Phase I Trial Evaluating the Pharmacokinetics of Single Ascending Oral Doses of IRL757 in Healthy Elderly Volunteers

A Single-centre, Open-label, Phase I Trial Evaluating the Pharmacokinetics of Single Ascending Oral Doses of IRL757 in Healthy Elderly Volunteers

This is a phase I trial evaluating the pharmacokinetics of single ascending oral doses of IRL757 in healthy elderly volunteers.

Study Overview

• Status: Completed
• Conditions: Apathy; Not Applicable as This is a Mass Balance/Pharmacokinetic Study Performed in Healthy Subjects
• Intervention / Treatment: Drug: IRL757

Detailed Description

The trial is open label single oral dose trial in elderly healthy volunteers that will assess the pharmacokinetics of two dose levels of IRL757.

Eligible and consenting participants will be included in one of two dose groups, with 6 participants in each dose group.

At the screening visit, consenting subjects will be screened for eligibility according to study specific inclusion/exclusion criteria within 4 weeks before Investigational Medicinal Product (IMP) administration.

If eligible, participants will be admitted to the phase 1 clinic for the single dose administration of the IMP. All participants will receive active treatment (IRL757).

A follow-up visit will be performed for all participants, 5-10 days after IMP administration.

Blood and urine sampling will be performed for determination of pharmacokinetic parameters. Safety assessments will also be performed throughout the study: review and collection of adverse events, physical examination, suicidality ideation, electrocardiogram recording, vital signs, safety laboratory assessments.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • CTC Clinical Trial Consultants AB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Willing and able to give written informed consent for participation in the trial.
• Healthy male or postmenopausal female subject at ≥ 65 and below 90 years of age.
• Weight of at least 50 kg and no more than 110 kg at screening.
• Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
• Willing to use highly effective methods of contraception

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the trial, or influence the results or the subject's ability to participate in the trial.
• GFR less than 45 mL/min at screening.
• History or present clinically significant psychiatric diagnosis, at discretion of the Investigator.
• Any suicidal ideation of type 4 or 5 in the C-SSRS in the past 3 months (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent).
• History of seizures, including febrile seizure in childhood.
• Any clinically significant illness, medical/surgical procedure or trauma within four (4) weeks of the first administration of IMP.
• Any planned major surgery within the duration of the trial.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and Human Immunodeficiency Virus (HIV).

• After 10 minutes supine rest at the time of screening, any vital signs values outside the following ranges:

  • Systolic blood pressure above 150 mm Hg
  • Diastolic blood pressure above 90 mm Hg
  • Heart rate less than 40 or above 90 beats per minute
• Prolonged QTcF (above 450 ms for male subjects or 470 ms for female subjects), cardiac arrhythmias or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the Investigator.
• History of severe allergy/hypersensitivity or on-going allergy/hypersensitivity, as judged by the Investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to IRL757.
• Use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within two (2) weeks prior to the first administration of IMP
• Administration of another new chemical entity (defined as a compound which has not been approved for marketing) or has participated in any other clinical trial that included drug treatment within three (3) months of the first administration of IMP in this trial.
• Current smokers or users of nicotine products. Irregular use of nicotine (e.g. smoking, snuffing, chewing tobacco) less than three (3) times per week is allowed before screening visit.
• History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
• Positive screen for drugs of abuse at screening or on admission to the unit or positive screen for alcohol at screening or on admission to the unit prior to administration of the IMP.
• Use of anabolic steroids.
• Current excessive use of caffeine, as judged by the Investigator.
• Plasma donation within one (1) month of screening or any blood donation/blood loss more than 450 mL during the three (3) months prior to screening.
• Investigator considers the subject unlikely to comply with trial procedures, restrictions and requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IRL757 Dose Level 1; IRL757 lower dose, single dose	Drug: IRL757; IRL757 capsules
Experimental: IRL757 Dose Level 2; IRL757 higher dose, single dose	Drug: IRL757; IRL757 capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of Maximum Plasma Concentration [Cmax] of IRL757	Cmax after single dosing	PK followed until 48 hours
Determination of the AUC of IRL757 and Its Main Metabolites	AUC 0 - inf for IRL757 and main metabolites M1 and M5 determined from PK sampling 0-48h post dosing	PK followed until 48 hours
Determination of the Time for Maximum Concentration [Tmax] of IRL757 and Its Main Metabolites	Determination of the time for maximum concentration [Tmax] of IRL757 and its main metabolites M1 and M5	PK followed until 48 hours
Determination of the Half-life [t1/2] of IRL757 and Its Main Metabolites		PK followed until 48 hours
Determination of the Renal Clearance (CLr) of IRL757	Determination of the renal clearance (CLr) of IRL757 based on urine and plasma sampling over 48 h	PK followed until 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Frequency, Seriousness and Intensity of Adverse Events	Total number of AEs, and total number of AEs by severity and relationship to study treatment are presented. Refer to the Adverse Events section for more information	From enrollment (within 4 weeks before Investigational Medicinal Product (IMP) administration, until end of follow-up (5 to 10 days after lMP administration)
Description of Physical Examination Findings	Clinically significant abnormal findings will be summarized and categorized by dose group. The physical examination will include assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities.	Until 5-10 days after IMP administration
Description of Electrocardiogram Findings	Following parameters will be measured/calculated: heart rate, PR, QRS, QT and QTc intervals. The measures will be described as "normal", "abnormal, not clinically significant", or "abnormal, clinically significant". These will be summarized and categorized by dose group.	Until 5-10 days after IMP administration
Description of Vital Signs Findings	The following parameters will be measured as vital signs: systolic and diastolic blood pressure, heart rate and respiratory rate. Clinically significant findings will be summarized by dose group.	Until 5-10 days after IMP administration
Description of Safety Laboratory Measurements	Common laboratory parameters will be assessed: clinical biochemistry panel (including for example, ALAT, ASAT, ALP, CRP, CK, Calcium, Potassium, Sodium,...), hematology panel (including white blood cell differential count), coagulation parameters (INR, APTT). Safety laboratory data will be summarized by dose group. Safety laboratory interpretations (abnormal, significant) will be summarized by dose groups, using frequency tables.	Until 5-10 days after IMP administration
Description of C-SSRS (Columbia Suicide Severity Rating Scale) Findings	A physician rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent". Any abnormal finding will be listed.	Until 5-10 days after IMP administration

Collaborators and Investigators

• Sponsor: Integrative Research Laboratories AB

Study record dates

Study Major Dates

• Study Start (Actual): September 23, 2024
• Primary Completion (Actual): November 11, 2024
• Study Completion (Actual): November 11, 2024

Study Registration Dates

• First Submitted: October 22, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 21, 2024

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Lethargy
• Other Study ID Numbers: IRL757C002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No