The CANTATA-MSU Trial (CANagliflozin Treatment And Trial Analysis - Metformin and SUlphonylurea)

NCT ID: NCT01106625

Last Updated: 2013-06-20

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

469 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-05-31

Study Completion Date

2012-04-30

Brief Summary

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The purpose of this study is to evaluate the efficacy and safety of 2 different doses of canagliflozin compared with placebo in patients with type 2 diabetes mellitus who are receiving treatment with metformin and sulphonylurea and have inadequate glycemic (blood sugar) control.

Detailed Description

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Canagliflozin is a drug that is being tested to see if it may be useful in treating patients diagnosed with type 2 diabetes mellitus (T2DM). This is a randomized (study drug assigned by chance), double-blind (neither the patient or the study doctor will know the name of the assigned treatment), placebo-controlled, parallel-group, 3-arm (3 treatment groups) multicenter study to determine the efficacy, safety, and tolerability of canagliflozin (100 mg and 300 mg) compared to placebo (a capsule that looks like all the other treatments but has no real medicine) in patients with T2DM who are not achieving an adequate response from current antihyperglycemic therapy with metformin and sulphonylurea to control their diabetes. Approximately 450 patients with T2DM who are receiving treatment with metformin and sulphonylurea and have inadequate glycemic (blood sugar) control will receive once daily treatment with canagliflozin (100 mg or 300 mg) or placebo capsules for 52 weeks (includes 26 weeks of double-blind treatment followed by a 26-week extension period). In addition, all patients will take protocol-specified stable doses of metformin and sulphonylurea for the duration of the study. Patients will participate in the study for approximately 59 to 72 weeks. During the study, if a patient's fasting blood sugar remains high despite treatment with study drug, the patient will receive treatment with insulin (rescue therapy) consistent with local prescribing information. During treatment, patients will be monitored for safety by review of adverse events, results from laboratory tests, 12-lead electrocardiograms (ECGs), vital signs measurements, body weight, physical examinations, and self-monitored blood glucose (SMGB) measurements. The primary outcome measure in the study is to assess the effect of canagliflozin relative to placebo on hemoglobin A1c (HbA1c) after 26 weeks of treatment. Study drug will be taken orally (by mouth) once daily before the first meal each day unless otherwise specified. All patients will take single-blind placebo capsules for 2 weeks before randomization. After randomization, patients will take double-blind canagliflozin (100 mg or 300 mg) or matching placebo for 52 weeks.

Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Canagliflozin 100 mg

Each patient will receive 100 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Group Type EXPERIMENTAL

Canagliflozin

Intervention Type DRUG

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Metformin

Intervention Type DRUG

The patient's stable dose of background metformin therapy should be continued throughout the study.

Sulphonylruea

Intervention Type DRUG

The patient's stable dose of background sulphonylurea therapy should be continued throughout the study.

Canagliflozin 300 mg

Each patient will receive 300 mg of canagliflozin once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Group Type EXPERIMENTAL

Canagliflozin

Intervention Type DRUG

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Metformin

Intervention Type DRUG

The patient's stable dose of background metformin therapy should be continued throughout the study.

Sulphonylruea

Intervention Type DRUG

The patient's stable dose of background sulphonylurea therapy should be continued throughout the study.

Placebo

Each patient will receive matching placebo once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

One matching placebo capsule orally once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Metformin

Intervention Type DRUG

The patient's stable dose of background metformin therapy should be continued throughout the study.

Sulphonylruea

Intervention Type DRUG

The patient's stable dose of background sulphonylurea therapy should be continued throughout the study.

Interventions

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Canagliflozin

One 100 mg or 300 mg over-encapsulated tablet orally (by mouth) once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Intervention Type DRUG

Placebo

One matching placebo capsule orally once daily for 52 weeks with protocol-specified doses of metformin and sulphonylurea.

Intervention Type DRUG

Metformin

The patient's stable dose of background metformin therapy should be continued throughout the study.

Intervention Type DRUG

Sulphonylruea

The patient's stable dose of background sulphonylurea therapy should be continued throughout the study.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* All patients must have a diagnosis of T2DM and be currently treated with metformin and sulphonylurea
* Patients in the study must have a HbA1c between \>=7 and \<=10.5%
* Patients must have a fasting plasma glucose (FPG) \<270 mg/dL (15 mmol/L)

Exclusion Criteria

* History of diabetic ketoacidosis, type 1 diabetes mellitus (T1DM), pancreas or beta cell transplantation, or diabetes secondary to pancreatitis or pancreatectomy, or a severe hypoglycemic episode within 6 months before screening
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Janssen Research & Development, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Janssen Research & Development, LLC C. Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

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Huntsville, Alabama, United States

Site Status

Little Rock, Alaska, United States

Site Status

Phoenix, Arizona, United States

Site Status

Chino, California, United States

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Fair Oaks, California, United States

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Roseville, California, United States

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Wes Hills, California, United States

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Waterbury, Connecticut, United States

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Jacksonville, Florida, United States

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New Port Richey, Florida, United States

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Ocala, Florida, United States

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St. Petersburg, Florida, United States

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West Palm Beach, Florida, United States

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Augusta, Georgia, United States

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Roswell, Georgia, United States

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Chicago, Illinois, United States

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Lexington, Kentucky, United States

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New Orleans, Louisiana, United States

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Reisterstown, Maryland, United States

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Olive Branch, Mississippi, United States

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St Louis, Missouri, United States

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Westfield, New York, United States

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Greenville, North Carolina, United States

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Cincinnati, Ohio, United States

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Tulsa, Oklahoma, United States

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Medford, Oregon, United States

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Altoona, Pennsylvania, United States

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Harleysville, Pennsylvania, United States

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Levittown, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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Greer, South Carolina, United States

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Bryan, Texas, United States

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Dallas, Texas, United States

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DeSoto, Texas, United States

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Salt Lake City, Utah, United States

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South Burlington, Vermont, United States

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Wenatchee, Washington, United States

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Freemantle, , Australia

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Heidelberg Heights, , Australia

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Meadowbrook, , Australia

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Nedlands, , Australia

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Wollongong, , Australia

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Aalst, , Belgium

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Bonheiden, , Belgium

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Edegem, , Belgium

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Leuven, , Belgium

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Corbeil-Essonnes, , France

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La Rochelle, , France

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Le Creusot, , France

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Poitiers, , France

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Vénissieux, , France

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Guatemala City, , Guatemala

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Balatonfüred, , Hungary

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Budapest, , Hungary

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Győr, , Hungary

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Zalaegerszeg, , Hungary

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Haifa, , Israel

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Holon, , Israel

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Jerusalem, , Israel

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Tel Aviv, , Israel

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Guadalajara, , Mexico

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Monterrey, , Mexico

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Carolina, , Puerto Rico

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Trujillo Alto, , Puerto Rico

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Arkhangelsk, , Russia

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Saint Petersburg, , Russia

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Samara, , Russia

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Alicante, , Spain

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Almería, , Spain

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Málaga, , Spain

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Seville, , Spain

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Valencia, , Spain

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Belfast, , United Kingdom

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Bolton, , United Kingdom

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Liverpool, , United Kingdom

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Manchester, , United Kingdom

Site Status

Countries

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United States Australia Belgium France Guatemala Hungary Israel Mexico Puerto Rico Russia Spain United Kingdom

References

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Cai J, Delahanty LM, Akapame S, Slee A, Traina S. Impact of Canagliflozin Treatment on Health-Related Quality of Life among People with Type 2 Diabetes Mellitus: A Pooled Analysis of Patient-Reported Outcomes from Randomized Controlled Trials. Patient. 2018 Jun;11(3):341-352. doi: 10.1007/s40271-017-0290-4.

Reference Type DERIVED
PMID: 29313267 (View on PubMed)

Davies MJ, Merton K, Vijapurkar U, Yee J, Qiu R. Efficacy and safety of canagliflozin in patients with type 2 diabetes based on history of cardiovascular disease or cardiovascular risk factors: a post hoc analysis of pooled data. Cardiovasc Diabetol. 2017 Mar 21;16(1):40. doi: 10.1186/s12933-017-0517-7.

Reference Type DERIVED
PMID: 28327140 (View on PubMed)

Pfeifer M, Townsend RR, Davies MJ, Vijapurkar U, Ren J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: a post hoc analysis. Cardiovasc Diabetol. 2017 Feb 27;16(1):29. doi: 10.1186/s12933-017-0511-0.

Reference Type DERIVED
PMID: 28241822 (View on PubMed)

Gilbert RE, Mende C, Vijapurkar U, Sha S, Davies MJ, Desai M. Effects of Canagliflozin on Serum Magnesium in Patients With Type 2 Diabetes Mellitus: A Post Hoc Analysis of Randomized Controlled Trials. Diabetes Ther. 2017 Apr;8(2):451-458. doi: 10.1007/s13300-017-0232-0. Epub 2017 Feb 14.

Reference Type DERIVED
PMID: 28197834 (View on PubMed)

Qiu R, Balis D, Xie J, Davies MJ, Desai M, Meininger G. Longer-term safety and tolerability of canagliflozin in patients with type 2 diabetes: a pooled analysis. Curr Med Res Opin. 2017 Mar;33(3):553-562. doi: 10.1080/03007995.2016.1271780. Epub 2017 Jan 4.

Reference Type DERIVED
PMID: 27977934 (View on PubMed)

John M, Cerdas S, Violante R, Deerochanawong C, Hassanein M, Slee A, Canovatchel W, Hamilton G. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus living in hot climates. Int J Clin Pract. 2016 Sep;70(9):775-85. doi: 10.1111/ijcp.12868.

Reference Type DERIVED
PMID: 27600862 (View on PubMed)

Watts NB, Bilezikian JP, Usiskin K, Edwards R, Desai M, Law G, Meininger G. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab. 2016 Jan;101(1):157-66. doi: 10.1210/jc.2015-3167. Epub 2015 Nov 18.

Reference Type DERIVED
PMID: 26580237 (View on PubMed)

Lavalle-Gonzalez FJ, Eliaschewitz FG, Cerdas S, Chacon Mdel P, Tong C, Alba M. Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus from Latin America. Curr Med Res Opin. 2016;32(3):427-39. doi: 10.1185/03007995.2015.1121865. Epub 2016 Jan 14.

Reference Type DERIVED
PMID: 26579834 (View on PubMed)

Blonde L, Woo V, Mathieu C, Yee J, Vijapurkar U, Canovatchel W, Meininger G. Achievement of treatment goals with canagliflozin in patients with type 2 diabetes mellitus: a pooled analysis of randomized controlled trials. Curr Med Res Opin. 2015 Nov;31(11):1993-2000. doi: 10.1185/03007995.2015.1082991. Epub 2015 Sep 28.

Reference Type DERIVED
PMID: 26373629 (View on PubMed)

Gavin JR 3rd, Davies MJ, Davies M, Vijapurkar U, Alba M, Meininger G. The efficacy and safety of canagliflozin across racial groups in patients with type 2 diabetes mellitus. Curr Med Res Opin. 2015;31(9):1693-702. doi: 10.1185/03007995.2015.1067192. Epub 2015 Sep 4.

Reference Type DERIVED
PMID: 26121561 (View on PubMed)

Cefalu WT, Stenlof K, Leiter LA, Wilding JP, Blonde L, Polidori D, Xie J, Sullivan D, Usiskin K, Canovatchel W, Meininger G. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes. Diabetologia. 2015 Jun;58(6):1183-7. doi: 10.1007/s00125-015-3547-2. Epub 2015 Mar 27.

Reference Type DERIVED
PMID: 25813214 (View on PubMed)

Weir MR, Januszewicz A, Gilbert RE, Vijapurkar U, Kline I, Fung A, Meininger G. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J Clin Hypertens (Greenwich). 2014 Dec;16(12):875-82. doi: 10.1111/jch.12425. Epub 2014 Oct 20.

Reference Type DERIVED
PMID: 25329038 (View on PubMed)

Usiskin K, Kline I, Fung A, Mayer C, Meininger G. Safety and tolerability of canagliflozin in patients with type 2 diabetes mellitus: pooled analysis of phase 3 study results. Postgrad Med. 2014 May;126(3):16-34. doi: 10.3810/pgm.2014.05.2753.

Reference Type DERIVED
PMID: 24918789 (View on PubMed)

Weir MR, Kline I, Xie J, Edwards R, Usiskin K. Effect of canagliflozin on serum electrolytes in patients with type 2 diabetes in relation to estimated glomerular filtration rate (eGFR). Curr Med Res Opin. 2014 Sep;30(9):1759-68. doi: 10.1185/03007995.2014.919907. Epub 2014 May 22.

Reference Type DERIVED
PMID: 24786834 (View on PubMed)

Sinclair A, Bode B, Harris S, Vijapurkar U, Mayer C, Fung A, Shaw W, Usiskin K, Desai M, Meininger G. Efficacy and safety of canagliflozin compared with placebo in older patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. BMC Endocr Disord. 2014 Apr 18;14:37. doi: 10.1186/1472-6823-14-37.

Reference Type DERIVED
PMID: 24742013 (View on PubMed)

Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with type 2 diabetes. Diabetologia. 2014 May;57(5):891-901. doi: 10.1007/s00125-014-3196-x. Epub 2014 Mar 1.

Reference Type DERIVED
PMID: 24585202 (View on PubMed)

Nyirjesy P, Sobel JD, Fung A, Mayer C, Capuano G, Ways K, Usiskin K. Genital mycotic infections with canagliflozin, a sodium glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus: a pooled analysis of clinical studies. Curr Med Res Opin. 2014 Jun;30(6):1109-19. doi: 10.1185/03007995.2014.890925. Epub 2014 Feb 21.

Reference Type DERIVED
PMID: 24517339 (View on PubMed)

Other Identifiers

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28431754DIA3002

Identifier Type: OTHER

Identifier Source: secondary_id

CR017005

Identifier Type: -

Identifier Source: org_study_id

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