Healthy volunteers
Conditions
Interventions
Trade Name: Pennsaid
Pharmaceutical Form: Cutaneous solution
Sponsors
Nuvo research Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Non-smoking male or female subject aged between 18 and 40 years 2. Body mass index between 20 to 30 kg/m2. 3. Normal findings in the physical examination, 12-lead ECG and vital signs (blood pressure between 100-140/60-90 mm Hg, heart rate between 50-99 beats/minute, temperature between 35.8 and 37.5°C after 5 min rest in supine position). 4. Normal laboratory values unless the investigator does not consider abnormalities to be clinically significant. 5. Written informed consent. 6. Female subjects: negative for pregnancy (as evaluated by serum ß-HCG test). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known history of hypersensitivity to dimethyl sulfoxide and/or diclofenac sodium (e.g. Pennsaid®, Voltaren®, Arthrotec®) and/or related drugs acetylsalicylic acid (e.g. Aspirin®, Excedrin®), ibuprofen (e.g. Motrin®), dimethyl sulfoxide (e.g. Rimso® 50). 2. Known history or presence of cardiac, pulmonary, gastrointestinal, endocrine, musculoskeletal, neurological, hematological, liver or kidney disease, unless deemed not clinically significant by the Principal Investigator or Sub-investigator. 3. Presence of any significant physical or organ abnormality. 4. Presence of skin rashes, skin disorder, or skin conditions (e.g. dermatitis, eczema, psoriasis). 5. Significant trauma or surgery to the thigh and knee including diagnostic arthroscopy. 6. Any history or evidence of psychiatric or psychological disease (including depression) unless deemed not clinically significant by the Principal Investigator or Sub-investigator. 7. Any clinically significant illness during the 4 weeks before this study. 8. Known skin sensitivity to topical applications. 9. Any history of severe allergic reaction (including drugs, food, insect bites, environmental allergens). 10. Significant or recent history of asthma (after 12 years of age). 11. Any subject with a history of drug abuse. 12. Any subject with a recent (less than 1 year) history of alcohol abuse. 13. Use of any prescription medication within 14 days preceding this study (except for hormonal contraceptives). 14. Use of Pennsaid within 30 days preceding this study. 15. Use of over-the-counter (OTC) medication within 7 days preceding this study (except for spermicidal/barrier contraceptive products). 16. Female subjects: evidence of pregnancy or lactation. 17. Any subject who has had blood drawn within 1 month preceding this study. 18. Participation in a clinical trial with an investigational drug within 30 days preceding this study. 19. Any subject who has donated blood within 1 month preceding this study. 20. Any subject who has participated as a plasma donor in a plasmapheresis program within 7 days preceding this study. 21. Subjects who are not willing to continue their regular diet during the entire study period. 22. Intolerance to venipuncture or implantation of the microdialysate probe. 23. Allergy or hypersensitivity against NSAIDs. 24. Renal disease or family history of renal disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Asssess feasibility of using microdialysis for the assessment of local delivery of topical drugs developed for treatment of osteoarthritis in superficial joints. - Does the choice of the application site for the microdialysis study influence the penetration profile of the drug? - Does the tissue pharmacokinetics of the drug following single therapeutic dose predict tissue pharmacokinetics of the drug at steady state? The time-versus-concentration profiles of diclofenac in plasma and in the subdermal layer will be measured after a single dose and at steady state. Pharmacokinetic parameters will be determined using non-compartmental analysis. These pharmacokinetic parameters will be used to determine intra-individual probe-to-probe variability, inter-individual variability, variability between knee and thigh, and differences between single dose and multiple dosing.;Secondary Objective: Additional outcome variable: The time-versus-concentration profiles of DMSO and its metabolite dimethyl sulfone (DMSO2) in plasma and in the microdialysate will be measured after a single dose and at steady state at the same time points as diclofenac The pharmacokinetic parameters calculated for DMSO and DMSO2 will correspond to those of diclofenac. ;Primary end point(s): The project proposes to test the feasibility of using the technique of microdialysis to assess local delivery of topical drugs in healthy volunteers for further research application in the formulation optimization programs. The pharmacokinetics of diclofenac and DMSO together with its metabolite dimethyl sulfone (DMSO2) will be assessed in the subcutaneous layers and plasma following topical application of the test drug after a single dose and at steady state. The influence of the application site for the conduction of the microdialysis study will be additionally examined. The findings of the present pilot study will help to elaborate the optimal study design for further microdialysis studies wit | — |
Countries
Austria
Outcome results
None listed