Clinical trial NCT02370043: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Food-Effect of KQ-791
Official title: Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Food Effect of KQ-791 in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Insulin Resistance
Lead sponsor: Kaneq Bioscience Limited
Sponsor class: OTHER
First posted: 2015-02-24
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess the safety, tolerability, and the effect of food on KQ-791. Each participant may receive up to 3 single doses of KQ-791 (at up to 3 different dose levels) and 1 placebo dose over the course of the study. Up to 6 escalating dose levels may be studied, in two distinct groups or cohorts.


Eligibility criteria: Inclusion Criteria:

* Male or non-childbearing potential female, which includes post-menopausal female (absence of menses for 12 months prior to drug administration, bilateral oophorectomy or hysterectomy with bilateral oophorectomy at least 6 months prior to drug administration) or surgically sterile female (hysterectomy or tubal ligation at least 6 months prior to drug administration)
* Body Mass Index (BMI) greater than or equal to (≥) 27.0 and less than or equal to (≤) 35.0 kilogram per square meter (kg/m2)
* Healthy as defined by:

  1. absence of clinically significant illness and surgery within last 4 weeks. Participants vomiting within 24 hours pre-dose will be evaluated for upcoming illness/disease
  2. the absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, or metabolic disease
* Male participants who are not vasectomized for at least 6 months, and who are sexually active with non-sterile female partner (sterile female partners include post-menopausal females and surgically sterile females) must be willing to use one of the following acceptable contraceptive methods throughout the study and for 90 days after the last study drug administration:

  1. simultaneous use of a condom, and for the female partner hormonal contraceptives (used since at least 4 weeks) or intra-uterine contraceptive device (placed since at least 4 weeks)
  2. simultaneous use of a male condom, and for his female partner, a diaphragm with intravaginally applied spermicide
* Some degree of insulin resistance, as shown by:

  1. fasting blood glucose ≥95.4 and ≤126 milligrams per deciliter (mg/dL) (equivalent to 5.3 to 7.0 millimoles per liter (mmol/L), respectively) and
  2. fasting triglycerides ≤ 4.0 mmol/L, and/or
  3. Low-Density Lipoprotein Cholesterol (LDL-C) ≤ 6.0 mmol/L
* Capable of consent
* Non-smoker (no use of tobacco products within the last 3 months)

Exclusion Criteria:

* Any clinically significant abnormality or abnormal laboratory test results (other than glucose,triglycerides and LDL-C levels described in inclusion criterion)
* Positive test for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV)
* Evidence of clinically significant hepatic or renal impairment, including Alanine Aminotransferase (ALT) above 1.5x Upper Limit of Normal (ULN), Aspartate Aminotransferase (AST) above 2x ULN, total bilirubin above 2x ULN (total bilirubin accepted up to 2x ULN if direct bilirubin is within normal limits), or Estimated Glomerular Filtration Rate (eGFR) less than (\<) 90 milliliters per minute (mL/minute)
* Positive urine drug screen
* History of significant allergic reactions (e.g. angioedema) to any drug.
* Use of any drugs known to induce or inhibit hepatic drug metabolism within the last 30 days
* Positive pregnancy test
* Any reason which, in the opinion of the qualified investigator (QI) would prevent the subject from participating in the study
* Clinically significant electrocardiogram (ECG) abnormalities at screening, or clinically significant personal or family history (in a first-degree relative) of heart diseases, including:

  1. Confirmed corrected QT (QTcF) interval greater than (\>) 450 milliseconds (msec) for men and women
  2. Bundle branch blocks and other conduction abnormalities other than mild first degree atrio-ventricular block
  3. Irregular rhythms other than sinus arrhythmia or occasional, rare supraventricular ectopic beats
* History of unexplained syncope
* Family history of unexplained sudden death or sudden death due to long QT syndrome
* T-wave configurations are not of sufficient quality for assessing QT interval
* Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 150 mmHg, diastolic blood pressure lower than 50 or over 95 mmHg, or heart rate less than 50 or over 100 beats per minute (bpm))
* History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening (regular use of more than three units of alcohol per day for males and more than two units of alcohol per day for females \[1 unit = 150 (milliliter) mL of wine, 360 mL of beer, or 45 mL of 40% alcohol\]) or positive alcohol breath test
* History of significant drug abuse within the last year or use of soft drugs (such as marijuana) within 3 months prior, or hard drugs (such as cocaine, phencyclidine (PCP) and crack) within the last year
* Participation in a clinical trial involving the administration of an investigational or marketed drug within the last 30 days (90 days for biologics) or concomitant participation in an investigational study
* Use of medication other than topical products without significant systemic absorption:

  1. prescription medication within last 14 days
  2. over-the-counter products within the last 7 days, with the exception of the occasional use of acetaminophen (up to 2 grams (g) daily)
  3. natural health products (e.g. food supplements or herbal supplements) within last 14 days
  4. a depot injection or an implant of any drug within last 3 months
* Donation of plasma within the last 7 days. Donation or loss of blood of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days
* Hemoglobin \<128 grams per liter (g/L) (males) and \<115 g/L (females) and hematocrit \<0.37 L/L (males) and \<0.32 L/L (females)
* Breast-feeding participant

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug
timeFrame: Baseline to study completion (up to 11 weeks)
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, and 24 hours post-dose
measure: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg'
measure: Maximum Observed Drug Concentration (Cmax)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Residual Area
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Time to Observed Cmax (Tmax)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels
measure: Elimination Half-Life (T1/2 el)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Elimination Rate Constant (Kel)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Apparent Body Clearance (Cl/F)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Apparent Volume of Distribution (Vd/F)
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) in Fed Versus Fasting State
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Area Under the Concentration-time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) in Fed Versus Fasting State
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Maximum Observed Drug Concentration (Cmax) in Fed Versus Fasting State
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels, and on Day 28 for dose level 195 mg; on Days 14 and 28 for dose level 600 mg; and on Days 14, 28, and 56 for dose level 1800 mg
measure: Time to Maximum Drug Concentration (Tmax) in Fed Versus Fasting State
timeFrame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, 24, 48, 96, and 144 hours post-dose, and on Day 10 for all dose levels
measure: Amount of Drug Excreted in Urine
timeFrame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
measure: Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t)
timeFrame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
measure: Maximum Rate of Urinary Excretion (Rmax)
timeFrame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
measure: Time of Rmax Urinary Excretion (TRmax)
timeFrame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
measure: Renal Clearance (Clr)
timeFrame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Inventiv
state: Quebec
city: Quebec
country: Canada
facility: inVentiv
Study officials:
affiliation: Kaneq Bioscience
name: Email: daniel.bouthillier@Kaneq.ca
role: STUDY_DIRECTOR
References: