Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of KQ-791 in Diabetes Mellitus
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: KQ-791; Placebo
Intervention description: Capsules administered orally; Capsules administered orally
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      This study will consist of multiple ascending oral doses in up to 3 groups, for 29 days.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of Type 2 Diabetes Mellitus (T2DM)

          -  Be an adult between the ages of 18 (19 for Lincoln site) and 70 years

          -  Female participants must be of non-childbearing potential, and must be either 1)
             postmenopausal with amenorrhea for at least 1 year prior to the first dose and
             Follicle Stimulating Hormone (FSH) serum levels consistent with postmenopausal status,
             or 2) have undergone one of the following sterilization procedures at least 6 months
             prior to the first dose:

               -  hysteroscopic sterilization

               -  bilateral tubal ligation or bilateral salpingectomy

               -  hysterectomy

               -  bilateral oophorectomy

          -  Non-vasectomized males must agree to use a condom with spermicide or abstain from
             sexual intercourse during the study until 100 days beyond the last dose of study drug.
             (No restrictions are required for a vasectomized male provided his vasectomy has been
             performed 4 months or more prior to first dosing. A male who has been vasectomized
             less than 4 months prior to first dosing must follow the same restrictions as a
             non-vasectomized male)

          -  Males must agree to not donate sperm during the study and for 100 days following the
             last dose

          -  Have an HbA1c value between 7.0-10.0%

          -  Be on a stable treatment regimen of metformin, with or without diet/exercise, for at
             least 8 weeks

          -  Weigh 60 kilograms (kg) or more at screening and have a body mass index (BMI) greater
             than or equal to (≥) 25.0 and less than or equal to (≤) 40.0 kilograms/meters squared
             (kg/m2)

          -  Have laboratory test results within the normal range for T2DM population, or with
             abnormalities deemed clinically insignificant. Urine protein levels must be within
             normal limits

          -  Absence of active diabetic retinopathy (Stage 2 or greater by the International
             Clinical Disease Severity Scale for Diabetic Retinopathy)

          -  Are willing to comply with specific dietary restrictions (that is, [i] able to fast
             overnight for at least 8-12 hours on several days and [ii] able to consume the
             standard meals provided during specified confinement days)

          -  Have given written consent to allow collection of samples for Peripheral Blood
             Mononuclear Cells (PBMC) analysis and for possible biomarkers/safety analysis

          -  Have given written informed consent approved by the institutional review board (IRB)
             governing the site

        Exclusion Criteria:

          -  Are currently enrolled in a clinical trial involving an investigational product or
             off-label use of a drug or device, or are concurrently enrolled in any other type of
             medical research judged not to be scientifically or medically compatible with this
             study

          -  Participated (defined as the last dose of study drug) within 30 days prior to dosing
             in a clinical trial involving an investigational product or non-approved use of a drug
             with a short half-life or within 5 half-lives of an investigational product with a
             half-life longer than 6 days

          -  - Have a (QTcF) greater than (>) 450 milliseconds (msec), or clinical significant
             hypokalemia, a family history of long QT syndrome or any abnormality in the 12-lead
             Electrocardiogram (ECG)

          -  Abnormal blood pressure (sitting) defined as diastolic blood pressure > 95 or less
             than (<) 50 millimeter of mercury (mmHg) and/or systolic blood pressure > 160 or < 90
             mmHg

          -  Have a history or presence of cardiovascular, respiratory, hepatic, renal,
             gastrointestinal, endocrine, hematological, or neurological disorders capable of
             significantly altering the absorption, metabolism, or elimination of drugs

          -  Show evidence of regular use of known drugs of abuse and/or positive findings on
             urinary drug screening

          -  Evidence of human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C
             and/or positive results at screening for the respective antibodies for HIV, hepatitis
             B surface antigen (HBsAg), or hepatitis C antibodies (HCV)

          -  Have anemia that would interfere with the trial or have donated ≥500 mL of blood
             within 56 days before the first dose or have donated plasma within 7 days before the
             first dose or provided any blood donation within last 30 days

          -  Have an average weekly alcohol intake that exceeds 14 units per week (males) and 7
             units per week (females) [1 unit = 12 ounces (oz) or 360 mL of beer, 5 oz or 150 mL of
             wine, or 1.5 oz or 45 mL of distilled spirits] or are unwilling to stop alcohol
             consumption 48 hours prior to the first dosing and throughout the study

          -  Consume more than 10 cigarettes per day or the equivalent or are unable or unwilling
             to adhere to restricted smoking policies

          -  Have had >1 episode of documented severe hypoglycemia within last 6 months or are
             currently diagnosed as having hypoglycemia unawareness

          -  Have any of the following clinical laboratory test results:

               -  estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (impaired renal
                  function)

               -  alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 1.5
                  times (x) the upper limit of normal (ULN)

               -  triglycerides (TG) > 500 milligrams/deciliter (mg/dL)

          -  Have used insulin or other glycemic control medications, except metformin, for
             diabetic control within 3 months

          -  Intend to use non-steroidal anti-inflammatory drugs (except aspirin) and drugs known
             to prolong QT interval, herbal products, or vitamin supplements that change glucose
             levels. The following medications are allowed for participants:

               -  drugs for treatment of hypertension or lipid disorders (except bile acid resins,
                  niacin or fish oils), platelet inhibitors, and on stable dose for 12 weeks prior
                  to first dose

               -  thyroid replacement therapy, proton pump inhibitors, antidepressants,
                  antihistamines, regularly taken over-the-counter (OTC) and anti-emetics that do
                  not cause a corrected QT interval (QTc) prolongation, provided such drugs are not
                  specifically excluded

               -  hormonal replacement therapy