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Trial registered on ANZCTR


Registration number
ACTRN12615000013561
Ethics application status
Approved
Date submitted
16/12/2014
Date registered
9/01/2015
Date last updated
9/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized, Double-Blind, Crossover, Phase IIa Study Comparing a Single-Application TPM (registered trademark)/Oxycodone Patch versus Vehicle Patch on pain intensity in the Topical Treatment of Patients with Postherpetic Neuralgia
Scientific title
A Randomized, Double-Blind, Crossover, Phase IIa Study Comparing a Single-Application TPM/Oxycodone Patch versus Vehicle Patch in the Topical Treatment of Patients with Postherpetic Neuralgia
Secondary ID [1] 285815 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-herpetic neuralgia 293717 0
Condition category
Condition code
Anaesthesiology 294020 294020 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a Phase IIa, double-blind, randomized, 2 period crossover study in patients with PHN Eligible patients will be randomized in a 1:1 ratio to receive either POH001-05 (23.4 mg of oxycodone in a 40 cm2 patch) or placebo (vehicle) patch in Treatment Period 1. The patch will be applied on Visit Day 1 and will remain for 72 hours. Between Treatment Period 1 and 2, there will be a 10 day washout period. During Treatment Period 2, patients will cross over to receive the second treatment (i.e., either POH001-05 patch or vehicle patch), whichever treatment was not received during Treatment Period 1. The second patch will remain 72 hours. Each patch will be assessed for adherence and durability before it is removed by study site staff.
Intervention code [1] 290787 0
Treatment: Drugs
Comparator / control treatment
Placebo (vehicle patch)
Control group
Placebo

Outcomes
Primary outcome [1] 293796 0
Change from baseline of average pain intensity scores assessed using NPRS between Treatment Period 1 and Treatment Period 2 at 24 hours and 72 hours.
Timepoint [1] 293796 0
Changes in NPRS scores between Treatment Period 1 and Treatment Period 2 at 24 hours and 72 hours.
Secondary outcome [1] 312002 0
Change from baseline of AVERAGE pain intensity scores assessed using the NPRS
Timepoint [1] 312002 0
Change from baseline between Treatment Period 1 and Treatment Period 2 at 48 hours.
Secondary outcome [2] 312003 0
Change from baseline of WORST pain intensity scores assessed using NPRS
Timepoint [2] 312003 0
Change from baseline between Treatment Period 1 and Treatment Period 2 at 24 hours, 48 hours and 72 hours
Secondary outcome [3] 312004 0
Change from baseline of AVERAGE daily pain intensity scores assessed using the NPRS
Timepoint [3] 312004 0
Change from baseline between Treatment Period 1 and Treatment Period 2 from 72 hours until 168 hours after patch removal. During the washout phase after patch removal, the patients continue to take their daily pain scores to:
- assess any ongoing local effect after patch removal;
- keep patients in the habit of maintaining their daily diary.
Secondary outcome [4] 312005 0
Change from baseline in Neuropathic Pain Symptom Inventory (NPSI)
Timepoint [4] 312005 0
Change from baseline (prior to each patch application) to at least 30 minutes after each patch is removed
Secondary outcome [5] 312006 0
Changes over time in Oxycondone/noroxycodone plasma concentration
Timepoint [5] 312006 0
Baseline then 24 hours and 72 hours after patch application
Secondary outcome [6] 312092 0
Changes over time in clinical laboratory parameters (haematology, biochemistry, urinalysis)
Timepoint [6] 312092 0
Baseline and 72 hours after patch application
Secondary outcome [7] 312093 0
Changes over time in Electrocardiogram results
Timepoint [7] 312093 0
Baseline and 72 hours after patch application
Secondary outcome [8] 312094 0
Changes over time in physical examination findings (general appearance, skin, head, eyes, ears, nose, throat, neck and thyroid, chest and lungs, heart/vascular, musculoskeletal, abdomen and vital signs)
Timepoint [8] 312094 0
Baseline and 72 hours after patch application
Secondary outcome [9] 312096 0
Changes over time in neurological findings (assessment of mental status, gross motor strength, sensory assessment, and reflexes)
Timepoint [9] 312096 0
Baseline and 72 hours after patch application
Secondary outcome [10] 312097 0
Signs of cardio-respiratory or central nervous system depression will be evaluated by sedation score monitoring
Timepoint [10] 312097 0
24 hours and 72 hours after patch application
Secondary outcome [11] 312098 0
Skin irritation assessment
Timepoint [11] 312098 0
30 minutes after each patch removed

Eligibility
Key inclusion criteria
Patients with moderate to severe PHN pain present for at least 6 months after onset of herpes zoster (HZ) skin rash at the time of Screening.

Patients must have a NPRS average pain over the last 24 hours of more than 3 and less than 10 for 3 consecutive days prior to Baseline Visit

Patients must be willing and able to stop all protocol prohibited chronic current pain therapy for the duration of study
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Significant pain due to causes other than PHN

PHN painful areas located only on the face, above hairline of scalp, and / or in proximity to mucous membranes.

Any history of a dermatological condition or recurrent generalized skin disorder in the area to be treated within the last 5 years, including psoriasis, eczema or any other skin condition that might interfere with study assessments.

Current or recent use of any topically applied pain medication, such as non-steroidal anti-inflammatory drugs, aspirin, menthol, methyl salicylate, local anesthetics (including Lidoderm(registered trademark) patch), steroids, low-concentration capsaicin products on the painful areas within 3 days prior to Baseline assessment of pain and during the study.

Receiving treatment with more than one high dose medication for pain, such as anticonvulsants, within 10 days prior to Baseline assessment of pain and during the study.

Use of opioids (e.g. oxycodone, tramadol) within 10 days prior to Baseline assessment of pain and during the study.

Use of Central Nervous System (CNS) depressants including: neuroleptics, tranquillizers, skeletal muscle relaxants, sedating antihistamines within 30 days prior to Baseline assessment of pain and during the study. Exception: short acting night sedatives like benzodiazepines and non-benzodiazepines in small doses (e.g. sleep aids for insomnia) are allowed in consultation with the Medical Monitor (MM).

Antidepressant medications are allowed for anxiety and depression, if given on stable doses for a minimum of 6 months prior to Baseline assessment of pain and during the study. Such treatments should not be changed during the study without consultation with the MM. Exception: (TCA in dose up to 75 mg/ day or duloxetine [60 mg maximum daily] or venlafaxine [150 mg daily]) are permitted during the study

Use of neurotropin, N-methyl-D-aspartate receptor antagonists (dextromethorphan, ketamine, memantine, etc), muscle relaxants, sodium channel blockers (mexiletine, etc), centrally acting sympatholytic agents (clonidine, etc), and prostaglandin and related products (prescribed for PHN) 30 days prior to Baseline assessment of pain and during the study.

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)
PHN patients will be randomly allocated (via an online centrally randomization module) to receive either:
1. Oxycodone patch at treatment period 1 followed by vehicle (placebo) patch at treatment period 2
OR
2. Vehicle (placebo)patch at treatment period 1 followed by Oxycodone patch at treatment period 2
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A statistician who is not directly involved in the study or analysis of study results will prepare the study randomization code in a Statistical Analysis System (SAS) database. A randomization blocking scheme will be used to ensure that the balance between the treatment groups is maintained. Emergency Code Break will be possible in case of an emergency after consultation with the Medical Monitor.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Approximately 46 screened patients are needed (assuming an approximate 30-40 percent screen failure rate) to yield approximately 28 randomized patients (assuming a 20 percent drop-out rate) for a total of 22 evaluable patients (11 patients per treatment sequence). These calculations are based on a mean difference in NPRS at 72 hours of 1.4 units in the vehicle arm and 1.8 units in the TPM (registered trademark) /Oxycodone arm; a 1-sided test significance level of 0.05 with 80 percent power; standard deviation (SD) of 0.7; and a crossover analysis of variance (ANOVA) sqrt (MSE) of 0.495.

All statistical processing will be performed using Statistical Analysis System (SAS(registered trademark)) unless otherwise stated. Analyses will be of a descriptive nature. Descriptive statistics will consist of, summary statistics (number of observations, mean, standard error (SE), SD, minimum, median, and maximum) for continuous data and frequency counts and percentages for categorical data. For systemic exposure data, descriptive statistics will also include the coefficient of variation. Depending on the study population, data compiled up to the point of discontinuation will be used for analysis. Patients who are withdrawn prematurely from the study treatment will be included in all analyses (up to the date of withdrawal), regardless of the duration of treatment. There will be no imputation for missing data. Data will be summarized using descriptive statistics by treatment group. All data will be presented in patient data listings

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA,VIC
Recruitment hospital [1] 3269 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 3271 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 3272 0
Westmead Hospital - Westmead
Recruitment hospital [4] 4306 0
Linear Clinical Research - Nedlands
Recruitment hospital [5] 4307 0
Hunter Clinical Research - Broadmeadow
Recruitment hospital [6] 4308 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 10464 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 10465 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [3] 10460 0
2145 - Westmead
Recruitment postcode(s) [4] 10463 0
2292 - Hamilton North
Recruitment postcode(s) [5] 10462 0
3004 - St Kilda Road Melbourne
Recruitment postcode(s) [6] 10461 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 290429 0
Commercial sector/Industry
Name [1] 290429 0
Phosphagenics Pty Ltd
Address [1] 290429 0
11 Duerdin Street, Clayton VIC 3168
Country [1] 290429 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Phosphagenics Pty Ltd
Address
11 Duerdin Street, Clayton VIC 3168
Country
Australia
Secondary sponsor category [1] 289141 0
None
Name [1] 289141 0
Address [1] 289141 0
Country [1] 289141 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292111 0
Belberry Human Research Ethics Committee
Ethics committee address [1] 292111 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 292111 0
Australia
Date submitted for ethics approval [1] 292111 0
05/11/2014
Approval date [1] 292111 0
02/12/2014
Ethics approval number [1] 292111 0

Summary
Brief summary
This is a research study to see if the TPM (registered trademark)/Oxycodone Patch (“study drug patch”) is safe and effective in treating participants with PHN compared to a patch which contains no Oxycodone but includes all of the other non-active components of the TPM (registered trademark)/Oxycodone Patch (“placebo patch” or “vehicle patch”).
Oxycodone is an analgesic (pain reliever) which has been used, in tablet form, for the treatment of longstanding (chronic) moderate to severe pain, for many years. In tablet form it acts via the blood system. The patch also contains a form of vitamin E, called Tocopheryl Phosphate Mix (TPM), which can help some medications absorb across the skin.
The purpose of this study is to find out whether the study drug patch provides pain relief when applied to an affected painful area in participants with PHN when compared to a vehicle patch. The study drug patch is designed to treat the area of reported pain ‘locally’ (at the site of pain in the skin) rather than ‘systemically’ (via the blood system). This TPM helps the drug to enter through the skin.
Study participants will be required to wear a patch containing oxycodone (study drug patch) on one occasion and a vehicle patch on another occasion. Participants will be required to wear each patch for 3 days (approx. 72 hours) at the site of worst PHN pain.

In addition, this study will determine how safe the patch is:
1. measuring the level of oxycodone that enters into blood (this is expected to be low and thus avoiding issues associated with euphoria, sedation and addiction)
2. monitoring symptoms that may be experienced while wearing the patch
3. observing results from assessments carried out during the course of the study
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 53378 0
Dr Charles Brooker
Address 53378 0
Royal North Shore Hospital,
Pain Management & Research Centre,
Douglas Building,
Royal North Shore Hospital
St. Leonards,
New South Wales 2065
Country 53378 0
Australia
Phone 53378 0
+61 2 9463 1533
Fax 53378 0
+61 2 9463 1003
Email 53378 0
charles.brooker@sydney.edu.au
Contact person for public queries
Name 53379 0
Mr Ross Murdoch
Address 53379 0
Phosphagenics Pty Ltd
11 Duerdin Street,
Clayton VIC 3168
Country 53379 0
Australia
Phone 53379 0
+61 3 9565 1142
Fax 53379 0
Email 53379 0
rmurdoch@phosphagenics.com
Contact person for scientific queries
Name 53380 0
Dr Paul Gavin
Address 53380 0
Phosphagenics Pty Ltd
11 Duerdin Street,
Clayton VIC 3168
Country 53380 0
Australia
Phone 53380 0
+61 3 9565 1139
Fax 53380 0
Email 53380 0
pgavin@phophagenics.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary