Overview
Sponsor-declared trial summary
none, healthy subjects only
We will investigate the ability of an intravenous infusion of L-NAC on opioid-induced respiratory depression induced by fentanyl
Key facts
- Sponsor
- Leiden University Medical Center
- Participant type
- Healthy volunteers
- Age range
- 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Phenomena and Processes [G] - Physiological processes [G07], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]
- Trial duration
- 19 Jul 2023 → 9 Sep 2024
- Decision date (initial)
- 2023-05-12
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Leiden University Medical Center
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic, Pharmacodynamic
We will investigate the ability of an intravenous infusion of L-NAC on opioid-induced respiratory depression induced by fentanyl
Secondary objectives 1
- Assess effects of L-NAC or placebo on pH, arterial and end-tidal PCO2, oxygen saturation and respiratory rate
Conditions and MedDRA coding
none, healthy subjects only
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Age 18-40 years
- Body Mass Index 19-30 kg/m2
- Able to read and understand the subject information
Exclusion criteria 8
- A medical history of medical or psychiatric disease
- any allergy to food or medication
- weekly ethanol intake of more than 3 units/day or more than 21 units/week in women and 5 units/day and 35 units/week in men
- pregnancy or lactation
- women of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative urine pregnancy test prior to enrolment and must agree to use a medically acceptable means of contraception from screening through at least 1 month after the last dose of study drug
- participation in an investigational drug trial in the 3 months before the current study
- illicit drug use in the 30 days before the current study
- a positive drug urine dipstick on the screening or study days
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Minute ventilation
Secondary endpoints 5
- End-tidal carbon dioxide partial pressure
- Respiratory frequency
- Tidal volume
- Arterial blood gas analyses
- Blood plasma concentrations of fentanyl and L-NAC
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Fluimucil 200 mg/ml concentraat voor oplossing voor infusie
PRD476090 · Product
- Active substance
- Acetylcysteine
- Substance synonyms
- L-ALPHA-ACETAMIDO-BETA-MERCAPTOPROPIONIC ACID, N-ACETYLCYSTEINE, N-ACETYL-L-CYSTEINE
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 112.5 µg/Kg microgram(s)/kilogram
- Max total dose
- 112.5 µg/Kg microgram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- V03AB23 — ACETYLCYSTEINE
- Marketing authorisation
- RVG 10903
- MA holder
- ZAMBON NEDERLAND B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
0.9% NaCl solution for infusion
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 2000 ml millilitre(s)
- Max total dose
- 2000 ml millilitre(s)
- Max treatment duration
- 1 Day(s)
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
- Modified vs. Marketing Authorisation
- 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
- INTRAVENOUS INFUSION
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 4 mg milligram(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
- INTRAVENOUS INJECTION
- Max daily dose
- 90 mg milligram(s)
- Max total dose
- 90 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
- Monique van Velzen
Public contact point
- Organisation
- Leiden University Medical Center
- Contact name
- Monique van Velzen
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 18 | 1 |
| Rest of world | — | 0 | — |
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 |
|---|---|---|---|---|---|
| Netherlands | 2023-07-19 | 2024-09-09 | 2023-07-31 |
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 |
|---|---|---|---|
| Summary of results SUM-109634
|
2025-12-05T08:50:40 | Submitted | Summary of Results |
Layperson summary Annex V
| Title | Submission date | Status | Type |
|---|---|---|---|
| Lay person summary of results | 2025-12-05T08:50:57 | 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) | Summary of results | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-10 | Netherlands | Acceptable 2023-05-12
|
2023-05-12 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-03-22 | Netherlands | Acceptable 2024-04-22
|
2024-04-22 |