Pain
Conditions
Keywords
UVB Pain Model, PK, Topical, NSAIDs
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.
Interventions
DRUGIbuprofen
DRUGDiclofenac
DRUGMethyl-salicylate / Menthol
DRUGPlacebo
Sponsors
Parexel
Futura Medical Developments Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 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. |
| Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Recorded Abnormal Clinical Assessments | Estimated study duration for each subject will be approximately 6 weeks | Laboratory assessments - standard clinical trial assessments for clinical chemistry and haematology Listing of individual laboratory measurements by subjects and evaluation of each laboratory parameter |
| Physical Exams to Ensure Safety and Well Being of the Subjects | Estimated study duration for each subject will be approximately 6 weeks | Physical examinations - including assessments of the application site. examination. |
| Peak Plasma Concentration (Cmax) | 15 minutes before and 1, 2, 4 and 6 hours post administration | Maximum observed plasma concentration (Cmax), time corresponding to occurrence of Cmax (tmax) (up to 6 subjects per cohort only) laser Doppler imaging \[flux units\], up to 6 subjects per cohort) |
| 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 | To determine Vital Signs and Electrocardiograms (ECGs) that were abnormal to ensure safety and well being of the subjects |
| Adverse Events (AEs) | Estimated study duration for each subject will be approximately 6 weeks | Local and systemic Adverse Events (AEs). |
| Area Under the Plasma Concentration Versus Time Curve | 15 minutes before and 1, 2, 4 and 6 hours post administration | Area under the concentration vs. time curve from time zero to 6 hours (AUC0-6h) (up to 6 subjects per cohort only) laser Doppler imaging \[flux units\], up to 6 subjects per cohort) |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Cohort 1:
Ibuprofen: Single topical dose per 1.76 cm2 test site of: 22 microliters (μL) (20 ± l mg)\* of TIB200 Gel (ibuprofen 10% w/w) (Test Gel) or 22 μL (20 ± l mg)\* of matching placebo TIB200 Gel (placebo gel) or 22 μL (20 ± l mg)\* of Nurofen Maximum Strength Gel (ibuprofen 10% w/w) (reference gel) or Ibuprofen, Nurofen oral tablets (2 x 400 mg) | 20 |
| Cohort 2: Cohort 2:
Diclofenac: Subjects were randomised to receive 22 uL (20 ± l mg) DCF100 Gel (diclofenac 2% w/w) / DCF100 Gel (diclofenac 4% w/w) / Matching Placebo DCF100 Gel / Voltarol® 12 Hour Emulgel® P 2.32% Gel. The gels were administered topically on two test sites on the lower back of the subject, each 1.76 cm2 in size. The two test sites were UVB irradiated on the previous day, between 22 and 26 hours (24 ± 2 hours) before dosing. | 20 |
| Cohort 3 Cohort 3:
Methyl-salicylate / Menthol: Subjects were randomised to receive 22 uL (20 ± l mg) SPR300 Gel / Matching Placebo SPR300 Gel. The gels were administered topically on two test sites on the lower back of the subject, each 1.76cm2 in size. The two test sites were UVB irradiated on the previous day, between 22 and 26 hours (24 ± 2 hours) before dosing. | 20 |
| Total | 60 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2: | Cohort 3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
| Region of Enrollment United Kingdom | 20 participants | 20 participants | 20 participants | 20 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 20 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 5 / 20 | 5 / 20 | 1 / 20 | 1 / 20 | 1 / 20 | 1 / 20 | 0 / 20 | 2 / 20 | 0 / 20 | 3 / 20 | 1 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 20 |
Outcome results
Primary
Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade -
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.
Time frame: 15 minutes before to 6 hours post administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: TIB200 Gel 10% | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.3635 Degrees Centigrade | Standard Deviation 1.0277 |
| Cohort 1: Nurofen Gel 10% | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.7358 Degrees Centigrade | Standard Deviation 1.0277 |
| Cohort 1: Nurofen Tablets | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.0887 Degrees Centigrade | Standard Deviation 0.9024 |
| Cohort 1: TIB200 Placebo Gel | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | -0.1983 Degrees Centigrade | Standard Deviation 0.4616 |
| Cohort 2: DCF100 Gel 2% | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.6679 Degrees Centigrade | Standard Deviation 1.0657 |
| Cohort 2: DCF100 Gel 4% | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.8722 Degrees Centigrade | Standard Deviation 1.043 |
| Cohort 2: Voltaren Gel 2% | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.7978 Degrees Centigrade | Standard Deviation 0.978 |
| Cohort 2: Voltarol Oral Tablet | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.6835 Degrees Centigrade | Standard Deviation 0.7344 |
| Cohort 2: DCF100 Placebo Gel | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.1688 Degrees Centigrade | Standard Deviation 0.7231 |
| Cohort 3: SPR300 Gel (15%:7%) | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | 0.3934 Degrees Centigrade | Standard Deviation 1.2384 |
| Cohort 3: SPR300 Placebo Gel | Heat Pain Tolerance Test (HPTT) Measured the Point at Which the Heat Became Painful - Degrees Centigrade - | -0.0123 Degrees Centigrade | Standard Deviation 1.0103 |
Primary
Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units])
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
Time frame: 15 minutes before to 6 hours post administration
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: TIB200 Gel 10% | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -313.3879 Laser doppler imaging (Flux Units) | Standard Deviation 105.7042 |
| Cohort 1: Nurofen Gel 10% | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -171.5589 Laser doppler imaging (Flux Units) | Standard Deviation 96.6485 |
| Cohort 1: Nurofen Tablets | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -262.0693 Laser doppler imaging (Flux Units) | Standard Deviation 88.5449 |
| Cohort 1: TIB200 Placebo Gel | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -95.3974 Laser doppler imaging (Flux Units) | Standard Deviation 81.4103 |
| Cohort 2: DCF100 Gel 2% | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -228.3016 Laser doppler imaging (Flux Units) | Standard Deviation 183.226 |
| Cohort 2: DCF100 Gel 4% | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -278.1918 Laser doppler imaging (Flux Units) | Standard Deviation 103.7333 |
| Cohort 2: Voltaren Gel 2% | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -198.1408 Laser doppler imaging (Flux Units) | Standard Deviation 133.2886 |
| Cohort 2: Voltarol Oral Tablet | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -198.1408 Laser doppler imaging (Flux Units) | Standard Deviation 211.2754 |
| Cohort 2: DCF100 Placebo Gel | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | -45.376 Laser doppler imaging (Flux Units) | Standard Deviation 104.4476 |
| Cohort 3: SPR300 Gel (15%:7%) | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | 12.2265 Laser doppler imaging (Flux Units) | Standard Deviation 111.1065 |
| Cohort 3: SPR300 Placebo Gel | Intensity of the UVB-induced Erythema (Determined by Assessment of Skin Blood Flow by Laser Doppler Imaging [Flux Units]) | 67.3931 Laser doppler imaging (Flux Units) | Standard Deviation 91.092 |
Secondary
Adverse Events (AEs)
Local and systemic Adverse Events (AEs).
Time frame: Estimated study duration for each subject will be approximately 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: TIB200 Gel 10% | Adverse Events (AEs) | 5 Events |
| Cohort 1: Nurofen Gel 10% | Adverse Events (AEs) | 5 Events |
| Cohort 1: Nurofen Tablets | Adverse Events (AEs) | 1 Events |
| Cohort 1: TIB200 Placebo Gel | Adverse Events (AEs) | 1 Events |
| Cohort 2: DCF100 Gel 2% | Adverse Events (AEs) | 1 Events |
| Cohort 2: DCF100 Gel 4% | Adverse Events (AEs) | 1 Events |
| Cohort 2: Voltaren Gel 2% | Adverse Events (AEs) | 0 Events |
| Cohort 2: Voltarol Oral Tablet | Adverse Events (AEs) | 2 Events |
| Cohort 2: DCF100 Placebo Gel | Adverse Events (AEs) | 0 Events |
| Cohort 3: SPR300 Gel (15%:7%) | Adverse Events (AEs) | 3 Events |
| Cohort 3: SPR300 Placebo Gel | Adverse Events (AEs) | 1 Events |
Secondary
Area Under the Plasma Concentration Versus Time Curve
Area under the concentration vs. time curve from time zero to 6 hours (AUC0-6h) (up to 6 subjects per cohort only) laser Doppler imaging \[flux units\], up to 6 subjects per cohort)
Time frame: 15 minutes before and 1, 2, 4 and 6 hours post administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: TIB200 Gel 10% | Area Under the Plasma Concentration Versus Time Curve | 47.7 h*ng/ml | Standard Deviation 64.3 |
| Cohort 1: Nurofen Gel 10% | Area Under the Plasma Concentration Versus Time Curve | 19.9 h*ng/ml | Standard Deviation 33.7 |
| Cohort 1: Nurofen Tablets | Area Under the Plasma Concentration Versus Time Curve | 90000 h*ng/ml | Standard Deviation 15400 |
| Cohort 1: TIB200 Placebo Gel | Area Under the Plasma Concentration Versus Time Curve | 0 h*ng/ml | Standard Deviation 0 |
| Cohort 2: DCF100 Gel 2% | Area Under the Plasma Concentration Versus Time Curve | 0 h*ng/ml | Standard Deviation 0 |
| Cohort 2: DCF100 Gel 4% | Area Under the Plasma Concentration Versus Time Curve | 0 h*ng/ml | Standard Deviation 0 |
| Cohort 2: Voltaren Gel 2% | Area Under the Plasma Concentration Versus Time Curve | 1030 h*ng/ml | Standard Deviation 463 |
| Cohort 2: Voltarol Oral Tablet | Area Under the Plasma Concentration Versus Time Curve | 0 h*ng/ml | Standard Deviation 0 |
| Cohort 2: DCF100 Placebo Gel | Area Under the Plasma Concentration Versus Time Curve | 0 h*ng/ml | Standard Deviation 0 |
Secondary
Number of Recorded Abnormal Clinical Assessments
Laboratory assessments - standard clinical trial assessments for clinical chemistry and haematology Listing of individual laboratory measurements by subjects and evaluation of each laboratory parameter
Time frame: Estimated study duration for each subject will be approximately 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: TIB200 Gel 10% | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 1: Nurofen Gel 10% | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 1: Nurofen Tablets | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 1: TIB200 Placebo Gel | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 2: DCF100 Gel 2% | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 2: DCF100 Gel 4% | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 2: Voltaren Gel 2% | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 2: Voltarol Oral Tablet | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 2: DCF100 Placebo Gel | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 3: SPR300 Gel (15%:7%) | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
| Cohort 3: SPR300 Placebo Gel | Number of Recorded Abnormal Clinical Assessments | 0 Assessments |
Secondary
Peak Plasma Concentration (Cmax)
Maximum observed plasma concentration (Cmax), time corresponding to occurrence of Cmax (tmax) (up to 6 subjects per cohort only) laser Doppler imaging \[flux units\], up to 6 subjects per cohort)
Time frame: 15 minutes before and 1, 2, 4 and 6 hours post administration
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: TIB200 Gel 10% | Peak Plasma Concentration (Cmax) | 11.5 ng/ml | Standard Deviation 14 |
| Cohort 1: Nurofen Gel 10% | Peak Plasma Concentration (Cmax) | 5.15 ng/ml | Standard Deviation 8.1 |
| Cohort 1: Nurofen Tablets | Peak Plasma Concentration (Cmax) | 29900 ng/ml | Standard Deviation 5490 |
| Cohort 1: TIB200 Placebo Gel | Peak Plasma Concentration (Cmax) | 0 ng/ml | Standard Deviation 0 |
| Cohort 2: DCF100 Gel 2% | Peak Plasma Concentration (Cmax) | 0 ng/ml | Standard Deviation 0 |
| Cohort 2: DCF100 Gel 4% | Peak Plasma Concentration (Cmax) | 0 ng/ml | Standard Deviation 0 |
| Cohort 2: Voltaren Gel 2% | Peak Plasma Concentration (Cmax) | 772 ng/ml | Standard Deviation 468 |
| Cohort 2: Voltarol Oral Tablet | Peak Plasma Concentration (Cmax) | 0 ng/ml | Standard Deviation 0 |
| Cohort 2: DCF100 Placebo Gel | Peak Plasma Concentration (Cmax) | 0 ng/ml | Standard Deviation 0 |
Secondary
Physical Exams to Ensure Safety and Well Being of the Subjects
Physical examinations - including assessments of the application site. examination.
Time frame: Estimated study duration for each subject will be approximately 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: TIB200 Gel 10% | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 1: Nurofen Gel 10% | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 1: Nurofen Tablets | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 1: TIB200 Placebo Gel | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 2: DCF100 Gel 2% | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 2: DCF100 Gel 4% | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 2: Voltaren Gel 2% | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 2: Voltarol Oral Tablet | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 2: DCF100 Placebo Gel | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 3: SPR300 Gel (15%:7%) | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
| Cohort 3: SPR300 Placebo Gel | Physical Exams to Ensure Safety and Well Being of the Subjects | 0 Abnormalities |
Secondary
To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects
To determine Vital Signs and Electrocardiograms (ECGs) that were abnormal to ensure safety and well being of the subjects
Time frame: Estimated study duration for each subject will be approximately 6 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: TIB200 Gel 10% | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 1: Nurofen Gel 10% | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 1: Nurofen Tablets | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 1: TIB200 Placebo Gel | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 2: DCF100 Gel 2% | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 2: DCF100 Gel 4% | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 2: Voltaren Gel 2% | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 2: Voltarol Oral Tablet | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 2: DCF100 Placebo Gel | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 3: SPR300 Gel (15%:7%) | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |
| Cohort 3: SPR300 Placebo Gel | To Determine Vital Signs and Electrocardiograms (ECGs) That Were Abnormal to Ensure Safety and Well Being of the Subjects | 0 Abnormal readings |