The acceptability, safety and tolerability of combined methadone-naloxone in methadone maintained individuals aged between 18 - 65

To investigate the pharmacokinetics and pharmacodynamics of orally administered methadone-naloxone in a 50:1 ratio in partcipants who are opioid dependant and methadone maintained individuals aged between 18- 65

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12608000024347

Enrollment

Registered

2008-01-17

Start date

2007-02-01

Completion date

Unknown

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

The acceptability, safety and tolerability of combined methadone-naloxone: Is oral methadone-naloxone indistinguishable from mono-methadone? Does injection of methadone-naloxone precipitate withdrawal? Robert Graham, Suzanne Rizzo, Kristy Korompay, James Bell Introduction: Daily methadone and buprenorphine dosing is associated with high costs and rigidity. Maintenance models that predominantly employ dispensed medication (i.e. unsupervised dosing) may be more cost effective and preferable to clients and health departments. However, takeaway doses are often used in unintended ways including being injected by the client or other persons. The addition of naloxone to methadone has the potential to discourage the diversion of takeaway doses. Aims: To ascertain the safety and tolerability of oral methadone-naloxone in a 50:1 ratio by investigating aspects of its pharmacokinetic and pharmacodynamic properties, and in a second study, to investigate the effectiveness of the combination in precipitating withdrawal when administered intramuscularly. Methods: A randomised phase II study, double-blind, crossover design was used for the oral study. 10 subjects attending methadone clinics who were on a stable dose of least 20mg methadone volunteered and were given either methadone-naloxone or methadone alone for 14 days and then switched to the alternative for a total of 28 day study period. The second study was a Phase II, single group before-after design. Five of the subjects from the first study were administered IM saline solution followed by IM 10mg methadone/0.2mg naloxone prior to their scheduled methadone dose and were observed for 60 minutes. In the absence of objective signs of withdrawal at 30 minutes, participants were administered an additional 20mg methadone/0.4mg naloxone intramuscularly and observed for a further 60 minutes. Findings: Oral methadone naloxone in a 50:1 ratio appeared to be well tolerated. The same preparation reliably precipitated opioid withdrawal upon injection among methadone maintained individuals.

Interventions

A cross over design is used for the trial, therefore both the subjects and controls will recieve 14 days of their usual daily oral methadone dose, and 14 days of the daily oral study medication: Methadone-Naloxone in a ratio of 50:1 (0.1mg/ml). Participants will be randomly allocated to either recieve 14 days of their usual methadone dose first or the study medication; methadone-naloxone first.

Study design

Allocation

Randomised controlled trial

Intervention model

Crossover

Primary purpose

Treatment

Masking

Blinded (masking used)

Eligibility

Sex/Gender

All

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

• Opioid dependent clients; • In treatment for greater than 2months • Stabilised on current dose for greater than 4 weeks • Willing to remain on current dose for duration of the trial • Venous access • Able to provide voluntary informed consent

Exclusion criteria

• Considered unwilling, unable or unlikely to comply with the study protocol • Lactating and pregnant women • Active psychotic illness

Outcome results