Healthy Volunteers, Insulin Resistance
Conditions
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.
Interventions
DRUGKQ-791
Capsules administered orally while fasting, in up to 3 periods
DRUGKQ-791 (after meal)
Single dose of KQ-791 in capsules, after a meal, in 1 period
DRUGPlacebo
Capsules, administered orally, in 1 period
Sponsors
Kaneq Bioscience Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | Baseline to study completion (up to 11 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | Pre-dose and 0.5, 1, 2, 4, 6, 8,10, and 24 hours post-dose | — |
| Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 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 Observed Drug Concentration (Cmax) | 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 | 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 | calculated as 100\*(1- AUC0-t / AUC0-inf) |
| Time to Observed Cmax (Tmax) | 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 | — |
| Elimination Half-Life (T1/2 el) | 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 Rate Constant (Kel) | 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 | — |
| Apparent Body Clearance (Cl/F) | 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 | — |
| Apparent Volume of Distribution (Vd/F) | 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) | 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 | 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 Observed Drug Concentration (Cmax) in Fed Versus Fasting State | 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 | 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 | — |
| Amount of Drug Excreted in Urine | 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) | Four hour intervals up to 12 hours, and then 12-24 hours post dose | — |
| Maximum Rate of Urinary Excretion (Rmax) | Four hour intervals up to 12 hours, and then 12-24 hours post dose | — |
| Time of Rmax Urinary Excretion (TRmax) | Four hour intervals up to 12 hours, and then 12-24 hours post dose | — |
| Renal Clearance (Clr) | Four hour intervals up to 12 hours, and then 12-24 hours post dose | Calculated by the following equation: Ae0-t/AUC0-24 |
| Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) in Fed Versus Fasting State | 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 | — |
Countries
Canada
Participant flow
Recruitment details
Sequence 60 mg/600 mg/Placebo subject discontinued after completion of 600 mg. Sequence Placebo/600 mg/1800 mg subject discontinued after completion of placebo.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 48.1 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment Canada | 19 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 2 / 6 | 3 / 6 | 2 / 6 | 2 / 6 | 2 / 6 | 4 / 6 | 8 / 17 | 1 / 3 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 17 | 0 / 3 |
Outcome results
Primary
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)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 15 mg KQ-791 (Fasting) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| 60 mg KQ-791 (Fasting) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| 195 mg KQ-791 (Fasting) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| 195 mg KQ-791 (Fed) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| 600 mg KQ-791 (Fasting) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| 1200 mg KQ-791 (Fasting) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| 1800 mg Kq-791 (Fasting) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| Placebo (Fed) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
| Placebo (Fasting) | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug | 0 participants |
Secondary
Amount of Drug Excreted in Urine
Time frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute the Amount of Drug Excreted in Urine.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Amount of Drug Excreted in Urine | 37.72 μg | Geometric Coefficient of Variation 27.71 |
| 60 mg KQ-791 (Fasting) | Amount of Drug Excreted in Urine | 155.51 μg | Geometric Coefficient of Variation 15.81 |
| 195 mg KQ-791 (Fasting) | Amount of Drug Excreted in Urine | 381.35 μg | Geometric Coefficient of Variation 34.71 |
| 195 mg KQ-791 (Fed) | Amount of Drug Excreted in Urine | 224.51 μg | Geometric Coefficient of Variation 31.25 |
| 600 mg KQ-791 (Fasting) | Amount of Drug Excreted in Urine | 739.07 μg | Geometric Coefficient of Variation 67.68 |
| 1200 mg KQ-791 (Fasting) | Amount of Drug Excreted in Urine | 1796.43 μg | Geometric Coefficient of Variation 29.85 |
| 1800 mg Kq-791 (Fasting) | Amount of Drug Excreted in Urine | 3069.11 μg | Geometric Coefficient of Variation 37.08 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute CI/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Apparent Body Clearance (Cl/F) | 0.3696 Liters per hour (L/h) | Geometric Coefficient of Variation 48.4762 |
| 60 mg KQ-791 (Fasting) | Apparent Body Clearance (Cl/F) | 0.4666 Liters per hour (L/h) | Geometric Coefficient of Variation 43.0267 |
| 195 mg KQ-791 (Fasting) | Apparent Body Clearance (Cl/F) | 0.5027 Liters per hour (L/h) | Geometric Coefficient of Variation 32.8329 |
| 195 mg KQ-791 (Fed) | Apparent Body Clearance (Cl/F) | 1.6219 Liters per hour (L/h) | Geometric Coefficient of Variation 9.8091 |
| 600 mg KQ-791 (Fasting) | Apparent Body Clearance (Cl/F) | 0.7732 Liters per hour (L/h) | Geometric Coefficient of Variation 47.0999 |
| 1200 mg KQ-791 (Fasting) | Apparent Body Clearance (Cl/F) | 0.9150 Liters per hour (L/h) | Geometric Coefficient of Variation 37.9245 |
| 1800 mg Kq-791 (Fasting) | Apparent Body Clearance (Cl/F) | 0.8271 Liters per hour (L/h) | Geometric Coefficient of Variation 40.4976 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Vd/F.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Apparent Volume of Distribution (Vd/F) | 107.01 Liters | Geometric Coefficient of Variation 34.95 |
| 60 mg KQ-791 (Fasting) | Apparent Volume of Distribution (Vd/F) | 132.23 Liters | Geometric Coefficient of Variation 32.37 |
| 195 mg KQ-791 (Fasting) | Apparent Volume of Distribution (Vd/F) | 155.49 Liters | Geometric Coefficient of Variation 27.72 |
| 195 mg KQ-791 (Fed) | Apparent Volume of Distribution (Vd/F) | 179.83 Liters | Geometric Coefficient of Variation 13.14 |
| 600 mg KQ-791 (Fasting) | Apparent Volume of Distribution (Vd/F) | 245.08 Liters | Geometric Coefficient of Variation 46.56 |
| 1200 mg KQ-791 (Fasting) | Apparent Volume of Distribution (Vd/F) | 261.06 Liters | Geometric Coefficient of Variation 18.01 |
| 1800 mg Kq-791 (Fasting) | Apparent Volume of Distribution (Vd/F) | 257.25 Liters | Geometric Coefficient of Variation 29.61 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUC0-24.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | 3410.02 h*ng/mL | Geometric Coefficient of Variation 55.5 |
| 60 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | 12251.48 h*ng/mL | Geometric Coefficient of Variation 25.11 |
| 195 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | 33151.96 h*ng/mL | Geometric Coefficient of Variation 34.63 |
| 195 mg KQ-791 (Fed) | Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | 16718.65 h*ng/mL | Geometric Coefficient of Variation 17.76 |
| 600 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | 60448.26 h*ng/mL | Geometric Coefficient of Variation 46.92 |
| 1200 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | 113891.92 h*ng/mL | Geometric Coefficient of Variation 24.54 |
| 1800 mg Kq-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to 24-hour Post-Dose (AUC0-24) | 178100.82 h*ng/mL | Geometric Coefficient of Variation 44.64 |
Secondary
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'
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUC0-inf.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 40581.44 h*ng/mL | Geometric Coefficient of Variation 51.9 |
| 60 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 128600.49 h*ng/mL | Geometric Coefficient of Variation 37.47 |
| 195 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 387934.16 h*ng/mL | Geometric Coefficient of Variation 31.98 |
| 195 mg KQ-791 (Fed) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 120230.35 h*ng/mL | Geometric Coefficient of Variation 9.81 |
| 600 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 776014.78 h*ng/mL | Geometric Coefficient of Variation 37.64 |
| 1200 mg KQ-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 1311488.40 h*ng/mL | Geometric Coefficient of Variation 29.23 |
| 1800 mg Kq-791 (Fasting) | Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) | 2176168.42 h*ng/mL | Geometric Coefficient of Variation 34.65 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUC0-inf in Fed versus Fasting State.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) in Fed Versus Fasting State | 0.32 h*ng/mL | Geometric Coefficient of Variation 15.17 |
Secondary
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Area Under the Concentration-time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) in Fed Versus Fasting State | 0.31 h*ng/mL | Geometric Coefficient of Variation 37.61 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute AUC0-t.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) | 34699.23 h*ng/mL | Geometric Coefficient of Variation 44.87 |
| 60 mg KQ-791 (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) | 95223.95 h*ng/mL | Geometric Coefficient of Variation 32.54 |
| 195 mg KQ-791 (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) | 358380.52 h*ng/mL | Geometric Coefficient of Variation 36.34 |
| 195 mg KQ-791 (Fed) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) | 110566.98 h*ng/mL | Geometric Coefficient of Variation 17.39 |
| 600 mg KQ-791 (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) | 721393.21 h*ng/mL | Geometric Coefficient of Variation 32.49 |
| 1200 mg KQ-791 (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) | 1207610.37 h*ng/mL | Geometric Coefficient of Variation 29.83 |
| 1800 mg Kq-791 (Fasting) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Non-Zero Concentration (AUC0-t) | 2137673.75 h*ng/mL | Geometric Coefficient of Variation 34.74 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Ae0-t.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) | 90.60 μg | Geometric Coefficient of Variation 37.17 |
| 60 mg KQ-791 (Fasting) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) | 350.68 μg | Geometric Coefficient of Variation 19.39 |
| 195 mg KQ-791 (Fasting) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) | 859.41 μg | Geometric Coefficient of Variation 39.32 |
| 195 mg KQ-791 (Fed) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) | 421.70 μg | Geometric Coefficient of Variation 27.23 |
| 600 mg KQ-791 (Fasting) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) | 1893.11 μg | Geometric Coefficient of Variation 57.89 |
| 1200 mg KQ-791 (Fasting) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) | 3793.47 μg | Geometric Coefficient of Variation 34.98 |
| 1800 mg Kq-791 (Fasting) | Cumulative Urinary Excretion From Time Zero to Time t (Ae0-t) | 6680.04 μg | Geometric Coefficient of Variation 38.34 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute T1/2 el.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Elimination Half-Life (T1/2 el) | 200.67 Hours | Geometric Coefficient of Variation 16.89 |
| 60 mg KQ-791 (Fasting) | Elimination Half-Life (T1/2 el) | 196.45 Hours | Geometric Coefficient of Variation 17.67 |
| 195 mg KQ-791 (Fasting) | Elimination Half-Life (T1/2 el) | 214.42 Hours | Geometric Coefficient of Variation 28.77 |
| 195 mg KQ-791 (Fed) | Elimination Half-Life (T1/2 el) | 76.86 Hours | Geometric Coefficient of Variation 22.8 |
| 600 mg KQ-791 (Fasting) | Elimination Half-Life (T1/2 el) | 219.71 Hours | Geometric Coefficient of Variation 7.83 |
| 1200 mg KQ-791 (Fasting) | Elimination Half-Life (T1/2 el) | 197.77 Hours | Geometric Coefficient of Variation 24.28 |
| 1800 mg Kq-791 (Fasting) | Elimination Half-Life (T1/2 el) | 215.58 Hours | Geometric Coefficient of Variation 12.61 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Kel.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Elimination Rate Constant (Kel) | 0.0035 Per hour | Geometric Coefficient of Variation 18.9823 |
| 60 mg KQ-791 (Fasting) | Elimination Rate Constant (Kel) | 0.0035 Per hour | Geometric Coefficient of Variation 16.0482 |
| 195 mg KQ-791 (Fasting) | Elimination Rate Constant (Kel) | 0.0032 Per hour | Geometric Coefficient of Variation 32.1756 |
| 195 mg KQ-791 (Fed) | Elimination Rate Constant (Kel) | 0.0090 Per hour | Geometric Coefficient of Variation 22.803 |
| 600 mg KQ-791 (Fasting) | Elimination Rate Constant (Kel) | 0.0032 Per hour | Geometric Coefficient of Variation 7.9026 |
| 1200 mg KQ-791 (Fasting) | Elimination Rate Constant (Kel) | 0.0035 Per hour | Geometric Coefficient of Variation 28.6322 |
| 1800 mg Kq-791 (Fasting) | Elimination Rate Constant (Kel) | 0.0032 Per hour | Geometric Coefficient of Variation 14.2298 |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Maximum Observed Drug Concentration (Cmax) | 188.65 ng/mL | Geometric Coefficient of Variation 65.96 |
| 60 mg KQ-791 (Fasting) | Maximum Observed Drug Concentration (Cmax) | 637.51 ng/mL | Geometric Coefficient of Variation 29.32 |
| 195 mg KQ-791 (Fasting) | Maximum Observed Drug Concentration (Cmax) | 1857.08 ng/mL | Geometric Coefficient of Variation 45.29 |
| 195 mg KQ-791 (Fed) | Maximum Observed Drug Concentration (Cmax) | 923.51 ng/mL | Geometric Coefficient of Variation 20.32 |
| 600 mg KQ-791 (Fasting) | Maximum Observed Drug Concentration (Cmax) | 3238.86 ng/mL | Geometric Coefficient of Variation 52.73 |
| 1200 mg KQ-791 (Fasting) | Maximum Observed Drug Concentration (Cmax) | 5828.97 ng/mL | Geometric Coefficient of Variation 32.07 |
| 1800 mg Kq-791 (Fasting) | Maximum Observed Drug Concentration (Cmax) | 9418.01 ng/mL | Geometric Coefficient of Variation 44.09 |
Secondary
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
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Maximum Observed Drug Concentration (Cmax) in Fed Versus Fasting State | 0.50 ng/mL | Geometric Coefficient of Variation 59.94 |
Secondary
Maximum Rate of Urinary Excretion (Rmax)
Time frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Rmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Maximum Rate of Urinary Excretion (Rmax) | 5.13 μg/hour | Geometric Coefficient of Variation 44.88 |
| 60 mg KQ-791 (Fasting) | Maximum Rate of Urinary Excretion (Rmax) | 21.09 μg/hour | Geometric Coefficient of Variation 29.33 |
| 195 mg KQ-791 (Fasting) | Maximum Rate of Urinary Excretion (Rmax) | 49.05 μg/hour | Geometric Coefficient of Variation 39.75 |
| 195 mg KQ-791 (Fed) | Maximum Rate of Urinary Excretion (Rmax) | 25.53 μg/hour | Geometric Coefficient of Variation 29.88 |
| 600 mg KQ-791 (Fasting) | Maximum Rate of Urinary Excretion (Rmax) | 123.11 μg/hour | Geometric Coefficient of Variation 48.42 |
| 1200 mg KQ-791 (Fasting) | Maximum Rate of Urinary Excretion (Rmax) | 206.83 μg/hour | Geometric Coefficient of Variation 33.25 |
| 1800 mg Kq-791 (Fasting) | Maximum Rate of Urinary Excretion (Rmax) | 377.72 μg/hour | Geometric Coefficient of Variation 38.11 |
Secondary
Renal Clearance (Clr)
Calculated by the following equation: Ae0-t/AUC0-24
Time frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Clr.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Renal Clearance (Clr) | 0.0266 Liters per hour | Geometric Coefficient of Variation 31.5426 |
| 60 mg KQ-791 (Fasting) | Renal Clearance (Clr) | 0.0286 Liters per hour | Geometric Coefficient of Variation 19.7181 |
| 195 mg KQ-791 (Fasting) | Renal Clearance (Clr) | 0.0259 Liters per hour | Geometric Coefficient of Variation 19.7678 |
| 195 mg KQ-791 (Fed) | Renal Clearance (Clr) | 0.0252 Liters per hour | Geometric Coefficient of Variation 20.7044 |
| 600 mg KQ-791 (Fasting) | Renal Clearance (Clr) | 0.0313 Liters per hour | Geometric Coefficient of Variation 17.2647 |
| 1200 mg KQ-791 (Fasting) | Renal Clearance (Clr) | 0.0333 Liters per hour | Geometric Coefficient of Variation 18.614 |
| 1800 mg Kq-791 (Fasting) | Renal Clearance (Clr) | 0.0375 Liters per hour | Geometric Coefficient of Variation 9.5596 |
Secondary
Residual Area
calculated as 100\*(1- AUC0-t / 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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Residual Area.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15 mg KQ-791 (Fasting) | Residual Area | 4.59 Percentage residual area under the AUC | Geometric Coefficient of Variation 107.28 |
| 60 mg KQ-791 (Fasting) | Residual Area | 11.51 Percentage residual area under the AUC | Geometric Coefficient of Variation 45.28 |
| 195 mg KQ-791 (Fasting) | Residual Area | 3.58 Percentage residual area under the AUC | Geometric Coefficient of Variation 113.37 |
| 195 mg KQ-791 (Fed) | Residual Area | 13.23 Percentage residual area under the AUC | Geometric Coefficient of Variation 50.26 |
| 600 mg KQ-791 (Fasting) | Residual Area | 4.25 Percentage residual area under the AUC | Geometric Coefficient of Variation 88.29 |
| 1200 mg KQ-791 (Fasting) | Residual Area | 4.53 Percentage residual area under the AUC | Geometric Coefficient of Variation 84.07 |
| 1800 mg Kq-791 (Fasting) | Residual Area | 1.55 Percentage residual area under the AUC | Geometric Coefficient of Variation 47.64 |
Secondary
Time of Rmax Urinary Excretion (TRmax)
Time frame: Four hour intervals up to 12 hours, and then 12-24 hours post dose
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute TRmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 15 mg KQ-791 (Fasting) | Time of Rmax Urinary Excretion (TRmax) | 5.93 Hours |
| 60 mg KQ-791 (Fasting) | Time of Rmax Urinary Excretion (TRmax) | 5.93 Hours |
| 195 mg KQ-791 (Fasting) | Time of Rmax Urinary Excretion (TRmax) | 5.91 Hours |
| 195 mg KQ-791 (Fed) | Time of Rmax Urinary Excretion (TRmax) | 9.88 Hours |
| 600 mg KQ-791 (Fasting) | Time of Rmax Urinary Excretion (TRmax) | 5.88 Hours |
| 1200 mg KQ-791 (Fasting) | Time of Rmax Urinary Excretion (TRmax) | 9.90 Hours |
| 1800 mg Kq-791 (Fasting) | Time of Rmax Urinary Excretion (TRmax) | 5.96 Hours |
Secondary
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 15 mg KQ-791 (Fasting) | Time to Maximum Drug Concentration (Tmax) in Fed Versus Fasting State | 3 Hours |
Secondary
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
Population: All randomized participants who received at least 1 dose of KQ-791and had sufficient evaluable PK data to compute Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 15 mg KQ-791 (Fasting) | Time to Observed Cmax (Tmax) | 4 Hours |
| 60 mg KQ-791 (Fasting) | Time to Observed Cmax (Tmax) | 5 Hours |
| 195 mg KQ-791 (Fasting) | Time to Observed Cmax (Tmax) | 4 Hours |
| 195 mg KQ-791 (Fed) | Time to Observed Cmax (Tmax) | 8 Hours |
| 600 mg KQ-791 (Fasting) | Time to Observed Cmax (Tmax) | 5.01 Hours |
| 1200 mg KQ-791 (Fasting) | Time to Observed Cmax (Tmax) | 8 Hours |
| 1800 mg Kq-791 (Fasting) | Time to Observed Cmax (Tmax) | 7.06 Hours |