Bioequivalence Study
Conditions
Brief summary
Study Objectives Primary To evaluate the average bioequivalence in healthy volunteers between medicinal product of Diclofenac Sodium 140mg Medicated Plaster EQI7 in comparison to the reference medicinal product Flector®, applied once and twice a day. Secondary To evaluate pharmacokinetic profile on Day 1, adhesivity, local tolerability and safety of medicinal product Diclofenac Sodium 140mg Medicated Plaster EQI7 in healthy volunteers in comparison to the reference medicinal product Flector®, applied once and twice a day.
Detailed description
Study Objectives Primary To evaluate the average bioequivalence in healthy volunteers between medicinal product of Diclofenac Sodium 140mg Medicated Plaster EQI7 in comparison to the reference medicinal product Flector®, both formulated as topical plasters applied once and twice a day. Secondary To evaluate pharmacokinetic profile on Day 1, adhesivity, local tolerability and safety of medicinal product Diclofenac Sodium 140mg Medicated Plaster EQI7 in healthy volunteers in comparison to the reference medicinal product Flector®, both formulated as topical plasters applied once and twice a day.
Interventions
DRUGDiclofenac Sodium 140mg Medicated Plaster
Part 1: two seven-day study periods, separated by at least 7 days of wash-out. In the first period, a single plaster of Test Drug or Reference Drug will be applied on the back (lumbar region) for seven consecutive days. In the second period, a single plaster of the Reference Drug or Test Drug will be applied on the back (lumbar region) daily for seven consecutive days. Part 2: two seven-day study periods separated by at least 7 days of wash-out. In the first period, the Test Drug or Reference Drug plaster will be applied on the back (lumbar region) twice a day. In the second period, the Reference Drug or Test Drug plaster will be applied on the back (lumbar region) twice a day.
DRUGFlector® topical plaster containing 180 mg of diclofenac hydroxyethylpyrrolidine equivalent to 140 mg of sodium diclofenac
Part 1: two seven-day study periods, separated by at least 7 days of wash-out. In the first period, a single plaster of Test Drug or Reference Drug will be applied on the back (lumbar region) for seven consecutive days. In the second period, a single plaster of the Reference Drug or Test Drug will be applied on the back (lumbar region) daily for seven consecutive days. Part 2: two seven-day study periods separated by at least 7 days of wash-out. In the first period, the Test Drug or Reference Drug plaster will be applied on the back (lumbar region) twice a day. In the second period, the Reference Drug or Test Drug plaster will be applied on the back (lumbar region) twice a day.
Sponsors
Fidia Farmaceutici s.p.a.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Males and females, Caucasian/White aged between 18 and 55 years. 2. BMI between 19 and 29 kg/m² included 3. Normal or non-clinical significant findings on the physical examination 4. Normal or non-clinical significant finding on the laboratory evaluations. Laboratory values outside the normal range will be carefully evaluated by the clinical investigator. Subject showing safety laboratory values outside the normal range, but judged not clinically significant, may be allowed to enter the study. For sodium and potassium no values outside the normal range will be allowed. 5. Willing and able to understand and sign an approved Informed Consent form. 6. If female, they must not be pregnant or breast feeding and using an effective contraception method during the study (hormonal, such as birth control pill, or barrier method, such as condom or diaphragm, or intrauterine, such as spiral).
Exclusion criteria
1. History of alcohol or drug abuse. 2. Smokers of more than 10 cigarettes/day. 3. History of gastrointestinal, renal, hepatic, pulmonary or cardiovascular disease; or history of epilepsy, asthma, diabetes, psychosis or glaucoma. 4. History of allergic response to diclofenac or related drugs, namely non-steroidal anti-inflammatory agents 5. Presence or history of allergies requiring acute or chronic treatment (except seasonal allergic rhinitis) 6. Participation in a previous clinical trial within the past 6 months. 7. Blood donation of 250 ml or more within the past 3 months. 8. Treatment with any known enzyme inhibiting or inducing agents (barbiturates, phenothiazines, etc.) within the past 4 weeks. 9. Positive to HIV test and/or Hepatitis B and C tests. 10. Positive to drugs of abuse qualitative screen in urine. 11. Use of any prescription or over-the-counter medication on a regular basis. 12. Drinking excessive amounts of tea, cacao, coffee and/or beverages containing caffeine (\> 5 cups/day) or wine (\> 0,5 l/day) or spirits (\> 50 ml/day) 13. In the judgement of the Clinical Investigator subjects likely to be not compliant or cooperative during the study. 14. Irritation scale score higher than zero at the sites of application. 15. Presence of skin injuries at the sites of application. 16. An acquired tan (by sun or lamp) in the previous 2 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Css max (ng/mL) of Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 7 through Day 9 | Day 7 through Day 9 | Css max on Day 7 through Day 9 |
| AUCττ (ng/mL*h) of Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 7 through Day 9 | Day 7 through Day 9 | AUCττ on Day 7 through Day 9 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adhesivity of Diclofenac Sodium 140mg Medicated Plaster EQI7 in comparison to Flector® topical plasters applied once and twice a day with a 5-point ordinal scale, where 0= >90%adhered and 4=plaster detached, from Day 1 for the entire study period | From Day 1 for the entire study duration | Adhesivity of plasters with adhesivity 5-point ordinal scale: 0 = \>90% adhered; 1 = \>75% to \<90% adhered; 2 = \>50% to \<75% adhered; 3 =\< 50% adhered but not detached; 4 = Plaster detached, from Day 1 for the entire study period |
| Local tolerability of Diclofenac Sodium 140mg Medicated Plaster EQI7 in comparison to Flector® topical plasters applied once and twice a day, with the irritation8-point scale, where 0=no evidence of irritation and 7=strong reaction, from Day1 onward | From Day 1 for the entire study duration | Local tolerability: irritation 8-point categorical scale:0=no evidence of irritation;1=minimal erythema, barely perceptible;2=definite erythema, readily visible;3=minimal edema or minimal papular response;3=erythema and papules;4=definite edema;5=erythema, edema, and papules;6=vescicular eruption;7=strong reaction spreading beyond test site, from Day1 for the entire study duration |
| Local tolerability of Diclofenac Sodium 140mg Medicated Plaster EQI7 in comparison to Flector® topical plasters applied once and twice a day, with the syntoms 4-point categorical scale score, where 0=absent and 3=severe, from Day1 onward | From Day 1 for the entire study duration | Local tolerability: symptoms 4-point categorical scale:0=absent;1=mild;2=moderate;3=severe), from Day1 for the entire study duration |
| Measurement of heart rate in bpm during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | Heart rate measurement in bpm on Day 1 of period 1 and Day 9 of period 2 |
| Measurement of systolic/diastolic blood pressure in mmHg during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | Systolic/diastolic blood pressure in mmHg measurement on Day 1 of period 1 and Day 9 of period 2 |
| Measurement of body temperature in C degree during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | Body temperature in C degrees measurement on Day 1 of period 1 and Day 9 of period 2 |
| Cmax (ng/mL) of Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 | Day 1 | Cmax on Day 1 |
| Biochemical analysis during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | Biochemical analysis on Day 1 of period 1 and Day 9 of period 2 |
| Virological tests during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | Virological tests on Day 1 of period 1 and Day 9 of period 2 |
| Urinalysis during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | Urinalysis on Day 1 of period 1 and Day 9 of period 2 |
| 12-lead ECG evaluation during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | 12-lead ECG on Day 1 of period 1 and Day 9 of period 2 |
| Incidence of adverse events using Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day from Day 1 for the entire study duration | From Day 1 for the entire study duration | Incidence of adverse events from Day 1 for the entire study duration |
| Haematological analysis during treatment with Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 of period 1 and Day 9 of period 2 | Day 1 of period 1 and Day 9 of period 2 | Haematological analysis on Day 1 of period 1 and Day 9 of period 2 |
| AUC (ng/mL*h) of Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1 | Day 1 | AUC on Day 1 |
Countries
Italy
Outcome results
None listed