryMean Change From Baseline in Total Body Weight at Week 24

To compare the mean change from baseline in total body weight with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment

Time frame:
Baseline and Week 24
Reported as:
Least squares mean · kg
Mean Change From Baseline in Total Body Weight at Week 24
kgDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Mean Change From Baseline in Total Body Weight at Week 24-1.50 (-1.89 to -1.11)2.14 (1.75 to 2.54)
Statistical analysis
  • Dapagliflozin + Saxagliptin + Metformin vs Titrated Insulin + Metformin · Mixed Models Analysis · p = <0.001 · Mean difference (final values): -3.64 · 95% CI -4.20 to -3.09Adjusted for treatment, baseline body weight, randomization stratification factor, visit, treatment-by-visit, and baseline body weight-by-visit.
SecondaryPercentage of Subjects With Confirmed Hypoglycaemia at Week 24

Hypoglycemia defined as plasma glucose ≤70 mg/dL (3.9 mmol/L)

Time frame:
Baseline and Week 24
Reported as:
Number · Adjusted % Participants
Percentage of Subjects With Confirmed Hypoglycaemia at Week 24
Adjusted % ParticipantsDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Percentage of Subjects With Confirmed Hypoglycaemia at Week 2421.3 (17.03 to 26.22)38.4 (32.94 to 44.07)
Statistical analysis
  • Dapagliflozin + Saxagliptin + Metformin vs Titrated Insulin + Metformin · Regression, Logistic · p = <0.001 · Odds ratio (or): 0.4 · 95% CI 0.30 to 0.62Adjusted for baseline HbA1c and randomization stratification factor (background medication of metformin with or without SU).
SecondaryPercentage of Subjects Achieving a Therapeutic Glycemic Response, Without Hypoglycaemia, at Week 24

To compare the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, without any reported hypoglycemia, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU versus titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

Time frame:
Baseline and Week 24
Reported as:
Number · Adjusted % Participants
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Without Hypoglycaemia, at Week 24
Adjusted % ParticipantsDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Percentage of Subjects Achieving a Therapeutic Glycemic Response, Without Hypoglycaemia, at Week 2420.9 (16.69 to 25.83)13.1 (9.72 to 17.33)
Statistical analysis
  • Dapagliflozin + Saxagliptin + Metformin vs Titrated Insulin + Metformin · Regression, Logistic · p = 0.008 · Odds ratio (or): 1.8 · 95% CI 1.16 to 2.67
SecondaryPercentage of Subjects Achieving a Therapeutic Glycemic Response at Week 24

To examine whether the percentage of subjects achieving a therapeutic glycemic response, defined as HbA1c \<7.0%, with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior (noninferiority margin of 10%) to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.

Time frame:
Baseline and Week 24
Reported as:
Number · Adjusted % Participants
Percentage of Subjects Achieving a Therapeutic Glycemic Response at Week 24
Adjusted % ParticipantsDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Percentage of Subjects Achieving a Therapeutic Glycemic Response at Week 2433.2 (28.00 to 38.79)33.5 (28.28 to 39.26)
Statistical analysis
  • Dapagliflozin + Saxagliptin + Metformin vs Titrated Insulin + Metformin · Adjusted percent difference: -0.4 · 95% CI -7.42 to 6.54
SecondaryChange From Baseline in the Mean Value of 24-hour Glucose at Week 2

Change from baseline in the mean value of 24-hour glucose readings measured by Continuous Glucose Monitoring with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is noninferior to titrated insulin glargine plus metformin with or without SU after 2 weeks of open-label treatment.

Time frame:
Baseline and Week 2
Reported as:
Least squares mean · mg/deciliter (dL)
Change From Baseline in the Mean Value of 24-hour Glucose at Week 2
mg/deciliter (dL)Dapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Change From Baseline in the Mean Value of 24-hour Glucose at Week 2-48.53 (-53.47 to -43.59)-28.54 (-33.47 to -23.61)
Statistical analysis
  • Dapagliflozin + Saxagliptin + Metformin vs Titrated Insulin + Metformin · Mixed Models Analysis · p = <0.0001 · Mean difference (final values): -19.99 · 95% CI -26.98 to -13.00Adjusted for treatment, baseline measurement, randomization stratification factor, visit, treatment-by-visit, and baseline-by-visit.

Adverse events

Collected over From baseline (Day 1) up to Week 52 (24-week short-term treatment period + 28-week long-term treatment period).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Dapagliflozin + Saxagliptin + Metformin2/324 (0.6%)20/324 (6.2%)55/324 (17%)
Titrated Insulin + Metformin0/319 (0%)13/319 (4.1%)73/319 (22.9%)
Most frequent serious events
Showing 10 of 39
Most frequent serious events
EventDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Coronary artery diseaseCardiac disorders3/3241/319
Acute coronary syndromeCardiac disorders1/3242/319
Cardiac failure congestiveCardiac disorders2/3240/319
ContusionInjury, poisoning and procedural complications1/3241/319
Road traffic accidentInjury, poisoning and procedural complications0/3241/319
Cerebrovascular accidentNervous system disorders0/3241/319
DepressionPsychiatric disorders0/3241/319
GangreneInfections and infestations0/3241/319
SepsisInfections and infestations0/3241/319
Colon cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/3241/319
Most frequent other events
Most frequent other events
EventDapagliflozin + Saxagliptin + MetforminTitrated Insulin + Metformin
Viral upper respiratory tract infectionInfections and infestations25/32419/319
Upper respiratory tract infectionInfections and infestations17/32423/319
HeadacheNervous system disorders12/32422/319
InfluenzaInfections and infestations8/32416/319

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Dapagliflozin + Saxagliptin + MetforminTitrated Insulin + MetforminTotal
Mean55.7 ± 9.5255.3 ± 9.6355.5 ± 9.57
Sex: Female, Male
Sex: Female, Male(Participants)Dapagliflozin + Saxagliptin + MetforminTitrated Insulin + MetforminTotal
Female148148296
Male176171347
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Dapagliflozin + Saxagliptin + MetforminTitrated Insulin + MetforminTotal
American Indian Or Alaska Native12618
Asian121224
Black Or African American283563
Native Hawaiian Or Other Pacific Islander011
Other91120
White263254517
08

Study locations

40 sites
  • Research Site
    Anaheim, California 92801, United States
  • Research Site
    Los Angeles, California 90057, United States
  • Research Site
    Miami, Florida 33144, United States
  • Research Site
    Miami, Florida 33155, United States
  • Research Site
    Saint Petersburg, Florida 33709, United States
  • Research Site
    Norcross, Georgia 30071, United States
  • Research Site
    Chicago, Illinois 60612, United States
  • Research Site
    Lexington, Kentucky 40502, United States
  • Research Site
    Quincy, Massachusetts 02169, United States
  • Research Site
    Beavercreek, Ohio 45432, United States
  • Research Site
    Norman, Oklahoma 73069, United States
  • Research Site
    Barto, Pennsylvania 19504, United States
  • Research Site
    Columbia, South Carolina 29204, United States
  • Research Site
    Bristol, Tennessee 37620, United States
  • Research Site
    Kingsport, Tennessee 37660, United States
  • Research Site
    Houston, Texas 77004, United States
  • Research Site
    Mesquite, Texas 74194, United States
  • Research Site
    San Antonio, Texas 78230, United States
  • Research Site
    San Antonio, Texas 78258, United States
  • Research Site
    Bountiful, Utah 84010, United States
  • Research Site
    Karlovy Vary, 360 01, Czechia
  • Research Site
    Olomouc, 772 00, Czechia
  • Research Site
    Koebenhavn, 2400, Denmark
  • Research Site
    Budapest, 1032, Hungary
  • Research Site
    Budapest, 1097, Hungary
  • Research Site
    Budapest, 1171, Hungary
  • Research Site
    Guadalajara, 44670, Mexico
  • Research Site
    Mexico, 03800, Mexico
  • Research Site
    Monterrey, 64460, Mexico
  • Research Site
    Zapopan, Jalisco, 45200, Mexico
  • Research Site
    Lodz, 92-003, Poland
  • Research Site
    Nowy Duninow, 09-505, Poland
  • Research Site
    Sochaczew, 96-500, Poland
  • Research Site
    Craiova, 200349, Romania
  • Research Site
    Ploiesti, 100018, Romania
  • Research Site
    Timisoara, 300125, Romania
  • Research Site
    Timișoara, 300456, Romania
  • Research Site
    Lenasia, 1827, South Africa
  • Research Site
    La Coruña, 15006, Spain
  • Research Site
    Uddevalla, 451 80, Sweden
09

References and documents

Publications

  • Vilsboll T, Ekholm E, Johnsson E, Dronamraju N, Jabbour S, Lind M. Dapagliflozin Plus Saxagliptin Add-on Therapy Compared With Insulin in Patients With Type 2 Diabetes Poorly Controlled by Metformin With or Without Sulfonylurea Therapy: A Randomized Clinical Trial. Diabetes Care. 2019 Aug;42(8):1464-1472. doi: 10.2337/dc18-1988. Epub 2019 Jun 4. PubMed 31167892 ↗

Study documents

  • Statistical analysis plan · Sep 21, 2017
  • Study protocol · Mar 17, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 11, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02551874
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Sep 16, 2015
Start date
Oct 20, 2015
Primary completion
May 8, 2017
Completion
Nov 10, 2017
Results posted
Sep 18, 2018
Last update
Dec 11, 2018

Study contacts

AstraZeneca
study director · AstraZeneca

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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