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Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of KQ-791 in Diabetes Mellitus

K

Kaneq Bioscience

Status and phase

Completed
Phase 1

Conditions

Diabetes Mellitus, Type 2

Treatments

Drug: Placebo
Drug: KQ-791

Study type

Interventional

Funder types

Other

Identifiers

NCT02445911
KQ-791-02

Details and patient eligibility

About

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

Enrollment

81 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

81 participants in 4 patient groups, including a placebo group

KQ-791 Dose 1
Experimental group
Description:
Single loading dose on day 1, followed by single doses on days 8, 15, 22, 29
Treatment:
Drug: KQ-791
KQ-791 Dose 2
Experimental group
Description:
Single loading dose on day 1, followed by a daily dose for 28 days
Treatment:
Drug: KQ-791
KQ-791 Dose 3
Experimental group
Description:
Single loading dose on day 1 or days 1-2, followed by a daily dose for 28 days
Treatment:
Drug: KQ-791
Placebo
Placebo Comparator group
Description:
Multiple ascending doses matching KQ-791 dose
Treatment:
Drug: Placebo

Trial contacts and locations

4

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Data sourced from clinicaltrials.gov

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