MetAddon: Methadone as co-analgesic for patients with metastatic bone pain: a double-blind randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universiteit Maastricht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Decision date (initial)

2025-10-20

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: Therapy

To assess whether methadone as add-on to already used (primairy) opioids is more effective in achieving a pain reduction in patients with metastatic bone pain compared to morphine.

Secondary objectives 9

1. Difference between methadone and morphine as add-on in time to response.
2. Difference between methadone and morphine as add-on in change in mean and worst pain
3. Difference between methadone and morphine as add-on in global perceived effect.
4. Difference between methadone and morphine as add-on in use of rescue medication.
5. Difference between methadone and morphine as add-on in opioid increase ratio.
6. Difference between methadone and morphine as add-on in side effects.
7. Difference between methadone and morphine as add-on in complications.
8. Difference between methadone and morphine as add-on in health-related quality of life.
9. Difference between methadone and morphine as add-on in costs.

Conditions and MedDRA coding

Cancer, bone metastasis, pain

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patients have metastatic bone pain reflected by a mean pain intesity score of ≥5 on an 11-point scale.
2. Patients use strong opioids at a stable dose for at least seven days with a minimal daily dose of 60 mg MME (morphine milligram equivalence) (oxycodone SR 40 mg, fentanyl TD 25 mcg/hr, hydromorphine SR 12 mg).
3. Patients are 18 years or older.
4. Female patients of childbearing potential use contraceptives to prevent pregnancy during the study period.

Exclusion criteria 15

1. Patients who have prolonged QT syndrome.
2. Patients who have a QTc-time > 500 ms (ECG max three months old).
3. Patients with an eGFR < 30 mL/min (max. six weeks old).
4. Patients who use buprenorphine, morphine SR or methadone.
5. Patients who are not able to take oral medication.
6. Patients who experience pain caused by a pathologic fracture or (suspected) nerve root compression.
7. Patients who experience pain most likely not related to bone metastasis.
8. Patients who have had surgery within seven days before the start of the study.
9. Patients who received radiotherapy within the last six weeks on bone lesions.
10. Patients who are scheduled for radiotherapy on bone lesions during the study period.
11. Patients who have an indication for surgery to prevent pathological fractures.
12. Patients who use irreversible monoamine oxidase (MAO) inhibitors within the last 14 days or during the study period.
13. Patients who use enzalutamide in the last four weeks or during the study period.
14. Patients who have myasthenia gravis.
15. Patients who are pregnant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Difference in proportion of patients with ≥ 30% reduction in mean pain between both groups based on average scores of day 5, 6 and 7 using an 11-point scale.

Secondary endpoints 9

1. Mean and worst pain intensity after each week using an 11-point scale.
2. Time in days between start study medication andreaching ≥ 30% reduction in mean pain score.
3. Mean pain intesity using 11-point scale on day 21 compared to mean pain inensity at baseline.
4. Global perceibed effect after three weeks.
5. Frequency use of rescue medication throughout the study
6. Self-reported side effects on day 1, 7, 8, 14 and 21 using medcation and pain diary on an 7-point scale and complications via (S)AE reports.
7. Health-related quality of life at baseline and after 7, 14 and 21 days using EQ-5D-5L and FACT-BP questionnaires.
8. Health-care costs and cost-effectiveness at three weeks.
9. Opioid increased ratio: difference in daily opioid dose on day 21 compared to baseline.

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universiteit Maastricht

Sponsor organisation

Universiteit Maastricht

Address

P. O. Box 616

City

Maastricht

Postcode

6200 MD

Country

Netherlands

Scientific contact point

Organisation

Universiteit Maastricht

Contact name

Janna Schoenmaekers

Public contact point

Organisation

Universiteit Maastricht

Contact name

Janna Schoenmaekers

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

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

Documents 6 files

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

Application history

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