Evaluation of the Effects of Neurexan® on Short-Term Insomnia, Daytime Performance and Stress Response by Polysomnography (PSG), Electroencephalogram (EEG), Stress Biomarkers and Patient-Reported Outcomes (PROs) An Exploratory, Placebo-Controlled Trial in Short-Term Insomnia Patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biologische Heilmittel Heel GmbH

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Behavior and Behavior Mechanisms [F01]

Trial duration

16 Jun 2023 → 16 Feb 2026

Decision date (initial)

2024-08-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Biologische Heilmittel Heel GmbH, Dr.-Reckeweg-Straße 2-4, 76532 Baden-Baden, Germany

External identifiers

EU CT number

2024-514391-41-00

EudraCT number

2022-003565-38

ClinicalTrials.gov

NCT06278077

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to demonstrate an improvement of sleep efficiency (SE) at Visit 2 compared to Baseline 2 measured by
polysomnography on daily treatment with Neurexan® in short-term insomnia.

Secondary objectives 1

1. The secondary objectives are to assess further PSG-based objective as well as subjective sleep parameters, daytime performance and stress processing in patients with short-term insomnia treated daily with Neurexan® compared to placebo.

Conditions and MedDRA coding

Short-Term Insomnia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Insomnia definition according to DSM-5 criteria; episode duration less than 3 months 2. Short-term insomnia with moderate symptoms according to ISI of at least 8 and below 22 being present for at least one week, but no longer than 3 months prior to Screening Visit 3. Reports habitual bedtime, defined as the time the participant attempts to sleep, between 21:00 and 01:00 4. Reports regular time spent in bed, either sleeping or trying to sleep, between 6 and 9 hours 5. ≥18 years of age, not older than 65 years 6. Legally competent male or female patient 7. Signed Informed Consent 8. Females of childbearing potential must agree to maintain highly effective or acceptable birth control throughout the trial (CTFG 2020). Highly effective (failure rate of less than 1% per year) • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal • Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable • Intrauterine device • Intrauterine hormone-releasing system • Bilateral tubal occlusion • Vasectomized partner (provided partner is sole sexual partner and if vasectomized partner has received medical assessment of the surgical success) • Sexual abstinence (only if defined as refraining from heterosexual intercourse during the entire period of risk associated with investigational treatment) Acceptable birth control methods which may not be considered as highly effective (failure rate of more than 1% per year) • Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action • Male or female condom with or without spermicide • Cap, diaphragm or sponge with spermicide • Combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) 9. Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 at Screening Visit 10. Use of digital device e.g., smartphone, tablet or laptop 11. German speaking and reading.

Exclusion criteria 1

1. 1. Patients with insomnia symptoms present longer than 90 days prior to Screening Visit 2. Based on the diagnostic interview, reported history (within 2 years) of other sleep disorders (e.g., chronic insomnia, circadian rhythm sleep disorders, restless legs syndrome (RLS), obstructive sleep apnea (OSA)), i.e., STOPBang (SBQ) questionnaire score ≥5, International Restless Legs Scale score ≥16) 3. Based on the first polysomnographic screening night at Baseline 1, insomnia due to sleep apnea or periodic limb movement disorder (PLMD): OSA (Apnea Hypopnea Index of >5 events/ hour), PLMD (Periodic Limb Movement Index (PLMI) >15 events/ hour) 4. Rotating shift work with overnight shifts 5. History of psychiatric disorders within the last 6 months prior to Screening Visit according to the Structured Clinical Interview for DSM-5® Disorders – Clinician Version (SCID-5-CV) 6. History of sensitivity to any component of Neurexan® 7. Unwilling or unable to comply with all the requirements of the clinical trial protocol 8. Cognitive impairment (cut-off of 24 points in the Montreal Cognitive Assessment [MoCA]; Thomann, Berres et al. 2020) at Screening Visit 9. Any history of or current abuse of alcohol and/or amphetamines, benzodiazepines, cocaine, marijuana, methaqualone, methadone, opioids, propoxyphene, barbiturates, phencyclidine; or expected to take during trial participation (urine drug screening at Screening Visit and adaptation nights) 10. Current use of medication affecting sleep, i.e., antidepressants, antipsychotics, diuretics, blood pressure drugs, anti-dementia drugs (e.g., piracetam), herbal and homeopathic medicine, hormone preparations (e.g., thyroxine) with the exception of hormonal contraceptives 11. Use of Neurexan® within the last two weeks from Screening Visit 12. Non-pharmacological insomnia therapies (e.g., cognitive behavioral therapy within the last 6 months of Screening Visit, sleep restriction therapy, complementary and alternative therapies as meditation, Traditional Chinese Medicine, aromatherapy) 13. Excessive consumption of xanthine-containing beverages (more than 7 cups daily of coffee or tea or other beverages containing xanthines) 14. Use of nicotine during the last 6 months prior to Screening Visit 15. Participation in any interventional clinical study within the past 30 days prior to Screening Visit 16. Any relationship of dependence with the Sponsor or with the Investigator 17. Active infection/ disease (C-Reactive Protein [CRP] >5 mg/l) 18. Hypertension defined as systolic blood pressure ≥140 mmHg (Burnier, 2018) 19. History of neurological, rheumatic, chronic pain, immune, cardiovascular, pulmonary, liver/ kidney, or metabolic disorder within the last 6 months prior to Screening Visit 20. Nocturia 21. Pregnancy (as proven by positive urine pregnancy test at Screening Visit) or breastfeeding 22. Patients with moderate to severe skin allergies and/or eczema 23. Raynaud's disease 24. Donation of blood or platelets 3 months prior to or in-between in-hospital visits.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this trial is to assess Neurexan® related changes in SE at Visit 2 compared to Baseline 2 as revealed by polysomnography (PSG).

Secondary endpoints 1

1. Sleep Pattern by • Further objective sleep parameters revealed by polysomnography (PSG) to be assessed as change at Visit 2 compared to Baseline 2 • Objective in-home assessment of sleep pattern revealed by actigraphy (24/7) • Subjective sleep pattern assessed using sleep questionnaires and sleep diary (adapted from Deutsche Gesellschaft für Schlafforschung und Schlafmedizin, DGSM), to be recorded on AMS-ePRO® Daytime Performance by • Resting state EEG; Stress Processing; Blood sampling

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biologische Heilmittel Heel GmbH

Sponsor organisation

Biologische Heilmittel Heel GmbH

Address

Dr.-Reckeweg-Strasse 2-4, Oos Oos

City

Baden-Baden

Postcode

76532

Country

Germany

Scientific contact point

Organisation

Biologische Heilmittel Heel GmbH

Contact name

Dr. Christine Frank

Public contact point

Organisation

Biologische Heilmittel Heel GmbH

Contact name

Dr. Christine Frank

Locations

1 EU/EEA country · 1 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 18 files

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

Application history

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