Semalco

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

8 Jun 2023 → 8 Sep 2025

Decision date (initial)

2023-05-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Mental Health Services, Capital Region of Copenhagen · The Novo Nordisk Foundation · The Augustinus Foundation · The Novavi Foundation · The Hartmann Foundation

External identifiers

EU CT number

2023-503371-25-00

WHO UTN

U1111-1286-6919

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Does the glucagon-like peptide 1 (glp-1) receptor agonist semaglutide reduce alcohol intake in patients with alcohol use disorder and comorbid obesity?

Conditions and MedDRA coding

Alcohol Use Disorder

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Informed oral and written consent
2. Diagnosed with alcohol dependence according to the criteria of the International Classification of Diseases 10 (ICD-10), and diagnosed with alcohol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)
3. Alcohol use disorder identification test (AUDIT) score >15
4. Body mass index (BMI) above or equal to 30 kg/m2
5. Age 18 - 70 years (both included)
6. Heavy alcohol drinking defined as more than 6 days with alcohol consumption over 4 units (48 g alcohol) for women and 5 units (60 g alcohol) for men during a consecutive 30-day period, within 40 days prior to baseline evaluation, measured by the TLFB method. The 30-day period will be the 30 days with the biggest alcohol intake (most heavy drinking days and the largest amount of total alcohol) out of the 40 days.

Exclusion criteria 21

1. Severe psychiatric disease, defined as a diagnosis of schizophrenia, paranoid psychosis, bipolar disorder or mental retardation
2. A history of delirium tremens or alcohol withdrawal seizures
3. No serious withdrawal symptoms at inclusion (a score higher than 9 on the Clinical Institute With-drawal Assessment of Alcohol Scale, Revised (CIWA-Ar)) at baseline examinations
4. Present or former neurological disease, including traumatic brain injury
5. Type 1 diabetes, type 2 diabetes in poor glycaemic control (defined as HbA1c ≥48 mmol/l or fasting plasma glucose above 7.0 mmol/l at inclusion)
6. Females of childbearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant within the next 9 months (26 weeks plus three months after discontinuation of semaglutide), or are not using contraceptives (during the whole study period) considered as highly effective (combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device – IUD, IUS, bilateral tubal occlusion, vasectomised partner, sexual abstinence)
7. Pregnancy (serum human chorionic gonadotropin (hCG) > 3 U/L at inclusion)
8. Impaired hepatic function (liver transaminases >3 times the upper limit)
9. Impaired renal function (eGFR < 50 ml/min and/or plasma creatinine >150 µmol/l)
10. Impaired pancreatic function (any history of acute or chronic pancreatitis and/or amylase > 2 times upper limit)
11. Former medullary thyroid carcinoma (MTC) and/or family history with MTC and/or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
12. Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pec-toris and/or myocardial infarction within the last 12 months
13. Uncontrolled hypertension (systolic blood pressure >180 mmHg, diastolic blood pressure >110 mmHg)
14. Concomitant pharmacotherapy against alcohol use disorder i.e. disulfiram, naltrexone, acamprosate, or nalmefene, since the first of the 30 drinking days registered for inclusion at the TLFB-schedule.
15. Receiving any investigational drug within the last three months
16. Use of weight-lowering pharmacotherapy within the preceding 3 months
17. Any other active substance use defined as a DUDIT-score >1 (except nicotine)
18. Hypersensitivity to the active substance or any of the excipients
19. Only for patients undergoing brain scans: Contraindications for undergoing an MRI scan (magnetic implants, pacemaker, claustro-phobia, etc.)
20. Unable to speak and/or understand Danish
21. Any condition that the investigator feels would interfere with trial participation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in alcohol consumption, defined as the change in percentage of heavy drinking days during a period of 30 consecutive days* , after 26 weeks of treatment adjusted for baseline (percentage points (pp)). The 30-day period will be the 30 consecutive days with the biggest alcohol intake (most heavy drinking days and the largest amount of total alcohol intake) out of the 40 days prior to the evaluation, measured by the TLFB method

Secondary endpoints 25

1. Change in total alcohol consumption (gram/last 30 consecutive days)
2. Change in number of days without alcohol consumption (last 30 consecutive days)
3. Change in drinks per day (last 30 consecutive days)
4. Time to relapse, defined as the time to first alcohol intake
5. Time to first heavy drinking day
6. Reduction in WHO alcohol risk level (last 30 consecutive days)
7. Change in Penn Alcohol Craving Scale (PACS) score
8. Change in Alcohol Use Disorder Identification Test (AUDIT) score
9. Change in Drug Use Disorders Identification Test (DUDIT) score
10. Change in Fibrosis-4 (FIB4) score
11. Change in measures of health (WHOQOL-BREF-score)
12. Change in Fagerströms Test for Nicotine Dependence score
13. Change in blood gamma-glutamyl transferase (GGT)
14. Change in blood alanine transaminase (ALAT)
15. Change in plasma levels of phosphatidyl ethanol (PEth)
16. Change in blood mean cell volume (MCV)
17. Change in body weight
18. Change in blood pressure
19. Change in pulse
20. Change in waist circumference
21. Change in glycaemic control parameters (HbA1c)
22. Change in brain GABA levels (cortical, caudate, and putamen) assessed by MRS brain scans
23. Change in brain alcohol cue-response in reward-processing brain regions (ventral and dorsal striatum, putamen, nucleus accumbens, and caudate), including the septal area assessed by fMRI brain scans
24. Change in heavy drinking days during a period of 30 consecutive days measured by the TLFB, after 26 weeks of treatment adjusted for baseline (percentage points (pp)) and maximum tolerable semaglutide dose given.
25. Change in heavy drinking days during a period of 30 consecutive days measured by the TLFB, after 26 weeks of treatment adjusted for baseline (percentage points (pp)) and weight loss during the 26 weeks of treatment.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Nordre Fasanvej 57, 1st Floor Entrance 2 1st Floor Entrance 2

City

Frederiksberg

Postcode

2000

Country

Denmark

Scientific contact point

Organisation

Psykiatrisk Center Kobenhavn

Contact name

Anders Fink-Jensen

Public contact point

Organisation

Psykiatrisk Center Kobenhavn

Contact name

Mette Kruse Klausen

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

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

Documents 14 files

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

Application history

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