A proof of concept study comparing the skin penetration abilities of the novel penetration enhancer Tocopheryl Phosphate Mix (TPM)/Diclofenac compared with Voltaren Gel
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.
Phosphagenics Limited
12 participants
Oct 17, 2008
Interventional
Conditions
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.
Eligibility
Inclusion Criteria9
- Mare or female, aged between 18 to 55 years, inclusive.
- 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.
- Have Body Mass Index (BMI) 19-30kg/m2 and weight > 50 kg.
- Have adequate venous access on left or right arm to allow collection of a number of samples.
- Are willing to undergo frequent blood sampling.
- Fluent in the English language.
- Able to understand and sign the written Informed Consent Form.
- Willing to follow the protocol requirements and comply with protocol restrictions.
- Individuals free of any dermatological or systemic disorder that will interfere with the results, at the discretion of the Investigator.
Exclusion Criteria13
- 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.
- History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs or any other medications.
- 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.
- Participation in any clinical trial during the 30 days preceding the screening period for this trial.
- 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.
- Blood donation within 28 days prior to screeing.
- is planning to have surgery, including dental surgery at any point during the trial.
- Individuals diagnosed with chronic, contagious viral infections such as Human Immunodeficiency Virus (HIV), hepatitis or herpes.
- 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.
- 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.
- Individuals diagnosed with chronic skin allergies.
- Individuals with blemishes, nevi, sunburn, suntan, scars, moles, active dermal lesions, uneven pigmentation in the test sites.
- Individuals with known hypersensitivity to cosmetic products in general and moisturizers in particular.
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Interventions
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).
Locations(1)
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ACTRN12608000574347