Unitas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Orion Corporation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

28 Jul 2023 → 25 Sep 2025

Decision date (initial)

2023-05-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacodynamic, Pharmacokinetic

To evaluate efficacy of tasipimidine in patients with insomnia disorder

Secondary objectives 4

1. To evaluate safety and tolerability of tasipimidine
2. To study pharmacokinetics (PK) of tasipimidine and its metabolite ORM-18662 in patients with insomnia disorder
3. Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationship
4. To evaluate efficacy of tasipimidine in patients with insomnia disorder

Conditions and MedDRA coding

Insomnia disorder

Study design 1 period

Regulatory references

Plan to share IPD

Yes

IPD plan description

Clinical data sharing, including IPD sharing, for this trial will follow the Clinical Data Sharing Policy of the Sponsor (Orion Corporation). Further information can be found at https://www.orion.fi/en/sustainability/ethical-business/research-development-ethics-policy/sharing-clinical-data/.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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 child-bearing 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 last menstrual cycle) are considered not to be reproductive and can be included.

Exclusion criteria 35

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 half-life, 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 (C-SSRS) 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Wake after sleep onset (WASO) assessed with polysomnography (PSG) for Day 1 and Day 2 data combined from Part 1 and Part 2
2. Latency to persistent sleep (LPS) assessed with polysomnography (PSG) for Day 1 and Day 2 data combined from Part 1 and Part 2

Secondary endpoints 10

1. Adverse events (AEs)
2. Heart rate (HR)
3. Diastolic blood pressure (DBP)
4. Systolic blood pressure (SBP)
5. Mean arterial pressure (MAP)
6. Orthostatic changes in blood pressure (BP)
7. Morning sleepiness
8. Safety laboratory tests
9. Pharmacokinetic (PK) variables
10. WASO and LPS assessed with PSG for Day 1 and Day 2 data separately from Part 1 and Part 2; in Part 2 WASO and LPS assessed with PSG for Day 27 and Day 28

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Orion Corporation

Sponsor organisation

Orion Corporation

Address

P. O. Box 65

City

Espoo

Postcode

02101

Country

Finland

Scientific contact point

Organisation

Orion Corporation

Contact name

Clinical Study Director

Public contact point

Organisation

Orion Corporation

Contact name

Clinical Study Director

Third parties 10

Locations

3 EU/EEA countries · 29 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 100 files

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

Application history

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