Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ended
Participants planned
22
Countries
1
Sites
1
Healthy volunteers
The number IM and IN administrations needed to restore ventilation to baseline levels in healthy volunteers
Key facts
- Sponsor
- Leiden University Medical Center
- Participant type
- Healthy volunteers, Patients
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Physiological processes [G07], Diseases [C] - Respiratory Tract Diseases [C08]
- Trial duration
- 21 Sep 2023 → 6 Sep 2024
- Decision date (initial)
- 2023-08-14
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacodynamic, Pharmacokinetic, Safety
The number IM and IN administrations needed to restore ventilation to baseline levels in healthy volunteers
Secondary objectives 4
- The number IM and IN administrations needed to restore ventilation to baseline levels in chronic opioid users
- Naloxone-induced changes in minute ventilation, end-tidal PCO2 and plasma concentrations of naloxone upon naloxone (either IM or IN) administration as a function of time.
- Naloxone and fentanyl pharmacokinetics
- Effect of fentanyl and naloxone on pupil diameter and muscle tone
Conditions and MedDRA coding
Healthy volunteers
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Aged 18-65 years with body mass index 19-40 kg/m2
- Opioid users: use opioids at daily doses ≥ 60 mg oral morphine equivalents. . No upper limit is set as would like to study an as large as possible range of opioid use. It is our experience that the majority of patients uses 60-600 mg oral morphine equivalents.
- Opioid users: • Stable as defined by the Investigator, based on a medical evaluation that includes the subject’s medical and surgical history, physical examination, vital signs, 12-lead ECG, hematology, and blood chemistry.
Exclusion criteria 8
- A medical history of medical or psychiatric disease (incl. drug or alcohol addiction);
- • Pregnancy or lactation
- • A positive drug urine dipstick on the screening or study days
- • History or presence of allergic response to study medication
- for chronic opioid users: • Currently meet the criteria for diagnosis of moderate or severe substance use disorder according to the DSM-5 criteria on any substances other than opioids, caffeine, or nicotine;
- Chronic opioid users: Any active medical condition, organ disease or concurrent medication or treatment that may either compromise subject safety or interfere with study endpoints;
- Chronic opioid users: Currently receiving medication-assisted treatment for the treatment of opioid-use disorder;
- Treatment with mixed agonists-antagonists (such as buprenorphine) or use of benzodiazepines.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- • Number of naloxone administrations
Secondary endpoints 4
- • Number of naloxone administrations
- • Timing of minute ventilation, end-tidal PCO2 and plasma concentrations of naloxone
- • Plasma concentrations of naloxone and fentanyl
- • Pupil diameter and muscle tone
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
ZIMHI™ (naloxone hydrochloride injection) for intramuscular or subcutaneous use
PRD10392615 · Product
- Active substance
- Naloxone Hydrochloride
- Substance synonyms
- N-ALLYLNOROXYMORPHONE HYDROCHLORIDE
- Pharmaceutical form
- INJECTION
- Route of administration
- INTRAMUSCULAR USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 40 mg milligram(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- LEIDEN UNIVERSITY MEDICAL CENTER
- Paediatric formulation
- No
- Orphan designation
- No
NARCAN® (naloxone hydrochloride) nasal spray
PRD10392616 · Product
- Active substance
- Naloxone Hydrochloride
- Substance synonyms
- N-ALLYLNOROXYMORPHONE HYDROCHLORIDE
- Pharmaceutical form
- NASAL SPRAY
- Route of administration
- NASAL SPRAY
- Max daily dose
- 16 mg milligram(s)
- Max total dose
- 32 mg milligram(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- LEIDEN UNIVERSITY MEDICAL CENTER
- Paediatric formulation
- No
- Orphan designation
- No
Auxiliary 2
Fentanyl hameln 50 microgram/ml, oplossing voor injectie
PRD3238668 · Product
- Active substance
- Fentanyl Citrate
- Substance synonyms
- FENTANYL DIHYDROGEN CITRATE, 2-HYDROXYPROPANE-1,2,3-TRICARBOXYLIC ACID, N-(1-PHENETHYL-4-PIPERIDYL)-N-PHENYL-PROPANAMIDE
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 1000 µg microgram(s)
- Max total dose
- 2000 µg microgram(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- N01AH01 — FENTANYL
- Marketing authorisation
- RVG 25458
- MA holder
- HAMELN PHARMA GMBH
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Naloxone 400 micrograms/ml solution for injection/infusion
PRD716893 · Product
- Active substance
- Naloxone Hydrochloride Dihydrate
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 2 Day(s)
- Authorisation status
- Authorised
- ATC code
- V03AB15 — NALOXONE
- Marketing authorisation
- PL25215/0012
- MA holder
- HAMELN PHARMA GMBH
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Leiden University Medical Center
- Sponsor organisation
- Leiden University Medical Center
- Address
- Albinusdreef 2
- City
- Leiden
- Postcode
- 2333 ZA
- Country
- Netherlands
Scientific contact point
- Organisation
- Leiden University Medical Center
- Contact name
- Albert Dahan, MD PhD
Public contact point
- Organisation
- Leiden University Medical Center
- Contact name
- Albert Dahan, MD PhD
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 22 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Leids Universitair Medisch Centrum (LUMC)
Anesthesiology, Albinusdreef 2, 2333 ZA, Leiden
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 |
|---|---|---|---|---|---|
| Netherlands | 2023-09-21 | 2024-09-06 | 2023-10-05 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Summary of results Art. 37(4) CTR
| Title | Submission date | Status | Type |
|---|---|---|---|
| IMVIN results SUM-97497
|
2025-09-12T08:17:56 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Lay person summary of results | 2025-12-05T08:53:08 | Submitted | Laypersons Summary of Results |
Documents 2 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Laypersons summary of results (for publication) | Lay person summary of results | 1 |
| Summary of results (for publication) | IMVIN results | 1 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-06-02 | Netherlands | Acceptable 2023-08-14
|
2023-08-14 |