We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Collaborator:
Parexel
Information provided by (Responsible Party):
Futura Medical Developments Ltd.

Tracking Information
First Submitted Date  ICMJE January 20, 2016
First Posted Date  ICMJE January 28, 2016
Results First Submitted Date  ICMJE December 14, 2019
Results First Posted Date  ICMJE September 29, 2020
Last Update Posted Date January 27, 2021
Study Start Date  ICMJE March 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2020)
  • 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.
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: January 25, 2016)
  • Heat Pain Tolerance Test [ Time Frame: 15 minutes before to 6 hours post administration ]
    To assess the pharmacodynamic effect by Heat Pain Tolerance Test (HPTT) 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 [ 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 6 subjects per cohort)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2020)
  • 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)
  • 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)
  • 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
  • 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.
  • Adverse Events (AEs) [ Time Frame: Estimated study duration for each subject will be approximately 6 weeks ]
    Local and systemic Adverse Events (AEs).
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2016)
  • Peak Plasma Concentration (Cmax) [ Time Frame: 15 minutes before to 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)
  • Area Under the Plasma Concentration versus Time Curve [ Time Frame: 15 minutes before to 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)
  • Laboratory assessments [ Time Frame: Estimated study duration for each subject will be approximately 6 weeks; 4 week (28 days) Screening period, a 4 to 7 day treatment period and up to a 2 week (7 to 9 days) Follow-up period. ]
    Laboratory assessments - clinical chemistry and haematology
  • Physical exams [ Time Frame: Estimated study duration for each subject will be approximately 6 weeks; 4 week (28 days) Screening period, a 4 to 7 day treatment period and up to a 2 week (7 to 9 days) Follow-up period. ]
    Physical examinations - including assessments of the application site. examination.
  • Adverse Events (AEs) [ Time Frame: Estimated study duration for each subject will be approximately 6 weeks; 4 week (28 days) Screening period, a 4 to 7 day treatment period and up to a 2 week (7 to 9 days) Follow-up period. ]
    Local and systemic Adverse Events (AEs).
  • Vital Signs and Electrocardiograms (ECGs) [ Time Frame: Estimated study duration for each subject will be approximately 6 weeks; 4 week (28 days) Screening period, a 4 to 7 day treatment period and up to a 2 week (7 to 9 days) Follow-up period. ]
    Vital signs and ECGs.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Assess the Efficacy and Safety in Volunteers of DCF100, TIB200 and SPR300 vs. Placebo and Control(s) in a UV Pain Model
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Pain
Intervention  ICMJE
  • Drug: Ibuprofen
    Other Name: TIB200 gel 10%, Nurofen gel 10%, Nurofen tablets
  • Drug: Diclofenac
    Other Name: DCF100 gel 2%, DCF100 gel 4%, Voltaren gel 2%, Voltaren oral tablet
  • Drug: Methyl-salicylate / Menthol
    Other Name: SPR300 gel (15%/7%)
  • Drug: Placebo
    Other Name: TIB200 placebo gel, DCF100 placebo gel and SPR300 placebo gel
Study Arms  ICMJE
  • Experimental: Cohort 1: TIB200 gel 10%
    All Cohort 1 participants: TIB200 gel (10%, w/w ibuprofen)
    Intervention: Drug: Ibuprofen
  • Active Comparator: Cohort 1: Nurofen gel 10%
    All Cohort 1 participants: Nurofen Max Strength gel (10%, w/w ibuprofen)
    Intervention: Drug: Ibuprofen
  • Active Comparator: Cohort 1: Nurofen tablets
    All Cohort 1 participants: Nurofen oral tablets (2 x 400 mg ibuprofen)
    Intervention: Drug: Ibuprofen
  • Placebo Comparator: Cohort 1: TIB200 Placebo gel
    All Cohort 1 Participants: TIB200 matching placebo gel
    Intervention: Drug: Placebo
  • Active Comparator: Cohort 2: DCF100 gel 2%
    All Cohort 2 Participants: DCF100 gel (2% w/w diclofenac)
    Intervention: Drug: Diclofenac
  • Experimental: Cohort 2: DCF100 gel 4%
    All Cohort 2 Participants: DCF100 gel (4% w/w diclofenac)
    Intervention: Drug: Diclofenac
  • Active Comparator: Cohort 2: Voltaren gel 2%
    All Cohort 2 Participants: Voltaren Emulgel (2% diclofenac)
    Intervention: Drug: Diclofenac
  • Active Comparator: Cohort 2: Voltarol oral tablet
    All Cohort 2 Participants: Voltarol oral tablet (50 mg - diclofenac)
    Intervention: Drug: Diclofenac
  • Placebo Comparator: Cohort 2: DCF100 Placebo gel
    All Cohort 2 Participants: DCF100 matching placebo gel
    Intervention: Drug: Placebo
  • 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)
    Intervention: Drug: Methyl-salicylate / Menthol
  • Placebo Comparator: Cohort 3: SPR300 Placebo gel
    All Cohort 3 Participants: SPR300 matching placebo gel
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 25, 2016)
60
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02666846
Other Study ID Numbers  ICMJE FM52
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Futura Medical Developments Ltd.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Futura Medical Developments Ltd.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Parexel
Investigators  ICMJE
Principal Investigator: Annelize Koch, MBChB PAREXEL Ltd.
PRS Account Futura Medical Developments Ltd.
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP