This is a randomized, double-blind, placebo-controlled study conducted in healthy adult volunteers to assess the safety, tolerability and pharmacokinetics of iQ-007. iQ-007 may be indicated for use in patients with Focal Seizures and Drug-resistant Epilepsy (DRE).
This is a randomized, double-blind, placebo-controlled study conducted in healthy adult volunteers. The study will be conducted in 2 parts: a single ascending dose (SAD) component and a multiple ascending dose (MAD) component. Part A (SAD) will involve the administration of a single oral dose of iQ-007 or placebo capsules on Day 1 in Cohorts Al, A2, A3, A5 and A6. Participants in Cohort A4, will be required to fast overnight (minimum of 8 hours) prior to eating a high fat breakfast 30 minutes prior to a single oral administration of iQ-007 or placebo capsules on Day 1. Part B (MAD) will involve the administration of multiple twice daily oral doses of iQ-007 or placebo capsules on Days 1 to 14 (total of 27 doses) in cohorts B1, B2, B3.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
72
CMAX Clinical Research Pty Ltd
Adelaide, South Australia, Australia
Incidence, severity and relationship of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs.
Adverse event (AE) - graded using the categories Mild, Moderate or Severe and will be classified as normal, abnormal not clinically significant (NCS), or abnormal CS.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in Blood pressure measurements
Vital signs assessed as normal, abnormal not clinically significant (NCS), or abnormal clinically significant (CS) with Blood pressure assessed using digital sphygmomanometer
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in electrocardiogram (ECG) parameters
Twelve-lead Electrocardiogram's (ECG's) including the measurement of ventricular heart rate \[HR\] will be conducted in triplicate.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in clinical laboratory results
Clinical laboratory results assessed using blood and urine samples and will be classified as normal, abnormal not clinically significant (NCS), or abnormal CS.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in heart rate measurements
Vital signs assessed as normal, abnormal not clinically significant (NCS), or abnormal CS with heart rate and respiratory rate assessed using pulse oximeter
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
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Changes from baseline in temperature measurements
Vital signs assessed as normal, abnormal not clinically significant (NCS), or abnormal CS with temperature assessed using digital thermometer.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in ECG PR interval
Twelve-lead Electrocardiogram's (ECG's) including the measurement of PR interval will be conducted in triplicate.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in ECG QRS duration
Twelve-lead Electrocardiogram's (ECG's) including the measurement of QRS duration will be conducted in triplicate.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in ECG QT interval
Twelve-lead Electrocardiogram's (ECG's) including the measurement of QT interval will be conducted in triplicate.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Changes from baseline in ECG QTcF
Twelve-lead Electrocardiogram's (ECG's) including the measurement of QTcF will be conducted in triplicate.
Time frame: From baseline to the end of observation on Day 8 for Single ascending dose. From baseline to the end of observation on Day 21 for Multiple ascending dose.
Single Ascending Dose: Plasma PK parameter - Maximum observed concentration (Cmax)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1, then 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose, Day 2, 24 hours post-dose, Day 3, 48 hours post-dose, Day 4, 72 hours post-dose and Day 5, 96 hours post-dose.
Multiple Ascending Dose: Plasma PK parameters - Maximum observed concentration (Cmax)
Blood plasma samples will be assessed
Time frame: pre-dose Day 1 then 0.5, 1, 2, 3, 4, 6, 8, & 12 hrs post-dose, pre-dose on Days 2 - 13, pre-dose Day 14 then 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hrs post-dose, Day 15 24 hrs post-dose, Day 16 48 hrs post-dose, Day 17 72 hrs post-dose & Day 18 96 hrs post-dose
Multiple ascending dose: Urine PK endpoints include • Cumulative amount of un-changed drug excreted inurine (Ae)
Urine samples will be assessed
Time frame: Pre-dose Day 1 - up to 12 hours post AM (first) dose, Day 14 and Day 15, up to 12 hours post AM (final) dose, 12 to 24 hours post AM (final) dose, Day 16, 24 to 48 hours post-dose, Day 17, 48 to 72 hours post-dose and Day 18, 72 to 96 hours post-dose.
Single Ascending Dose: Plasma PK parameter - Time to maximum observed concentration (Tmax)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1, then 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose, Day 2, 24 hours post-dose, Day 3, 48 hours post-dose, Day 4, 72 hours post-dose and Day 5, 96 hours post-dose.
Single Ascending Dose: Plasma PK parameter - Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUClast)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1, then 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose, Day 2, 24 hours post-dose, Day 3, 48 hours post-dose, Day 4, 72 hours post-dose and Day 5, 96 hours post-dose.
Single Ascending Dose: Plasma PK parameter - Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1, then 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose, Day 2, 24 hours post-dose, Day 3, 48 hours post-dose, Day 4, 72 hours post-dose and Day 5, 96 hours post-dose.
Single Ascending Dose: Plasma PK parameter - Apparent terminal elimination half-life (T1/2)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1, then 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose, Day 2, 24 hours post-dose, Day 3, 48 hours post-dose, Day 4, 72 hours post-dose and Day 5, 96 hours post-dose.
Single Ascending Dose: Plasma PK parameter - Volume of distribution (Vz/F)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1, then 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose, Day 2, 24 hours post-dose, Day 3, 48 hours post-dose, Day 4, 72 hours post-dose and Day 5, 96 hours post-dose.
Single Ascending Dose: Plasma PK parameter - Clearance (CL/F)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1, then 0.5, 1, 2, 3, 4, 6, 8, 12 and 16 hours post-dose, Day 2, 24 hours post-dose, Day 3, 48 hours post-dose, Day 4, 72 hours post-dose and Day 5, 96 hours post-dose.
Multiple Ascending Dose: Plasma PK parameters - Time to maximum observed concentration (Tmax)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple Ascending Dose: Plasma PK parameter - Area under the concentration-time curve from 0 to time of last quantifiable concentration (AUClast)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple Ascending Dose: Plasma PK parameter - Area under the concentration versus time curve for the dosing interval (AUCtau)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple Ascending Dose: Plasma PK parameter - Area under the concentration-time curve from time 0 extrapolated to infinity (AUCinf)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple Ascending Dose: Plasma PK parameter - Apparent terminal elimination half-life (T1/2)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple Ascending Dose: Plasma PK parameter - Volume of distribution (Vz/F)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple Ascending Dose: Plasma PK parameter - Clearance (CL/F)
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple Ascending Dose: Plasma PK parameter - Accumulation ratio for Maximum observed concentration (Cmax) and Area under the concentration versus time curve for the dosing interval (AUCtau) using the first and last dose
Blood plasma samples will be assessed
Time frame: Pre-dose Day 1 0.5, 1, 2, 3, 4, 6, 8, & 12 hours post-dose, pre-dose Days 2 - 13, pre-dose Day 14 0.5, 1, 2, 3, 4, 6, 8, 12 & 16 hours post-dose, Day 15 24 hours post-dose, Day 16 48 hours post-dose, Day 17 72 hours post-dose, Day 18 96 hours post-dose
Multiple ascending dose: Urine PK endpoints include • Fraction of the dose excreted in urine (Fe)
Urine samples will be assessed
Time frame: Pre-dose Day 1 - up to 12 hours post AM (first) dose, Day 14 and Day 15, up to 12 hours post AM (final) dose, 12 to 24 hours post AM (final) dose, Day 16, 24 to 48 hours post-dose, Day 17, 48 to 72 hours post-dose and Day 18, 72 to 96 hours post-dose.
Multiple ascending dose: Urine PK endpoints include • Renal clearance (CLr).
Urine samples will be assessed
Time frame: Pre-dose Day 1 - up to 12 hours post AM (first) dose, Day 14 and Day 15, up to 12 hours post AM (final) dose, 12 to 24 hours post AM (final) dose, Day 16, 24 to 48 hours post-dose, Day 17, 48 to 72 hours post-dose and Day 18, 72 to 96 hours post-dose.