A Study in Adults with Parkinson's Disease and a Lack of Interest or Motivation to Test How Different Doses of IRL757 Given for Multiple Days are Tolerated in the Body

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Integrative Research Laboratories Sweden AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

23 Jan 2026 → ongoing

Decision date (initial)

2025-12-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Integrative Research Laboratories Sweden AB (IRLAB)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Pharmacokinetic, Efficacy, Pharmacogenomic

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.

Secondary objectives 1

1. To assess the change from baseline in apathy symptoms in participants with PD who have moderate to severe symptoms of apathy.

Conditions and MedDRA coding

Parkinson's Disease and Apathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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, 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 Section 6.6.1), and ChEIs is permitted if doses are stable for 1 month before randomization and remain stable during the trial.

Exclusion criteria 33

1. Any active, current psychiatric comorbidity (such as major depressive disorder, obsessive-compulsive disorder, etc) a) as assessed by the MINI at screening. b) 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: a) 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 b) 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 c) 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 d) 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: a) Systolic blood pressure (SBP) > 150 mmHg b) Diastolic blood pressure (DBP) > 90 mmHg c) 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 (see Table 6.6.1-1).
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, per the guidelines in Section 10.3. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency, seriousness, and severity of AEs; change from baseline in physical examinations, clinical laboratory tests, vital signs, ECGs, C-SSRS, the QUIP-RS, and daytime sleepiness (ESS)

Secondary endpoints 1

1. Change from baseline in: • NPI-C (apathy domain) • LARS

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Integrative Research Laboratories Sweden AB

Sponsor organisation

Integrative Research Laboratories Sweden AB

Address

Arvid Wallgrens Backe 20

City

Goteborg

Postcode

413 46

Country

Sweden

Scientific contact point

Organisation

Integrative Research Laboratories Sweden AB

Contact name

Joakim Tedroff

Public contact point

Organisation

Integrative Research Laboratories Sweden AB

Contact name

Joakim Tedroff

Third parties 10

Locations

4 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 161 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications