Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Temporarily halted
Participants planned
50
Countries
1
Sites
1
restless leg syndrome
to investigate the efficacy of 30 days of daily dosing with 25 mg REL-1017 compared to placebo in patients with primary, moderate to very severe RLS.
Key facts
- Sponsor
- Ente Ospedaliero Cantonale (EOC), Ente Ospedaliero Cantonale (EOC)
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 12 Mar 2024 → ongoing
- Decision date (initial)
- 2024-02-28
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- ente Ospedaliero Cantonale
External identifiers
- EU CT number
- 2024-510968-22-00
- EudraCT number
- 2019-003359-12
- WHO UTN
- U1111-1304-5658
- ClinicalTrials.gov
- NCT04145674
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
to investigate the efficacy of 30 days of daily dosing with 25 mg REL-1017 compared to placebo in patients with primary, moderate to very severe RLS.
Secondary objectives 3
- to evaluate the effect of 10 and 30 days of daily dosing with 25 mg REL- 1017 compared to placebo on: • RLS symptoms and severity • objective sleep parameters measured by actigraphy
- to evaluate the effect of 10 days of daily dosing with 25 mg REL-1017 compared to placebo on: • efficacy • PLMS index • objective sleep parameters derived from polysomnography (PSG) recording
- to assess the safety and tolerability of 25 mg daily doses of REL-1017 over a period of 30 days compared to placebo in patients with primary, moderate to very severe RLS.
Conditions and MedDRA coding
restless leg syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10058920 | Restless legs syndrome | 100000004852 |
Study design 5 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | screening phase (-28 to -1 day) Consecutive adults patients affected by primary RLS from moderate to very severe based on the standard diagnostic criteria will be screened with assessment including medical and medication history, physical and neurological examination, electrocardiogram (ECG), routine blood examination, actigraphy and the following questionnaires: International RLS Rating Scale (IRLS-RS), Epworth Sleepiness Scale (ESS), RLS Quality of Life (RLSQoL), Insomnia Severity Index (ISI).
Any other concomitant treatment for RLS or any medication reported under §8.6 must be stopped for at least 7 days before initiating study drug treatment.
|
Not Applicable | None | ||
| 2 | Baseline assessment and start of treatment (Day 1) If the inclusion and exclusion criteria are met, the participant will enter in the baseline assessment phase undergoing 1 week baseline actigraphy and 1 night baseline polysomnography (PSG), video-PSG is highly recommended whenever possible. If all entry criteria are met, the patient will be randomized to be treated with placebo or 25 mg/day of d- methadone at 6 pm for 30 days.
|
Randomised Controlled | Double | [{"id":104298,"code":2,"name":"Investigator"},{"id":104299,"code":4,"name":"Analyst"},{"id":104297,"code":3,"name":"Monitor"},{"id":104300,"code":1,"name":"Subject"}] | d-Methadone: active treatment arm placebo: control arm |
| 3 | End of 10-day dosing period (Day 11, +3 days) After ten days of treatment, clinical evaluations, questionnaires (including Clinical Global Impression [CGI]-Efficacy index), actigraphy (during the 10-day of study treatment), ECG, and PSG, video-PSG is highly recommended whenever possible, will be repeated.
|
Randomised Controlled | Double | [{"id":104304,"code":4,"name":"Analyst"},{"id":104303,"code":2,"name":"Investigator"},{"id":104302,"code":1,"name":"Subject"},{"id":104305,"code":3,"name":"Monitor"}] | |
| 4 | End of treatment (Day 31, +3 days) Clinical evaluations, questionnaires, ECG and actigraphy (starting from Day 24) will be repeated on Day 31 after 30 days of study treatment,
|
Randomised Controlled | Double | [{"id":104307,"code":2,"name":"Investigator"},{"id":104308,"code":1,"name":"Subject"},{"id":104310,"code":4,"name":"Analyst"},{"id":104309,"code":3,"name":"Monitor"}] | |
| 5 | End of study (Day 37, +3 days) Seven days after stopping the study treatment, all outcomes, except PSG and actigraphy, will be repeated again.
|
Not Applicable | None |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Male and female aged between 18 and 75 years old, inclusive
- Diagnosis of primary RLS.
- Moderate to very severe RLS defined as IRLS-RS score > 10
Exclusion criteria 8
- Positive history of known causes of secondary RLS.
- Any other concomitant treatment for RLS (wash-out period: at least 7 days)
- Moderate-severe sleep apnea defined as Apnea Hypopnea Index ≥ 15
- Evidence of clinically significant hepatic or renal impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 x upper limit of normal (ULN) total bilirubin > 1 x ULN creatinine > 1 x ULN
- History or family history of sudden unexplained death or long QT syndrome
- Any 12-lead ECG with demonstration of QTc ≥ 450 msec or a QRS interval ≥ 120 msec at Screening.
- Concomitant use of psycho-drugs (e.g., benzodiazepines, antidepressants), dopamine agonists and opioids (wash-out period: at least 7 days)
- History of allergy or hypersensitivity to methadone or related drugs (e.g., opioids).
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The percentage of responders to REL-1017 treatment. A responder is defined as a patient with ≥ 50% reduction in the International RLS Rating Scale (IRLS-RS) score from baseline (Day 1) to end of the treatment period (Day 30) with assessments performed on Day 1, Day 31 and Day 37.
Secondary endpoints 5
- Change in RLS symptoms and severity from baseline (Day 1) to the end of 10-day dosing period and to end of the treatment period (Day 30) as measured by the IRLS-RS score with assessments performed on Day 1, Day 11, Day 31 and Day 37.
- Change from baseline (Day 1) to the end of 10-day dosing period and to end of the treatment period (Day 30) on Total Sleep Time (TST), Sleep Latency (SL) and Sleep Efficacy (SE) acquired by actigraphy with measurements performed prior to the start of treatment (from Day -7 to Day -1), during the 10-day dosing period (from Day 1 to Day 11) and at the end of the treatment (from Day 24 to Day 31)
- Percentage of responders to 10-day dosing with REL-1017. A responder is defined as a patient with ≥ 50% reduction in the IRLS-RS score from baseline (Day 1) to end of 10-day dosing period with assessments performed on Day 1 and Day 11.
- Change from baseline (Day 1) to end of 10-day dosing period on PLMS index with measurements performed on Day 1 and Day 11
- Change from baseline (Day 1) to end of 10-day dosing period on TST, SL and SE, number of awakenings, arousal index, recorded by PSG with measurements performed on Day 1 and Day 11.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
PRD10994051 · Product
- Active substance
- Dextromethadone Hydrochloride
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- MGGM LLC
- Paediatric formulation
- No
- Orphan designation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Ente Ospedaliero Cantonale (EOC)
- Sponsor organisation
- Ente Ospedaliero Cantonale (EOC)
- Address
- Via Tesserete 46
- City
- Lugano
- Postcode
- 6900
- Country
- Switzerland
Scientific contact point
- Organisation
- Ente Ospedaliero Cantonale (EOC)
- Contact name
- Mauro Manconi
Public contact point
- Organisation
- Ente Ospedaliero Cantonale (EOC)
- Contact name
- Tatiana Terrot
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Mediolanum Cardio Research S.r.l. ORG-100010094
|
Milan, Italy | On site monitoring, Code 5, Code 8 |
Ente Ospedaliero Cantonale (EOC)
- Sponsor organisation
- Ente Ospedaliero Cantonale (EOC)
- Address
- Via Tesserete 46
- City
- Lugano
- Postcode
- 6900
- Country
- Switzerland
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Italy | Temporarily halted | 12 | 1 |
| Rest of world
Switzerland
|
— | 38 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Italy | 2024-03-12 | 2024-03-12 | 2025-05-31 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-85732
- Halt date
- 2025-05-31
- Member states concerned
- Italy
- Publication date
- 2025-06-06
- Reason
- Sponsor decision
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 3 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | doc | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 5.0 |
| Subject information and informed consent form (for publication) | L2_Informativa_consenso privacy | 1.0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-21 | Italy | Acceptable 2024-02-27
|
2024-02-28 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-04-11 | Italy | Acceptable 2024-02-27
|
2024-04-11 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2024-11-11 | Italy | Acceptable 2024-02-27
|
2024-11-11 |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2025-01-24 | Italy | Acceptable 2024-02-27
|
2025-01-24 |