Clinical trial NCT01820260: Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis
Official title: Safety and Efficacy of Escalating Doses of Ingenol Mebutate Once Daily for Two or Three Consecutive Days When Used on Full Face, Full Balding Scalp or Approximately 250 cm2 on the Chest in Subjects With Actinic Keratosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Actinic Keratosis
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2013-03-28
Enrollment: 395
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1 was an open-label, dose escalation. Part 2 was a randomised, double-blind, parallel group
Primary purpose: TREATMENT

Brief summary: To identify the Maximum Tolerated Dose levels of ingenol mebutate gel after once daily treatment for 2 or 3 consecutive days and to evaluate efficacy of ingenol mebutate gel in different doses after once daily treatment for 2 or 3 consecutive days compared to vehicle gel


Eligibility criteria: Inclusion Criteria:

* Subjects must be competent to understand the nature of the trial and provide informed consent
* Part 1: Subjects with 5 to 20 clinically typical, visible and discrete AKs on the face Part 2: Subjects with 5 to 20 clinically typical, visible and discrete AKs on either the face, the balding scalp (the balding part of the scalp should be at least 25 cm2) or a contiguous area of approximately 250 cm2 on the chest
* Subject at least 18 years of age
* Female subjects must be of either:

  1. Non-childbearing potential, i.e. post-menopausal or have a confirmed clinical history of sterility (e.g. the subject is without a uterus) or,
  2. Childbearing potential, provided there is a confirmed negative urine pregnancy test prior to trial treatment, to rule out pregnancy
* Female subjects of childbearing potential1 must be willing to use effective contraception at trial entry and until completion

Exclusion Criteria:

* Location of the treatment area (full face, full balding scalp or chest)

  * within 5 cm of an incompletely healed wound,
  * within 10 cm of a suspected basal cell carcinoma (BCC) or squamous cell carcinoma (SCC
* Prior treatment with ingenol mebutate gel within the treatment area
* Lesions in the treatment areas that have:

  * atypical clinical appearance (e.g., hypertrophic, hyperkeratotic or cutaneous horns) and/or,
  * recalcitrant disease (e.g., did not respond to cryotherapy on two previous occasions
* History or evidence of skin conditions other than the trial indication that would interfere with the evaluation of the trial medication (e.g., eczema, unstable psoriasis, xeroderma pigmentosum)
* Use of cosmetic or therapeutic products and procedures which could interfere with the assessments of the treatment areas.
* Clinical diagnosis/history or evidence of any medical condition that would expose a subject to an undue risk of a significant AE or interfere with assessments of safety and efficacy during the course of the trial, as determined by the investigator's clinical judgment
* Any abnormal laboratory tests that are medically significant and would impact the safety of the subjects or the interpretation of the trial results, as determined by the investigator's judgment
* Anticipated need for hospitalisation or out-patient surgery during the first 15 days after the first trial medication application. Note that cosmetic/therapeutic procedures are not excluded if they fall outside of the criteria detailed in Prohibited Therapies or Medications
* Known sensitivity or allergy to any of the ingredients in ingenol mebutate gel
* Presence of acute sunburn within the treatment areas
* Current enrolment or participation in an investigational clinical trial within 30 days of entry into this trial.
* Subjects previously assigned to treatment in Part 1 or rand
* Female subjects who are breastfeeding.
* In the opinion of the investigator, the subject is unlikely to comply with the Clinical Study Protocol (e.g. alcoholism, drug dependency or psychotic state)

Primary outcomes:
measure: Part 1: To Identify the Maximum Tolerated Dose (MTD) Levels After Once Daily Treatment for 2 or 3 Days
timeFrame: 8 days after initial treatment
measure: Part 2: Number of Subjects With Complete Clearance of AKs
timeFrame: 8 weeks
Secondary outcomes:
measure: Part 2: Reduction in AK Count
timeFrame: From baseline to Week 8
measure: Part 2: Number of Subjects With Partial Clearance of AKs
timeFrame: Week 8
Other outcomes:
Locations:
city: Carmel
country: United States
facility: Laser & Skin Surgery Center of Inidana
state: Indiana
Study officials:
affiliation: Laser & Skin Surgery Center of Indiana
name: C. William Hanke, MD
role: PRINCIPAL_INVESTIGATOR
References: