Safety and Efficacy of Bexagliflozin in Subjects With Moderate Hepatic Impairment
Condition: Type2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Bexagliflozin
Intervention description: Single oral dose of bexagliflozin tablet, 20 mg
Intervention MeSH terms: Bexagliflozin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to examine the drug exposure and drug effects on subjects with
      moderate hepatic impairment after a single oral dose of bexagliflozin tablets, 20mg. The
      study will also evaluate how safe the study drug is and how well the study drug is tolerated
      in subjects with moderate hepatic impairment.
    

Eligibility criteria:

        Each subject had to meet the following criteria to be eligible for the study:

          1. Be male or female adults between the age of 18 and 75 years

          2. Have a body mass index (BMI) of 18.0 kg/m2 to 40.0 kg/m2

          3. Have adequate venous access at multiple sites in both arms

          4. Be willing to be confined to the clinical research facility as required by the
             protocol

          5. Be able to comprehend the explanation of the informed consent and be willing to
             provide written informed consent in accordance with institutional and regulatory
             guidelines

          6. For subjects in the hepatic impairment group only: Be diagnosed with moderate hepatic
             impairment with a Child-Pugh score 7 to 9 and be in stable general health apart from
             hepatic impairment and its related conditions.

          7. For subjects in the healthy control group only:

               -  Be in general good health with matching demographics and baseline characteristics
                  to individual subjects in the hepatic impairment group by age (± 10 years),
                  weight (± 10%), sex, and smoking status

               -  Exhibit neither evidence of an active infection nor undergoing any treatment with
                  antibiotics at the time of Screening.

        Prospective subjects who met any of the following criteria were ineligible to participate:

          1. A clinically significant history of allergy to drugs or latex

          2. A positive alcohol or drug result based on urine sample or breathalyzer testing at
             Screening or at clinic admission

          3. A donation of 400 mL of whole blood within two months, 200 mL of whole blood within
             one month, or blood components or plasma within 14 days prior to Day 0

          4. A history of exposure to an investigational drug within 30 days or 5 half-lives of the
             investigational drug prior to Day 0, whichever was longer

          5. A history of exposure to any SGLT2 inhibitor within 3 months prior to Day 0 or
             participation in previous bexagliflozin clinical trials

          6. A history of exposure to probenecid, rifampin, or any potential strong UGT1A9 inducers
             or inhibitors within 2 months of Day 0

          7. A clinically significant abnormal electrocardiogram (ECG) that includes but is not
             limited to: heart rate < 40 or > 110 bpm, QRS> 160 ms, QTc> 480 ms (corrected by
             Bazett's formula), or any clinically significant arrhythmia including Mobitz type II
             2nd Degree Heart block and bifascicular block

          8. A history of human immunodeficiency virus (HIV) infection or a positive titer for HIV
             antibody

          9. A history of vaccination (with the exception of the flu vaccine) within 30 days prior
             to Day 0

         10. An estimated glomerular filtration rate (eGFR) < 60 mL·min-1 per 1.73 m2 as calculated
             by the modification of diet in renal disease study equation

         11. Severe or moderate renal dysfunction or a history of kidney, other organ, bone marrow,
             or stem cell transplant

         12. If male, unwilling to refrain from donating sperm or to use appropriate birth control
             when engaging in sexual intercourse for the duration of the study and a period of 14
             days after discharge from the clinic. Surgically sterile male subjects were eligible

         13. If female and of childbearing potential, unwilling to use an adequate method of
             contraception to avoid or prevent pregnancy for the duration of the study and 14 days
             after discharge from the clinic. Surgically sterile (as a result of hysterectomy or
             bilateral oophorectomy), or postmenopausal (absence of menses greater than 12 months
             and age > 45 years) female subjects were eligible. All females were to have had a
             negative pregnancy test at Screening and at clinic admission

         14. Unwillingness to forgo consumption of grapefruit and grapefruit products from 7 days
             prior to Day 0 through discharge from the clinic

         15. Pre existing thrombocytopenia (platelet blood count < 30,000 platelets) at Screening
             or other clinically significant findings in complete blood count (CBC) test.

         16. A history of current febrile illness, hepatocellular carcinoma, acute liver disease,
             severe hepatic encephalopathy, or biliary liver cirrhosis.

         17. A history of significant acute medical illness (new conditions and/or exacerbation of
             pre existing conditions or major surgery within 4 weeks of study drug administration),
             active alcoholic hepatitis, current or recent (within 2 months before Day 0) history
             of significant gastrointestinal disease

         18. Clinical evidence of severe ascites, as judged by the Investigator

         19. A history of surgical portosystemic shunt

         20. For subjects in the healthy control group only:

               -  A seated systolic blood pressure (SBP) of < 90 or > 140 mmHg, confirmed by repeat
                  measurement

               -  A seated diastolic blood pressure (DBP) of < 40 or > 90 mmHg

               -  A history of vitamin preparation or supplement use (including St. John's Wort and
                  ginseng) within 7 days prior to Day 0, or caffeine and methylxanthine (e.g., tea,
                  chocolate) containing foods/beverages within 48 h prior to Day 0

               -  A history of prescription or over-the-counter (OTC) drug use within 7 days or 5
                  half lives of the drug, whichever was longer, prior to Day 0

               -  A history of liver disease or liver injury as indicated by an alanine
                  aminotransferase (ALT), aspartate aminotransferase (AST), > 2.5 × the upper limit
                  of normal (ULN) at Screening, or serum bilirubin > 1.5 × ULN

               -  Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

         21. For subjects in the hepatic impairment group only:

               -  A seated SBP of < 80 or > 160 mmHg, confirmed by repeat measurement

               -  A seated DBP of < 40 or > 100 mmHg

               -  A history of any new prescription medication within 30 days prior to Day 0

               -  A history of fluctuating or rapidly deteriorating hepatic function or the
                  production of widely varying or worsening clinical and/or laboratory signs of
                  hepatic impairment within the screening period

         22. Any other serious medical condition that, in the opinion of the Investigator, would
             pose a significant risk to the subject or interfere with the interpretation of safety,
             PK, or PD data