Clinical trial NCT02390050: A Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets in Subjects With Type 2 Diabetes Mellitus
Official title: A Phase 2b, Multi-center, Double-blind, Placebo-controlled, Dose Range Finding Study to Evaluate the Effect of Bexagliflozin Tablets on HbA1c in Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Theracos
Sponsor class: INDUSTRY
First posted: 2015-03-17
Enrollment: 292
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in HbA1c After 12 Weeks of Treatment
timeFrame: 12 weeks
Secondary outcomes:
measure: Proportion of Subjects With HbA1c < 7%
timeFrame: Baseline to up to 12 weeks
measure: Change in Body Weight Over Time
timeFrame: Baseline to Week 2, Week 6 and Week 12
measure: Change in Fasting Plasma Glucose (FPG) Over Time
timeFrame: Baseline to Week 2, Week 6 and Week 12
measure: Change in Systolic and Diastolic Blood Pressure Over Time
timeFrame: Baseline to Week 2, Week 6 and Week 12
measure: Change in HbA1c Over Time
timeFrame: Baseline to Week 2, Week 6 and Week 12
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Phoenix Medical Research Institute LLC
state: Arizona
city: Tucson
country: United States
facility: Advanced Arizona Clinical Research
state: Arizona
city: Canoga Park
country: United States
facility: Hope Clinical Research, LLC
state: California
city: Chino
country: United States
facility: Catalina Research Institute
state: California
city: Huntington Park
country: United States
facility: National Research Institute
state: California
city: Long Beach
country: United States
facility: Long Beach Clinical Trials
state: California
city: National City
country: United States
facility: Synergy San Diego
state: California
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research, LLC
state: California
city: West Hills
country: United States
facility: Infosphere Clinical Research, Inc
state: California
city: Fort Lauderdale
country: United States
facility: M&O Clinical Research LLC
state: Florida
city: Hialeah
country: United States
facility: AGA Clinical Trials
state: Florida
city: Leesburg
country: United States
facility: Compass Research North
state: Florida
city: Miami Lakes
country: United States
facility: Sweet Hope Research Specialty, Inc
state: Florida
city: Opa-locka
country: United States
facility: Sunshine Research Center
state: Florida
city: Orlando
country: United States
facility: Compass Research LLC
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Atlanta
country: United States
facility: PICR Clinic
state: Georgia
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Trenton
country: United States
facility: Premier Research Ltd
state: New Jersey
city: Endwell
country: United States
facility: Regional Clinical Research, Inc
state: New York
city: Calabash
country: United States
facility: Calabash Medical Center
state: North Carolina
city: Morehead City
country: United States
facility: Diabetes & Endocrinology Consultants PC
state: North Carolina
city: Salisbury
country: United States
facility: PMG Research of Salisbury
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Research
state: Ohio
city: Stow
country: United States
facility: Summit Research Group, LLC
state: Ohio
city: Portland
country: United States
facility: Columbia Research Group, Inc.
state: Oregon
city: Lansdale
country: United States
facility: Detweiler Family Medicine and Associate, P.C.
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: North Myrtle Beach Family Practice
state: South Carolina
city: DeSoto
country: United States
facility: Global Medical Research
state: Texas
city: Fort Worth
country: United States
facility: Rockwood Medical Clinic
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research
state: Utah
city: Yokohama Naka-ku
country: Japan
facility: Medical Corporation Hitomi-kai Motomachi Takatsuka Naika Clinic
state: Kanagawa
city: Nishikyo-ku
country: Japan
facility: Medical Corporation Hayashi katagihara Clinic
state: Kyoto
city: Ukyou-ku
country: Japan
facility: Medical Corporation KEISEIKAI Kajiyama clinic
state: Kyoto
city: Joto-ku
country: Japan
facility: Ikeoka Medical Corp. Ikeoka Clinic
state: Osaka
city: Takatsuki-shi
country: Japan
facility: Miyauchi Medical Center
state: Osaka
city: Toyonaka-shi
country: Japan
facility: Medical Corporation Senrichuo Ekimae Clinic
state: Osaka
city: Hikigun Ogawamachi
country: Japan
facility: Medical Corporation Segawa Hospital
state: Saitama
city: Kawagoe-shi
country: Japan
facility: Medical Corporation Yukeikai Asano Clinic
state: Saitama
city: Kawaguchi
country: Japan
facility: Medical Corporation Ishii Internal Medicine Clinic
state: Saitama
city: Saitama-shi
country: Japan
facility: Medical Corporation Fusanokai Shimizu Clinic Fusa
state: Saitama
city: Hachioji-shi
country: Japan
facility: Medical Corp. SEIKOUKAI New Medical Research System Clinic
state: Tokyo
city: Katsushika-ku
country: Japan
facility: Medical Corporation Jototowakai Shinkoiwa ekimae sogo Clinic
state: Tokyo
city: Minato-ku
country: Japan
facility: Medical Corporation IHL Pedi Shiodome Medical Clinic
state: Tokyo
city: Minato-ku
country: Japan
facility: Medical Corporation IHL Shinagawa East One Medical Clinic
state: Tokyo
city: Ota-ku
country: Japan
facility: Kenkokan Suzuki Clinic
state: Tokyo
city: Shibuya-ku
country: Japan
facility: Medical Corporation Souyu-kai Hirahata Clinic
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Medical Corporation Yuhokai Miho-Clinic
state: Tokyo
city: Toshima-ku
country: Japan
facility: Ikebukuro Metropolitan Clinic
state: Tokyo
Study officials:
affiliation: Theracos
name: J Paul Lock, M.D.
role: STUDY_DIRECTOR
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citation: 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.
citation: 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.
citation: 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.
citation: 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.
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