A Study to Assess an ATX Inhibitor (IOA-289) in Healthy Volunteers

Randomized, Double-blind, Placebo-controlled, Dose Escalation Study for the Assessment of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of IOA-289 in Healthy Male Volunteers

The purpose of Part 1 of this First-in-Human trial is to evaluate the safety and tolerability after single ascending oral doses of IOA-289 given to healthy male subjects, compared to placebo. After the oral dose administrations, the amount of IOA-289 present in serum will be determined for pharmacokinetic characterisation. Also the reduction of LPA in plasma will be determined as a pharmacodynamic biomarker.

Part 2 is optional and its conduct will be dependent on the pharmacokinetic data generated in Part 1. Part 2 will be a randomized, crossover, open label, single oral dose administration of IOA-289 to healthy male subjects either in a fasted state, or after a high-fat meal.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Single ascending doses of IOA-289; Drug: Placebo single doses

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Verona, Italy, 37134
    • Centro Ricerche Cliniche di Verona srl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects between 18 and 50 years of age (inclusive) at the screening visit
• Body mass index between 18.0 and 30.0 kg/m2 (inclusive) at the screening visit
• In good health as determined by medical history, physical examination, ECG, serum/urine, clinical chemistry, haematology, and serology tests
• Able to provide written, informed consent prior to initiation of any trial-related procedures, and able, in the opinion of the Principal Investigator, to comply with all the requirements of the trial
• Male subjects who are surgically sterile (i.e., have undergone bilateral orchidectomy); and male subjects who agree to remain abstinent or to practice double-barrier forms of birth control and refrain from sperm donation from trial screening through 90 days from the last dose of IMP

Exclusion Criteria:

• Clinically significant abnormality in past medical history, or at the screening physical examination, that in the Investigator's or Sponsor's opinion may place the subject at risk or interfere with outcome variables including absorption, distribution, metabolism, and excretion of IMP
• History of drug and/or alcohol abuse within 2 years prior to the screening visit
• History of or current hepatitis or acquired immunodeficiency syndrome or carriers of HBsAg, anti-HCV, and/or HIV antibodies
• History of any significant drug allergy
• Positive alcohol breath test and/or urine drug screen for substance of abuse at the screening visit or upon check-in to the clinical trial site
• History of having taken an investigational drug within 30 days preceding trial entry
• History of significant bleeding or haemorrhagic tendencies
• Donation of blood or plasma within 30 days prior to dosing
• Use of prescription medication, over-the-counter medication, herbal medication, or vitamin supplements within 14 days prior to dosing and antibiotics within 30 days prior to dosing. The Sponsor may allow exceptions only if the medication's administration is deemed unlikely to impact the PK result
• Exposure to any substances known to stimulate hepatic microsomal enzymes within 30 days prior to screening (e.g., occupational exposure to pesticides, organic solvents)
• Supine blood pressure, after resting for ≥3 minutes, higher than 140/90 mmHg or lower than 100/50 mmHg. The Sponsor may allow exceptions if they are not deemed clinically significant
• Supine pulse rate, after resting for ≥3 minutes, outside the range of 50 to 90 bpm. The Sponsor may allow exceptions if they are not deemed clinically significant
• History of serious mental disorders that, in the opinion of the Investigator, would exclude the subject from participating in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Drug: IOA-289 single dose; Single oral dose of IOA-289 liquid filled capsule formulation - ascending doses	Drug: Single ascending doses of IOA-289; Single dose, oral administration of liquid-filled capsules, with a starting dose of 30 mg
PLACEBO_COMPARATOR: Placebo single dose; Single oral dose of placebo liquid filled caspule formulation	Drug: Placebo single doses; Single dose, oral administration of liquid-filled capsules, matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numbers of participants with treatment-related adverse events as assessed by MedDRA v24	Adverse Events will be assessed by nondirective questioning of the participants during the screening process and at each visit during the study	Day 1: Predose and at 0.5,1, 2, 4, 8, 10 and 24 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic profile of IOA-289	Blood samples for plasma IOA-289 concentrations	Day 1: Predose and at 0.5,1, 2, 4, 8, 10 and 24 hours postdose
Cmax	The maximum observed plasma concentration	Day 1: Predose and at 0.5,1, 2, 4, 8, 10 and 24 hours postdose
Tmax	The time at which Cmax occurs	Day 1: Predose and at 0.5,1, 2, 4, 8, 10 and 24 hours postdose
AUCinf	The area under the plasma concentration-time curve from time of dosing to infinity	Day 1: Predose and at 0.5,1, 2, 4, 8, 10 and 24 hours postdose
To determine the change from baseline of LPA levels	Measurement of LPA levels in plasma	Day 1: Predose and at 0.5,1, 2, 4, 8, 10 and 24 hours postdose

Collaborators and Investigators

• Sponsor: iOnctura

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 5, 2021
• Primary Completion (ACTUAL): September 7, 2021
• Study Completion (ACTUAL): December 20, 2021

Study Registration Dates

• First Submitted: July 16, 2021
• First Submitted That Met QC Criteria: August 24, 2021
• First Posted (ACTUAL): August 30, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: IOA-289-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No