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Trial registered on ANZCTR


Registration number
ACTRN12608000574347
Ethics application status
Approved
Date submitted
15/10/2008
Date registered
12/11/2008
Date last updated
22/01/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
A proof of concept study comparing the skin penetration abilities of the novel penetration enhancer Tocopheryl Phosphate Mix (TPM)/Diclofenac compared with Voltaren Gel
Scientific title
A Phase I study to assess the bioavailability of topically applied Diclofenac in combination with the novel penetration enhancer Tocopheryl Phosphate Mix (TPM), compared with Voltaren Gel in 12 healthy male or female participants.
Secondary ID [1] 283964 0
N/A
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Transdermal drug delivery 3832 0
Musculoskeletal conditions 3965 0
Condition category
Condition code
Musculoskeletal 4021 4021 0 0
Other muscular and skeletal disorders
Musculoskeletal 4161 4161 0 0
Osteoarthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subjects will be dosed once a week over a 4 week period and will receive each treatment regime. Subjects will be randomised at their Period 1 Visit (Day 1) to receive either a single dose of 1.0g TPM/Diclofenac HS (high solvent), a single dose of 2.0g TPM/Diclofenac LS (low solvent) or the reference treatment, a single dose of 2.0g Voltaren Gel. This single dose equates to an applied dose of 20mg of Diclofenace. The single topical dose will be applied to the subjects back area at their Period 1 Visit (Day 1). At the Period 2 Visit (Day 8) subjects will have been randomally allocated to receive either a single dose of 1g TPM/Diclofenac HS (high solvent), a single dose of 2.0g TPM/Diclofenac LS (low solvent) or the reference treatment, a single dose of 2.0g Voltaren Gel. This single dose equates to an applied dose of 20mg of Diclofenace. This treatment will be an alternate treatment to the treatment they received at their Period 1 Visit. Subjects will receive a single topical dose to their back area at their Period 2 Visit (Day 8). At the Period 3 Visit (Day 15) subjects will have been randomally allocated to receive either a single dose of 1.0g TPM/Diclofenac HS (high solvent), a single dose of 2.0g TPM/Diclofenac LS (low solvent) or the reference treatment, a single dose of 2.0g Voltaren Gel. This single dose equates to an applied dose of 20mg of Diclofenace. This treatment will be an alternate treatment to the treatments they received at their Period 1 and 2 Visits. Subjects will receive a single topical dose to their back area at their Period 3 Visit (Day 15). Therefore over Periods 1, 2 and 3 Visits subjects will have received a single dose of all three treatments TPM/Diclofenac HS (high solvent), TPM/Diclofenac LS (low solvent) and the reference treatment Voltaren Gel in a randomised cross-over design. At the Period 4 Visit (Day 22) subjects will receive all three treatments TPM/Diclofenac HS (high solvent), TPM/Diclofenac LS (low solvent) and the reference treatment Voltaren Gel simultaneously to 3 different areas of their back on this Visit 22 study day. Approximately 31.25mg of TPM/Diclofenac HS Gel will be applied topically to the first area of the the subject's back, approximatley 62.5mg of TPM/Diclofenac LS Gel will be applied topically to the second area of the subject's back and 62.5mg of the reference treatment Voltaren Gel will be applied topically to the third area of the subject's back. This equates to a total applied dose of 2.5mg of diclofenac for each formulation (7.5mg total).
Intervention code [1] 3556 0
Treatment: Drugs
Comparator / control treatment
The Reference Treatment is Voltaren Gel. Subject's will receive a single topical 2.0g dose of Voltaren Gel at either Period 1 (Day 1), Period 2 (Day 8) or Period 3 (Day 15) of the study. This equates to an applied dose of 20mg of Diclofenac. They will be randomised to receive a single dose of this reference treatment at one of the 3 visits over this 3 week period in a open label, randomised cross-over design. At the Period 4 Visit (Day 22) subject's will receive a single topical application of 62.5mg Voltaren Gel applied to the third area of the subject's back. This equates to a total applied dose of 2.5mg.
Control group
Active

Outcomes
Primary outcome [1] 4922 0
To determine the single dose pharmacokinetics of TPM/Diclofenac HS and TPM/Diclofenac LS. Eight blood samples will be collected in Periods 1, 2 and 3 for assessment of systemic pharmacokinetics.
Timepoint [1] 4922 0
Weeks 1, 2 and 3: 8 Blood samples on each study day for plasma pharmacokinetics with be collected pre-dose, then 0.5, 1, 2, 3, 4, 5 and 6 hours post-dose.
Secondary outcome [1] 8304 0
To compare the systemic pharmacokinetics of TPM/Diclofenac HS, TPM/Diclofenac LS and Voltaren Gel after topical application. Eight blood samples will be collected in Periods 1, 2 and 3 for assessment of systemic pharmacokinetics.
Timepoint [1] 8304 0
Weeks 1, 2 and 3: 8 Blood samples on each study day for plasma pharmacokinetics will be collected pre-dose, then 0.5, 1, 2, 3, 4, 5 and 6 hours post-dose. Week 4: Skin stripping will be performed pre-dose, then 1, 2, 4 and 6 hours post-dose.
Secondary outcome [2] 8305 0
To assess the safety and tolerability of TPM/Diclofenac HS and TPM/Diclofenac LS compared with Voltaren Gel. Clinical trial staff will monitor each participant for adverse events during the trial. All adverse events reported between commencement of study treatment and follow-up will be recorded in the Adverse Event Source Document. An adverse event is any untoward medical event experienced by a subject during the course of a clinical trial whether or not it is related to the investigational product. Examples of an adverse event may be a headache or a rash. The Principal Investigator or delegate will review each adverse event and will determine the 'relationship to treatment' classifying it as either not related, possible, probable or definite. For example a rash at the treatment site that developed after dosing would be determined to be definitely related to treatment.
Timepoint [2] 8305 0
Clinical trial staff will monitor each participant for adverse events during the trial. All adverse events reported between commencement of study treatment and follow-up with be recorded in the Adverse Event Source Document and reviewed by the Principal Investigator.
Secondary outcome [3] 8306 0
To compare the dermatopharmacokinetics of TPM/Diclofenac HS, TPM/Diclofenac LS and Voltaren Gel after topical application. Skin stripping will be performed at 5 time-points to collect samples for assessment of Dermatopharmacokinetics.
Timepoint [3] 8306 0
Week 4: Skin stripping will be performed pre-dose, then 1, 2, 4 and 6 hours post-dose.

Eligibility
Key inclusion criteria
Inclusion Criteria:
1. Mare or female, aged between 18 to 55 years, inclusive.
2. Healthy, defined as free from clinically significant illness or disease as determined by their medical history, physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory determinations.
3. Have Body Mass Index (BMI) 19-30kg/m2 and weight > 50 kg.
4. Have adequate venous access on left or right arm to allow collection of a number of samples.
5. Are willing to undergo frequent blood sampling.
6. Fluent in the English language.
7. Able to understand and sign the written Informed Consent Form.
8. Willing to follow the protocol requirements and comply with protocol restrictions.
9. Individuals free of any dermatological or systemic disorder that will interfere with the results, at the discretion of the Investigator.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion Criteria:
1. Hypersensitivity to, or persons considered at increase risk of hypersensitivity to diclofenac; other non-steroidal anti-inflammatory drugs (NSAIDS) such as arylalkanoic acids (indomethacin), salicylates (aspirin), profens (ibuprofen), fenamic acids, pyrazolidine derivates (phenazone), ozicams (piroxicam), COX-2 inhibitors (celecoxib), sulphonanilides (nimesulid); propylene glycol, isopropyl alcohol or other ingredients of the gel; or any other medications.
2. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs or any other medications.
3. Treatment with any medication that may mask or interfere with the results, including: another non-steroidal anti-inflammatory drug (NSAIDS), aspirin, corticosteroids, cyclosporine, methotrexate, digoxin, lithium, warfarin or any other anticoagulants or blood thinning medications.
4. Participation in any clinical trial during the 30 days preceding the screening period for this trial.
5. Pregnant or nursing females; females of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined in section 9.4.6 from at least 14 days prior to the first dose of trial medication until completion of follow-up procedures.
6. Blood donation within 28 days prior to screeing.
7. is planning to have surgery, including dental surgery at any point during the trial.
8. Individuals diagnosed with chronic, contagious viral infections such as Human Immunodeficiency Virus (HIV), hepatitis or herpes.
9. Participants diagnosed with diabetes mellitus, stomach and/or duodennal ulceration or gastrointestinal bleeding, hemorrhoids, inflammative intestinal disorders such Crohn's disease or ulcerative colitis, kidney stones, renal insufficiency, cardiovascular failure, fluid retention (swelling of feet or edema), anemia, hepatic porphyria, asthma, epilepsy, Parkinson's disease or any disease that would increase the risk associated with study participation.
10. Participants with a history of any form of skin cancer, melanoma, lupus, psoriasis, connective tissue disease, diabetes or any disease that would increase the risk associated with study participation.
11. Individuals diagnosed with chronic skin allergies.
12. Individuals with blemishes, nevi, sunburn, suntan, scars, moles, active dermal lesions, uneven pigmentation in the test sites.
13. Individuals with known hypersensitivity to cosmetic products in general and moisturizers in particular.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

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)

Funding & Sponsors
Funding source category [1] 4013 0
Commercial sector/Industry
Name [1] 4013 0
Phosphagenics Limited
Address [1] 4013 0
Level 2, 90 William Street, Melbourne, Victoria, 3000
Country [1] 4013 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Phosphagenics Limited
Address
Level 2, 90 William Street, Melbourne, Victoria, 3000
Country
Australia
Secondary sponsor category [1] 3605 0
None
Name [1] 3605 0
Address [1] 3605 0
Country [1] 3605 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
The purpose of this study is to compare the penetration of Diclofenac with the penetration enhancer Tocopheryl Phosphate Mix (TPM) across intact skin against a currently marketed treatment Voltaren Gel.
For the first visit you will be randomly allocated to receive a topical application of one of TPM/Diclofenac HS, TPM/Diclofenac LS or Voltaren Gel applied to your back. At the second visit you will receive a topical application of another one of TPM/Diclofenac HS, TPM/Diclofenac LS or Voltaren Gel, different to the treatment you received at the first visit. At the third visit you will receive a topical application of the other one of TPM/Diclofenac HS, TPM/Diclofenac LS or Voltaren Gel, different to the treatments you received at the first and second visits. At the fourth visit, you will receive all three treatments and undergo a procedure called skin stripping to evaluate how well Diclofenac penetrates the skin. For each of the visits you will stay at the study centre for approximately 6 hours after the gel has been applied.
You will then be required to return to the study centre for approximately 1 hour for a follow up visit. Blood samples will be collected in visits 1, 2 and 3 (8 samples per visit) by either cannula or venipuncture. A total of 192 mL of blood will be collected during the study, which includes the amount required for the clinical laboratory tests and for the measurement of Diclofenac in your blood.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29040 0
Prof Professor Allan Evans
Address 29040 0
University of South Australia Level 4, Reid Building, Frome Road, Adelaide, South Australia 5000
Country 29040 0
Australia
Phone 29040 0
+61 8 8302 2310
Fax 29040 0
Email 29040 0
allan.evans@unisa.edu.au
Contact person for public queries
Name 12197 0
Ms Donna Schubert
Address 12197 0
Sansom Institute
University of South Australia
Level 4, Reid Building, Frome Road, Adelaide, South Australia 5000
Country 12197 0
Australia
Phone 12197 0
+61 8 8302 2502
Fax 12197 0
Email 12197 0
donna.schubert@unisa.edu.au
Contact person for scientific queries
Name 3125 0
Prof Professor Allan Evans
Address 3125 0
University of South Australia
Level 4, Reid Building, Frome Road, Adelaide, South Australia 5000
Country 3125 0
Australia
Phone 3125 0
+61 8 8302 2310
Fax 3125 0
Email 3125 0
allan.evans@unisa.edu.au

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