safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of kq-791 in diabetes mellitus

Conditions: Diabetes Mellitus, Type 2

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 (\ 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