A Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets in Subjects With Type 2 Diabetes Mellitus

NCT02390050 | Completed Phase 2 Results DMC

• 1 other identifier: THR-1442-C-449
• Study Type: interventional
• Target: 292
• Locations: 2 countries
• Sites: 50

Brief Summary

The purpose of this study was to investigate the effect of bexagliflozin in lowering hemoglobin A1c (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). Bexagliflozin is an orally administered drug for the treatment of T2DM and is classified as a Sodium Glucose co-Transporter 2 (SGLT2) Inhibitor. This study was to enroll both treatment naive and those subjects previously treated with one oral hypoglycemic agent (OHA). Approximately 320 subjects eligible for randomization was to receive bexagliflozin tablets, 5, 10, 20 mg or placebo, once daily for 12 weeks in an outpatient setting.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c After 12 Weeks of Treatment

  Mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA) with baseline HbA1c as a covariate will be fit to the available data, incorporating all visits at which HbA1c was measured for each subject including scheduled visits at Weeks 2, 6, and 12 as well as unscheduled visits for measurements of HbA1c. Treatment (placebo, 5 mg, 10 mg, 20 mg), study center, prior anti-diabetic treatment status, study visit and treatment-by-visit interaction will be applied as fixed effects and subject as a random effect. The least square mean (LSM) change from baseline to Week 12 was analyzed using the Mixed-Effect Model Repeated Measure (MMRM) Analysis of Covariance (ANCOVA) model using 95% Confidence Intervals (CIs) for the between-group mean changes.

  12 weeks

Secondary Outcomes (5)

• Proportion of Subjects With HbA1c < 7%

  Baseline to up to 12 weeks

• Change in Body Weight Over Time

  Baseline to Week 2, Week 6 and Week 12

• Change in Fasting Plasma Glucose (FPG) Over Time

  Baseline to Week 2, Week 6 and Week 12

• Change in Systolic and Diastolic Blood Pressure Over Time

  Baseline to Week 2, Week 6 and Week 12

• Change in HbA1c Over Time

  Baseline to Week 2, Week 6 and Week 12

Study Arms (4)

Bexagliflozin tablets, 5 mg

ACTIVE COMPARATOR

Bexagliflozin tablets, 5 mg, once daily by mouth before breakfast

Drug: Bexagliflozin tablets

Bexagliflozin tablets, 10 mg

ACTIVE COMPARATOR

Bexagliflozin tablets, 10 mg, once daily by mouth before breakfast

Drug: Bexagliflozin tablets

Bexagliflozin tablets, 20 mg

ACTIVE COMPARATOR

Bexagliflozin tablets, 20 mg, once daily by mouth before breakfast

Drug: Bexagliflozin tablets

Bexagliflozin tablets, placebo

PLACEBO COMPARATOR

Bexagliflozin tablets, placebo, once daily by mouth before breakfast

Drug: Bexagliflozin tablets, placebo

Interventions

Bexagliflozin tablets DRUG

Bexagliflozin tablets are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.

Also known as: Code name: EGT0001442

Bexagliflozin tablets, 10 mg; Bexagliflozin tablets, 20 mg; Bexagliflozin tablets, 5 mg

Bexagliflozin tablets, placebo DRUG

Bexagliflozin tablets, placebo, are blue caplet-shaped, film-coated tablets that are intended for use in investigational studies in humans.

Bexagliflozin tablets, placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

The following subjects were eligible for randomization: 1. men or women ≥ 20 years of age at screening. Women of childbearing potential must test negative by urine pregnancy test. 2. were treatment naïve or taking one oral anti-diabetic medication in combination with diet and exercise 3. were diagnosed with T2DM with HbA1c levels at screening between 7.0% and 8.5% (inclusive) if treatment naïve or with HbA1c levels between 6.5 and 8.5% (inclusive) if on one oral anti-diabetic medication 4. had a body mass index (BMI) ≤ 40 kg/m2 5. were taking stable doses of medication for hypertension or hyperlipidemia that has not changed for at least 30 days prior to screening (if applicable) 6. were able to comprehend the study participation requirements and willing to provide written informed consent in accordance with institutional and regulatory guidelines 7. were able to maintain adequate glycemic control at the run-in visit (for subjects who complete the washout) 8. had an HbA1c between 7.0 and 8.5% (inclusive) prior to randomization (day -3 to -5) 9. were capable of adhering to the investigational product administration requirements as evidenced by omission of no more than one dose of run-in medication Subjects who exhibited any of the following characteristics were to be ineligible for randomization: 1. Diagnosis of type 1 diabetes mellitus or maturity-onset diabetes of the young 2. Used parenteral therapy for treatment of diabetes 3. Pregnancy or current breastfeeding status 4. Hemoglobinopathy or carrier status for hemoglobin alleles that affect HbA1c measurement 5. Genitourinary tract infection within 6 weeks of screening or history of ≥3 genitourinary infections requiring treatment within 6 months of screening 6. Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2 at screening. 7. Uncontrolled hypertension at screening 8. A positive result on hepatitis B surface antigen, hepatitis C, or positive result from screen for drugs of abuse 9. History of human immunodeficiency virus infection 10. Life expectancy \< 2 years 11. History of New York Heart Association Class 4 heart failure within 3 months of screening 12. History of myocardial infarction, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening 13. History of treatment with an investigational drug within 30 days or within 7 half lives of the investigational drug, whichever is longer 14. Previous treatment with bexagliflozin 15. Had taken or within 6 months of taking any Sodium Glucose Transporter 2 (SGLT2) inhibitors prior to screening 16. Participation of another interventional trial 17. Not able to comply with the study scheduled visits 18. Affected by any condition, disease, disorder, or clinically relevant abnormality that, in the opinion of the investigator, would jeopardize the subject's appropriate participation in this study. 19. Liver function tests resulting in Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 2.5 x upper limit of normal (ULN) or total bilirubin ≥ 1.5 x ULN, with the exception of isolated Gilbert's syndrome ,at screening 20. Exhibited fasting plasma glucose ≥ 250 mg/dL (13.9 mmol/L) on two or more consecutive days prior to randomization or exhibited severe clinical signs or symptoms of hyperglycemia during the washout or run-in periods, including weight loss, blurred vision, increased thirst, or increased urination, or fatigue 21. Fasting Plasma Glucose ≥ 250 mg/dL at randomization 22. Prior renal transplantation or evidence of nephrotic syndrome, defined as a urine albumin-to-creatinine ratio (UACR) \> 2000 mg/g at screening

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Theracos: lead

Study Sites (50)

Phoenix Medical Research Institute LLC

Peoria, Arizona, 85381, United States

Location

Advanced Arizona Clinical Research

Tucson, Arizona, 85712, United States

Location

Hope Clinical Research, LLC

Canoga Park, California, 91303, United States

Location

Catalina Research Institute

Chino, California, 91710, United States

Location

National Research Institute

Huntington Park, California, 90255, United States

Location

Long Beach Clinical Trials

Long Beach, California, 90806, United States

Location

Synergy San Diego

National City, California, 91950, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Artemis Institute for Clinical Research, LLC

San Diego, California, 92103, United States

Location

Infosphere Clinical Research, Inc

West Hills, California, 91307, United States

Location

M&O Clinical Research LLC

Fort Lauderdale, Florida, 33316, United States

Location

AGA Clinical Trials

Hialeah, Florida, 33012, United States

Location

Compass Research North

Leesburg, Florida, 34748, United States

Location

Sweet Hope Research Specialty, Inc

Miami Lakes, Florida, 33016, United States

Location

Sunshine Research Center

Opa-locka, Florida, 33054, United States

Location

Compass Research LLC

Orlando, Florida, 32806, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

PICR Clinic

Atlanta, Georgia, 30338, United States

Location

Sundance Clinical Research

St Louis, Missouri, 63141, United States

Location

Premier Research Ltd

Trenton, New Jersey, 08611, United States

Location

Regional Clinical Research, Inc

Endwell, New York, 13760, United States

Location

Calabash Medical Center

Calabash, North Carolina, 28467, United States

Location

Diabetes & Endocrinology Consultants PC

Morehead City, North Carolina, 28557, United States

Location

PMG Research of Salisbury

Salisbury, North Carolina, 28144, United States

Location

CTI Research

Cincinnati, Ohio, 45255, United States

Location

Summit Research Group, LLC

Stow, Ohio, 44224, United States

Location

Columbia Research Group, Inc.

Portland, Oregon, 97239, United States

Location

Detweiler Family Medicine and Associate, P.C.

Lansdale, Pennsylvania, 19446, United States

Location

North Myrtle Beach Family Practice

Myrtle Beach, South Carolina, 29582, United States

Location

Global Medical Research

DeSoto, Texas, 75115, United States

Location

Rockwood Medical Clinic

Fort Worth, Texas, 76164, United States

Location

Wasatch Clinical Research

Salt Lake City, Utah, 84107, United States

Location

Medical Corporation Hitomi-kai Motomachi Takatsuka Naika Clinic

Yokohama Naka-ku, Kanagawa, 231-0023, Japan

Location

Medical Corporation Hayashi katagihara Clinic

Nishikyo-ku, Kyoto, 615-8125, Japan

Location

Medical Corporation KEISEIKAI Kajiyama clinic

Ukyou-ku, Kyoto, 615-0035, Japan

Location

Ikeoka Medical Corp. Ikeoka Clinic

Joto-ku, Osaka, 536-0008, Japan

Location

Miyauchi Medical Center

Takatsuki-shi, Osaka, 569-1123, Japan

Location

Medical Corporation Senrichuo Ekimae Clinic

Toyonaka-shi, Osaka, 560-0082, Japan

Location

Medical Corporation Segawa Hospital

Hikigun Ogawamachi, Saitama, 355-0328, Japan

Location

Medical Corporation Yukeikai Asano Clinic

Kawagoe-shi, Saitama, 350-0851, Japan

Location

Medical Corporation Ishii Internal Medicine Clinic

Kawaguchi, Saitama, 333-0844, Japan

Location

Medical Corporation Fusanokai Shimizu Clinic Fusa

Saitama-shi, Saitama, 336-0963, Japan

Location

Medical Corp. SEIKOUKAI New Medical Research System Clinic

Hachioji-shi, Tokyo, 192-0046, Japan

Location

Medical Corporation Jototowakai Shinkoiwa ekimae sogo Clinic

Katsushika-ku, Tokyo, 124-0024, Japan

Location

Medical Corporation IHL Pedi Shiodome Medical Clinic

Minato-ku, Tokyo, 105-7390, Japan

Location

Medical Corporation IHL Shinagawa East One Medical Clinic

Minato-ku, Tokyo, 108-0075, Japan

Location

Kenkokan Suzuki Clinic

Ōta-ku, Tokyo, 143-0015, Japan

Location

Medical Corporation Souyu-kai Hirahata Clinic

Shibuya-ku, Tokyo, 150-0002, Japan

Location

Medical Corporation Yuhokai Miho-Clinic

Shinagawa-ku, Tokyo, 141-0032, Japan

Location

Ikebukuro Metropolitan Clinic

Toshima-ku, Tokyo, 171-0021, Japan

Location

Related Publications (10)

• American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.

  PMID: 24357209 BACKGROUND

• Look AHEAD Research Group; Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med. 2013 Jul 11;369(2):145-54. doi: 10.1056/NEJMoa1212914. Epub 2013 Jun 24.

  PMID: 23796131 BACKGROUND

• Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A; Collaborators developing the Japanese equation for estimated GFR. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009 Jun;53(6):982-92. doi: 10.1053/j.ajkd.2008.12.034. Epub 2009 Apr 1.

  PMID: 19339088 BACKGROUND

• National Research Council (US) Panel on Handling Missing Data in Clinical Trials. The Prevention and Treatment of Missing Data in Clinical Trials. Washington (DC): National Academies Press (US); 2010. Available from http://www.ncbi.nlm.nih.gov/books/NBK209904/

  PMID: 24983040 BACKGROUND

• Palaniappan LP, Wong EC, Shin JJ, Fortmann SP, Lauderdale DS. Asian Americans have greater prevalence of metabolic syndrome despite lower body mass index. Int J Obes (Lond). 2011 Mar;35(3):393-400. doi: 10.1038/ijo.2010.152. Epub 2010 Aug 3.

  PMID: 20680014 BACKGROUND

• Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, Brodehl J, Daschner M, Ehrich JH, Kemper M, Li Volti S, Neuhaus T, Skovby F, Swift PG, Schaub J, Klaerke D. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol. 2003 Nov;14(11):2873-82. doi: 10.1097/01.asn.0000092790.89332.d2.

  PMID: 14569097 BACKGROUND

• Scheen AJ, Van Gaal LF. Combating the dual burden: therapeutic targeting of common pathways in obesity and type 2 diabetes. Lancet Diabetes Endocrinol. 2014 Nov;2(11):911-22. doi: 10.1016/S2213-8587(14)70004-X. Epub 2014 Feb 19.

  PMID: 24731666 BACKGROUND

• Schwartz S, Fabricatore AN, Diamond A. Weight reduction in diabetes. Adv Exp Med Biol. 2012;771:438-58. doi: 10.1007/978-1-4614-5441-0_31.

  PMID: 23393695 BACKGROUND

• van den Heuvel LP, Assink K, Willemsen M, Monnens L. Autosomal recessive renal glucosuria attributable to a mutation in the sodium glucose cotransporter (SGLT2). Hum Genet. 2002 Dec;111(6):544-7. doi: 10.1007/s00439-002-0820-5. Epub 2002 Sep 27.

  PMID: 12436245 BACKGROUND

• Japan Diabetes Society (2012). Treatment Guidance for Diabetes 2012-2013.

  BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

bexagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Albert Collinson
• Organization: Theracos Sub, LLC

acollinson@theracos.com

(508) 630-2129

Study Officials

• J Paul Lock, M.D.

  Theracos

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2015
• First Posted: March 17, 2015
• Study Start: May 12, 2015
• Primary Completion: June 3, 2016
• Study Completion: June 3, 2016
• Last Updated: June 29, 2021
• Results First Posted: April 20, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (32); JP (18)