Efficacy and tolerability of tasipimidine in sleepless patients
| ISRCTN | ISRCTN35042256 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN35042256 |
| EudraCT/CTIS number | 2022-502483-21-00 |
| ClinicalTrials.gov number | NCT06956495 |
| Secondary identifying numbers | 3110012 |
- Submission date
- 09/08/2023
- Registration date
- 15/08/2023
- Last edited
- 14/05/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Insomnia (sleeplessness) disorder is characterised by difficulties in initiating or maintaining sleep and can cause impairment in daytime functioning. It is a common condition, with an approximate general population prevalence of 10%. Cognitive behavioural therapy is currently recommended for insomnia as a first-line treatment, but not all insomnia patients benefit from it, and it might not be available for all. The available sleep medications can be modest in efficacy, can have abuse potential and have a risk of tolerance. Based on the mode of action, tasipimidine is expected to decrease arousal and cause sedation. The purpose of this study is to see if tasipimidine will help in the treatment of insomnia and how safe it is to use in people.
Who can participate?
Adult patients with insomnia aged between 18 and 65 years old
What does the study involve?
The trial consists of 2 consecutive parts and participants will be included either in Part 1 or Part 2. Part 2 will start only after Part 1 completion. Both parts include a screening period (up to 6 weeks), a treatment period (3 consecutive days and nights) and a post-treatment period (up to 10 days). Part 2 includes an additional 4-week extension part, where the participants take tasipimidine or placebo every evening at home and return to the sleep clinic for 2 last treatment nights. The study visits will take place in sleep centres where a sleep polysomnography (PSG) recording is done. The PSG will be done using equipment that records brain waves and other sleep parameters. Participants will use equipment to record sleep parameters also at home (Part 2) and a sleep diary is used.
What are the possible benefits and risks of participating?
Tasipimidine may favour sleep but in this study, the study drug will be administered for 3 nights only in Part 1 and 4 weeks in Part 2. Patients may also experience benefits due to getting information on their health. Participation may help other insomnia people in the future. There are no costs to participants to be in the trial.
Tasipimidine has been well tolerated in a trial with healthy volunteers. Based on that trial and the mode of action, tasipimidine may cause dizziness when standing up. To minimise the risk associated with taking part in the trial, patients are frequently monitored and evaluated for any side effects.
Where is the study run from?
Sleep centres in Finland, Poland, Germany and United States of America
When is the study starting and how long is it expected to run for?
October 2022 to December 2025
Who is funding the study?
Orion Corporation (Finland)
Who is the main contact?
clinicaltrials@orionpharma.com
Contact information
Public
Tengströminkatu 8
Turku
20360
Finland
| Phone | +358104267792 |
|---|---|
| jutta.hanninen@orionpharma.com |
Scientific
Tengströminkatu 8
Turku
20360
Finland
| Phone | +358104267790 |
|---|---|
| juha.rouru@orionpharma.com |
Principal Investigator
Valimotie 21
Helsinki
00380
Finland
| Phone | +358505604999 |
|---|---|
| Markku.Partinen@terveystalo.com |
Study information
| Study design | Multisite interventional double-blind randomized placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | 44087_PIS_16Dec2022.pdf |
| Scientific title | Efficacy and tolerability of tasipimidine after 3 repeated bed-time doses in patients with insomnia disorder with a 4-week extension part |
| Study acronym | UNITAS |
| Study hypothesis | Tasipimidine is superior to placebo assessed in patients with insomnia disorder. |
| Ethics approval(s) |
1. Approved 24/05/2023, National Committee on Medical Research Ethics (Tukija) (Tukija, Valvira P.O. Box 43, Helsinki, FI-00521, Finland; +358 295209111; info@tukija.fi), ref: 2022-502483-21-00 2. Approved 29/05/2023, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products (Al. Jerozolimskie 181C, Warsaw, 02-222, Poland; +48224921100; urpl@urpl.gov.pl), ref: 2022-502483-21-00 3. Approved 11/07/2024, Ethics Committee of the Bavarian State Medical Association (Mühlbaurstraße 16, Munich, 81677, Germany; +49894147165; ethikkommission@blaek.de), ref: B_01899 |
| Condition | Insomnia |
| Intervention | Current interventions as of 13/05/2025: The study drug, tasipimidine, is a highly specific α2 adrenoceptor agonist, selective for α2A receptor subtype. In experimental animals, it induces typical α2-adrenoceptor agonist effects like sedation, analgesia, and relief of anxiety. In humans, it is expected to decrease arousal and cause sedation. The trial consists of 2 consecutive parts and participants will be included either in Part 1 or Part 2. In Part 1 of the trial, escalating dose levels of tasipimidine will be administered to sequential cohorts of subjects. Subjects will be allocated at random to tasipimidine and placebo groups by the IVRS system. The study drug is given by the study site personnel as an oral liquid on 3 consecutive nights. Study subjects will stay at the study site for 3 consecutive nights and days from the evening of Day 1 until the afternoon of Day 4. Part 2 includes an additional 4-week extension part, where the participants take tasipimidine or placebo every evening at home and return to the sleep clinic for 2 last treatment nights. _____ Previous interventions: The study drug, tasipimidine, is a highly specific α2 adrenoceptor agonist, selective for α2A receptor subtype. In experimental animals, it induces typical α2-adrenoceptor agonist effects like sedation, analgesia, and relief of anxiety. In humans, it is expected to decrease arousal and cause sedation. In this study, the effect of tasipimidine on sleep is investigated in a sleep laboratory setting. Three escalating adaptive dose levels of tasipimidine are planned to be administered to 3 sequential cohorts of subjects and the placebo will be randomised into each dose level in a 1:3 ratio. Subjects will be allocated at random to tasipimidine and placebo groups by the IVRS system. After each cohort, the Data and Safety Monitoring Board will evaluate the data and agree on the dose level for the next cohort. The study drug is given by the study site personnel as an oral liquid on 3 consecutive nights. Study subjects will stay at the study site for 3 consecutive nights and days from the evening of Day 1 until the afternoon of Day 4. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Pharmacodynamic, Dose response, Pharmacogenetic, Pharmacogenomic |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Tasipimidine |
| Primary outcome measure | Effect on sleep is measured using sleep polysomnography measurement on 2 baseline nights and on 2 treatment nights |
| Secondary outcome measures | Current secondary outcome measures as of 13/05/2025: 1. Effect on sleep measured using sleep polysomnography measurement on 2 last treatment nights and home EEG device on 5 nights during both screening and treatment period in Part 2 of the trial. 2. Safety and tolerability measured by collecting adverse events throughout the trial, vital signs on study visits, morning sleepiness and daytime symptom scales throughout the trial, safety laboratory tests on screening, Day 1, Day 4 and end-of-study visit. Additionally, safety laboratory tests on Day 14 and Day 29 in Part 2 of the trial 3. Pharmacokinetics (PK) measured by collecting samples for PK analysis during Night 3 and Day 4 _____ Previous secondary outcome measures: 1. Safety and tolerability measured by collecting adverse events throughout the study, vital signs on study visits, morning sleepiness scale after each of the 3 nights, safety laboratory tests on screening, Day 1, Day 4 and end-of-study visit 2. Pharmacokinetics (PK) measured by collecting samples for PK analysis during Night 3 and Day 4 |
| Overall study start date | 01/10/2022 |
| Overall study end date | 31/12/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | The planned maximum number of subjects is in total 272 for both parts together (128 in Part 1 and 144 in Part 2). |
| Participant inclusion criteria | Current inclusion criteria as of 13/05/2025: 1. Signed informed consent (IC) for participation in the study. 2. Male or female subjects with age between 18 and 65 years (inclusive) at screening visit. 3. Insomnia disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Text Revision (DSM-5-TR®). 4. Self-reported history of the following on at least 3 nights per week and for at least 3 months prior to the screening: ≥ 30 minutes to fall asleep, subjective total sleep time (sTST) ≤ 6 hours at screening visit. 5. Insomnia Severity Index© (ISI©) score ≥ 15 in Part 1 and ≥ 11 in Part 2. 6. Usual bedtime between 21:00 and 02:00. 7. Regular time in bed between 6 and 9 hours. 8. Meeting the following sleep parameter criteria in PSG on the 2 screening PSG nights: mean latency to persistent sleep (LPS) ≥ 25 minutes (with none of the 2 nights < 15 minutes) and mean total sleep time (TST) ≤ 6 h in Part 1 and ≤ 6.5 h in Part 2. 9. Female subjects with fertile male partner, and male subjects with female partners of childbearing potential, must adhere to a highly effective form of contraception, if sexually active and not permanently sterilised (see section 5.7 for more information). Additionally, women who are postmenopausal (1 year since last menstrual cycle) are considered not to be reproductive and can be included. _____ Previous inclusion criteria: 1. Signed informed consent (IC) for participation in the study 2. Male or female subjects aged between 18 and 65 years (inclusive) at the screening visit 3. Insomnia disorder according to Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Text Revision (DSM-5-TR®) 4. Self-reported history of the following on at least 3 nights per week and for at least 3 months prior to the screening: ≥ 30 minutes to fall asleep, subjective total sleep time (sTST) ≤ 6 hours. 5. Insomnia Severity Index© (ISI©) score ≥ 15 6. Usual bedtime between 21:00 and 02:00 7. Regular time in bed between 6 and 9 hours 8. Meeting the following sleep parameter criteria on the 2 screening PSG nights: mean latency to persistent sleep (LPS) ≥ 25 minutes (with none of the 2 nights < 15 minutes) and mean total sleep time (TST) ≤ 6 h 9. Female subjects with fertile male partners, and male subjects with female partners of childbearing potential, must adhere to a highly effective form of contraception, if sexually active and not permanently sterilised. Additionally, women who are postmenopausal (1 year since the last menstrual cycle) are considered not to be reproductive and can be included. |
| Participant exclusion criteria | Current exclusion criteria as of 13/05/2025: 1. A predictable poor compliance or inability to understand and comply with protocol requirements, instructions and protocol-stated restrictions, or communicate well with the investigator. 2. Body mass index below 18.5 or above 40.0 kg/m2. 3. Self-reported usual daytime napping ≥ 1 hour per day, and ≥ 3 days per week. 4. Shift work within 2 weeks prior to the screening visit, or planned shift work during the study. 5. Travel across ≥ 3 time zones within 2 weeks prior to the screening visit, or planned travel across ≥ 3 time zones during the study. 6. Use of medications with known relevant alpha-2 AR affinity (e.g. mirtazapine, mianserine, dexmedetomidine, clonidine, guanfacine or tizanidine) or known strong or moderate CYP2D6 inhibitors (e.g. in Part 1 paroxetine, fluoxetine, bupropion, in both parts quinidine) within 14 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG.As an exception, antidepressants listed in section 5.6.2 are allowed in Part 2. 7. Use of benzodiazepines, z-drugs (zolpidem, zopiclone, eszopiclone, zaleplon), melatonin, sedative H1 antagonists, sedative antidepressants (e.g. doxepine and trazodone), orexin receptor antagonists (e.g. daridorexant) or antipsychotics within 7 days or 5 times the halflife, whichever is longer, prior to 1st screening PSGs. 8. Use of amphetamine derivatives like methylphenidate, dexamphetamine and lisamphetamine within 14 days, or 5 times the half-life, whichever is longer, prior to the 1st screening PSG. 9. Use of other CNS-active drugs, including over-the-counter or herbal medicines, for 7 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG. In Part 2 the use of one of the following antidepressants is allowed: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, bupropion, duloxetine, milnacipran, venlafaxine, vortioxetine, providing that the dose has been stable at least 4 weeks prior to the 1st screening PSG and planned to be stable throughout the study. 10. Start of other new chronic medication within 14 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG and in Part 2 also a planned change to an ongoing chronic medication during the study. 11. Cognitive behavioural therapy (CBT) for any indication is allowed only if the CBT started at least 1 month prior to the 1st screening PSG and the subject agreed to continue the CBT throughout the study. 12. Any lifetime history of a diagnosed sleep-related breathing disorder, including chronic obstructive pulmonary disease and sleep apnoea. 13. Acute or unstable psychiatric conditions as judged by the investigator (including but not restricted to current bipolar disorder, schizophrenia or obsessive compulsive disorder) that are diagnosed by the Mini International Neuropsychiatric Interview© (MINI©) or that require pharmacological treatment for these disorders. N.B.: subjects with a history of major depressive disorder or anxiety disorder that are currently stable, and without requiring pharmacological treatment are eligible. In Part 2 antidepressants specified in exclusion criterion 9 and section 5.6.2 are allowed. 14. Part 1: positive answer to item 4 or 5 on the Colombia-Suicide Severity Rating Scale (CSSRS) or current risk of suicide based on the investigator’s judgement at screening visit. Part 2: positive answer to item 4 or 5 in the past 6 months or any suicidal behaviour in the past 10 years or current risk of suicide based on the investigator’s judgement at screening visit. 15. Diagnosis of alcohol or substance use disorder within 2 years prior to the screening visit or inability to refrain from drinking alcohol for at least 3 consecutive days. 16. Myocardial infarction or other clinically significant ischemic cardiac disease, heart failure, sick-sinus syndrome or arrhythmia tendency within the past 2 years. 17. History of clinically significant orthostatic hypotension, syncope or syncopial attacks within the past 2 years. 18. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological (e.g. epilepsy or dementia) or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator may interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part in the study. 19. Heavy tobacco use (at least one pack of cigarettes a day or corresponding heavy use of other nicotine containing products or inability to refrain from smoking during the night). 20. Caffeine consumption ≥ 600 mg per day or regular caffeine consumption after 4 p.m. 21. Supine HR < 50 bpm or > 100 bpm after a 5-minute rest at screening visit. 22. Systolic blood pressure (SBP) < 100 or > 160 mmHg or diastolic blood pressure (DBP) < 50 or > 100 mmHg after a 5-minute rest at screening visit. 23. Orthostatic hypotension (decrease of 20 mmHg for SBP or decrease of 10 mmHg for DBP) or dizziness in orthostatic test at screening visit. 24. Abnormal 12-lead ECG finding of clinical relevance at the screening visit, (after 5 min rest in supine position, confirmed by a repeat measurement) for example: QTc (calculated through the Fridericia’s formula) repeatedly > 450 ms in males or > 470 ms in females at screening visit. Pacemaker rhythm as such does not need to lead to exclusion. (If QTc interval measured by the ECG machine algorithm is > 450 ms, 2 additional recordings will be done and QTcF values confirmed) 2° or 3° AV block. 25. AST and/or ALT > 2 × ULN and/or direct bilirubin > 1.5 × ULN. 26. Positive urine drug screen or presence of alcohol in exhaled breath at screening visit, screening PSG nights or on Day 1. 27. Any other abnormal value in laboratory tests, vital signs or 12-lead ECG which may in the opinion of the investigator interfere with the interpretation of the study results or cause a health risk for the subject if he/she takes part in the study. 28. Pre-planned elective surgery for the study period. 29. Known hypersensitivity to the active substance or to any of the excipients of the study treatment. 30. Pregnant or lactating females. 31. Blood donation or loss of significant amount of blood within 60 days prior to the screening. 32. Participation in a drug study within 60 days prior to the screening or earlier participation in clinical study with tasipimidine. 33. Periodic limb movement disorder with arousal index (PLMAI) ≥ 15/h (assessed on the 1st screening PSG night), restless legs syndrome, circadian rhythm disorder, REM behaviour disorder, or narcolepsy. 34. Apnoea/hypopnea index (AHI) ≥ 15/h according to American Academy of Sleep Medicine criteria or event associated with blood oxygen saturation level by pulse oximetry (SpO2) < 80%, as assessed on the 1st screening PSG night. 35. Any other condition that in the opinion of the investigator may interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part in the study. _____ Previous exclusion criteria: 1. A predictable poor compliance or inability to understand and comply with protocol requirements, instructions and protocol-stated restrictions, or communicate well with the investigator 2. Body mass index below 18.5 or above 40.0 kg/m2 3. Self-reported usual daytime napping ≥ 1 hour per day, and ≥ 3 days per week 4. Shift work within 2 weeks prior to the screening visit, or planned shift work during the study 5. Travel across ≥ 3 time zones within 2 weeks prior to the screening visit, or planned travel across ≥ 3 time zones during the study 6. Use of medications with known relevant alpha-2 AR affinity (e.g. mirtazapine, mianserine, dexmedetomidine, clonidine, guanfacine or tizanidine) or known strong or moderate CYP2D6 inhibitors (e.g. paroxetine, fluoxetine, bupropion, quinidine) within 14 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG 7. Use of benzodiazepines, z-drugs (zolpidem, zopiclone, eszopiclone, zaleplon), melatonin, sedative H1 antagonists, sedative antidepressants (e.g. doxepine and trazodone), orexin receptor antagonists (e.g. daridorexant) or antipsychotics within 14 days or 5 times the halflife, whichever is longer, prior to 1st screening PSGs 8. Use of amphetamine derivatives like methylphenidate, dexamphetamine and lisamphetamine within 14 days, or 5 times the half-life, whichever is longer, prior to the 1st screening PSG 9. Use of other CNS-active drugs, including over-the-counter or herbal medicines, for 14 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG 10. Start other new chronic medication within 14 days or 5 times the half-life, whichever is longer, prior to the 1st screening PSG 11. Cognitive behavioural therapy (CBT) for any indication is allowed only if the CBT started at least 1 month prior to the 1st screening PSG and the subject agreed to continue the CBT throughout the study 12. Any lifetime history of sleep-related breathing disorders, including chronic obstructive pulmonary disease and sleep apnoea 13. Acute or unstable psychiatric conditions as judged by the investigator (including but not restricted to current bipolar disorder, schizophrenia or obsessive-compulsive disorder) that are diagnosed by the Mini International Neuropsychiatric Interview© (MINI©) or that require pharmacological treatment for these disorders. N.B.: subjects with a history of major depressive disorder or anxiety disorder that are currently stable, and without requiring pharmacological treatment are eligible 14. Positive answer to item 4 or 5 on the Colombia-Suicide Severity Rating Scale (C-SSRS) or current risk of suicide based on the investigator’s judgement at the screening visit 15. Diagnosis of alcohol or substance use disorder within 2 years prior to the screening visit or inability to refrain from drinking alcohol for at least 3 consecutive days. 16. Myocardial infarction or other clinically significant ischemic cardiac disease, heart failure, sick sinus syndrome or arrhythmia tendency within the past 2 years 17. History of clinically significant orthostatic hypotension, syncope or syncopial attacks within the past 2 years 18. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological (e.g. epilepsy or dementia) or psychiatric disorder or any other major concurrent illness that in the opinion of the investigator may interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part in the study 19. Heavy tobacco use (at least one pack of cigarettes a day or inability to refrain from smoking during the night) 20. Caffeine consumption ≥ 600 mg per day or regular caffeine consumption after 4 p.m. 21. Supine HR < 50 bpm or > 100 bpm after a 5-minute rest at the screening visit 22. Systolic blood pressure (SBP) < 100 or > 160 mmHg or diastolic blood pressure (DBP) < 50 or > 100 mmHg after a 5-minute rest at screening visit 23. Orthostatic hypotension (decrease of ≥ 20 mmHg for SBP or decrease of ≥10 mmHg for DBP) or dizziness in orthostatic test at screening visit 24. Abnormal 12-lead ECG finding of clinical relevance at the screening visit, (after 5 min rest in the supine position, confirmed by a repeat measurement) for example: QTc (calculated through the Fridericia’s formula) repeatedly > 450 ms in males or > 470 ms in females at the screening visit. Pacemaker rhythm as such does not need to lead to exclusion. (If the QTc interval measured by the ECG machine algorithm is > 450 ms, 2 additional recordings will be done and QTcF values confirmed) -2° or 3° AV block. 25. AST and/or ALT > 2 × ULN and/or direct bilirubin > 1.5 × ULN 26. Positive urine drug screen or presence of alcohol in an exhaled breath at screening visit, screening PSG nights or on Day 1 27. Any other abnormal value in laboratory tests, vital signs or 12-lead ECG which may in the opinion of the investigator interfere with the interpretation of the study results or cause a health risk for the subject if he/she takes part in the study 28. Pre-planned elective surgery for the study period 29. Known hypersensitivity to the active substance or to any of the excipients of the study treatment 30. Pregnant or lactating females 31. Blood donation or loss of a significant amount of blood within 60 days prior to the screening 32. Participation in a drug study within 60 days prior to the screening 33. Periodic limb movement disorder with arousal index (PLMAI) ≥ 15/h (assessed on the 1st screening PSG night), restless legs syndrome, circadian rhythm disorder, REM behaviour disorder, or narcolepsy 34. Apnoea/hypopnea index (AHI) ≥ 15/h according to American Academy of Sleep Medicine criteria or event associated with blood oxygen saturation level by pulse oximetry (SpO2) < 80%, as assessed on the 1st screening PSG night 35. Any other condition that in the opinion of the investigator may interfere with the interpretation of the study results or constitute a health risk for the subject if he/she takes part in the study |
| Recruitment start date | 28/07/2023 |
| Recruitment end date | 30/12/2025 |
Locations
Countries of recruitment
- Finland
- Germany
- Poland
Study participating centres
Helsinki
00380
Finland
Helsinki
00100
Finland
Kuopio
70100
Finland
Turku
20520
Finland
Lodz
92-216
Poland
Poznan
61-360
Poland
Gdansk
80-546
Poland
Warszawa
02-172
Poland
Krakow
30-539
Poland
Marburg
35043
Germany
Berlin
10115
Germany
Berlin
10787
Germany
Hannover
30449
Germany
Essen
45239
Germany
Berlin
12203
Germany
Kraków
30-727
Poland
Sponsor information
Industry
Orionintie 1A
Espoo
02200
Finland
| Phone | +358104261 |
|---|---|
| clinicaltrials@orionpharma.com | |
| Website | http://www.orion.fi/en |
"ROR" |
https://ror.org/0296s4x19 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/05/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | Data sharing statement to be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | 16/12/2022 | 15/08/2023 | No | Yes | |
| Participant information sheet | Part 2 | 25/09/2024 | 14/05/2025 | No | Yes |
Additional files
Editorial Notes
14/05/2025: The participant information sheet (part 2) was uploaded as an additional file.
13/05/2025: The following changes were made to the trial record:
1. The scientific title was changed from "Efficacy and tolerability of tasipimidine after 3 repeated bed-time doses in patients with insomnia disorder" to "Efficacy and tolerability of tasipimidine after 3 repeated bed-time doses in patients with insomnia disorder with a 4-week extension part".
2. The clincialtrials.gov number was added.
3. The overall end date was changed from 31/05/2025 to 31/12/2025.
4. The interventions were changed.
5. The secondary outcome measures were changed.
6. The inclusion criteria were changed.
7. The target number of participants was changed from "The planned number of subjects is 96, 32 patients in each cohort." to "The planned maximum number of subjects is in total 272 for both parts together (128 in Part 1 and 144 in Part 2).".
8. The exclusion criteria were changed.
9. The recruitment end date was changed from 30/04/2025 to 30/12/2025.
10. The plain English summary was updated to reflect these changes.
11. The participant level data sharing statement was changed from "The datasets generated during and/or analysed during the current study are/will be available upon request from https://www.orion.fi/en/sustainability/ethical-business/research-development-ethics-policy/sharing-clinical-data/"; to "Data sharing statement to be made available at a later date".
28/01/2025: The following changes were made:
1. The overall study end date was changed from 31/01/2025 to 31/05/2025.
2. The recruitment end date was changed from 31/12/2024 to 30/04/2025.
3. The intention to publish date was changed from 31/12/2025 to 31/05/2026.
14/11/2024: The following changes were made:
1. Ethics approval details added.
2. Germany was added to the countries of recruitment.
3. The study participating centres were updated to remove Terveystalo Turku Pulssi and add University Hospital Giessen and Marburg, Intellux Berlin GmbH c/o St. Hedwig-Krankenhaus, Velocity Clinical Research Berlin, Siteworks GmbH, Zentrum für Schlaf- und Telemedizin, Charité Campus Benjamin Franklin, and Advanced Sleep Research GmbH.
02/07/2024: The following changes were made:
1. The overall study end date was changed from 31/10/2024 to 31/01/2025.
2. The recruitment end date was changed from 30/09/2024 to 31/12/2024.
3. The study participating centres Centrum Badan Klinicznych PI-House, MTZ Clinical Research Powered by Pratia and Specjalistyczne Gabinety were added.
28/02/2024: The following changes were made to the trial record:
1. The overall study end date was changed from 15/03/2024 to 31/10/2024.
2. The recruitment end date was changed from 26/02/2024 to 30/09/2024.
3. The participant-level data-sharing statement was added.
4. The intention to publish date was changed from 01/05/2025 to 31/12/2025.
15/08/2023: Trial's existence confirmed by European Medicines Agency.
