Assess the Efficacy and Safety in Volunteers of DCF100, TIB200 and SPR300 vs. Placebo and Control(s) in a UV Pain Model
Condition: Pain
Intervention: Ibuprofen; Diclofenac; Methyl-salicylate / Menthol; Placebo
Intervention MeSH terms: Ibuprofen; Diclofenac; Salicylates; Methyl salicylate; Menthol
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: UVB Pain Model; PK; Topical; NSAIDs

Summary:

      This is a randomised, double blind, cross over clinical study in healthy human volunteers
      (including pharmacokinetic [PK] sampling and laser Doppler assessment of local blood flow in
      a subset of up to 6 subjects per cohort of 20) to assess the efficacy and safety of three
      different topical analgesics (DCF100, TIB200 and SPR300) versus placebo and active control(s)
      in a model of UV-induced inflammatory pain.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Were able to provide written informed consent.

          2. Male between 18 and 65 years old, inclusive, at the time of screening.

          3. Good general health as ascertained by detailed medical history and physical
             examination.

          4. Body mass index (BMI) ≥18 and ≤29 kg/m2 (BMI = weight/height2), at the time of
             screening.

          5. No clinically relevant abnormalities in 12-lead ECG as per PI's judgement, e.g.,
             absence of cardiac rhythm disorder, in particular bradycardia (<40 beats per minute),
             conduction abnormalities such as atrioventricular block, absence of active ischemia
             (such as unstable angina pectoris) or recent myocardial infarction, no QTcF interval
             >450 milliseconds, no QRS complex ≥120 milliseconds, at Screening.

          6. No clinically relevant abnormalities in results of laboratory tests as per PI's
             judgement; in particular, no significant liver impairment defined as aspartate
             aminotransferase (AST), alanine aminotransferase (ALT) 1.5x upper limit of normal
             (ULN); no significant kidney impairment defined as serum creatinine 2x ULN; abnormal
             thyroid function as defined by thyroid-stimulating hormone (TSH) and total thyroxin
             (T4) (TSH within range 0.27 to 4.2 mIU/L, total T4 within range 59 to 154 nmol/L).

          7. Had a skin type II or III (Fitz Patrick classification).

          8. Non-smokers or ex-smokers for at least 6 months prior to the Screening Visit, as
             confirmed by a urine cotinine test.

          9. Subjects were able to communicate well with the PI/designee. -

        Exclusion Criteria:

          1. History of hypersensitivity to the IMP or any of the excipients or to medicinal
             products with similar chemical structures.

          2. Presence of any clinically relevant acute or chronic disease which could interfere
             with the subject safety during the study, expose the subject to undue risk, limit the
             biological sampling (e.g., blood collection), interfere with the absorption of the IMP
             (e.g., active dermatological conditions at the application sites, or ulcers, irritable
             bowel syndrome) or interfere with the study objectives.

          3. Skin type I, IV, V or VI (Fitzpatrick Classification).

          4. History of chronic pain symptoms (>6 months) or ongoing pain.

          5. Any condition that required regular concomitant medication including herbal products,
             or predicted need of any concomitant medication from Screening Visit until the end of
             the study.

          6. Intake of any medication including over the counter (OTC) medication (in particular
             any pain killers), herbal and dietary supplements such as St John's Wort, vitamins and
             minerals that could affect the outcome of the study, within 48 hours before the first
             administration of the investigational product and for the duration of the study.

          7. Use of photosensitising medication, such as phenothiazines, tetracyclines, quinolones,
             sulphonamides, nalidixic acid, non-steroidal anti-inflammatories, furosemides,
             hydrochlorothiazides, fibrate, phytotherapeutic drugs (herbal supplements),
             phenothiazines, quinidines, psoralens and amiodarone within 4 weeks before the first
             UVB irradiation and for the duration of the study.

          8. Any skin disease, acute or chronic (e.g., psoriasis vulgaris, neurodermatitis) or auto
             immune diseases associated with increased light sensitisation.

          9. Any active dermatological conditions, local pigmentary disorders, body art (e.g.,
             tattoos), or excessive hair growth at the lower back that might interfere with the
             study assessments or absorption of the IMP.

         10. History of skin cancer (i.e., melanoma, squamous cell carcinoma or basal cell
             carcinoma).

         11. History of conditions that increase risk for melanoma (e.g., dysplastic nevus [>5
             nevi], xeroderma pigmentosum, Fanconi anaemia, Bloom's syndrome, Werner syndrome,
             Cockayne syndrome, trichothiodystrophy, or familial mole melanoma syndrome).

         12. History of bleeding disorders, peptic ulceration or gastro intestinal bleeding, heart
             burn, cardiovascular disease, myocardial infarction or stroke.

         13. Inability to give reproducible HPPT ratings on naïve skin at screening, (defined as
             HPTT test re-test difference ≥1.0 °C)

         14. Heat pain perception threshold <40°C or >51°C on naïve skin at Screening.

         15. Supine systolic blood pressure (SBP) <90 mmHg or >140 mmHg, or supine diastolic blood
             pressure (DBP) <50 mmHg or >90 mmHg after 5 minutes supine, at the Screening Visit.

         16. Positive test results for HBsAg, HCVAb or HIV-1 and/or -2 antibodies at Screening.

         17. Excessive use of caffeine-containing beverages exceeding 500 mg caffeine/day (5 cups
             of coffee) and the inability to refrain from the use of caffeine-containing beverages
             during confinement in the Clinical Unit.

         18. Excessive alcohol consumption (regular alcohol intake ≥21 units per week). Use of
             alcohol 48 hours before any study visit, as confirmed by urine alcohol testing at
             Screening, Day -2, and with any additional tests at the discretion of the PI.

         19. History in the last year or presence of drug addiction (positive urine drug screen) at
             Screening and Day -2.

         20. Presence or history of alcohol abuse in the last year, as confirmed by subject's
             general practitioner (GP).

         21. Blood donation within 8 weeks before the first IMP administration.

         22. Participation in another study with an experimental drug within 3 months before the
             first dosing day.

         23. Any psychological, emotional problems, any disorder or resultant therapy that was
             likely to invalidate informed consent, or limited the ability of the subject to comply
             with the protocol requirements.

         24. Unlikely to comply with the protocol requirements, instructions and study-related
             restrictions; e.g., uncooperative attitude, inability to return for Follow-up visits
             and improbability of completing the clinical study.

         25. Planned surgery, dental procedure, or hospitalisation from the Screening Visit until
             the end of the study.

         26. Inability to give written informed consent or to comply fully with the protocol.

         27. Subjects who, in the opinion of the PI, were considered unsuitable for any other
             reason.

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