Hypoxic ventilatory response (HVR): Effect of Esketamine

2023-504229-37-00 Therapeutic use (Phase IV) Ended

Start 4 Aug 2023 · End 14 Mar 2025 · Status Ended · 1 EU/EEA countries · 1 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ended
Participants planned 18
Countries 1
Sites 1

healthy volunteers

• Part 1 Effect of esketamine on the sustained hypoxic ventilatory response with hypoxia lasting 25 min. • Part 2 Reversal of remifentanil-induced depression of the acute hypoxic ventilatory response by esketamine with hypoxia lasting 2 times 7 min (once at low and once at high CO2 levels)

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]
Trial duration
4 Aug 2023 → 14 Mar 2025
Decision date (initial)
2023-06-12
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

• Part 1 Effect of esketamine on the sustained hypoxic ventilatory response with hypoxia lasting 25 min.
• Part 2 Reversal of remifentanil-induced depression of the acute hypoxic ventilatory response by esketamine with hypoxia lasting 2 times 7 min (once at low and once at high CO2 levels)

Secondary objectives 2

  1. Psychomimetic side effects at the end of a hypoxic episode.
  2. Esketamine plasma concentrations

Conditions and MedDRA coding

healthy volunteers

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

  1. aged 18-45 years
  2. • Body mass index 19-30 kg/m2;
  3. • Able to read and understand the subject information.

Exclusion criteria 9

  1. • A potential subject who meets any of the following criteria will be excluded from participation in this study:
  2. •• A history of clinically significant (as deemed by the investigators) medical or psychiatric disease. These include: clinically significant illness or disease (e.g., psychiatric disorders, disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or any clinically significant abnormal symptom or organ impairment, as judged by the investigator, found by medical history, physical examinations or vital signs at screening;
  3. • any allergy to food or medication;
  4. • weekly alcohol 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;
  5. • pregnancy or lactation;
  6. • 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. By contraception we mean for women: intrauterine device (IUD), diaphragm with spermicide, oral contraceptive, injectable progesterone, subdermal implant or a tubal ligation. Males who are sexually active and whose partners are females of childbearing potential must agree to use condoms.
  7. • participation in an investigational drug trial in the 3 months before the current study;
  8. • illicit drug use in the 30 days before the current study;
  9. • a positive drug urine dipstick on the screening or study days.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Hypoxic ventilatory response

Secondary endpoints 2

  1. Psychomimetic side effects at the end of a hypoxic episode.
  2. Esketamine plasma concentrations

Investigational products

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

Test 2

Ketanest-S® 5, oplossing voor injectie 5 mg/ml

PRD6796180 · Product

Active substance
Esketamine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENOUS INFUSION
Max daily dose
100 mg milligram(s)
Max total dose
200 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
N01AX14 — ESKETAMINE
Marketing authorisation
RVG 22550
MA holder
PFIZER B.V.
MA country
Netherlands
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Remifentanil-hameln 1 mg, poeder voor concentraat voor oplossing voor injectie of infusie

PRD8934385 · Product

Active substance
Remifentanil
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS
Max daily dose
100 mg milligram(s)
Max total dose
200 mg milligram(s)
Max treatment duration
2 Day(s)
Authorisation status
Authorised
ATC code
N01AH06 — REMIFENTANIL
Marketing authorisation
RVG 103427
MA holder
HAMELN PHARMA GMBH
MA country
Netherlands
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

normal saline 0.9% NaCl

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

Auxiliary 1

Naloxon Orpha 0,4 mg/ml, oplossing voor injectie of infusie

PRD308843 · Product

Active substance
Naloxone Hydrochloride
Pharmaceutical form
SOLUTION FOR INJECTION/INFUSION
Route of administration
INTRAVENOUS USE
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
RVG 30938
MA holder
ORPHA-DEVEL HANDELS UND VERTRIEBS GMBH
MA country
Netherlands
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

Public contact point

Organisation
Leiden University Medical Center
Contact name
Albert Dahan

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Netherlands Ended 18 1
Rest of world 0

Investigational sites

Netherlands

1 site · Ended
Leiden University Medical Center
Anesthesiology, Albinusdreef 2, 2333 ZA, Leiden

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Netherlands 2023-08-04 2025-03-14 2023-08-22

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

TitleSubmission dateStatusType
Summary of results
SUM-97495
2025-09-12T08:14:58 Submitted Summary of Results

Documents 1 file

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

TypeTitleVersion
Summary of results (for publication) HEOE results 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2023-04-07 Netherlands Acceptable
2023-06-12
2023-06-12