UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	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
Title of the study (Brief title)	A Phase 2b Study of Bexagliflozin Tablets on HbA1c in Subjects with Type 2 Diabetes Mellitus
Region	Japan North America

Condition
Condition	Type 2 Diabetes Mellitus
Classification by specialty	Medicine in general
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Primary Objective The primary objective of this study is to identify the optimal dose(s) through the comparison of mean HbA1c change in subjects who receive bexagliflozin tablets, 5 mg, 10 mg, 20 mg, or placebo, after 12 weeks of treatment.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Change in HbA1c over 12 weeks of treatment
Key secondary outcomes

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit
Blinding	Double blind -all involved are blinded
Control	Placebo
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	4
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Intervention 1 After wash-out (6-10wks)and run-in period (2wks) or run-in period (2wks) only, 12wks of treatment with study drug (Placebo)
Interventions/Control_2	Intervention 2 After wash-out (6-10wks)and run-in period (2wks) or run-in period (2wks) only, 12wks of treatment with study drug (5mg)
Interventions/Control_3	Intervention 3 After wash-out (6-10wks)and run-in period (2wks) or run-in period (2wks) only, 12wks of treatment with study drug (10mg)
Interventions/Control_4	Intervention 4 After wash-out (6-10wks)and run-in period (2wks) or run-in period (2wks) only, 12wks of treatment with study drug (20mg)
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1. Men or women =>20 years of age at screening. Women of childbearing potential must test negative by urine pregnancy test and agree to abstain from coitus or use contraception during the entire study period to avoid any possible pregnancy. Females who are surgically sterile (by reason of hysterectomy or oophorectomy) or postmenopausal (most recent menses more than 12 months prior to screening) are eligible if they test negative by urine pregnancy test. 2. Treatment na&iuml;ve (i.e., have never received prescription anti-diabetic medications or have received no more than 14 days of prescription medications for diabetes in the 12 weeks prior to enrollment) or currently taking one OHA in combination with diet and exercise 3. Diagnosed with T2DM with HbA1c levels at screening between 7.0% and 8.5% (inclusive) if treatment na&iuml;ve or with HbA1c levels between 6.5 and 8.5% (inclusive) if on one oral anti-diabetic medication 4. Currently having a body mass index (BMI) =< 40 kg/m2 5. Taking stable doses of medication for hypertension or hyperlipidemia as determined by adherence to a regimen that has not changed for at least 30 days prior to screening (if applicable) 6. Able to comprehend the study participation requirements and willing to provide written informed consent in accordance with institutional and regulatory guidelines 7. Able to maintain adequate glycemic control at the run-in visit (for subjects who complete the washout) 8. Having an HbA1c between 7.0 and 8.5% (inclusive) prior to randomization (day -3 to -5) 9. Capable of adhering to the investigational product administration requirements as evidenced by omission of no more than one dose of run-in medication
Key exclusion criteria	1.A diagnosis of type 1 diabetes mellitus or maturity onset diabetes of the young (MODY) 2.Current use of parenteral therapy for treatment of diabetes (insulin or glucagon-like peptide-1 (GLP-1) receptor agonist therapy) 3.Hemoglobinopathy or carrier status for hemoglobin alleles that affect HbA1c measurement 4.Genitourinary tract infection (e.g. urinary tract infection, vaginitis, balanitis) within 6 weeks of screening or history of =>genitourinary infections requiring treatment within 6 months of screening 5.Estimated glomerular filtration rate (eGFR), as calculated by the modification of diet in renal disease study equation (MDRD), < 60 mL/min/1.73 m2 at screening (Appendix 2) 6.Uncontrolled hypertension (average of two sitting measurements of systolic blood pressure >160 mmHg or diastolic blood pressure > 95 mmHg) at screening 7.History of New York Heart Association (NYHA) Class 4 heart failure within 3 months of screening 8.History of MI, unstable angina, stroke, or hospitalization for heart failure within 3 months of screening 9.History of treatment with an investigational drug within 30 days or within 7 half lives of the investigational drug, whichever is longer 10.Previous treatment with bexagliflozin or EGT0001474 11.Currently or within 6 months of taking any SGLT2 inhibitors from screening 12.ALT or 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 13.Exhibiting fasting plasma glucose=> 250 mg/dL (13.9 mmol/L) on two or more consecutive days prior to randomization or exhibiting 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 14.FPG =>250 mg/dL at randomization 15.Prior renal transplantation or evidence of nephrotic syndrome, defined as a urine albumin-to-creatinine ratio (UACR) > 2000 mg/g at screening
Target sample size	320

Research contact person
Name of lead principal investigator	Yuan-Di C.Halvorsen
Organization	Massachusetts General Hospital
Division name	NA
Address	55 Fruit Street,Boston,MA 02114 US
TEL	+1-617-467-4590
Email	YHALVORSEN@CCIB.MGH.HARVARD.EDU

Public contact
Name of contact person	Yoshitaka Ando
Organization	Integraed Development Associates k.k
Division name	Clinical and Regulatory Operation
Address	11F 1-11-44 Akasaka, Minato-ku, Tokyo
TEL	03-6685-5191
Homepage URL
Email	yoshitaka.ando@i-d-a.com

Sponsor
Institute	Theracos, Sub., LLC
Institute
Department

Funding Source
Organization	Theracos, Sub., LLC
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2015 Year 04 Month 01 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2015 Year 02 Month 16 Day
Anticipated trial start date	2015 Year 05 Month 18 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2015 Year 04 Month 01 Day
Last modified on	2016 Year 10 Month 11 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019628