Condition category
Not Applicable
Date applied
11/01/2017
Date assigned
19/01/2017
Last edited
19/01/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Sponsor information

Organisation

IBSA Institut Biochimique S.A

Sponsor details

Via del Piano
PO Box 266
Pambio-Noranco
CH-6915
Switzerland

Sponsor type

Industry

Website

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

Publication citations

Additional files

Editorial Notes