Comparison of the Bioavailability of Diclofenac in a Combination Product (Diclofenac 2% + Capsaicin 0.075% Topical Gel) With Two Diclofenac Only Products, Diclofenac Mono Gel 2% and Voltarol® 12 Hour Emulgel 2.32% Gel, in Healthy Volunteers
Condition: Healthy
Intervention: Diclofenac Sodium; Diclofenac & Capsaicin; Diclofenac Sodium Topical Gel
Intervention description: twice daily; twice daily; twice daily
Intervention MeSH terms: Diclofenac; Capsaicin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      The main objective of this study is to assess the relative systemic bioavailability of
      diclofenac in the presence and absence of capsaicin by comparing the systemic bioavailability
      of diclofenac from a combination product (Diclofenac 2% + Capsaicin 0.075% Topical Gel) with
      two diclofenac only products, Diclofenac Mono Gel 2% and Voltarol® 12 Hour Emulgel 2.32% Gel,
      following topical administration.

      In order to examine potential racial differences in pharmacokinetics (PK), the study
      population will be stratified 50:50, Caucasian versus Black people. With respect to the main
      objective, additionally a supportive analysis will be performed to investigate the influence
      of race on the intra-individual bioavailability ratios.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy males and females, 18 to 50 years (inclusive) at time of screening.

          -  Body mass index (BMI) between 18.5 and 29.9 kg/m2 (inclusive).

          -  Body mass not less than 50 kg for males and females.

          -  Findings for medical history, vital signs, physical examination, standard 12-lead
             electrocardiogram (ECG) and laboratory investigations must be normal or within
             laboratory reference ranges for the relevant laboratory tests, unless the PI considers
             the deviation to be not clinically significant for the purpose of the study.

          -  Non-smokers.

          -  Females, if:

               -  Not of childbearing potential,

               -  Of childbearing potential, the following conditions are to be met:

                    -  Negative pregnancy test.

                    -  Not lactating.

                    -  Abstaining from sexual activity (if this is the usual lifestyle of the
                       subject) or must agree to use an accepted method of contraception, and agree
                       to continue with the same method throughout the study.

          -  Written informed consent given for participation in the study.

          -  Further inclusion criteria apply.

        Exclusion Criteria:

          -  Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional
             or intellectual problems likely to limit the validity of consent to participate in the
             study or limit the ability to comply with protocol requirements.

          -  Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol
             per week for females. One unit (10 g alcohol) is equal to beer (330 mL), wine (200
             mL), or distilled spirits (25 mL) per day.

          -  Regular exposure to substances of abuse (other than alcohol) within the past year.

          -  Use of any medication, prescribed or over-the-counter (especially products containing
             diclofenac or use of other oral nonsteroidal anti-inflammatory drugs [NSAIDS]) or
             herbal remedies, within 2 weeks before the first administration of Investigational
             medicinal product (IMP) except if this will not affect the outcome of the study in the
             opinion of the PI (Principal Investigator) (in collaboration with the Sponsor). In
             this study the concomitant use of hormonal contraceptives is allowed.

          -  Participation in another study with an experimental drug, where the last
             administration of the previous IMP was within 8 weeks (or within 5 elimination
             half-lives for chemical entities or 2 elimination half-lives for anti-bodies or
             insulin), whichever is the longer before administration of IMP in this study, at the
             discretion of the PI.

          -  Treatment within the previous 3 months before the first administration of IMP with any
             drug with a well-defined potential for adversely affecting a major organ or system.

          -  A major illness during the 3 months before commencement of the screening period.

          -  History of hypersensitivity or allergy (acute rhinitis, angioedema, urticaria or
             bronchial asthma) to the IMP or its excipients or any related medication (Aspirin or
             any other NSAID).

          -  History of hypersensitivity or allergy to cayenne pepper or other capsaicinoids
             (paprika plants).

          -  History of bronchospasm or bronchial asthma, arterial hypertension, myocardial
             infarction, thrombotic events, stroke, congestive heart failure, impaired renal
             function or liver disease.

          -  History or current diagnosis of gastrointestinal bleeding or peptic ulcer disease.

          -  Relevant history or laboratory or clinical findings indicative of acute or chronic
             disease, likely to influence study outcome.

          -  Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the
             first administration of IMP (Investigational medicinal product) .

          -  Bruises, damaged skin, eczema or wounds on the application site, or the application
             site inappropriate for applying the IMP in the opinion of the PI (Principal
             Investigator).

          -  Further exclusion criteria apply.