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

NCT02666846 | Completed Phase 1 Results

• 1 other identifier: FM52
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Pain

Keywords

UVB Pain Model; PK; Topical; NSAIDs

Outcome Measures

Primary Outcomes (2)

• 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.

  15 minutes before to 6 hours post administration

• 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

  15 minutes before to 6 hours post administration

Secondary Outcomes (6)

• Peak Plasma Concentration (Cmax)

  15 minutes before and 1, 2, 4 and 6 hours post administration

• Area Under the Plasma Concentration Versus Time Curve

  15 minutes before and 1, 2, 4 and 6 hours post administration

• Number of Recorded Abnormal Clinical Assessments

  Estimated study duration for each subject will be approximately 6 weeks

• 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

Study Arms (11)

Cohort 1: TIB200 gel 10%

EXPERIMENTAL

All Cohort 1 participants: TIB200 gel (10%, w/w ibuprofen)

Drug: Ibuprofen

Cohort 1: Nurofen gel 10%

ACTIVE COMPARATOR

All Cohort 1 participants: Nurofen Max Strength gel (10%, w/w ibuprofen)

Drug: Ibuprofen

Cohort 1: Nurofen tablets

ACTIVE COMPARATOR

All Cohort 1 participants: Nurofen oral tablets (2 x 400 mg ibuprofen)

Drug: Ibuprofen

Cohort 1: TIB200 Placebo gel

PLACEBO COMPARATOR

All Cohort 1 Participants: TIB200 matching placebo gel

Drug: Placebo

Cohort 2: DCF100 gel 2%

ACTIVE COMPARATOR

All Cohort 2 Participants: DCF100 gel (2% w/w diclofenac)

Drug: Diclofenac

Cohort 2: DCF100 gel 4%

EXPERIMENTAL

All Cohort 2 Participants: DCF100 gel (4% w/w diclofenac)

Drug: Diclofenac

Cohort 2: Voltaren gel 2%

ACTIVE COMPARATOR

All Cohort 2 Participants: Voltaren Emulgel (2% diclofenac)

Drug: Diclofenac

Cohort 2: Voltarol oral tablet

ACTIVE COMPARATOR

All Cohort 2 Participants: Voltarol oral tablet (50 mg - diclofenac)

Drug: Diclofenac

Cohort 2: DCF100 Placebo gel

PLACEBO COMPARATOR

All Cohort 2 Participants: DCF100 matching placebo gel

Drug: Placebo

Cohort 3: SPR300 gel (15%:7%)

ACTIVE COMPARATOR

All Cohort 3 Participants: Methyl-salicylate / Menthol, SPR300 gel (15%:7%, w/w; ratio of Methylsalicylate / Menthol)

Drug: Methyl-salicylate / Menthol

Cohort 3: SPR300 Placebo gel

PLACEBO COMPARATOR

All Cohort 3 Participants: SPR300 matching placebo gel

Drug: Placebo

Interventions

Ibuprofen DRUG

Also known as: TIB200 gel 10%, Nurofen gel 10%, Nurofen tablets

Cohort 1: Nurofen gel 10%; Cohort 1: Nurofen tablets; Cohort 1: TIB200 gel 10%

Diclofenac DRUG

Also known as: DCF100 gel 2%, DCF100 gel 4%, Voltaren gel 2%, Voltaren oral tablet

Cohort 2: DCF100 gel 2%; Cohort 2: DCF100 gel 4%; Cohort 2: Voltaren gel 2%; Cohort 2: Voltarol oral tablet

Methyl-salicylate / Menthol DRUG

Also known as: SPR300 gel (15%/7%)

Cohort 3: SPR300 gel (15%:7%)

Placebo DRUG

Also known as: TIB200 placebo gel, DCF100 placebo gel and SPR300 placebo gel

Cohort 1: TIB200 Placebo gel; Cohort 2: DCF100 Placebo gel; Cohort 3: SPR300 Placebo gel

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. -

You may not qualify if:

• 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).
• 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).
• History of bleeding disorders, peptic ulceration or gastro intestinal bleeding, heart burn, cardiovascular disease, myocardial infarction or stroke.
• Inability to give reproducible HPPT ratings on naïve skin at screening, (defined as HPTT test re-test difference ≥1.0 °C)
• Heat pain perception threshold \<40°C or \>51°C on naïve skin at Screening.
• 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.

Sponsors & Collaborators

• Futura Medical Developments Ltd.: lead
• Parexel: collaborator

Study Sites (1)

PAREXEL EPCU Northwick Park

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

MeSH Terms

Conditions

Pain

Interventions

Ibuprofen; Diclofenac; methyl salicylate; Menthol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Phenylacetates; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Cyclohexane Monoterpenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Monoterpenes; Terpenes; Lipids

Results Point of Contact

• Title: Director of Clinical Development
• Organization: Futura Medical Developments Limited

tim.holland@futuramedical.com

01483685683

Study Officials

• Annelize Koch, MBChB

  PAREXEL Ltd.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2016
• First Posted: January 28, 2016
• Study Start: March 1, 2015
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: January 27, 2021
• Results First Posted: September 29, 2020

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)