The dual orexin receptor antagonist daridorexant as an adjunct to improve buprenorphine maintenance therapy of opioid use disorder

2024-517482-16-00 Protocol BUDA Therapeutic exploratory (Phase II) Ongoing, recruiting

Start 4 Apr 2025 · Status Ongoing, recruiting · 1 EU/EEA countries · 7 sites · Protocol BUDA

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Ongoing, recruiting
Participants planned 192
Countries 1
Sites 7

Opioid Use Disorder [OUD]

To evaluate whether daridorexant can reduce illicit substance use compared compared to placebo, when provided as an adjuntive treatment to OUD patients maintained on depot buprenorphine.

Key facts

Sponsor
Linkopings Universitet
Participant type
Patients
Age range
18-64 years
Gender
Male and Female
Therapeutic area
Psychiatry and Psychology [F] - Mental Disorders [F03]
Trial duration
4 Apr 2025 → ongoing
Decision date (initial)
2024-11-26
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
Indivior (Auxilliary Medicinal Product) · Idorsia (Investigational Medicinal Product and placebo) · Region Östergötland (funding)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate whether daridorexant can reduce illicit substance use compared compared to placebo, when provided as an adjuntive treatment to OUD patients maintained on depot buprenorphine.

Secondary objectives 7

  1. Will adjunct treatment with daridorexant result in improvements in retention in treatment (survival)
  2. Will adjunct treatment with daridorexant result in improvements in opioid craving;
  3. Will adjunct treatment with daridorexant result in improvements in opioid withdrawal symptoms
  4. Will adjunct treatment with daridorexant result in improvements in the need for provision of sublingual buprenorphine as supplemental rescue doses
  5. Will adjunct treatment with daridorexant result in improvements in substance-related problem severity and associated service needs
  6. Will adjunct treatment with daridorexant result in improvements in sleep quality
  7. Will adjunct treatment with daridorexant result in improvements in level of functioning

Conditions and MedDRA coding

Opioid Use Disorder [OUD]

VersionLevelCodeTermSystem organ class
20.1 LLT 10079385 Opioid use disorder 10037175

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Daridorexant adjunct vs placebo
12 randomized, double blind, placebo-controlled 2 arm, parallell arm design of daridorexant vs placebo as adjunct treatment in opioid use disorder patients maintained on depot buprenorphin
 Randomised Controlled Double [{"id":165398,"code":1,"name":"Subject"},{"id":165399,"code":2,"name":"Investigator"},{"id":165397,"code":4,"name":"Analyst"},{"id":165400,"code":5,"name":"Carer"}] Active: Daridorexant 50 daily
Placebo: Matching placebo daily

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

  1. Men and women aged 20 - 65 years
  2. Meet criteria for moderate-to-severe OUD ”opioid dependence” according to ICD-10, confirmed using a checklist of DMS-5 criteria for OUD by a trained nurse or physician. Other, co-morbid substance use disorders will be evaluated by obtaining a history and carrying out a chart review; these will be confirmed using a checklist of DSM-criteria for the respective substance, and will be recorded, but will not influence eligibility except as specified below.
  3. ≥1 year duration of OUD
  4. Prospective participants will be eligible if they are not in stable remission, or if, despite being in stable remission from opioid use, they continue to use other substances in a manner that indicates they stand to potentially benefit from participating.
  5. Both patients not enrolled in OMT at the time of screening, and those with ongoing OMT with transmucosal buprenorphine formulations at that time will be eligible. Patients not currently enrolled in OMT will first be stabilized on transmucosal buprenorphine according to clinical routine.
  6. Able to speak and read Swedish.
  7. Willing to provide informed consent.

Exclusion criteria 10

  1. Patients with any serious psychiatric condition unless stable under treatment.
  2. Patients already in OMT with a depot formulation of buprenorphine.
  3. Patients enrolled in OMT with methadone
  4. Patients with severe respiratory insufficiency
  5. Patients with a diagnosis of narcolepsy
  6. Patients with any other serious medical condition, unless stable under treatment.
  7. Patients with concomitant use of strong CYP3A4 inhibitors (see Appendix 1 of protocol)
  8. Women who are pregnant or plan on becoming pregnant, or who are nursing.
  9. Women of child-bearing potential will have to agree to practice reliable contraception (see Appendix 2 of protocol), or document that they intend to abstain from sexual intercourse.
  10. Patients with any other condition or circumstances that, in the assessment of the investigator, lead to participation in the study not being in the best interest of the patient.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Frequency of negative urine samples (obtained weekly, with missing samples coded as positive) throughout weeks 1-13, supported by Time-Line Follow-Back (TLFB) self-report

Secondary endpoints 7

  1. Retention in treatment (survival)
  2. Opioid craving (OC-VAS; weekly)
  3. Opioid withdrawal (Subjective Opioid Withdrawal Scale, SOWS [weekly])
  4. Substance-related problem severity and associated service needs (Addiction Severity Index, validated Swedish Self-report version, ASI-SR]) [monthly]
  5. Sleep quality (Pittsburgh Sleep Quality Index: PSQI) [weekly]
  6. Insomnia Severity Index (ISI]) [monthly]
  7. Level of functioning (WHODAS) [monthly]

Investigational products

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

Test 1

QUVIVIQ 25 mg film-coated tablets

PRD11409551 · Product

Active substance
Daridorexant
Substance synonyms
ACT-541468, [(2S)-2-(5-CHLORO-4-METHYL-1H-BENZIMIDAZOL-2-YL)-2-METHYLPYRROLIDIN-1-YL][5-METHOXY-2-(2H-1,2,3-TRIAZOL-2-YL)PHENYL]METHANONE, NEMOREXANT
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL USE
Max daily dose
50 mg milligram(s)
Max total dose
4200 mg milligram(s)
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
N05CJ03 — -
Marketing authorisation
EU/1/22/1638/001
MA holder
IDORSIA PHARMACEUTICALS DEUTSCHLAND GMBH
MA country
Liechtenstein
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
Yes
Modification description
Modification is described in detail in the uploaded document

Placebo 1

Film coated tablets matched to the test product as specified further in uploaded documents

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 3

Subutex 100 mg injektionsvätska, depotlösning

PRD8022787 · Product

Active substance
Buprenorphine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
10.7 mg milligram(s)
Max total dose
100 mg milligram(s)
Max treatment duration
4 Week(s)
Authorisation status
Authorised
ATC code
N07BC01 — BUPRENORPHINE
Marketing authorisation
58558
MA holder
INDIVIOR EUROPE LIMITED
MA country
Sweden
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Suboxone 8 mg/2 mg sublingual tablets

PRD3489603 · Product

Active substance
Buprenorphine
Pharmaceutical form
SUBLINGUAL TABLET
Route of administration
SUBLINGUAL USE
Max daily dose
24 mg milligram(s)
Max total dose
2016 mg milligram(s)
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
N07BC51 — -
Marketing authorisation
EU/1/06/359/004
MA holder
INDIVIOR EUROPE LIMITED
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Subutex 300 mg injektionsvätska, depotlösning

PRD8022790 · Product

Active substance
Buprenorphine
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
10.7 mg milligram(s)
Max total dose
600 mg milligram(s)
Max treatment duration
8 Week(s)
Authorisation status
Authorised
ATC code
N07BC01 — BUPRENORPHINE
Marketing authorisation
58559
MA holder
INDIVIOR EUROPE LIMITED
MA country
Sweden
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Linkopings Universitet

6 Total trials 4 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Linkopings Universitet
Address
Sandbacksgatan 7, Linkopings Domkyrkofors. Linkopings Domkyrkofors.
City
Linkoping
Postcode
582 25
Country
Sweden

Scientific contact point

Organisation
Linkopings Universitet
Contact name
Markus Heilig

Public contact point

Organisation
Linkopings Universitet
Contact name
Markus Heilig

Locations

1 EU/EEA country · 7 investigational sites

By country

CountryMS statusPlanned subjectsSites
Sweden Ongoing, recruiting 192 7
Rest of world — 0 —

Investigational sites

Sweden

7 sites · Ongoing, recruiting
Capio Hjärnhälsa AB
Capio Maria, Wollmar Yxkullsgatan 25, 11850, Stockholm
Region Joenkoepings Laen
Beroendemottagningen Psykiatriska kliniken, Lanssjukhuset Ryhov, Sjukhusgatan, Jonkoping
Region Skane Skanes Universitetssjukhus
Beroendecentrum Malmö, St. Johns, Fritz Bauers Gata 5, Malmo
Region Stockholm – SLSO
Beroendecentrum Stockholm, Solnavagen 1 E, S:t Matteus, Stockholm
Uppsala University Hospital
Beroendemedicinska mottagningen, Akademiska Sjukhuset, 751 85, Uppsala
Region Vaesternorrland
Psykiatriska kliniken Sundsvall, Lasarettsvagen 21, 856 43, Sundsvall
Region Oestergoetland
Psykiatriska kliniken i Linköping, Universitetssjukhuset I, 58185, Linkoping

Country notifications

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

Country Trial startTrial end Recruitment startRecruitment end Early termination
Sweden 2025-04-04 2025-09-02

Results and documents

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

Documents 18 files

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

TypeTitleVersion
Protocol (for publication) 2024 09 10 BUDA Protocol incl Appendices FINAL FOR SUBMISSION 1
Recruitment arrangements (for publication) K1_Rekryteringsforfarande_2024-517482-16-00 1
Recruitment arrangements (for publication) K2_Annons_2024-517482-16-00 1
Recruitment arrangements (for publication) L2_Annons_ 2024-517482-16-00_version 2_ clean 2
Recruitment arrangements (for publication) L2_Annons_ 2024-517482-16-00_version 2_ tracked changes 2
Subject information and informed consent form (for publication) 1 Questionnaire CPRS-SA SV 1
Subject information and informed consent form (for publication) 2 Questionnaire TLFB SV 1
Subject information and informed consent form (for publication) 3 Questionnaire OC-VAS SV 1
Subject information and informed consent form (for publication) 4 Questionnaire SOWS SV 1
Subject information and informed consent form (for publication) 5 Questionnaire PSQI SV 1
Subject information and informed consent form (for publication) 6 Questionnaire ISI SV 1
Subject information and informed consent form (for publication) 7 Questionnaire ASI-SR 1
Subject information and informed consent form (for publication) 8 Questionnaire WHODAS SV 1
Subject information and informed consent form (for publication) L1_Forsokspersonsinformation och samtycke_2024-517482-16-00 1
Subject information and informed consent form (for publication) L1_Forsokspersonsinformation och samtycke_2024-517482-16-00_version 2_ clean 2
Subject information and informed consent form (for publication) L1_Forsokspersonsinformation och samtycke_2024-517482-16-00_version 2_tracked changes 2
Summary of Product Characteristics (SmPC) (for publication) quviviq-epar-product-information_en 1
Synopsis of the protocol (for publication) 2024 09 15 Synopsis - Daridorexant as adjuvant in OUD FINAL 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-16 Sweden Acceptable
2024-10-30
 2024-11-26
2 SUBSTANTIAL MODIFICATION SM-1 2025-05-11 Sweden Acceptable 2025-05-26
3 SUBSTANTIAL MODIFICATION SM-2 2026-01-16 Sweden Acceptable 2026-02-09

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