Comparative Bioavailability and Local Tolerability of Two Topical Diclofenac Plasters Applied Once and Twice a Day

Comparative Bioavailability and Local Tolerability of Two Topical Diclofenac Plasters Applied Once and Twice a Day to Healthy Volunteers With a Repeat Dose Regimen

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.

Study Overview

• Status: Completed
• Conditions: Bioequivalence Study
• Intervention / Treatment: Drug: Diclofenac Sodium 140mg Medicated Plaster; Drug: Flector® topical plaster containing 180 mg of diclofenac hydroxyethylpyrrolidine equivalent to 140 mg of sodium diclofenac

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Verona, Italy, 37134
    • CRC Centro Ricerche Cliniche di Verona s.r.l. c/o Azienda Ospedaliera Universitaria Integrata Verona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: T-R; Part 1 (QD) and part 2 (BID): Period 1: Test drug (T): Diclofenac Sodium 140mg Medicated Plaster EQI7, topical plaster. Period 2: Reference drug (R): Flector® topical plaster containing 180 mg of diclofenac hydroxyethylpyrrolidine equivalent to 140 mg of sodium diclofenac.	Drug: Diclofenac 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.; Other Names: EQI7; Drug: Flector® 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.; Other Names: Flector
Other: R-T; Part 1 (QD) and part 2 (BID): Period 1: Reference drug (R): Flector® topical plaster containing 180 mg of diclofenac hydroxyethylpyrrolidine equivalent to 140 mg of sodium diclofenac. Period 2: Test drug (T): Diclofenac Sodium 140mg Medicated Plaster EQI7, topical plaster.	Drug: Diclofenac 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.; Other Names: EQI7; Drug: Flector® 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.; Other Names: Flector

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Css max on Day 7 through Day 9	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	AUCττ on Day 7 through Day 9	Day 7 through Day 9

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax (ng/mL) of Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1	Cmax on Day 1	Day 1
AUC (ng/mL*h) of Diclofenac Sodium 140mg Medicated Plaster EQI7 and Flector® topical plasters applied once and twice a day on Day 1	AUC on Day 1	Day 1
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	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	From Day 1 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 irritation8-point scale, where 0=no evidence of irritation and 7=strong reaction, from Day1 onward	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	From Day 1 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	Local tolerability: symptoms 4-point categorical scale:0=absent;1=mild;2=moderate;3=severe), from Day1 for the entire study duration	From Day 1 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	Heart rate measurement in bpm on Day 1 of period 1 and Day 9 of period 2	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	Systolic/diastolic blood pressure in mmHg measurement on Day 1 of period 1 and Day 9 of period 2	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	Body temperature in C degrees measurement 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 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	Haematological analysis 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 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	Biochemical analysis 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 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	Virological tests on Day 1 of period 1 and Day 9 of period 2	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	Urinalysis 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 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	12-lead ECG on Day 1 of period 1 and Day 9 of period 2	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	Incidence of adverse events from Day 1 for the entire study duration	From Day 1 for the entire study duration

Collaborators and Investigators

• Sponsor: Fidia Farmaceutici s.p.a.

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2017
• Primary Completion (Actual): May 17, 2018
• Study Completion (Actual): May 17, 2018

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: October 7, 2020
• First Posted (Actual): October 14, 2020

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: October 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Diclofenac; Diclofenac hydroxyethylpyrrolidine
• Other Study ID Numbers: EQI7_17_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No