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

NCT ID: NCT02390050

Last Updated: 2021-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 292 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-12
• Study Completion Date: 2016-06-03

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.

Detailed Description

The study was a phase 2b multicenter, double-blind, placebo-controlled parallel group study to assess the effect of once daily bexagliflozin tablets on HbA1c in either treatment-naïve T2DM subjects or in subjects who were treated with one oral anti-diabetic agent. Treatment naïve subjects were eligible if their HbA1c values were between 7% and 8.5% at the screening visit while subjects who were treated with one oral hypoglycemic agent (OHA) were eligible if their HbA1c value was between 6.5% and 8.5% at screening and underwent a 6 or 10 week washout period. In addition, all eligible subjects underwent a two week placebo run-in period and those who showed good compliance in taking study medication (i.e., missed no more than one dose during the run-in period) during this period and whose HbA1c values were between 7 and 8.5% at the end of the run-in period were eligible for randomization.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Bexagliflozin tablets, 5 mg

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

Group Type: ACTIVE_COMPARATOR

Bexagliflozin tablets

Intervention Type: DRUG

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

Bexagliflozin tablets, 10 mg

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

Group Type: ACTIVE_COMPARATOR

Bexagliflozin tablets

Intervention Type: DRUG

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

Bexagliflozin tablets, 20 mg

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

Group Type: ACTIVE_COMPARATOR

Bexagliflozin tablets

Intervention Type: DRUG

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

Bexagliflozin tablets, placebo

Bexagliflozin tablets, placebo, once daily by mouth before breakfast

Group Type: PLACEBO_COMPARATOR

Bexagliflozin tablets, placebo

Intervention Type: DRUG

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

Interventions

Bexagliflozin tablets

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

Intervention Type: DRUG

Bexagliflozin tablets, placebo

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

Intervention Type: DRUG

Other Intervention Names

Code name: EGT0001442

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Theracos

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

J Paul Lock, M.D.

Role: STUDY_DIRECTOR

Theracos

Locations

Phoenix Medical Research Institute LLC

Peoria, Arizona, United States

Advanced Arizona Clinical Research

Tucson, Arizona, United States

Hope Clinical Research, LLC

Canoga Park, California, United States

Catalina Research Institute

Chino, California, United States

National Research Institute

Huntington Park, California, United States

Long Beach Clinical Trials

Long Beach, California, United States

Synergy San Diego

National City, California, United States

Northern California Research

Sacramento, California, United States

Artemis Institute for Clinical Research, LLC

San Diego, California, United States

Infosphere Clinical Research, Inc

West Hills, California, United States

M&O Clinical Research LLC

Fort Lauderdale, Florida, United States

AGA Clinical Trials

Hialeah, Florida, United States

Compass Research North

Leesburg, Florida, United States

Sweet Hope Research Specialty, Inc

Miami Lakes, Florida, United States

Sunshine Research Center

Opa-locka, Florida, United States

Compass Research LLC

Orlando, Florida, United States

Progressive Medical Research

Port Orange, Florida, United States

PICR Clinic

Atlanta, Georgia, United States

Sundance Clinical Research

St Louis, Missouri, United States

Premier Research Ltd

Trenton, New Jersey, United States

Regional Clinical Research, Inc

Endwell, New York, United States

Calabash Medical Center

Calabash, North Carolina, United States

Diabetes & Endocrinology Consultants PC

Morehead City, North Carolina, United States

PMG Research of Salisbury

Salisbury, North Carolina, United States

CTI Research

Cincinnati, Ohio, United States

Summit Research Group, LLC

Stow, Ohio, United States

Columbia Research Group, Inc.

Portland, Oregon, United States

Detweiler Family Medicine and Associate, P.C.

Lansdale, Pennsylvania, United States

North Myrtle Beach Family Practice

Myrtle Beach, South Carolina, United States

Global Medical Research

DeSoto, Texas, United States

Rockwood Medical Clinic

Fort Worth, Texas, United States

Wasatch Clinical Research

Salt Lake City, Utah, United States

Medical Corporation Hitomi-kai Motomachi Takatsuka Naika Clinic

Yokohama Naka-ku, Kanagawa, Japan

Medical Corporation Hayashi katagihara Clinic

Nishikyo-ku, Kyoto, Japan

Medical Corporation KEISEIKAI Kajiyama clinic

Ukyou-ku, Kyoto, Japan

Ikeoka Medical Corp. Ikeoka Clinic

Joto-ku, Osaka, Japan

Miyauchi Medical Center

Takatsuki-shi, Osaka, Japan

Medical Corporation Senrichuo Ekimae Clinic

Toyonaka-shi, Osaka, Japan

Medical Corporation Segawa Hospital

Hikigun Ogawamachi, Saitama, Japan

Medical Corporation Yukeikai Asano Clinic

Kawagoe-shi, Saitama, Japan

Medical Corporation Ishii Internal Medicine Clinic

Kawaguchi, Saitama, Japan

Medical Corporation Fusanokai Shimizu Clinic Fusa

Saitama-shi, Saitama, Japan

Medical Corp. SEIKOUKAI New Medical Research System Clinic

Hachioji-shi, Tokyo, Japan

Medical Corporation Jototowakai Shinkoiwa ekimae sogo Clinic

Katsushika-ku, Tokyo, Japan

Medical Corporation IHL Pedi Shiodome Medical Clinic

Minato-ku, Tokyo, Japan

Medical Corporation IHL Shinagawa East One Medical Clinic

Minato-ku, Tokyo, Japan

Kenkokan Suzuki Clinic

Ōta-ku, Tokyo, Japan

Medical Corporation Souyu-kai Hirahata Clinic

Shibuya-ku, Tokyo, Japan

Medical Corporation Yuhokai Miho-Clinic

Shinagawa-ku, Tokyo, Japan

Ikebukuro Metropolitan Clinic

Toshima-ku, Tokyo, Japan

Countries

United States; Japan

References

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.

Reference Type: BACKGROUND

PMID: 24357209 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23796131 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19339088 (View on PubMed)

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/

Reference Type: BACKGROUND

PMID: 24983040 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20680014 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14569097 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24731666 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23393695 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12436245 (View on PubMed)

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

Reference Type: BACKGROUND

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

THR-1442-C-449

Identifier Type: -

Identifier Source: org_study_id