Plain English Summary
Background and study aims
The Ibsa DHEP medicated plaster contains diclofenac, an anti-inflammatory pain killer. The aim of this study is to assess the amount of diclofenac in the bloodstream after the application for two consecutive days of two new DHEP medicated plasters that contain higher amounts of diclofenac (2.6% and 3.9% DHEP), in comparison with the marketed DHEP medicated plaster 1.3%. The higher amount of diclofenac should improve the painkiller/anti-inflammatory effects of the plaster by increasing the amount of diclofenac at the application site, while keeping the amount in the rest of the body very low so as to avoid side effects.
Who can participate?
Healthy volunteers aged 18-55
What does the study involve?
Participants attend three study periods where they stay at the clinical centre from the late afternoon before the plaster application (study day -1) until the morning of day 3. The three study periods are separated by breaks of at least 7 days. In each study period one DHEP medicated plaster (either 1.3%, 2.6% or 3.9%) is applied to the participant’s arm once a day for two consecutive days. The amount of diclofenac in the bloodstream is measured for 24 hours after plaster application, and any side effects are recorded.
What are the possible benefits and risks of participating?
No potential benefits expected for participating in this study. There are no significant risks related to the DHEP-medicated plasters. The side effects most frequently reported are mild to moderate skin reactions at the site of plaster application.
Where is the study run from?
CROSS Research Phase I Unit (Switzerland)
When is the study starting and how long is it expected to run for?
May 2015 to March 2016
Who is funding the study?
IBSA Institut Biochimique S.A (Switzerland)
Who is the main contact?
Dr Milko Radicioni
Trial website
Contact information
Type
Scientific
Primary contact
Dr Milko Radicioni
ORCID ID
http://orcid.org/0000-0002-3940-8375
Contact details
CROSS Research Phase I Unit
Via F.A. Giorgioli 14
Arzo
CH-6864
Switzerland
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Study CRO-PK-15-305 - Sponsor code 15CH-Fpf03
Study information
Scientific title
Bioavailability and tolerability study of two new DHEP-medicated plasters in comparison with the marketed DHEP-medicated plaster 1.3% (Flector®): a single-centre, multiple-dose, randomised, three-way cross-over, open-label, bioavailability and tolerability study
Acronym
Study hypothesis
Compare the pharmacokinetic (PK) profile and tolerability of diclofenac in plasma after o.d. application for 2 consecutive days of DHEP-medicated plaster (test 1, 2.6% or test 2, 3.9% or reference, 1.3%) in healthy male and female volunteers.
Ethics approval
1. Cantonal Ethics Committee, Ticino, Switzerland, 08/02/2016, ref: CE3010
2. Federal Health Authorities (Swissmedic), 29/01/2016, ref: 2016dr1021
Study design
Single-centre multiple-dose randomised three-way cross-over open-label bioavailability and tolerability study
Primary study design
Interventional
Secondary study design
Randomised cross over trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
No participant information sheet available’
Condition
DHEP-medicated plaster
Intervention
Test treatment 1: Diclofenac-N-(2-hydroxyethyl)-pyrrolidine (DHEP) medicated plaster 2.6%, corresponding approximately to 280 mg of diclofenac sodium
Test treatment 2: Diclofenac-N-(2-hydroxyethyl)-pyrrolidine (DHEP) medicated plaster 3.9%, corresponding approximately to 420 mg of diclofenac sodium
Reference formulation: Diclofenac-N-(2-hydroxyethyl)-pyrrolidine (DHEP) medicated plaster
DHEP 1.3%, corresponding approximately to 140 mg of diclofenac sodium
The study consisted of a screening visit, a treatment phase of three study periods separated by a wash-out interval of at least 7 days between the second plaster application of the previous period and the first application of the next period and a final visit/early termination visit (ETV). One DHEP medicated plaster (test 1, 2.6% or test 2, 3.9% or reference, 1.3%) was applied once a day for 2 consecutive days in the three study periods according to a three-way cross-over randomised study design. The plasters were applied to the same application area of the same arm in the three study periods.
Intervention type
Drug
Phase
Phase I
Drug names
Diclofenac-N-(2-hydroxyethyl)-pyrrolidine (DHEP)
Primary outcome measures
Pharmacokinetic profile of diclofenac in plasma after o.d. application for 2 consecutive days of DHEP-medicated plaster - plasma concentrations of diclofenac measured on day 1 at pre-dose (0) and on days 2-3 at pre-dose (0) and 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24 h post-dose (13 samples each study period)
Secondary outcome measures
Safety and tolerability after o.d. application for 2 consecutive days of DHEP-medicated plaster, based on the following assessments:
1. Record of adverse events, assessed throughout the study
2. Vital signs: blood pressure (BP) and heart rate (HR), measured at rest (5 min in sitting position) by the investigator or his deputy at the screening visit, on day -1, as well as on day 3 at 24 h post-dose in each period, and in case of ETV. The vital signs measurement at 24 h post-dose of day 3, period 3, was considered as the final assessment
3. Electrocardiograms: a 12-lead resting ECG performed in supine position and interpreted by the investigator at screening
4. Physical examination and body weight: a physical examination, including measurement of BW, performed at screening and final visit/ETV
5. Routine haematology, blood chemistry and urinalysis laboratory tests performed, under fasting conditions, at screening and at the final visit/ETV
6. Local tolerability, assessed giving a score according to the a 4-grade scale to each of the following parameters: Application site erythema, Application site dryness, Application site swelling, Application site exfoliation (If the score assigned was 1, 2 or 3, the local reaction was treated as an AE with intensity mild (score 1), moderate (score 2) or severe (score 3), while the severity of 0 score was none
7. Plaster adhesiveness, assessed using the 5-point scale in compliance with FDA suggested scoring system for adhesion of transdermal patches, immediately before plaster removal on days 2 and 3
Overall trial start date
15/05/2015
Overall trial end date
23/03/2016
Reason abandoned
Eligibility
Participant inclusion criteria
1. Informed consent: signed written informed consent before inclusion in the study
2. Males/females, 18-55 years old inclusive
3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
4. Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min at rest in the sitting position
5. Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
6. Contraception and fertility (females only): females of child-bearing potential were required to use 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 [IUD] 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 agreed to use a male condom with spermicide
6.4. A sterile sexual partner
Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year were admitted. For all female subjects, pregnancy test result had to be negative at screening and at each scheduled evaluation
Participant type
Healthy volunteer
Age group
Adult
Gender
Both
Target number of participants
Twelve (12) healthy male and female subjects
Participant exclusion criteria
1. Electrocardiogram (12-leads, supine position): clinically significant abnormalities
2. Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
3. Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
4. Allergy: ascertained or presumptive hypersensitivity to the active principle and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the investigator considered could affect the outcome of the study
5. Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases that could interfere with the aim of the study
6. Medications: medications, including over the counter medications and herbal remedies for 2 weeks before the start of the study. Hormonal contraceptives for females were allowed
7. Investigative drug studies: 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
8. Blood donation: blood donations for 3 months before this study
9. Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2010)], caffeine (>5 cups coffee/tea/day) or tobacco abuse (>10 cigarettes/day)
10. Drug test: positive result at the drug test at screening
11. Alcohol test: positive alcohol breath test at day -1
12. Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
13. Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women
Recruitment start date
29/02/2016
Recruitment end date
01/03/2016
Locations
Countries of recruitment
Switzerland
Trial participating centre
CROSS Research Phase I Unit
CH-6864
Switzerland
Funders
Funder type
Industry
Funder name
IBSA Institut Biochimique S.A
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal
IPD sharing plan
The datasets generated during and/or analysed during the current study are not expected to be made available and will be held in the Sponsor’s database.
Intention to publish date
23/03/2017
Participant level data
Not expected to be available
Results - basic reporting
Publication summary