Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000319370
Ethics application status
Approved
Date submitted
11/06/2008
Date registered
10/07/2008
Date last updated
3/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A one-year, open label, extension study of flupirtine for the treatment of painful Human Immunodeficiency Virus (HIV)-sensory neuropathy (SN) in patients who have pain inadequately controlled by opioids
Scientific title
A one-year, open label, extension study of flupirtine for the treatment of painful HIV-sensory neuropathy in patients who have pain inadequately controlled by opioids
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
painful HIV - sensory neuropathy 3254 0
Condition category
Condition code
Anaesthesiology 3418 3418 0 0
Pain management
Infection 3419 3419 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a one-year extension study to investigate the long-term safety, tolerability and efficacy of open label flupirtine for the treatment of painful HIV-SN in patients who have pain inadequately controlled by opioids.

The study will consist of a Dose Optimisation Stage (Stage 1) and a second Dose Maintenance Stage (Stage 2).

The Dose Optimisation Stage of the study consists of a variable number of 2-week study periods during which the dose of flupirtine will be optimised for each study subject individually in response to feedback regarding pain, side effects and Quality of Life (QoL) during study visits. Minor adjustments to opioid dose may also occur if pain control is maintained and side effects experienced by the study subjects suggest opioid excess.

Study subjects will begin the Dose Optimisation Stage with the introduction of 200-300mg/day flupirtine (2 - 3 capsules) to be taken orally along with their regular opioid medication. The dose of flupirtine and opioid medication may be adjusted fortnightly by the Principle Investigator using patient feedback, pain and QoL scores.

Dose optimisation will continue fortnightly until:
1.the study subject experiences effective pain relief at a flupirtine dose that does not produce side effects that in the opinion of the patient are unacceptable
2.the study subject has reached the maximum flupirtine dose of 600mg.
3.the patient does not wish to continue
4.it is the opinion of the Principle Investigator that dose optimisation should not continue.

it is anticipated that Dose Optimisation stage of the trial will last approximately 2 - 3 months. At the conclusion of the Dose Optimisation Stage the Principle Investigator shall, in consultation with the study subject and using pain scores, reported side effects and QoL responses as a guide, choose the best dose of flupirtine (to be taken in combination with opioids ) for the study subject. The study subject may remain on this dose combination during the Dose Maintenance Phase and the remainder of the extension study.

During the Dose Maintenance Stage of the study, subjects will be required to attend the study site monthly for assessment and dispensing of flupirtine. Drug doses may be re-optimised by the Principle Investigator (according to study subject feedback as per the Dose Optimisation Stage) during the Dose Maintenance Stage. It is anticipated that the Dose Maintenance Stage of the trial will last 9 - 10 months.
Intervention code [1] 2994 0
Treatment: Drugs
Comparator / control treatment
none
Control group
Uncontrolled

Outcomes
Primary outcome [1] 4313 0
To investigate the long-term safety of flupirtine for the treatment of painful HIV-SN in patients who have pain inadequately controlled by opioids. Safety will be assessed using study subject reports of adverse events and pathology results of liver, renal and blood function tests.
Timepoint [1] 4313 0
Study participants are assessed fortnightly during Stage 1 and monthly during stage 2 of the trial.
Secondary outcome [1] 7268 0
To investigate the long-term tolerability of flupirtine for the treatment of painful HIV-SN in patients who have pain inadequately controlled by opioids. Tolerability will be assessed using study subjects reports of side effects and adverse events.
Timepoint [1] 7268 0
Study participants are assessed fortnightly during Stage 1 and monthly during stage 2 of the trial.
Secondary outcome [2] 7269 0
To investigate the efficacy of flupirtine for the treatment of painful HIV-SN in patients who have pain inadequately controlled by opioids. Efficacy will be assessed using study subject feedback related to pain questionairres.
Timepoint [2] 7269 0
Study participants are assessed fortnightly during Stage 1 and monthly during stage 2 of the trial.
Secondary outcome [3] 7270 0
To describe doses of flupirtine and opioids which, when used concomitantly, may increase the pain relief and QoL of patients who have pain due to painful HIV-SN which is inadequately controlled by opioids alone.
Timepoint [3] 7270 0
Study participants are assessed fortnightly during Stage 1 and monthly during stage 2 of the trial.

Eligibility
Key inclusion criteria
In order to be eligible for this study, subjects must:
1.give informed consent
2.have completed the primary study identified by the protocol number CNSBio 01/07 . Study subjects who did not complete CNSBio 01/7 may be enrolled in this study with the approval of the Principle Investigator and the Sponsor.
3.be willing to maintain opioid use throughout the study
4.begin the study within 1 month of completing the CNSBio 01/07 (primary study) termination, 1 month or 3 month follow-up visit.
5.have a negative urine ßHcG pregnancy test, to be performed within 7 days of study enrolment and monthly during the extension study .
6.be willing to use effective methods of birth control and/or refrain from participating in a conception process during the study and for 30 days following IP exposure.
7.be willing and able to comply with protocol requirements for the duration of study participation. Such requirements include, but are not limited to attending all study visits for assessments and study drug dispensing.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
In order to be eligible for this study, subjects must not:
1.be pregnant or breast feeding.
2.be taking warfarin.
3.have myasthenia gravis or epilepsy .
4.have significant uncompensated abnormal liver or kidney function.
5.have hypertension, unless adequately controlled by medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/07/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 3476 0
Commercial sector/Industry
Name [1] 3476 0
CNSBio Pty Ltd
Country [1] 3476 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
CNSBio Pty Ltd
Address
Suite 1, 651 Victoria St
Abbotsford, 3067
Victoria
Country
Australia
Secondary sponsor category [1] 3119 0
None
Name [1] 3119 0
Address [1] 3119 0
Country [1] 3119 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5506 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 5506 0
63-65 Commercial Road Melbourne 3004 Victoria
Ethics committee country [1] 5506 0
Australia
Date submitted for ethics approval [1] 5506 0
Approval date [1] 5506 0
01/05/2008
Ethics approval number [1] 5506 0
97/08
Ethics committee name [2] 5909 0
St Vincents Hospital Human Research Ethics Committee
Ethics committee address [2] 5909 0
St Vincents Hospital
Ethics committee country [2] 5909 0
Australia
Date submitted for ethics approval [2] 5909 0
Approval date [2] 5909 0
14/05/2008
Ethics approval number [2] 5909 0
08/81

Summary
Brief summary
Painful HIV-SN is a neurological complication of HIV infection that can result from either the HIV disease process itself and/or from the use of some of the anti-retroviral medications that are used to treat HIV. There has been considerable research into the treatment of painful HIV-SN neuropathy. However, treatment with currently available pain killing medications rarely renders the patient pain free and the use of medications may be limited by side effects.

This current research project is only being offered to the participants who have taken part in the previous research project entitled “A placebo controlled multiple dose research project of Flupirtine for the treatment of painful HIV-SN”.

The previous study has the protocol number CNSBio 01/07. “CNSBio 01/07” is investigating the short-term (one week) effectiveness and safety of the pain killing medication Flupirtine when taken in combination with opioids for the treatment of painful HIV-SN. CNSBio 01/07 is not yet completed and the results of this clinical trial are not yet available.

The purpose of this research project is to investigate further if the drug Flupirtine is a safe and effective treatment for HIV-SN when taken in combination with opioids for longer than a week (up to one year).

Flupirtine is an experimental treatment. This means that currently the drug is not an approved treatment for painful HIV-SN in the United States by the Food and Drug Administration (FDA) or in Australia by the Therapeutic Goods Administration (TGA). It is however approved for the treatment of back pain, muscle stiffness and pain associated with surgery and arthritis in Germany, Russia, Portugal, China and Brazil. CNSBio Pty Ltd is sponsoring the current research project with the aim of developing Flupirtine for the treatment of painful HIV-SN in Australia and America if flupirtine proves to be safe and effective in this context.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28662 0
Address 28662 0
Country 28662 0
Phone 28662 0
Fax 28662 0
Email 28662 0
Contact person for public queries
Name 11819 0
Dr. Claudia Gregorio-King
Address 11819 0
Suite 1, 651 Victoria St
Abbotsford, 3067
Victoria
Country 11819 0
Australia
Phone 11819 0
03-8663 7301
Fax 11819 0
03-9421 0444
Email 11819 0
[email protected]
Contact person for scientific queries
Name 2747 0
Dr. Catherine Cherry
Address 2747 0
Infectious Diseases
Level 2
Burnet Institute
Commercial Road
Melbourne VIC 3004
Country 2747 0
Australia
Phone 2747 0
03-9282-2278
Fax 2747 0
03-95302836
Email 2747 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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