A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Food-Effect of KQ-791

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02370043
• Date of registration: 18/02/2015
• Prospective Registration: No
• Primary sponsor: Kaneq Bioscience Limited
• Public title: A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Food-Effect of KQ-791
• Scientific 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
• Date of first enrolment: February 2015
• Target sample size: 19
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02370043
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Basic Science. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Canada

Contacts

• Name: Email: [e-mail]
• Affiliation: Kaneq Bioscience

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Healthy Volunteers

Insulin Resistance

Intervention(s)

Drug: KQ-791

Drug: Placebo

Drug: KQ-791 (after meal)

Primary Outcome(s)

Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug [Time Frame: Baseline to study completion (up to 11 weeks)]

Secondary Outcome(s)

Maximum Observed Drug Concentration (Cmax) [Time Frame: 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]

Maximum Rate of Urinary Excretion (Rmax) [Time Frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose]

Apparent Volume of Distribution (Vd/F) [Time Frame: 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]

Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) [Time Frame: 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]

Time of Rmax Urinary Excretion (TRmax) [Time Frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose]

Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) [Time Frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose]

Elimination Rate Constant (Kel) [Time Frame: 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]

Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) [Time Frame: Pre-dose and 0.5, 1, 2, 4, 6, 8,10, and 24 hours post-dose]

Maximum Observed Drug Concentration (Cmax) in Fed Versus Fasting State [Time Frame: 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]

Amount of Drug Excreted in Urine [Time Frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose]

Apparent Body Clearance (Cl/F) [Time Frame: 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]

Time to Maximum Drug Concentration (Tmax) in Fed Versus Fasting State [Time Frame: 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]

Renal Clearance (Clr) [Time Frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose]

Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) [Time Frame: 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']

Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) in Fed Versus Fasting State [Time Frame: 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]

Area Under the Concentration-time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) in Fed Versus Fasting State [Time Frame: 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]

Elimination Half-Life (T1/2 el) [Time Frame: 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]

Residual Area [Time Frame: 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]

Time to Observed Cmax (Tmax) [Time Frame: 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]

Secondary ID(s)

KQ-791-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 30/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02370043