E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
- 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. |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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).
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | 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 with NUVO topical drug candidates.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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when the 5 study subjects are completed |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |