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

NCT02445911 | Completed Phase 1 Results

• 1 other identifier: KQ-791-02
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo

  Data table is change from baseline in Fasting Blood Glucose. Statistical Analysis includes results for difference in Change from baseline in Fasting Blood Glucose Between KQ-791 and Placebo.

  Baseline to Day 29

• Number of Participants With One or More Treatment-Emergent Adverse Events

  Baseline to Day 29

Secondary Outcomes (16)

• Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI)

  Baseline to Day 29

• Change From Baseline in the Insulin Sensitivity Index (ISI)

  Baseline to Day 29

• Change From Baseline in Beta Cell Function

  Baseline to Day 29

• Change From Baseline in Disposition Index

  Baseline to Day 29

• Change From Baseline in the Hepatic Insulin Resistance Index

  Baseline to Day 29

Study Arms (4)

KQ-791 Dose 1

EXPERIMENTAL

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

Drug: KQ-791

KQ-791 Dose 2

EXPERIMENTAL

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

Drug: KQ-791

KQ-791 Dose 3

EXPERIMENTAL

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

Drug: KQ-791

Placebo

PLACEBO COMPARATOR

Multiple ascending doses matching KQ-791 dose

Drug: Placebo

Interventions

KQ-791 DRUG

Capsules administered orally

KQ-791 Dose 1; KQ-791 Dose 2; KQ-791 Dose 3

Placebo DRUG

Capsules administered orally

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Kaneq Bioscience Limited: lead

Study Sites (4)

Celerion

Tempe, Arizona, 85283, United States

Location

Clinical Pharmacology of Miami, Inc.

Miami, Florida, 33014, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Celerion

Lincoln, Nebraska, 68502, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Dr. Gosse Bruinsma
• Organization: Kaneq Bioscience Limited

gosse.bruinsma@kaneqbioscience.ca

1-613-800-0955

Study Officials

• Email: daniel.bouthillier@Kaneq.ca

  Kaneq Bioscience

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 15, 2015
• Study Start: June 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: November 26, 2019
• Results First Posted: October 30, 2019

Record last verified: 2019-11

Locations

US (4)