E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Actinic Keratosis is a precancerous stage with lesions caused by sun exposure that has to be treated to avoid the development of skin cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the efficacy of 1.25% DFD-07 after 8 weeks of self-application by the patient (1g of cream per day).
The primary endpoint is the percent of patients with complete clearance of AK lesions at the End of Treatment Visit at 8 weeks (absence of clinically visible or palpable AK lesions in the treatment area). All lesions in the treatment area will be included in the count even if the lesion was a new lesion that was not identified at Baseline. |
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E.2.2 | Secondary objectives of the trial |
1. Percent of patients with complete clearance of AK lesions at Week 4 for 1.25% DFD-07 compared to placebo 2. Percent of patients with complete clearance of AK lesions at the End of Study (EOS) Visit (8 weeks treatment plus 30-day follow up) for 1.25% DFD-07 compared to placebo 3. Percent of patients with partial clearance of AK lesions at Weeks 4, 8, and the EOS Visit defined as at least a 75% reduction in the number of AK lesions in the treatment area compared to Baseline for 1.25% DFD-07 compared to placebo 4. Percent change from baseline in AK lesion count at Weeks 4, 8 and the EOS Visit for 1.25% DFD-07 compared to placebo 5. Local skin reactions by dose strength (1.25% DFD-07 or placebo): a. Erythema b. Edema c. Weeping/Exudate d. Flaking/Scaling/Dryness e. Scabbing/Crusting f. Erosion/Ulceration g. Vesiculation/Blistering
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent has been signed and dated prior to any study related procedure or the initiation of a wash-out period • Skin type I, II or III according to Fitzpatrick • 5-8 AK mild to moderate grade lesions in an approximately 25 cm2 region of scalp, forehead or face that are non-hypertrophic and non-hyperkeratotic • 18 years of age or older • Female patients of childbearing potential must agree to use contraception during the study which can include abstinence with a secondary contraceptive option should the patient become sexually active. All women of childbearing potential must have a negative urine pregnancy test (test must have a sensitivity of at least 25 IU/ML for human chorionic gonadotropin) at the Baseline Visit and be willing to be tested throughout the study. A female is considered of childbearing potential unless she is pre-menarche, postmenopausal with no menses for at least 12 months or surgically sterile. Reliable methods of contraception are hormonal methods or intrauterine devices in use for at least 90 days prior to the Baseline Visit or barrier methods plus spermicide use for at least 14 days prior to the Baseline Visit or a partner who has had a vasectomy at least 3 months prior to the Baseline Visit. • ≥ 60 days washout from prohibited medications: o Masoprocol o 5-Fluorouracil o Cyclosporine o Retinoids o Trichloroacetic Acid/Lactic Acid Peel o 50% Glycolic Acid Peel o Topical or systemic diclofenac, celecoxib or any other NSAID (however daily low-dose aspirin is allowed, as long as the patient has been on a stable dose, ≤ 100 mg once a day, for 60 days prior to the start of the study.) Note: Patients may use acetaminophen/paracetamol as needed o Photodynamic therapy o Topical or systemic immunomodulating agents including: Systemic, topical or intralesional interferon Imiquimod (Aldara, Zyclara) Topical ingenol mebutate (Picato) Topical tacrolimus Topical pimecrolimus Sirolimus Cyclosporin Intralesional BCG Topical coal tar products Topical or systemic corticosteroids
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E.4 | Principal exclusion criteria |
• Known or suspected hypersensitivity to any NSAID or any component of the formulation of the study medication • Clinical evidence of severe, uncontrolled autoimmune, cardiovascular, gastrointestinal, hematological, hepatic, neurologic, pulmonary or renal disease. • Significant history (within the past year) of alcohol or drug abuse • Participation in any clinical research study within 60 days of the Baseline Visit. • Pregnancy, lactation or plans to become pregnant • Concomitant use of cosmetics or other topical drug products on or near the selected treatment area. However, the use of topical sun screens is allowed. • Cosmetic or therapeutic procedures (e.g. laser, peeling, photodynamic therapy) within 2 weeks and within 2 cm of the selected treatment area • Other skin conditions within the selected treatment area (e.g. rosacea, psoriasis, atopic dermatitis, eczema, basal or squamous cell carcinoma or albinism) • Use of sun lamps or tanning beds or booths during the 14 days prior to the Baseline Visit or planned use during the study • Any systemic cancer therapy within 6 months of the Baseline Visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is complete clearance of AK lesions at the End of Treatment Visit at 8 weeks (absence of clinically visible or palpable AK lesions in the treatment area). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 8 weeks (End of treatment) |
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E.5.2 | Secondary end point(s) |
1. Partial clearance of AK lesions (at least 75% reduction in number of AK lesions) 2. Percent change in baseline from AK lesion counts 3. Local skin reaction |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of study (8 weeks + 30 days) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |