Bioavailability and tolerability study of two new diclofenac epolamine lecithin gel formulations (2.6% and 3.9%) in comparison with the marketed diclofenac epolamine lecithin gel formulation 1.3% (Effigel® IBSA)

• Register: ISRCTN
• Last refreshed on: 3 July 2017
• Main ID: ISRCTN80888941
• Date of registration: 16/05/2017
• Prospective Registration: No
• Primary sponsor: IBSA Institut Biochimique S.A
• Public title: Bioavailability and tolerability study of two new diclofenac epolamine lecithin gel formulations (2.6% and 3.9%) in comparison with the marketed diclofenac epolamine lecithin gel formulation 1.3% (Effigel® IBSA)
• Scientific title: Bioavailability and tolerability study of two new diclofenac epolamine lecithin gel formulations (2.6% and 3.9%) in comparison with the marketed diclofenac epolamine lecithin gel formulation 1.3% (Effigel® IBSA): an open-label three-way randomised cross-over pilot bioavailability study
• Date of first enrolment: 02/05/2016
• Target sample size: 12
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN80888941
• Study type: Interventional
• Study design: Open-label three-way randomised cross-over pilot bioavailability study (Other)
• Phase: Phase I

Countries of recruitment

Switzerland

Contacts

• Name: Milko Radicioni

Key inclusion & exclusion criteria

Inclusion criteria: 1. Signed written informed consent
2. Males/females, 18-55 year old inclusive
3. Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
4. Vital signs: systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 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 (women only): women 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 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 day 1
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 2015-2020)], 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 (women only): positive or missing pregnancy test at screening or day 1, pregnant or lactating women

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Bioavailability and tolerability study of two new diclofenac epolamine lecithin gel formulations
Not Applicable

Intervention(s)

The study consisted of a screening visit, a treatment phase of three study periods separated by wash-out intervals of at least 5 days between the start of the 2nd application of a period and the start of the 1st application of the following period, and a final visit/early termination visit.

Test 1 (T1): DHEP 2.6% (corresponding to 2% of diclofenac sodium) gel, IBSA Institut Biochimique S.A.,Switzerland. Batch N. 160101, re-test date JUL16
Test 2 (T2): DHEP 3.9% (corresponding to 3% of diclofenac sodium) gel, IBSA Institut Biochimique S.A.,Switzerland. Batch N. 160102, re-test date JUL16
Reference (R): Effigel®, DHEP 1.3% (corresponding to 1% of diclofenac sodium) gel, IBSA Institut Biochimique S.A., Switzerland. Batch N. 150606, expiry date JUN18

Each subject received a total of 16 g of each IMP. The total dose was subdivided into two applications of 8 g each. Considering the dose regimen of up to four daily applications recommended for Effigel®, two daily applications of 8 g each were tested in the present study. Each dose of 8 g of gel was applied to the maximum application area (800 cm2) as recommended for Effigel®.

Primary Outcome(s)

Pharmacokinetic parameters (Cmax, AUC0-t, AUC0-8, t1/2, ?z and tmax) of plasma diclofenac free acid after two applications of T1, T2 and R. Plasma concentrations of diclofenac are measured at the following time-points (13 samples in each study period):
1. On day 1 at pre-dose (0), i.e. before the start of the 1st application
2. On day 2 at pre-dose (0), i.e. 5 min before the start of the 2nd application, and at 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after the start of the 2nd application

Secondary Outcome(s)

1. Treatment-emergent adverse events; vital signs (blood pressure, heart rate); physical examinations and laboratory tests performed at screening and final visit/early termination visit
2. Local tolerability, evaluated according to a 4-grade score scale before the start and 2 h after the start of the 1st application and before the start and 4 and 12 h after the start of the 2nd application

Secondary ID(s)

CRO-PK-15-309 - Sponsor code 16CH-Fgf01

Source(s) of Monetary Support

IBSA Institut Biochimique S.A