Safety, Tolerability, and Pharmacokinetics (PK) of Single and Multiple Ascending Oral Doses of iQ-007

NCT06899230 | Active Not Recruiting Phase 1

• 1 other identifier: iQ-007-CL-001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Drug Resistant Epilepsy; Focal Seizure

Outcome Measures

Primary Outcomes (10)

• 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.

  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

  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.

  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.

  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

  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 temperature measurements

  Vital signs assessed as normal, abnormal not clinically significant (NCS), or abnormal CS with temperature assessed using digital thermometer.

  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.

  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.

  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.

  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.

  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.

Secondary Outcomes (19)

• Single Ascending Dose: Plasma PK parameter - Maximum observed concentration (Cmax)

  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)

  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)

  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)

  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)

  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.

Study Arms (2)

iQ-007

EXPERIMENTAL

Part A (SAD): a total of 48 healthy volunteers are planned to be enrolled across 6 SAD cohorts and will involve the administration of a single oral dose of iQ-007 (in the range of 200 mg up to 2800 mg) or placebo capsules on Day 1. Part B (MAD): a total of 24 healthy volunteers are planned to be enrolled across 3 MAD cohorts and will involve the administration of multiple twice daily oral doses of iQ-007 (in the range of 600 mg up to 2400mg total per day) or placebo capsules on Days 1 to 14.

Drug: iQ-007

Placebo

PLACEBO COMPARATOR

Part A (SAD): a total of 48 healthy volunteers are planned to be enrolled across 6 SAD cohorts and will involve the administration of a single oral dose of iQ-007 (in the range of 200 mg up to 2800 mg) or placebo capsules on Day 1. Part B (MAD): a total of 24 healthy volunteers are planned to be enrolled across 3 MAD cohorts and will involve the administration of multiple twice daily oral doses of iQ-007 (in the range of 600 mg up to 2400mg total per day) or placebo capsules on Days 1 to 14.

Drug: Placebo

Interventions

iQ-007 DRUG

Highly selective, orally bioavailable, positive allosteric modulator (PAM) of the excitatory amino acid transporter-2 (EAAT2) and its rodent homologue (glutamate transporter-1\[GLT-1).

iQ-007

Placebo DRUG

Oral capsules identical in appearance to drug and containing vehicle only (Gelucire/Capmul-M).

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must have given written informed consent before any study-related activities are performed and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
• Adult males or females, 18 to 55 years of age (inclusive) at screening.
• Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 32.0 kg/m2.
• Medically healthy (in the opinion of the PI), as determined by pre-study medical history, and without clinically significant (CS) abnormalities including the following:
• Physical examination without any clinically relevant findings.
• Systolic blood pressure in the range of 90 to 160 mmHg and diastolic blood pressure in the range of 50 to 95 mmHg after resting for 5 minutes in a supine or semi-supine position.
• Pulse rate in the range of 45 to 100 bpm after 5 minutes resting in a supine or semi-supine position.
• Body temperature (tympanic), between 35.5°C and 37.7°C. If temperature above 36.6°C, any infective etiology must be ruled out by the PI.
• Electrocardiogram without CS abnormalities including QT interval corrected for Fredericia (QTcF) \<450msec
• No CS findings in serum chemistry, hematology, coagulation, and urinalysis tests.
• Female volunteers:
• Must be of non-childbearing potential, i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone \[FSH\] level consistent with postmenopausal status, per local laboratory guidelines), or
• If of childbearing potential, must:
• i. Have a negative pregnancy test at the screening visit and on admission to the study site on Day-1.
• ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 90 days after the last dose of the study drug.

You may not qualify if:

• Known hypersensitivity to any of the study drug ingredients.
• History of anaphylaxis or other significant allergy which, in the opinion of the PI, would interfere with the volunteer's ability to participate in the study.
• History or presence of CS cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal/bariatric modification, endocrine, immunologic, dermatologic, psychiatric, or neurological disease/disorder, including any acute illness, within the past 3 months determined by the PI to be clinically relevant.
• Note: Participants with history of resolved childhood asthma, psoriasis, atopic dermatitis, non-hospitalized depression, anxiety and/or migraine are permitted to be included in the study.
• History of surgery or hospitalization within 3 months prior to screening, or elective surgery planned during the study.
• Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
• Presence or having sequelae of gastrointestinal, liver (including Gilbert's syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• Liver function test results elevated \>1.5-fold above the ULN for gamma glutamyl transferase, bilirubin(total), ALP, AST or ALT. Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the PI (or delegate), if the levels are unaccompanied by clinical signs and are determined to be normal variants.
• Estimated creatinine clearance \<60 mL/min using the Cockcroft-Gault formula or serum creatinine\>1.2-fold above the ULN.
• Positive drugs of abuse test, cotinine test or alcohol breath test results at the screening visit and/or on admission to the study site on Day -1.
• Regular consumption of more than 10 standard alcoholic drinks/week and/or more than 4 standard alcoholic drinks on any one day, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer \[4.9% Alc/Vol\], 100 mL wine \[12% Alc/Vol\], or 30 mL spirit \[40% Alc/Vol\]).
• Volunteer smokes more than 5 cigarettes or equivalent nicotine-containing products per week, and/or the volunteer is unwilling to abstain from smoking or the use of nicotine-containing products for 72 hours prior to check-in on Day -1 and throughout the confinement period at the study site.
• Females who are breastfeeding or planning to breastfeed.

Sponsors & Collaborators

• iQure Australia Pty Ltd: lead
• Avance Clinical Pty Ltd.: collaborator

Study Sites (1)

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, 5000, Australia

Location

MeSH Terms

Conditions

Drug Resistant Epilepsy; Seizures

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Henk de Wilde

  iQure Australia Pty Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2025
• First Posted: March 27, 2025
• Study Start: April 8, 2025
• Primary Completion: January 29, 2026
• Study Completion: January 29, 2026
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)