E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Actinic Keratosis are scaling epidermal lesions, which consist of dysplastic keratinocytes. They mostly appear in pale-skinned patients which are chronically overexposed to UV radiation. Actinic keratosis is a precancerous epidermal lesion, which can progress into a squamous cell carcinoma. According to Guenthner et al., 97% of squamous cell carcinomas (a nonmelanoma skin cancer) were associated with a cohesive AK lesion |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000614 |
E.1.2 | Term | Actinic keratosis |
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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 |
The primary study objective is to evaluate the efficacy of Fosfluridine tidoxil in patients with actinic keratosis. |
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E.2.2 | Secondary objectives of the trial |
The secondary study objective is to evaluate tolerability and safety of Fosfluridine tidoxil in patients with actinic keratosis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 10 or more lesions. The lesions should be located in the face and/or the balding scalp
- Actinic keratosis grade II (moderately thick AK, easily felt and seen on skin overexposed to the sun) or Actinic keratosis grade III (hyperkeratotic, very thick and/or obvious AK on skin overexposed to the sun), confirmed by biopsy taken from the most progressed lesion
- Postmenopausal female 50 years of age or older with a documented amneorrhoe of at least 2 years
- Males of 50 years of age or older. Male patients with a female partner of childbearing potential should use a form of contraception (e.g. condoms) as approved by the investigator for the treatment period and for at least 4 weeks after the last study dose is administered
- Ability to comply with treatment
- Signed informed consent prior to start of any study specific procedures |
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E.4 | Principal exclusion criteria |
- Concomitant severe diseases
- Known or suspected hypersensitivity to Fluorouracil
- Pretreatment with any therapy for AK lesions less than 4 weeks before Visit 2 (Baseline)
- Use of any immunomodulators, cytotoxic drugs or investigational drugs within 4 weeks before Visit 2 (Baseline)
- Patients who are using drugs which may effect dihydropyrimidine dehydrogenase activity (e.g. Brivudine, Sorivudine) or using calcium folinates (e.g. Leucovorin®)
- Pretreatment with Omeprazol or other proton pump inhibitors within the last week before Visit 2 (Baseline)
- Confirmed or suspected acute bacterial or acute viral infection less than 3 weeks before Visit 2 (Baseline)
- Diagnosed as having clinically relevant hematologic abnormalities or diseases, with haemoglobin, hematocrit, red blood cells, white blood cells, absolute neutrophil count, platelets < 0.7 x LNL or > 1.5 x UNL
- Diagnosed as having hepatic or gastrointestinal abnormalities or diseases
- Dependency on alcohol or other drugs
- Patients with malabsorption syndromes affecting drug absorption
- Patients who cannot swallow or patients with conditions that may hamper compliance and/or absorption of the tested product
- Major thoracic and/or abdominal surgery in the preceding 6 weeks before Visit 2
- No adequate hepatic function (bilirubin > 1.5 x UNL or alkaline phosphatase or transaminases > 2.5 x UNL)
- No adequate renal function (serum creatinine > 1.5 x UNL)
- History of or clinical evidence for Hepatitis B infection (if evidence is seen this should be confirmed laboratory tests on HBs-Ag, HBc antibodies or HBs antibodies)
- History of or clinical evidence for Hepatitis C infection (if evidence is seen this should be confirmed laboratory tests on HCV antibodies)
- History of or clinical evidence for HIV infection (if evidence is seen this should be confirmed laboratory tests on HIV antibodies)
- Any concomitant condition that could compromise the objectives of this study and the patient’s compliance
- Within the last six weeks, basal cell skin cancer within 10 cm from the study area chosen for the assessment of actinic keratosis
- Squamous cell carcinoma, porokeratosis, acute rosacea or any stage of lentigo maligna
- Patients with a homozygous inherited deficiency in Dihydropyrimidine dehydrogenase (DPD) activity
- Participation in another clinical trial within the last 4 weeks
- Unavoidable high exposure to sunshine or sunlamps expected during the trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage change from baseline compared to Visit 16 (Day 169) in the number of AK lesions in the observation site (the face and/or the balding scalp) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
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 | No |
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.8.3 |
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 | 5 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |