A 16-wk, Uni-center, Randomized, Double-blind, Parallel, Phase 3b Trial to Evaluate Efficacy of Saxagliptin + Dapagliflozin vs.Dapagliflozin With Regard to EGP in T2DM With Insufficient Glycemic Control on Metformin+/-Sulfonylurea Therapy
ESR-15-11293 - Saxa/Dapa, Safety and Efficacy Study
Sponsors
Source
The University of Texas Health Science Center at San Antonio
Oversight Info
Has Dmc
Yes
Brief Summary
This is a 16-week, single center, randomized, double-blind, active-controlled,
parallel-group, Phase 3b efficacy and safety study of simultaneous administration of
saxagliptin 5 mg plus dapagliflozin 10 mg once daily (QD) compared with dapagliflozin plus
placebo for saxagliptin, and placebo for saxagliptin plus placebo for dapagliflozin in
patients with Type 2 diabetes who have inadequate glycemic control on metformin or
metformin/sulfonylurea.
Detailed Description
The study is intended to demonstrate complimentary action of saxagliptin/dapagliflozin added
to metformin versus dapagliflozin added to metformin with regard to EGP.
Many medications are approved for the treatment of T2DM; however, the challenge of achieving
and maintaining treatment goals within the current sequential therapy approach is linked to
shortcomings of older classes of drugs. Metformin is in the biguanide drug class that acts to
decrease hepatic glucose output and subsequently, decreases fasting hyperglycemia. Metformin,
the oral first-line gold standard agent, is recommended as the initial pharmacological
therapy because of its glycemic efficacy, weight neutrality, low risk of hypoglycemia, and
beneficial cardiovascular (CV) profile. Current sequential add-on second and third line oral
therapy includes oral drugs such as sulfonylureas (SUs) and thiazolidinediones (TZDs). These
therapies and insulin are associated with increased risks for weight gain and hypoglycemia;
therefore, caution is recommended when using combination therapy with other agents known to
cause hypoglycemia. Hypoglycemia is a clinically important issue in optimizing treatment and
there is emerging evidence that hypoglycemia is associated with negative CV outcomes. Efforts
by patients to lose weight as part of a therapeutic lifestyle program are undermined by
therapies that lead to weight gain. The majority of patients with T2DM are overweight or
obese, and additional weight gain often results in reduced treatment efficacy.
Over the past few years, it has been widely recognized that the management approach for each
T2DM patients' needs to be personalized based on his or her clinical characteristics (e.g.,
the likelihood of weight gain, risk for hypoglycemia, and lifestyle preferences [e.g., many
patients may be reluctant to use injections]) (Inzucchi et al 2012). Based on data from the
National Health and Nutrition Examination Survey in 2007 to 2010, HbA1c is not appropriately
controlled in approximately one-third of patients using even less stringent targets (Ali et
al 2013).
Because of the challenge to achieve glycemic control in patients with T2DM, the progressive
nature of the disease, and the limitations of available oral and non-oral therapies, there is
a significant medical need for oral combination treatment options and dual add-on therapy in
patients with high baseline HbA1c. Expert groups have increasingly suggested making use of
combination therapy early after diagnosis to improve glycemic control (Inzucchi et al 2012,
Rodbard et al 2009). In a recent study, initiating triple therapy (pathophysiological-based
approach) in patients with new onset T2DM versus metformin followed by sequential addition of
SUs and basal insulin (treat-to-fail approach) demonstrated a more durable HbA1c reduction
over 24 months and less hypoglycemia with initial triple therapy (Abdul-Ghani et al 2014).
Initial combination therapy with saxagliptin and dapagliflozin added to metformin may have
similar potential for durable glucose lowering in combination with low risk of hypoglycemia.
Treatment with saxagliptin and dapagliflozin, both individually and in combination with
metformin, have demonstrated a favorable safety and tolerability profile. These drugs had a
low propensity for hypoglycemia, therefore addressing a potential key concern when adding 2
glucose lowering agents simultaneously. These drugs have demonstrated weight neutrality
(saxagliptin) or moderate weight reduction (dapagliflozin). Dapagliflozin has also been shown
to cause a persistent reduction in HbA1c and weight after 2 years of therapy. Dapagliflozin
was recently shown to increase EGP, which, in part, may be mediated by increased plasma
glucagon (Merovci et al). In contrast, saxagliptin has been demonstrated to reduce glucagon
levels, e.g., in response to a meal (Sjöstrand et al 2014) and vildagliptin, also a DPP-4
inhibitor, has been shown to inhibit EGP (Balas et al 2007).
A second-line oral dual add-on therapy with saxagliptin co-administered with dapagliflozin
could be a new option, as part of a triple therapy combination that includes drugs with
complementary mechanisms of action, opposing effects on plasma glucagon concentration, and
possibly EGP, low risk of hypoglycemia, and the potential for moderate weight loss, providing
a more effective and patient-friendly approach to the treatment of T2DM.
Overall Status
Completed
Start Date
2016-01-01
Completion Date
2018-06-30
Primary Completion Date
2018-06-30
Phase
N/A
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Change in Endogenous Glucose Production (EGP) |
Baseline and 16 weeks |
Secondary Outcome
Measure |
Time Frame |
Change in Body Weight |
Baseline to 16 weeks |
Change in BMI |
Change from baseline to 16 weeks |
HBA1c |
Change from baseline to 16 weeks |
Mean Oral Glucose Tolerance Test (OGTT) |
Change from baseline to 16 weeks |
Change in Lipid Oxidation |
Change from baseline to 16 weeks |
Change in Glucose Oxidation |
Change from baseline to 16 weeks |
Change in Fasting Plasma Glucagon (FPG) |
Change from baseline to 16 weeks |
Change in Free Fatty Acids (FFA) |
Change from baseline to 16 weeks |
Enrollment
56
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
Saxagliptin (Onglyza™) is approved by the US FDA as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. The 5 mg dose will be used for this study as it is the dose that is routinely used in the clinic. In addition, this dose is used in the pivotal studies in the saxagliptin/dapagliflozin clinical program.
Arm Group Label
DAPA/SAXA (dapagliflozin plus saxagliptin)
Other Name
Onglyza
Intervention Type
Drug
Intervention Name
Description
Dapagliflozin (Farxiga) is approved by the FDA as an adjunct to diet and exercise to improve glycemic control in adults with T2DM. Dapagliflozin (Farxiga) is also approved in the EU as an adjunct to diet and exercise to improve glycemic control in patients with T2DM for whom metformin use is considered inappropriate due to intolerance, and in combination with other glucose-lowering medicinal products when these, in combination with diet and exercise do not provide adequate glycemic control. The 10 mg dose was chosen for this study because it has been extensively studied in Phase 3 trials and has demonstrated a favorable benefit-risk profile. In addition, this dose is the most commonly used dose in most countries.
Arm Group Label
DAPA/SAXA (dapagliflozin plus saxagliptin)
DAPA (Dapagliflozin plus placebo)
Other Name
Farxiga
Intervention Type
Drug
Intervention Name
Description
Placebo
Arm Group Label
PCB (Placebo plus placebo)
Eligibility
Criteria
Inclusion Criteria:
1. Provision of informed consent prior to any study-specific procedures.
2. Is able to read, understand, and sign the Informed Consent Forms (ICFs) and, if
applicable, an Authorization to Use and Disclose Protected Health Information form
(consistent with Health Insurance Portability and Accountability Act of 1996
legislation), communicate with the Investigator, and understand and comply with
protocol requirements, including the use of diary and glucose meter measurements.
3. Age = 18-70 years.
4. Has a diagnosis of T2DM.
5. Has HbA1c ≥7.5% and ≤11.0% obtained at Screening.
6. Treated with a stable dose of metformin ≥1000 mg/day or stable dose of metformin (≥
1000 mg/day) plus sulfonylurea (glipizide, ≥ 5 mg/day; glyburide, ≥ 5 mg/day;
glimepiride, ≥ 4 mg/day) for at least 8 weeks prior to Screening.
7. Has a BMI of 20 to 45 kg/m2 (inclusive) at Screening.
8. Is male, or is female, and meets all the following criteria:
- Not pregnant or breastfeeding.
- Negative pregnancy test result at Visit 1 (Screening).
- Women of childbearing potential (WOCBP; [including perimenopausal women who have
had a menstrual period within 1 year]) must practice and be willing to continue
to practice appropriate birth control (defined as a method that results in a low
failure rate, i.e., less than 1% per year, when used consistently and correctly,
such as implants, injectables, hormonal contraceptives [pills, vaginal rings, or
patches], some intrauterine contraceptive devices [levonorgestrel-releasing or
copper-T], tubal ligation or occlusion, or a vasectomized partner) during the
entire duration of the study. As applicable, all methods must be in effect prior
to receiving the first dose of study medication.
Exclusion Criteria:
Target Disease Exceptions
1. Clinically diagnosed with Type I diabetes .
2. History of diabetic ketoacidosis, hyperosmolar nonketotic coma, or corticosteroid
induced Type 2 diabetes.
Medical History and Concurrent Diseases
3. History of bariatric surgery or lap-band surgery, or either procedure is planned
during the time period of the study.
4. History of any unstable endocrine, psychiatric, rapidly progressing, or unstable renal
disease, or rheumatic disorder, as judged by the Investigator.
5. Patients who, in the judgment of the Investigator, may be at risk for dehydration or
volume depletion that may affect the patient's safety and/or the interpretation of
efficacy or safety data.
6. Has evidence of current abuse of drugs or alcohol or a history of abuse within the
past 52 weeks that, in the Investigator's opinion, would cause the individual to be
noncompliant.
Cardiovascular Conditions
7. Cardiovascular disease within 3 months of Screening (i.e., MI, cardiac surgery,
revascularization, unstable angina, stroke, transient ischemic attack, or arrhythmia).
8. Presence or history of severe congestive heart failure (New York Heart Association
Class III and IV [CCNYHA 1994]), unstable or acute congestive heart failure, and/or
known left ventricular ejection fraction of ≤40%.
Note: Eligible patients with congestive heart failure, especially those who are on
diuretic therapy, should have careful monitoring of their volume status throughout the
study.
Kidney Conditions
9. Estimated (eGFR) <60±5 mL/min/1.73 m2 or a measured serum creatinine of >1.4 mg/dL for
female patients and >1.5 mg/dL for male patients. If the serum creatinine is ≤ 1.4
(female) or ≤ 1.5 (male) and the eGFR is ≥ 60±5 ml/min/1.73m2, the subject is eligible
to participate in the study.
10. Congenital renal glucosuria. Hepatic Conditions
11. Significant hepatic disease, including, but not limited to, severe hepatic
insufficiency and/or significant abnormal liver function defined as aspartate
aminotransferase (AST) and/or alanine aminotransferase (ALT) of >3x upper limit of
normal (ULN).
12. Serum total bilirubin (TB) >2 mg/dL.
13. History of, or currently have, acute or chronic pancreatitis or have triglyceride
concentrations ≥500 mg/dL at Visit 1 (Screening).
14. Suspicion that the patient is infected with an infectious substance according to World
Health Organization risk categories A and B (see Appendix C).
15. Known severe hepatic disease, including chronic active hepatitis.
16. Positive serologic evidence of current infectious liver disease, including patients
positive for hepatitis B viral antibody IgM, hepatitis B surface antigen, and
hepatitis C virus antibody.
Hematological/Oncological Conditions
17. Malignancy within 5 years of Visit 1 (Screening), with the exception of treated in
situ basal cell or squamous cell carcinoma of the skin.
18. Hematocrit of <34% for both males and females. Prohibited Medications
19. Administration of any antihyperglycemic therapy, other than metformin or
metformin/sulfonylurea, for more than 14 days (consecutive or not) during the 12 weeks
prior to Visit 1 (Screening) and during the study unless per protocol for rescue.
20. Current treatment with potent cytochrome P450 3A4/5 inhibitors (e.g., atazanavir,
clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir,
saquinavir, and telithromycin).
21. Administration of any other investigational drug or participation in any
interventional clinical studies 30 days prior to Visit 1 (Screening).
22. Treatment with systemic corticosteroids for the last 3 months prior to Visit 1
(Screening).
23. Prescription or over-the-counter weight loss medications within 3 months prior to
Visit 1 (Screening).
Other
24. Patients with abnormal thyroid stimulating hormone (TSH) or free thyroxine (T4) values
at Visit 1 (Screening) will be excluded.
25. Has a clinically significant medical condition that could potentially affect study
participation and/or personal well-being, as judged by the Investigator.
26. Has clinically significant abnormal laboratory test values (clinical chemistry,
hematology, and urinalysis) as judged by the Investigator at Visit 1 (Screening).
27. Has known contraindications, allergies, or hypersensitivities to any study medication
or excipient as outlined in the IBs or local package inserts for saxagliptin and
dapagliflozin.
28. Has a contraindication to metformin use, including known metabolic or lactic acidosis,
or any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.
29. Is currently pregnant (confirmed with positive pregnancy test) or breast feeding.
30. Is on a commercial weight loss program with ongoing weight loss more than 5% over the
last 3 months prior to Visit 1 (Screening), or is on an intensive exercise program.
31. Involvement in the planning and/or conduct of the study (applies to both the study
sponsor staff and/or staff at the study site).
32. Patient with any condition that, in the judgment of the Investigator, may render the
patient unable to complete the study or which may pose a significant risk to the
patient or patient suspected or with confirmed poor protocol or medication compliance.
33. Previous randomization in the present study.
Gender
All
Minimum Age
18 Years
Maximum Age
70 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Eugenio Cersosimo, MD |
Principal Investigator |
The University of Texas Health Science Center at San Antonio |
Ralph A DeFronzo, MD |
Study Director |
The University of Texas Health Science Center at San Antonio |
Location
Facility |
The University of Texas Health Science Center at San Antonio San Antonio Texas 78229 United States |
Location Countries
Country
United States
Verification Date
2019-06-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Has Expanded Access
No
Condition Browse
Number Of Arms
3
Intervention Browse
Mesh Term
Metformin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Saxagliptin
Arm Group
Arm Group Label
DAPA/SAXA (dapagliflozin plus saxagliptin)
Arm Group Type
Active Comparator
Description
Dapagliflozin 10mg + Saxagliptin 5mg (plus standard of care treatment of metformin or metformin plus sulfonylurea).
Arm Group Label
DAPA (Dapagliflozin plus placebo)
Arm Group Type
Active Comparator
Description
Dapagliflozin 10mg + Placebo (plus standard of care treatment of metformin or metformin plus sulfonylurea).
Arm Group Label
PCB (Placebo plus placebo)
Arm Group Type
Placebo Comparator
Description
Placebo (for dapagliflozin) + placebo (for saxagliptin) (plus standard of care treatment of metformin or metformin plus sulfonylurea).
Firstreceived Results Date
N/A
Reference
Citation
Rodbard HW, Blonde L, Braithwaite SS, Brett EM, Cobin RH, Handelsman Y, Hellman R, Jellinger PS, Jovanovic LG, Levy P, Mechanick JI, Zangeneh F; AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007 May-Jun;13 Suppl 1:1-68. Erratum in: Endocr Pract. 2008 Sep;14(6):802-3. multiple author names added.
PMID
17613449
Citation
Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev. 2011 Aug;32(4):515-31. doi: 10.1210/er.2010-0029. Epub 2011 May 23. Review.
PMID
21606218
Citation
Abdul-Ghani MA, Puckett C, Triplitt C, Maggs D, Adams J, Cersosimo E, DeFronzo RA. Initial combination therapy with metformin, pioglitazone and exenatide is more effective than sequential add-on therapy in subjects with new-onset diabetes. Results from the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT): a randomized trial. Diabetes Obes Metab. 2015 Mar;17(3):268-75. doi: 10.1111/dom.12417. Epub 2015 Jan 7.
PMID
25425451
Citation
Ali MK, Bullard KM, Gregg EW. Achievement of goals in U.S. Diabetes Care, 1999-2010. N Engl J Med. 2013 Jul 18;369(3):287-8. doi: 10.1056/NEJMc1306652.
PMID
23863067
Citation
Balas B, Baig MR, Watson C, Dunning BE, Ligueros-Saylan M, Wang Y, He YL, Darland C, Holst JJ, Deacon CF, Cusi K, Mari A, Foley JE, DeFronzo RA. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007 Apr;92(4):1249-55. Epub 2007 Jan 23.
PMID
17244786
Citation
The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. (9th ed.). Boston: Little, Brown & Co. 1994; 253-256.
Citation
Centers for Disease Control and Prevention (CDC). Prevalence of overweight and obesity among adults with diagnosed diabetes--United States, 1988-1994 and 1999-2002. MMWR Morb Mortal Wkly Rep. 2004 Nov 19;53(45):1066-8.
PMID
15549021
Citation
CHMP 2009 European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). Guideline on Clinical Development of Fixed Combination Medicinal Products. CHMP/EWP/240/95 Rev. 1. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003686.pdf. Published 19 February 2009. Accessed 19 June 2014.
Citation
CHMP 2012 European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP). Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus. CPMP/EWP/1080/00 Rev. 1. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500129256.pdf. Published 14 May 2012. Accessed 19 June 2014.
Citation
Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009 Apr;58(4):773-95. doi: 10.2337/db09-9028.
PMID
19336687
Citation
Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab. 2011 Mar;13(3):258-67. doi: 10.1111/j.1463-1326.2010.01350.x.
PMID
21205122
Citation
Dicker D. DPP-4 inhibitors: impact on glycemic control and cardiovascular risk factors. Diabetes Care. 2011 May;34 Suppl 2:S276-8. doi: 10.2337/dc11-s229. Review.
PMID
21525468
Citation
Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O, Davis M, Rand L, Siebert C. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86.
PMID
8366922
Citation
Ferrannini E, Bjorkman O, Reichard GA Jr, Pilo A, Olsson M, Wahren J, DeFronzo RA. The disposal of an oral glucose load in healthy subjects. A quantitative study. Diabetes. 1985 Jun;34(6):580-8.
PMID
3891471
Citation
Göke B, Hershon K, Kerr D, Calle Pascual A, Schweizer A, Foley J, Shao Q, Dejager S. Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naïve patients with type 2 diabetes: comparison with metformin. Horm Metab Res. 2008 Dec;40(12):892-5. doi: 10.1055/s-0028-1082334. Epub 2008 Aug 22.
PMID
18726829
Citation
Gomis R, Espadero RM, Jones R, Woerle HJ, Dugi KA. Efficacy and safety of initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2011 Jul;13(7):653-61. doi: 10.1111/j.1463-1326.2011.01391.x.
PMID
21410628
Citation
Hansen L, Iqbal N, Ekholm E, Cook W, Hirshberg B. Postprandial dynamics of plasma glucose, insulin, and glucagon in patients with type 2 diabetes treated with saxagliptin plus dapagliflozin add-on to metformin therapy. Endocr Pract. 2014 Nov;20(11):1187-97. doi: 10.4158/EP14489.OR.
PMID
25370334
Citation
Hoerger TJ, Segel JE, Gregg EW, Saaddine JB. Is glycemic control improving in U.S. adults? Diabetes Care. 2008 Jan;31(1):81-6. Epub 2007 Oct 12.
PMID
17934153
Citation
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR; American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012 Jun;35(6):1364-79. doi: 10.2337/dc12-0413. Epub 2012 Apr 19. Review. Erratum in: Diabetes Care. 2013 Feb;36(2):490.
PMID
22517736
Citation
Jani R, Molina M, Matsuda M, Balas B, Chavez A, DeFronzo RA, Abdul-Ghani M. Decreased non-insulin-dependent glucose clearance contributes to the rise in fasting plasma glucose in the nondiabetic range. Diabetes Care. 2008 Feb;31(2):311-5. Epub 2007 Nov 13.
PMID
18000182
Citation
Klein S, Sheard NF, Pi-Sunyer X, Daly A, Wylie-Rosett J, Kulkarni K, Clark NG; American Diabetes Association; North American Association for the Study of Obesity; American Society for Clinical Nutrition. Weight management through lifestyle modification for the prevention and management of type 2 diabetes: rationale and strategies: a statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition. Diabetes Care. 2004 Aug;27(8):2067-73. Review.
PMID
15277443
Citation
Komoroski B, Vachharajani N, Boulton D, Kornhauser D, Geraldes M, Li L, Pfister M. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther. 2009 May;85(5):520-6. doi: 10.1038/clpt.2008.251. Epub 2009 Jan 7.
PMID
19129748
Citation
Merovci A, Solis-Herrera C, Daniele G, Eldor R, Fiorentino TV, Tripathy D, Xiong J, Perez Z, Norton L, Abdul-Ghani MA, DeFronzo RA. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014 Feb;124(2):509-14. doi: 10.1172/JCI70704. Epub 2014 Jan 27. Erratum in: J Clin Invest. 2014 May 1;124(5):2287.
PMID
24463448
Citation
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy. Update regarding the thiazolidinediones. Diabetologia. 2008 Jan;51(1):8-11.
PMID
18026926
Citation
NHLBI 1998 National Heart, Lung, and Blood Institute (NHLBI) Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NIH publication No. 98 4083. Available at: http://www.nhlbi.nih.gov/guidelines/obesity/ob_home.htm. Published September 1998. Accessed 19 June 2014.
Citation
Owens DR, Swallow R, Dugi KA, Woerle HJ. Efficacy and safety of linagliptin in persons with type 2 diabetes inadequately controlled by a combination of metformin and sulphonylurea: a 24-week randomized study. Diabet Med. 2011 Nov;28(11):1352-61. doi: 10.1111/j.1464-5491.2011.03387.x. Erratum in: Diabet Med. 2012 Jan;29(1):158.
PMID
21781152
Citation
Qaseem A, Vijan S, Snow V, Cross JT, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Glycemic control and type 2 diabetes mellitus: the optimal hemoglobin A1c targets. A guidance statement from the American College of Physicians. Ann Intern Med. 2007 Sep 18;147(6):417-22.
PMID
17876024
Citation
Rodbard HW, Jellinger PS, Davidson JA, Einhorn D, Garber AJ, Grunberger G, Handelsman Y, Horton ES, Lebovitz H, Levy P, Moghissi ES, Schwartz SS. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009 Sep-Oct;15(6):540-59. Erratum in: Endocr Pract. 2009 Nov-Dec;15(7):768-70.
PMID
19858063
Citation
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013 Oct 3;369(14):1317-26. doi: 10.1056/NEJMoa1307684. Epub 2013 Sep 2.
PMID
23992601
Citation
Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013 May;36(5):1384-95. doi: 10.2337/dc12-2480. Epub 2013 Apr 15.
PMID
23589542
Citation
Sjöstrand M, Iqbal N, Lu J, Hirshberg B. Saxagliptin improves glycemic control by modulating postprandial glucagon and C-peptide levels in Chinese patients with type 2 diabetes. Diabetes Res Clin Pract. 2014 Aug;105(2):185-91. doi: 10.1016/j.diabres.2014.05.006. Epub 2014 May 29.
PMID
24947443
Citation
Taskinen MR, Rosenstock J, Tamminen I, Kubiak R, Patel S, Dugi KA, Woerle HJ. Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Diabetes Obes Metab. 2011 Jan;13(1):65-74. doi: 10.1111/j.1463-1326.2010.01326.x.
PMID
21114605
Citation
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53. Erratum in: Lancet 1999 Aug 14;354(9178):602.
PMID
9742976
Citation
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):854-65. Erratum in: Lancet 1998 Nov 7;352(9139):1558.
PMID
9742977
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Study First Submitted
November 12, 2015
Study First Submitted Qc
November 20, 2015
Study First Posted
November 25, 2015
Last Update Submitted
July 22, 2019
Last Update Submitted Qc
July 22, 2019
Last Update Posted
August 14, 2019
Results First Submitted
June 14, 2019
Results First Submitted Qc
July 22, 2019
Results First Posted
August 14, 2019
Provided Document Section
Provided Document
Document Type
Study Protocol and Statistical Analysis Plan
Document Has Protocol
Yes
Document Has Icf
No
Document Has Sap
Yes
Document Date
September 30, 2016
Document Url
https://ClinicalTrials.gov/ProvidedDocs/97/NCT02613897/Prot_SAP_000.pdf
ClinicalTrials.gov processed this data on December 13, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.