E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study population is a healthy population who are voluntarily participating in this clinical trial. This study will compare the PK profile after e.c. and oral application of the same dosage of ketoprofen and in a dosage range as intended for clinical use in OA. It will also indicate whether application on muscle will result in a different PK profile as compared to application on a joint. The intended use for Diractin® will be osteoarthritis of the knee |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028332 |
E.1.2 | Term | Muscle soreness |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary: – Evaluation of reduction in pain caused by muscle soreness after application of 200 mg ketoprofen from Diractin® per b.i.d. in comparison to placebo. – Evaluation of reduction in pain caused by muscle soreness after application of 100 mg ketoprofen from Diractin® b.i.d. in comparison to placebo.
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E.2.2 | Secondary objectives of the trial |
Secondary: –Evaluation of reduction in pain caused by muscle soreness after application of 100 mg ketoprofen from oral application b.i.d. in comparison to placebo;Evaluation of reduction in pain caused by muscle soreness after application of 200 mg ketoprofen from Diractin® in comparison to 100 mg ketoprofen from oral application b.i.d.; Evaluation of reduction in pain caused by muscle soreness after application of 100 mg ketoprofen from Diractin® in comparison to 100 mg ketoprofen from oral application b.i.d.; Evaluation of the plasma pharmacokinetics after single application; 100 mg ketoprofen from Diractin®; 200 mg ketoprofen from Diractin®;100 mg from oral ketoprofen; Comparison of the plasma pharmacokinetics after 7 days of b.i.d. application of –100 mg ketoprofen from Diractin® –200 mg ketoprofen from Diractin® –100 mg from oral ketoprofen –Evaluation of safety and tolerability of Diractin® in comparison to placebo and oral ketoprofen
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Understands nature and provision of the study • Have been informed about the study by the investigator and gave signed and dated informed consent prior to participation • Male and female subjects • Age 18-55 years • Subjects in good health as determined by the Investigator • Woman of childbearing potential using reliable methods of contraception with a low failure rate (i.e. less than 1% per year),e.g. implants, injectables, combined oral contraceptives, reliable intrauterine-devices, vasectomised/ infertile partner or surgically sterile (uterus removed or both tubes tied) or postmenopausal (at least 2 years without periods) • Muscle soreness with a pain score of at least 3 on a 10 point categorical pain scale at 12-16h after exercise
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E.4 | Principal exclusion criteria |
• Investigator or any other team member involved directly or indirectly in the conduct of the clinical trial • Subjects who are inmates of psychiatric wards, prisons, or other state institutions • Participation in another clinical trial within the last 30 days and during study • Not willing to refrain from exposing target areas after treatment to excessive ultraviolet light (solar radiation or solarium) • Pregnancy or lactation • History of dermal allergic reactions • Known hypersensitivity or allergy (including photoallergy) to NSAID´s including ketoprofen, and ingredients used in pharmaceutical products • Alcohol or drug abuse • Malignancy within the past 2 years • Skin lesions, dermatological diseases or tattoo in the treatment area • Major surgery 3 months before enrolment • NSAID idiosyncrasy • Impaired haematopoesis and coagulation • Gastric and duodenal ulcer and gastrointestinal bleedings • Systemic lupus erythematodes, mixed connective tissue disease • Major heart disease / uncontrolled hypertension • Hepatic failure with ALT and/or AST > 2.0 ULN • Renal failure with serum creatinine levels > 1.5 milligrams/deciliter (mg/dL) • Varicosis, thrombophlebitis and other vascular disorders of the lower extremities • Major traumatic lesions (e.g. fracture, tendon or muscle ruptures) of the musculo-sceletal system of the lower limbs • HIV - Infection • Hepatitis B or C • Blood donation one month before screening and during the study • Asthma bronchiale • Medication during the study observation period (Screening to final Visit) containing o Digoxin o Phenytoin o Lithium o Glucocorticoids o NSAID´s o Probenecid o Sulfinpyrazon • Diuretics during the study observation period (Screening to final Visit) • ACE inhibitors during the study observation period (Screening to final Visit) • Anticoagulants during the study observation period (Screening to final Visit) • Methotrexat during the study observation period (Screening to final Visit) • Antacids during the study observation period (Screening to final Visit)
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint : The area under the curve of muscle pain scores evaluated by a 10 point categorical pain scale at 15 min, 30 min, 1h, 2h, 4h, 8h, 12 h after the first application (the 12 h evaluation should be done immediately the before 2nd application) and then always before the next application. Secondary endpoints: The area under the curve of muscle soreness within the first 12 hours after the first application. AUCss, Cmax,ss, Cmin,ss for day 7 assessments AUC0-12, Cmax for day 1 assessments
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | No |
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) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
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 | No |
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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End of study is defined by Database Closure |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 29 |