Assess the Efficacy and Safety in Volunteers of DCF100, TIB200 and SPR300 vs. Placebo and Control(s) in a UV Pain Model

• ClinicalTrials.gov Identifier: NCT02666846
• Recruitment Status: Completed
• First Posted: January 28, 2016
• Results First Posted: September 29, 2020
• Last Update Posted: January 27, 2021
• Sponsor: Futura Medical Developments Ltd.
• Collaborator: Parexel
• Information provided by (Responsible Party): Futura Medical Developments Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Pain	Drug: Ibuprofen; Drug: Diclofenac; Drug: Methyl-salicylate / Menthol; Drug: Placebo	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: March 2015
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1: TIB200 gel 10%; All Cohort 1 participants: TIB200 gel (10%, w/w ibuprofen)	Drug: Ibuprofen; Other Name: TIB200 gel 10%, Nurofen gel 10%, Nurofen tablets
Active Comparator: Cohort 1: Nurofen gel 10%; All Cohort 1 participants: Nurofen Max Strength gel (10%, w/w ibuprofen)	Drug: Ibuprofen; Other Name: TIB200 gel 10%, Nurofen gel 10%, Nurofen tablets
Active Comparator: Cohort 1: Nurofen tablets; All Cohort 1 participants: Nurofen oral tablets (2 x 400 mg ibuprofen)	Drug: Ibuprofen; Other Name: TIB200 gel 10%, Nurofen gel 10%, Nurofen tablets
Placebo Comparator: Cohort 1: TIB200 Placebo gel; All Cohort 1 Participants: TIB200 matching placebo gel	Drug: Placebo; Other Name: TIB200 placebo gel, DCF100 placebo gel and SPR300 placebo gel
Active Comparator: Cohort 2: DCF100 gel 2%; All Cohort 2 Participants: DCF100 gel (2% w/w diclofenac)	Drug: Diclofenac; Other Name: DCF100 gel 2%, DCF100 gel 4%, Voltaren gel 2%, Voltaren oral tablet
Experimental: Cohort 2: DCF100 gel 4%; All Cohort 2 Participants: DCF100 gel (4% w/w diclofenac)	Drug: Diclofenac; Other Name: DCF100 gel 2%, DCF100 gel 4%, Voltaren gel 2%, Voltaren oral tablet
Active Comparator: Cohort 2: Voltaren gel 2%; All Cohort 2 Participants: Voltaren Emulgel (2% diclofenac)	Drug: Diclofenac; Other Name: DCF100 gel 2%, DCF100 gel 4%, Voltaren gel 2%, Voltaren oral tablet
Active Comparator: Cohort 2: Voltarol oral tablet; All Cohort 2 Participants: Voltarol oral tablet (50 mg - diclofenac)	Drug: Diclofenac; Other Name: DCF100 gel 2%, DCF100 gel 4%, Voltaren gel 2%, Voltaren oral tablet
Placebo Comparator: Cohort 2: DCF100 Placebo gel; All Cohort 2 Participants: DCF100 matching placebo gel	Drug: Placebo; Other Name: TIB200 placebo gel, DCF100 placebo gel and SPR300 placebo gel
Active Comparator: Cohort 3: SPR300 gel (15%:7%); All Cohort 3 Participants: Methyl-salicylate / Menthol, SPR300 gel (15%:7%, w/w; ratio of Methylsalicylate / Menthol)	Drug: Methyl-salicylate / Menthol; Other Name: SPR300 gel (15%/7%)
Placebo Comparator: Cohort 3: SPR300 Placebo gel; All Cohort 3 Participants: SPR300 matching placebo gel	Drug: Placebo; Other Name: TIB200 placebo gel, DCF100 placebo gel and SPR300 placebo gel

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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

Secondary Outcome Measures :

1. Peak Plasma Concentration (Cmax) [ Time Frame: 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)
2. Area Under the Plasma Concentration Versus Time Curve [ Time Frame: 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)
3. Number of Recorded Abnormal Clinical Assessments [ Time Frame: 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

4. Physical Exams to Ensure Safety and Well Being of the Subjects [ Time Frame: Estimated study duration for each subject will be approximately 6 weeks ]
   Physical examinations - including assessments of the application site. examination.
5. Adverse Events (AEs) [ Time Frame: Estimated study duration for each subject will be approximately 6 weeks ]
   Local and systemic Adverse Events (AEs).
6. 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 ]
   To determine Vital Signs and Electrocardiograms (ECGs) that were abnormal to ensure safety and well being of the subjects

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

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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Contacts and Locations

Locations

United Kingdom

PAREXEL EPCU Northwick Park

Harrow, Middlesex, United Kingdom, HA1 3UJ

Sponsors and Collaborators

Futura Medical Developments Ltd.

Parexel

Investigators

• Principal Investigator: Annelize Koch, MBChB; PAREXEL Ltd.

More Information

• Responsible Party: Futura Medical Developments Ltd.
• ClinicalTrials.gov Identifier: NCT02666846
• Other Study ID Numbers: FM52
• First Posted: January 28, 2016
• Results First Posted: September 29, 2020
• Last Update Posted: January 27, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Futura Medical Developments Ltd.:

UVB Pain Model; PK; Topical; NSAIDs

Additional relevant MeSH terms:

Ibuprofen; Diclofenac; Salicylates; Methyl salicylate; Menthol; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antipruritics; Dermatologic Agents