A Randomised, Double Blind, Cross Over Clinical Study in Healthy Human Volunteers to Assess the Efficacy and Safety of Three Different Topical Analgesics (DCF100, TIB200 And SPR300) Versus in a Model of UV-Induced Inflammatory Pain
Overview
- Phase
- Phase 1
- Intervention
- Ibuprofen
- Conditions
- Pain
- Sponsor
- Futura Medical Developments Ltd.
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units])
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief 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.
Detailed Description
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, 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. The study will consist of 3 cohorts of subjects (n=20 subjects per cohort). Subjects of each cohort will receive test and reference products (no reference product for Cohort 3) of one investigational medicinal product (IMP) and a placebo. Test Products: Cohort 1: Ibuprofen, TIB200 gel (10%, w/w) Cohort 2: Diclofenac, DCF100 gel (2% or 4%, w/w) Cohort 3: Methyl-salicylate and Menthol, SPR300 gel (15%:7%, w/w; ratio of Methylsalicylate to Menthol) Reference Products: Cohort 1: Ibuprofen, Nurofen Max Strength gel (10%, w/w), Ibuprofen, Nurofen, oral tablet (400 mg) Cohort 2: Voltaren Emulgel (2%), Voltarol oral tablet (50 mg) Placebo: All Cohorts:Test product matching vehicle gel. Pharmacodynamic tests and PK blood draws will be performed at: pre-dose, 1, 2, 4, and 6 hours post dose for all treatment cohorts and treatment days (PK blood sampling in up to 6 subjects per cohort only). Safety will be evaluated by the incidence of local and systemic treatment-emergent adverse events (TEAEs) reported after each treatment. Safety assessments will also include vital signs, 12-Lead Electrocardiograms (ECGs), laboratory tests and a physical examination at Screening and the Follow-up visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Were able to provide written informed consent.
- •Male between 18 and 65 years old, inclusive, at the time of screening.
- •Good general health as ascertained by detailed medical history and physical examination.
- •Body mass index (BMI) ≥18 and ≤29 kg/m2 (BMI = weight/height2), at the time of screening.
- •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.
- •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).
- •Had a skin type II or III (Fitz Patrick classification).
- •Non-smokers or ex-smokers for at least 6 months prior to the Screening Visit, as confirmed by a urine cotinine test.
- •Subjects were able to communicate well with the PI/designee. -
Exclusion Criteria
- •History of hypersensitivity to the IMP or any of the excipients or to medicinal products with similar chemical structures.
- •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.
- •Skin type I, IV, V or VI (Fitzpatrick Classification).
- •History of chronic pain symptoms (\>6 months) or ongoing pain.
- •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.
- •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.
- •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.
- •Any skin disease, acute or chronic (e.g., psoriasis vulgaris, neurodermatitis) or auto immune diseases associated with increased light sensitisation.
- •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.
- •History of skin cancer (i.e., melanoma, squamous cell carcinoma or basal cell carcinoma).
Arms & Interventions
Cohort 1: Nurofen tablets
All Cohort 1 participants: Nurofen oral tablets (2 x 400 mg ibuprofen)
Intervention: Ibuprofen
Cohort 1: TIB200 gel 10%
All Cohort 1 participants: TIB200 gel (10%, w/w ibuprofen)
Intervention: Ibuprofen
Cohort 1: Nurofen gel 10%
All Cohort 1 participants: Nurofen Max Strength gel (10%, w/w ibuprofen)
Intervention: Ibuprofen
Cohort 1: TIB200 Placebo gel
All Cohort 1 Participants: TIB200 matching placebo gel
Intervention: Placebo
Cohort 2: DCF100 gel 2%
All Cohort 2 Participants: DCF100 gel (2% w/w diclofenac)
Intervention: Diclofenac
Cohort 2: DCF100 gel 4%
All Cohort 2 Participants: DCF100 gel (4% w/w diclofenac)
Intervention: Diclofenac
Cohort 2: Voltaren gel 2%
All Cohort 2 Participants: Voltaren Emulgel (2% diclofenac)
Intervention: Diclofenac
Cohort 2: Voltarol oral tablet
All Cohort 2 Participants: Voltarol oral tablet (50 mg - diclofenac)
Intervention: Diclofenac
Cohort 2: DCF100 Placebo gel
All Cohort 2 Participants: DCF100 matching placebo gel
Intervention: Placebo
Cohort 3: SPR300 gel (15%:7%)
All Cohort 3 Participants: Methyl-salicylate / Menthol, SPR300 gel (15%:7%, w/w; ratio of Methylsalicylate / Menthol)
Intervention: Methyl-salicylate / Menthol
Cohort 3: SPR300 Placebo gel
All Cohort 3 Participants: SPR300 matching placebo gel
Intervention: Placebo
Outcomes
Primary Outcomes
Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units])
Time Frame: 15 minutes before to 6 hours post administration
Intensity of the Ultra Violet B radiation (UVB)-induced erythema (determined by assessment of skin blood flow by laser Doppler imaging \[flux units\], up to 8 subjects per cohort) - Change from baseline
Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade -
Time Frame: 15 minutes before to 6 hours post administration
To assess the pharmacodynamic effect by Heat Pain Tolerance Test (HPTT) which measured the point at which the heat became painful (degrees centigrade) of three topical analgesics, DCF100, TIB200, and SPR300 versus topical placebo and active topical reference products in a model of UV-induced inflammatory pain.
Secondary Outcomes
- Area Under the Plasma Concentration Versus Time Curve(15 minutes before and 1, 2, 4 and 6 hours post administration)
- Physical Exams to Ensure Safety and Well Being of the Subjects(Estimated study duration for each subject will be approximately 6 weeks)
- Adverse Events (AEs)(Estimated study duration for each subject will be approximately 6 weeks)
- To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects(Estimated study duration for each subject will be approximately 6 weeks)
- Number of Recorded Abnormal Clinical Assessments(Estimated study duration for each subject will be approximately 6 weeks)
- Peak Plasma Concentration (Cmax)(15 minutes before and 1, 2, 4 and 6 hours post administration)