Safety and Tolerability of IRL757 in Participants With Parkinson's Disease and Apathy (LIFT-PD)

A Phase 1b, Prospective, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Safety and Tolerability of Multiple Oral Doses of IRL757 in Participants With Parkinson's Disease and Apathy

This clinical trial's goal is to evaluate if the IRL757 is safe and has a good tolerability in participants with Parkinson's disease and experiencing apathy (a lack of interest or motivation). In addition, the trial is aiming to learn if IRL757 has effects on the symptoms of Parkinson's disease. Researchers will compare the effects of IRL757 to a placebo (a look-alike substance that contains no drug).

Participants who fit the study criteria will be treated with the study drug (either the active drug IRL757 or placebo) for 12 weeks and will visit the clinic at 5 defined timepoints for check-ups and tests. A follow-up call after the end of treatment will be done 4 weeks after the last study drug intake.

Study Overview

• Status: Recruiting
• Conditions: Safety; Apathy; PARKINSON DISEASE (Disorder)
• Intervention / Treatment: Drug: IRL757; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Joakim Tedroff; Phone Number: +46 31 757 38 00; Email: info@irlab.se

Study Locations

• Bulgaria
  • Pleven, Bulgaria
    • Recruiting
    • Medical Center "Galileo" OOD
    • Contact: Plamen Bozhinov, Prof.
  • Sofia, Bulgaria
    • Recruiting
    • First University Multiprofile Hospital for Active Treatment MHAT - Neurology Clinic
    • Contact: PI Prof. Dimitar Maslarov
  • Sofia, Bulgaria
    • Not yet recruiting
    • University Multiprofile Hospital for Active Treatment "Alexandrovska" EAD, Clinic of Neurological Diseases
    • Contact: PI Prof. Latchezar Traykov
• Germany
  • Berlin, Germany
    • Recruiting
    • Neurologie Berlin
    • Contact: PI Dr. Marie Perle Brinckmann
  • Dresden, Germany
    • Not yet recruiting
    • Universitaetsklinikum Carl Gustav Carus
    • Contact: Prof. Björn Falkenburger
• Poland
  • Bydgoszcz, Poland
    • Recruiting
    • Centrum Medyczne NEUROMED
    • Contact: PI Dr. Pawel Lisewski
  • Katowice, Poland
    • Recruiting
    • Neuro-Care sp. z o.o. sp. Komandytowa
    • Contact: PI Dr. Gabriela Klodowska
  • Lodz, Poland
    • Recruiting
    • NeuroKlinika Prof. Andrzej Bogucki
    • Contact: PI Prof. Andrzej Bogucki
  • Szczecin, Poland
    • Recruiting
    • Euromedis Sp. z o.o.
    • Contact: PI Dr. Marcin Ratajczak
  • Warsaw, Poland
    • Not yet recruiting
    • Centrum Medyczne NeuroProtect
    • Contact: Dr. Maciej Hyla
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau, Unidad de trastornos del movimiento
    • Contact: PI Dr. Javier Pagonabarraga Mora
  • Elche, Spain
    • Not yet recruiting
    • Hospital General Universitario de Elche
    • Contact: PI Dr. Eric Freyre Alvarez
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramon y Cajal
    • Contact: Jose Lopez Sendon Moreno

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male and female participants between 50 and 90 years of age, inclusive, with diagnosed Parkinson's disease according to the Movement Disorders Society Clinical Diagnostic Criteria for Parkinson's disease.
2. Hoehn and Yahr stage ≤ 4 at screening.
3. MoCA score of 20 or greater at screening and baseline.

4. Meets the ISCTM definition of apathy (criterion B), defined as exhibiting ≥ 1 symptom in ≥ 2 of the following 3 dimensions, that is persistent or frequently recurrent (ie, ≥ 3 days per week) for ≥ 4 weeks prior to screening:

   • Diminished initiative (less spontaneous and/or active than usual self; less likely to initiate usual activities such as hobbies, chores, self-care, conversation, work-related or social activities),
   • Diminished interest (less enthusiastic about usual activities, less interested in, or less curious about, events in their environment, less interested in activities and plans made by others, less interested in friends and family, less persistence in maintaining or completing tasks or activities), or
   • Diminished emotional expression/responsiveness (less spontaneous emotions, less affectionate compared to their usual self, expresses less emotion in response to positive or negative events, less concerned about the impact of their actions on other people, less empathy).

   The symptoms must represent a significant change from the participant's usual behaviour and cause significant impairment in personal, social, or occupational functioning. Finally, the symptoms must not be due to psychiatric illness, intellectual disability, physical/motor disabilities, or changes in level of consciousness or the effects of substances.

5. Participants with moderate to severe apathy based on a score of at least -16 on the LARS at screening and baseline.
6. Availability of the primary caregiver, any adult who spends greater than 10 hours a week with the participant and supervises his or her care, to accompany the participant to trial visits and to participate in the trial.
7. Treatment with anti-Parkinson drugs, antidepressants (except for those listed as prohibited medications in the protocol), and Choline esterase inhibitors is permitted if doses are stable for 1 month before randomization and remain stable during the trial.

Exclusion Criteria:

Participants will be excluded if they meet any of the following exclusion criteria when assessed:

1. Any active, current psychiatric comorbidity (such as major depressive disorder, obsessive-compulsive disorder, etc)

   1. as assessed by the MINI at screening,
   2. as assessed by the MADRS at the baseline visit with a score > 18.
2. Score of > 2 in the MDS-UPDRS Part 1, Question 1.2 (hallucinations and psychosis).
3. Need for acute psychiatric hospitalization.

4. Participants who:

   1. Answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) within the last 6 months prior to screening or the baseline visit, OR
   2. Answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) within the last 6 months prior to screening or at the baseline visit, OR
   3. Answer "Yes" on any of the 5 C-SSRS Suicidal Behaviour Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behaviour) within 2 years prior to screening or at the baseline visit, OR
   4. In the opinion of the investigator, present a serious risk of suicide.
5. Subthalamic stimulation of less than 1 year from screening.
6. Subthalamic stimulation without stable parameters for 3 months from screening.
7. Clinically significant impulse control disorders (ICDs) as assessed by the QUIP RS (score > 6).
8. Renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73m2 calculated based on cystatin C).
9. Moderately impaired hepatic function or advanced hepatic dysfunction as assessed by a Child Pugh score B or C.
10. Significant communicative impairments that prohibit meaningful participation in the trial assessments.
11. Central nervous system abnormalities (eg, cerebral aneurysm) and/or other vascular abnormalities such as vasculitis or pre-existing stroke, motor tics, or family history or diagnosis of Tourette's syndrome, seizures (convulsions, epilepsy), or historical clinically significant abnormal electroencephalograms (EEGs).
12. History of cancer within 5 years prior to screening, with the following exceptions: adequately treated non-melanomatous skin cancers, localized bladder cancer, non metastatic prostate cancer, or in situ cervical cancer. The cancer must not be active or currently under treatment except for potentially long-term stable medications.
13. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
14. Any planned major surgery within the duration of the trial.
15. Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody, or HIV.

16. Any vital signs values outside of the following ranges after 10 minutes of supine rest at the time of screening:

    1. Systolic blood pressure (SBP) > 150 mmHg
    2. Diastolic blood pressure (DBP) > 90 mmHg
    3. Heart rate < 50 or > 100 beats per minute.
17. Participants with a history of hypertension must have stable blood pressure for the 3 months prior to the trial, defined as blood pressure < 150/90 mmHg. If this criterion is not met the participant is not eligible for the trial.
18. Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF) > 450 msec for male participants or > 470 msec for female participants, cardiac arrhythmias, or any clinically significant abnormalities in the resting ECG at the time of screening, as judged by the investigator.
19. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to IRL757.
20. Current nicotine use; irregular nicotine use less than 3 times per week is allowed before the screening visit.
21. Positive screen for illicit drugs (including cannabinoids) and/or abuse or positive screen for alcohol at screening or on Day 1 prior to administration of the IMP.
22. Use of anabolic steroids.
23. Use of antipsychotics.
24. The participant is unwilling or unable to discontinue taking alpha-2 adrenergic receptor antagonists and/or cytochrome P450 (CYP) inhibitor or substrate drugs at least 14 days or 5 times the half-life of the drug (whichever is longer) before randomization.
25. Excessive or variable daily caffeine consumption (ie, exceeding 3 cups per day) for the 2 weeks prior to screening.
26. Plasma donation within 1 month of screening or any blood donation/blood loss > 450 mL during the 3 months prior to screening.
27. Participants who are breastfeeding.
28. Participants who have a positive pregnancy test result prior to receiving IMP.
29. Heterosexually active participants of reproductive potential (PORP) / POCBP who do not agree to use a highly effective method of birth control or remain fully abstinent from sexual activity with the potential for conception. Female participants of nonchildbearing potential (permanently sterilized [ie, hysterectomy, bilateral oophorectomy], postmenopausal for at least 12 months, or otherwise incapable of pregnancy) and male participants who have had a bilateral orchiectomy are eligible for enrolment.
30. Participants who do not agree to refrain from donating sperm or eggs from trial screening through 90 days (for sperm) and 30 days (for eggs) after the last dose of IMP.
31. Participants who have participated in a clinical trial involving an investigational drug or device within the last 90 days or who participated in more than 2 clinical trials involving an investigational drug or device within the past year.
32. The investigator considers the participant unlikely to comply with trial procedures, restrictions, and requirements.
33. Any condition that, in the opinion of the investigator, makes it medically inappropriate or risky for the participant to enrol in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IRL757 Low Dose; This is the low dose IRL757. IRL757 will be administered daily for 12 weeks. The study drug is available as capsules for oral administration.	Drug: IRL757; IRL757 will be administered daily for 12 weeks. The study drug is available as capsules for oral administration.
Experimental: IRL757 High Dose; This is the low dose IRL757. IRL757 will be administered daily for 12 weeks. The study drug is available as capsules for oral administration.	Drug: IRL757; IRL757 will be administered daily for 12 weeks. The study drug is available as capsules for oral administration.
Placebo Comparator: Placebo; The study drug is administered daily for 12 weeks. The placebo is available in form of capsules to be administered orally, not containing the active substance.	Drug: Placebo; The study drug is administered daily for 12 weeks. The placebo is available in form of capsules to be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of IRL757 after repeated daily dosing for 12 weeks in participants with PD who have moderate to severe symptoms of apathy	Number of participants with adverse events, classified by severity and relationship to study drug.	From enrollment [signature of informed consent form] to end of study [4 weeks after last study drug administration]
To evaluate the safety and tolerability of IRL757 after repeated daily dosing for 12 weeks in participants with PD who have moderate to severe symptoms of apathy	Number of abnormal clinically significant measures in vital signs (blood pressure, heart rate, respiratory rate) and electrocardiogram (ECG parameters) assessments.	From enrollment [signature of informed consent form] to end of study [4 weeks after last study drug administration]
To evaluate the safety and tolerability of IRL757 after repeated daily dosing for 12 weeks in participants with PD who have moderate to severe symptoms of apathy	Number of participants with abnormal clinically significant findings at physical examination.	From enrollment [signature of informed consent form] to end of study [4 weeks after last study drug administration]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the change from baseline in apathy symptoms using the Neuropsychiatric Inventory Clinician (NPI-C)	Change from baseline in the apathy domain of the Neuropsychiatric Inventory Clinician (NPI-C). Higher NPI-C scores indicate more severe behavioral symptoms and higher caregiver burden.	From baseline [last assessment before the first administration of the study drug] until end of treatment at 12 weeks
To assess the change from baseline in apathy symptoms using the Lille Apathy Rating Scale (LARS)	The Lille Apathy Scale (LARS) is a semi-structured interview used to assess apathy and its severity in participants with Parkinson's disease. The global score ranges from -36 to +36, with higher scores indicating a greater degree of apathy.	From baseline [last assessment before the first administration of the study drug] until end of treatment at 12 weeks

Collaborators and Investigators

• Sponsor: Integrative Research Laboratories AB
• Collaborators: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: March 4, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurobehavioral Manifestations; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Parkinson Disease; Lethargy
• Other Study ID Numbers: IRL757C003

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