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Trial registered on ANZCTR


Registration number
ACTRN12608000024347
Ethics application status
Approved
Date submitted
27/02/2007
Date registered
17/01/2008
Date last updated
17/01/2008
Type of registration
Retrospectively registered

Titles & IDs
Public title
The acceptability, safety and tolerability of combined methadone-naloxone in methadone maintained individuals aged between 18 - 65
Scientific title
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
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Participants are opiod dependant and methadone maintained individuals aged between 18-65 2131 0
Condition category
Condition code
Mental Health 2227 2227 0 0
Addiction

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 2465 0
Treatment: Drugs
Comparator / control treatment
Methadone
Control group
Active

Outcomes
Primary outcome [1] 3087 0
The primary outcome measure is severity of opioid withdrawal symptoms.
Measured: Subjective opioid withdrawal scale (SOWS)
Measure: Objective opioid withdrawal scale (OOWS)
Timepoint [1] 3087 0
Research assessments will occur on day 0 and 2, and then twice weekly for the duration of the study prior to medication administration
Secondary outcome [1] 5163 0
Craving
measured: by mean difference in visual analogue scale scores
Timepoint [1] 5163 0
Twice weekly for the duration of the study prior to medication administration
Secondary outcome [2] 5164 0
Mood
Measured: by mean difference in Profile Of Mood States (POMS) score
Timepoint [2] 5164 0
Day 0, 13, 27
Secondary outcome [3] 5165 0
Opioid Use:
Measured: by mean difference in days of self reported opioid use
Timepoint [3] 5165 0
Research assessments will occur on day 0 and 2, and then twice weekly for the duration of the study
Secondary outcome [4] 5166 0
Intoxication
Measured: by mean difference in Morphine-Benzedrine Group Scale (MBG)
Timepoint [4] 5166 0
Research assessments will occur on day 0 and 2, and then twice weekly for the duration of the study
Secondary outcome [5] 5167 0
Absorption
Measured: by mean difference in peak and trough ng/ml of racemic methadone
Timepoint [5] 5167 0
Research assessments will occur on day 0 and 2, and then twice weekly for the duration of the study
Secondary outcome [6] 5168 0
Sleep quality
Measured: by mean difference in Pittsburgh Sleep Quality Index score
Timepoint [6] 5168 0
0, 13, 27
Secondary outcome [7] 5169 0
Constipation
Measured: by mean difference in number of bowel movements
Timepoint [7] 5169 0
Research assessments will occur on day 0 and 2, and then twice weekly for the duration of the study

Eligibility
Key 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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Considered unwilling, unable or unlikely to comply with the study protocol
• Lactating and pregnant women
• Active psychotic illness

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
centralised by fax
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation. The sequence will be generated by drawing slips of paper from an envelope
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
The subjects, researcher, therapist and data analyst are blind in the study.
Phase
Phase 2 / Phase 3
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 557 0
2010

Funding & Sponsors
Funding source category [1] 2979 0
Commercial sector/Industry
Name [1] 2979 0
Biomed Pty Ltd
Country [1] 2979 0
New Zealand
Primary sponsor type
Hospital
Name
Langton Centre
Address
Surry Hills
Country
Australia
Secondary sponsor category [1] 2161 0
None
Name [1] 2161 0
Nil
Address [1] 2161 0
Country [1] 2161 0
Secondary sponsor category [2] 2689 0
None
Name [2] 2689 0
Address [2] 2689 0
Country [2] 2689 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4215 0
The Langton Centre
Ethics committee address [1] 4215 0
Ethics committee country [1] 4215 0
Australia
Date submitted for ethics approval [1] 4215 0
Approval date [1] 4215 0
28/06/2006
Ethics approval number [1] 4215 0
05/270

Summary
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.
Trial website
N/A
Trial related presentations / publications
Australasian Professional Society for Alcohol and Drugs (APSAD) Conference, November 2007 Auckland New Zealand
Public notes

Contacts
Principal investigator
Name 27557 0
Address 27557 0
Country 27557 0
Phone 27557 0
Fax 27557 0
Email 27557 0
Contact person for public queries
Name 10812 0
Anni Ryan
Address 10812 0
The Langton Centre
591 South Dowling St
Surry Hill 2010
Country 10812 0
Australia
Phone 10812 0
9332 8777
Fax 10812 0
Email 10812 0
[email protected]
Contact person for scientific queries
Name 1740 0
Anni Ryan
Address 1740 0
The Langton Centre
591 South Dowling St
Surry Hill 2010
Country 1740 0
Australia
Phone 1740 0
9332 8777
Fax 1740 0
Email 1740 0
[email protected]

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No Supporting Document Provided



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