Efficacy of Ketamine for the Prevention of Relapse in Patients with Opioid-Use Disorders (OUD)

2025-520843-34-00 Protocol EXCELLENCE/0421/0543 Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 1 sites · Protocol EXCELLENCE/0421/0543

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 20
Countries 1
Sites 1

Opioid Use Disorder

The primary objective of this study is to evaluate the efficacy of adjunctive ketamine in reducing depressive symptom severity in individuals with opioid use disorder receiving methadone or buprenorphine/naloxone (suboxone) maintenance treatment.

Key facts

Sponsor
University of Cyprus
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nervous System Diseases [C10]
Decision date (initial)
2025-01-29
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Research and Innovation Foundation (RIF) Cyprus

External identifiers

EU CT number
2025-520843-34-00
EudraCT number
2022-001997-70

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of this study is to evaluate the efficacy of adjunctive ketamine in reducing depressive symptom severity in individuals with opioid use disorder receiving methadone or buprenorphine/naloxone (suboxone) maintenance treatment.

Secondary objectives 1

  1. A secondary objective is to identify stress-related and neurophysiological biomarkers associated with treatment response and relapse vulnerability, in order to better understand the biological mechanisms underlying clinical outcomes.

Conditions and MedDRA coding

Opioid Use Disorder

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

  1. Age between 18 to 65 years old
  2. Currently into maintenance treatment for opioid use disorder
  3. Patient Health Questionnaire-9 score of ≥ 10
  4. Primary Care-PTSD-5 Screen ≤ 2

Exclusion criteria 9

  1. ECG findings showing: Tachycardia, Prior myocardial infarction, Myocardial ischemia, Aberrant conduction
  2. Hypertension (defined as): Systolic blood pressure > 140 mmHg; or Diastolic blood pressure > 90 mmHg
  3. Pregnancy (positive urine screen)
  4. Inaccessible veins for phlebotomy/infusion procedures
  5. Liver function abnormalities: Baseline alkaline phosphatase > 2.5 times upper limit of normal; Baseline aspartate aminotransferase > 3 times upper limit of normal
  6. Current bipolar disorder (DSM-5 criteria)
  7. Current or history of psychotic spectrum disorders
  8. Current or previous recreational use of ketamine or PCP
  9. Active suicidal ideation (score >4 on item 10 of the MADRS assessment)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

  1. Reversal of comorbid negative affective behaviors
  2. Prolongation/maintenance of abstinence in OUD patients
  3. Reduction in cravings

Secondary endpoints 2

  1. Identification of predictive biomarkers: (i) Emotion regulation ability; (ii) Stress response biomarkers; (iii) Changes in neural activity
  2. Association between ketamine-induced changes in brain activity and treatment outcomes

Investigational products

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

Test 1

Ketamine

SUB08365MIG · Substance

Active substance
Ketamine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
INTRAVENIOUS INFUSION
Max daily dose
0.5 mg/kg milligram(s)/kilogram
Max total dose
3 mg/kg milligram(s)/kilogram
Max treatment duration
6 Day(s)
Authorisation status
Authorised
ATC code
- — -
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University of Cyprus

Sponsor organisation
University of Cyprus
Address
Panepistimiou 1
City
Aglantzia
Postcode
2109
Country
Cyprus

Scientific contact point

Organisation
University of Cyprus
Contact name
Panos Zanos

Public contact point

Organisation
University of Cyprus
Contact name
Panos Zanos

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Cyprus Authorised, recruitment pending 20 1
Rest of world 0

Investigational sites

Cyprus

1 site · Authorised, recruitment pending
State Health Services Organisation
Mental Health Services, Limassol Old Road 215, 2029, Nicosia

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

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

TypeTitleVersion
Protocol - Extract (for publication) Ketamine Protocol-01-Not to be published 1
Protocol (for publication) Ketamine Protocol-01- To be published 1
Recruitment arrangements (for publication) Blanc 1
Subject information and informed consent form (for publication) 03 information and consent form_to be published 1
Summary of Product Characteristics (SmPC) (for publication) Ketamin_10 ml_EN_PIL_SmPC Juli 21 beglaubigt 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-01-27 Cyprus Acceptable with conditions
2025-01-28
2025-01-29
2 NON SUBSTANTIAL MODIFICATION NSM-1 2026-02-17 Cyprus Acceptable with conditions
2025-01-28
2026-02-17
3 NON SUBSTANTIAL MODIFICATION NSM-2 2026-02-17 Cyprus Acceptable with conditions
2025-01-28
2026-02-17
4 NON SUBSTANTIAL MODIFICATION NSM-4 2026-03-02 Acceptable with conditions
2025-01-28