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

NCT ID: NCT02445911

Last Updated: 2019-11-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-30
• Study Completion Date: 2016-02-29

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

KQ-791 Dose 1

Single loading dose on day 1, followed by single doses on days 8, 15, 22, 29

Group Type: EXPERIMENTAL

KQ-791

Intervention Type: DRUG

Capsules administered orally

KQ-791 Dose 2

Single loading dose on day 1, followed by a daily dose for 28 days

Group Type: EXPERIMENTAL

KQ-791

Intervention Type: DRUG

Capsules administered orally

KQ-791 Dose 3

Single loading dose on day 1 or days 1-2, followed by a daily dose for 28 days

Group Type: EXPERIMENTAL

KQ-791

Intervention Type: DRUG

Capsules administered orally

Placebo

Multiple ascending doses matching KQ-791 dose

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Capsules administered orally

Interventions

KQ-791

Capsules administered orally

Intervention Type: DRUG

Placebo

Capsules administered orally

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kaneq Bioscience Limited

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Email: daniel.bouthillier@Kaneq.ca

Role: STUDY_DIRECTOR

Kaneq Bioscience

Locations

Celerion

Tempe, Arizona, United States

Clinical Pharmacology of Miami, Inc.

Miami, Florida, United States

Orlando Clinical Research Center

Orlando, Florida, United States

Celerion

Lincoln, Nebraska, United States

Countries

United States

Other Identifiers

KQ-791-02

Identifier Type: -

Identifier Source: org_study_id