Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000315314
Ethics application status
Approved
Date submitted
12/09/2007
Date registered
1/07/2008
Date last updated
3/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
A placebo controlled multiple dose study of flupirtine in the treatment of painful Human Immunodeficiency Virus (HIV) -associated neuropathy.
Scientific title
A placebo controlled, randomised, double blind study to assess the safety and efficacy of multiple doses of oral flupirtine for the treatment of painful HIV-associated neuropathy.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
painful HIV-associated neuropathy 2027 0
Condition category
Condition code
Infection 2117 2117 0 0
Acquired immune deficiency syndrome (AIDS / HIV)
Neurological 2118 2118 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are six treatment groups in this study;
A. Placebo to be taken orally four times daily (QID)
B. Placebo to be taken orally QID
C. 25mg flupirtine to be taken orally (QID)
D. 50mg flupirtine to be taken orally QID
E. 75mg flupirtine to be taken orally QID
F. 100mg flupirtine to be taken orally QID

Patients will be randomised in a double blind fashion to receive each of the six treatment groups.

Patients will be asked to take one of the doses of the study drug for one week, followed by a week where no study drug is taken. This will be followed by another week of study drug, and so on until each of the study drug doses is taken.

Patients will be exposed to the study drug for a total of 6 weeks over a 13 week period.
Intervention code [1] 1842 0
Treatment: Drugs
Comparator / control treatment
Double Placebo (lactose)
Control group
Placebo

Outcomes
Primary outcome [1] 2951 0
To assess the efficacy of flupirtine for the treatment of pain due to HIV-Sensory Neuropathy (SN), in patients who have pain inadequately controlled by opioids.

Efficacy will be assessed using patient responses to the Brief Pain Inventory and pain rating on a visual analogue safety.
Timepoint [1] 2951 0
Study participants are assessed weekly for 13 weeks.
Primary outcome [2] 2952 0
To assess the safety of flupirtine for the treatment of pain due to HIV-SN, in patients who have pain inadequately controlled by opioids.

Safety will be assessed using patient rating of reported side effects and adverse events, and from the results of blood, liver and renal function tests.
Timepoint [2] 2952 0
Study participants are assessed weekly for 13 weeks.
Secondary outcome [1] 4997 0
To describe doses of flupirtine and opioids which, when used concomitantly increase quality of life (QoL).

QoL will be assessed using patient responses to a health and activity survey.
Timepoint [1] 4997 0
Study participants are assessed weekly for 13 weeks.
Secondary outcome [2] 7322 0
To describe doses of flupirtine and opioids which, when used concomitantly increase pain relief.

Pain relief will be assessed using patient responses to the Brief Pain Inventory and pain rating on a visual analogue safety.
Timepoint [2] 7322 0
Study participants are assessed weekly for 13 weeks.

Eligibility
Key inclusion criteria
1.Between 18 and 80 years of age and able to speak and understand English
2.Documented evidence of HIV infection.
3.Documented baseline diagnosis of painful HIV-Sensory Neuropathy (HIV-SN) resulting from HIV disease and/or antiretroviral drug exposure for at least 3 months prior to the beginning of the study .
4.The pain is classified as neuropathic during screening according to the neuropathic pain questionnaire.
5. Average score (as assessed by a modified brief pain inventory) for HIV-SN associated pain during screening of > 5.
6.Must be on a stable pain medication regimen for at least 21 days prior to Day -1 of the study and willing to maintain medications at same stable dose(s) and schedule throughout the study.
7.Must be taking opioids for 3 months prior to the trial and must be willing to maintain opioid use at same stable dose(s) and schedule throughout the study (excluding the use of break-through pain medication).
8.Female subjects with child-bearing potential must have a negative urine beta human chorionic gonadotropin (hCG) pregnancy test, to be performed within 7 days of study enrolment, and each week before study drug is to be ingested (total of 7 times)
9.All subjects must 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 study drug exposure.
10.Be willing and able to comply with protocol requirements for the duration of study participation. (Such requirements include, but are not limited to: completing a daily pain diary, attending all study visits which includes refraining from extensive travel during study participation.)
11.Subjects must sign an informed consent form for this study approved by the Investigator’s Institutional ethics committee.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 Are Pregnant or breast feeding
2.Suffer from significant lactose intolerance that in the opinion of the investigator would interfere either with the ability to complete the study or the evaluation of the investigative drugs safety and efficacy
3.Are taking warfarin
4.Have myasthenia gravis or epilepsy
5.Have significant uncompensated abnormal liver or kidney function (liver and renal function tests three times (or greater) than the upper limit for the normal reference ranges).
6.Have an active substance abuse or psychiatric problem that in the opinion of the investigator is deemed likely to interfere with the study.
7.Have started or stopped treatment with one or more of the known neurotoxic antiretroviral agents during the eight weeks prior to Day -1 os the study.
8.Have evidence of another contributing cause for peripheral neuropathy, e.g. current uncontrolled diabetes mellitus, hereditary neuropathy, or treatment (within 90 days prior to Screening Visit) with any drug that may have contributed to the sensory neuropathy .
9.Have hypertension, unless adequately controlled by medication.
10.Have significant pain of an etiology other than painful HIV-SN which the investigators deem likely to interfere with judging HIV-SN related pain.
11.Have had any implanted medical device (spinal cord stimulator, intrathecal pump or peripheral nerve stimulator), nerve block or anesthetic procedure to the presumed site of nerve damage for the treatment of neuropathic pain within two weeks of the study.
12.Have significant medical abnormalities or conditions that in the opinion of the investigator would interfere either with the ability to complete the study or the evaluation of the investigative drugs safety and efficacy.
13.Have a recent history of a significant medical-surgical intervention that in the judgment of the Investigator would interfere either with the ability to complete the study or the evaluation of the investigative drugs safety and efficacy.
14.Are to be commenced on anticonvulsants or antidepressants during the course of the trial, or are likely to require the doses of these drugs to be altered during the trial.

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)
Eligibility criteria will be assessed and eligible subjects enrolled into the study by the principal investigator.

Master randomisation schedules have been sent in sealed envelopes to The Clinical Trial Pharmacy. Staff of The Clinical Trial Pharmacy will, upon request from the principal investigator, randomise all patients enrolled in the study according to the master randomisation schedule.

Allocation to the treatment schedule for each study participant will be concealed from the study investigators, and the participant at all times.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The master randomisation schedule has been generated by a qualified statistician. Patients have been randomised by a partially balanced Latin square design whereby;
(i) each patient receives each treatment just once (A - F), and
(ii) no treatment (A - F) occurs more than one less than any other treatment in any treatment period.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/09/2007
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)
Recruitment postcode(s) [1] 430 0
3004

Funding & Sponsors
Funding source category [1] 2619 0
Commercial sector/Industry
Name [1] 2619 0
CNSBio Pty Ltd
Country [1] 2619 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
CNSBio Pty Ltd
Address
Level 15
1 Nicholson Street
Melbourne 3000
Victoria
Country
Australia
Secondary sponsor category [1] 2052 0
None
Name [1] 2052 0
N/A
Address [1] 2052 0
Country [1] 2052 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4538 0
The Alfred Hospital Ethics Committee
Ethics committee address [1] 4538 0
Ethics committee country [1] 4538 0
Australia
Date submitted for ethics approval [1] 4538 0
Approval date [1] 4538 0
20/08/2007
Ethics approval number [1] 4538 0
161/07
Ethics committee name [2] 5908 0
St Vincents Hospital Human research Ethics Committee
Ethics committee address [2] 5908 0
Ethics committee country [2] 5908 0
Australia
Date submitted for ethics approval [2] 5908 0
Approval date [2] 5908 0
14/07/2008
Ethics approval number [2] 5908 0
08/080

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27656 0
Address 27656 0
Country 27656 0
Phone 27656 0
Fax 27656 0
Email 27656 0
Contact person for public queries
Name 11031 0
Claudia Gregorio-King
Address 11031 0
Level 15
1 Nicholson Street
Melbourne VIC 3001
Country 11031 0
Australia
Phone 11031 0
03-8663 7301
Fax 11031 0
03-9639 3022
Email 11031 0
[email protected]
Contact person for scientific queries
Name 1959 0
Dr. Catherine Cherry
Address 1959 0
Infectious Diseases
Level 2
Burnet Institute
Commercial Road
Melbourne VIC 3004
Country 1959 0
Australia
Phone 1959 0
03- 9282-2278
Fax 1959 0
03-9530-2836
Email 1959 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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