A study to assess the amount of drug that reaches the blood circulation of a new anti-inflammatory medicated plaster applied once a day in comparison with the similar medicated plaster (Flector®) applied twice a day in healthy volunteers

• Register: ISRCTN
• Last refreshed on: 9 January 2023
• Main ID: ISRCTN13261615
• Date of registration: 07/04/2021
• Prospective Registration: No
• Primary sponsor: IBSA Institut Biochimique (Switzerland)
• Public title: A study to assess the amount of drug that reaches the blood circulation of a new anti-inflammatory medicated plaster applied once a day in comparison with the similar medicated plaster (Flector®) applied twice a day in healthy volunteers
• Scientific title: Bioavailability study of a new 2.6% DHEP medicated plaster applied o.d. in comparison with the marketed 1.3% DHEP medicated plaster (Flector®) applied b.i.d.
• Date of first enrolment: 22/01/2020
• Target sample size: 24
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN13261615
• Study type: Interventional
• Study design: Single-centre open-label randomized 2-way cross-over, single and repeated applications, bioavailability study (Treatment)
• Phase: Phase I

Countries of recruitment

Switzerland

Contacts

• Name: Carol Caverzasio

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed written informed consent
2. Aged between 18 and 55 years, inclusive
3. Body Mass Index (BMI) between 18.5 and 30 kg/m² inclusive
4. Systolic blood pressure between 100 and 139 mmHg, diastolic blood pressure between 50 and 89 mmHg, and heart rate between 50 and 90 bpm, measured after 5 min at rest in the sitting position
5. The ability to comprehend the full nature and purpose of the study, including possible risks and side effects, and the ability to co-operate with the Investigator and to comply with the requirements of the entire study
6. Women of child-bearing potential must be using at least one of the following reliable methods of contraception:
6.1. Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
6.2. A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
6.3. A male sexual partner who agrees to use a male condom with spermicide
6.4. A sterile sexual partner
7. Female participants of non-child-bearing potential or in post-menopausal status for =1 year
8. Negative pregnancy test result at screening and day -1

Exclusion criteria:
1. Clinically significant abnormalities on electrocardiogram (12-leads, supine position)
2. Clinically significant abnormal physical findings which could interfere with the objectives of the study
3. Clinically significant abnormal laboratory values indicative of physical illness
4. Diseased-skin, skin wounds, open injuries, tattoos, or the use of makeup, creams, lotions, powders, or other topical products at the application site
5. Ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients or history of anaphylaxis to drugs or allergic reactions in general, which in the opinion of the Investigator could affect the outcome of the study
6. History of significant renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that could interfere with the aim of the study
7. Medications including over the counter medications and herbal remedies, for 2 weeks before the start of the study, with the exception of hormonal contraceptives for women
8. Participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval was calculated as the time between the first calendar day of the month that followed the last visit of the previous study and the first day of the present study.
9. Blood donations for 3 months before this study
10. History of drug, alcohol (>1 drink/day for women and >2 drinks/day for men, defined according to the USDA Dietary Guidelines 2015-2020), caffeine (>5 cups coffee/tea/day), or tobacco abuse (=10 cigarettes/day)
11. Positive result at the drug test at screening or day -1
12. Positive alcohol breath test at day -1
13. Abnormal diets (<1600 or >3500 kcal/day), substantial changes in eating habits in the 4 weeks before this study, or a vegetarian diet
14. Pregnant or lactating


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

DHEP-medicated plaster for analgesia or anti-inflammatory effects
Not Applicable

Intervention(s)

Participants will be randomly allocated to receive either the test (T) or reference (R) medicated plaster for the first part of the study (period 1). In the second part of the study (period 2), participants will receive the treatment/intervention that they did not receive in the first part of the study. Regarding the randomisation process, subjects were assigned to a sequence of treatments (e.g. T/R or R/T) according to the computer-generated randomisation list supplied to the study site before study start. Subjects were randomly allocated to one of the 2 treatment sequences according to their randomisation number. The randomisation number was given to the subjects on study Day -1 of period 1, following a chronological order.

The DHEP medicated plaster will be applied to the inner upper arm of each participant for 5 consecutive days. A wash-out interval of at least 5 days will separate the last application of period 1 and the first application of period 2. The T medicated plaster will be applied once daily in the morning at 08:00 ±1 h each day, and will be kept in place for 24 h each day from day 1 to day 5. The R medicated plaster will be applied twice daily at 8:00 ±1 h and 20:00 ±1 h, and will be kept in place for 12 h each day from day 1 to day 5. T and R plasters will be kept in place using a loose fitting elastic net sleeve (the same supplied in the commercial package of the reference product Flector ® and approved for use both in Europe and USA) to avoid inadvertent detachment. The plasters will be applied to the same application area of the same arm in the 2 study periods.

The following assessments were performed during the interventional phase:
1. Vital signs measurement on Days 1 and 5 at pre-

Primary Outcome(s)

Bioavailability and pharmacokinetic parameters measured using the diclofenac plasma concentrations in blood samples collected at 0 (pre-application), 0.5, 1, 2, 3, 4, 6, 9, 12, 12.5, 13, 14, 15, 16, 18, 21, and 24 h post-application (or after the first application for the Reference plaster) on day 1 of both study periods; at 0 h on day 3 of both study periods; and at 0 (pre-application), 1, 2, 4, 6, 9, 12, 13, 14, 16, 18, 21, and 24 h post-application (or after the first application for the Reference plaster) on day 5 of both study periods

Secondary Outcome(s)

Safety and tolerability measured using the following:
1. Incidence of treatment-emergent adverse events (TEAEs) throughout the study period
2. Vital signs (blood pressure and heart rate) at 0 and 24 h on day 1 and day 5 of both study periods
3. Clinical laboratory assays of blood and urine samples at 6 days during period 2

Secondary ID(s)

CRO-PK-19-338 - Sponsor code 19CH-Fpf06

Nil known

Source(s) of Monetary Support

IBSA Institut Biochimique S.A.

Ethics review

Status:
Approval date:
Contact:

Approved 08/11/2019, Cantonal Ethics Committee Canton Ticino (c/o Health Office, Via Orico 5, 6501 Bellinzona, Switzerland; [phone]; [e-mail]), ref: 2019-01923 CE 3528

Results

• Results available: Yes
• Date Completed: 06/07/2020