Safety and Efficacy of Ingenol Mebutate Once Daily for 2 or 3 Consecutive Days in Subjects With Actinic Keratosis

LEO Pharma

Status and phase: Completed; Phase 2; Phase 1

Conditions: Actinic Keratosis

Treatments: Drug: placebo; Drug: Ingenol mebutate gel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01820260

LP0105-1012

Details and patient eligibility

About

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

Enrollment: 395 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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395 participants in 14 patient groups, including a placebo group

Part 1A: Ingenol mebutate gel 0.005%

Experimental group

Description:

Open-label, dose escalation, 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.018% for 3 days treatment

Active Comparator group

Description:

Randomized, 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.018% for 2 days treatment

Active Comparator group

Description:

Randomized 2 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.027% for 3 days treatment

Active Comparator group

Description:

Randomized 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 2: Ingenol mebutate gel 0.027% for 2 days treatment

Active Comparator group

Description:

Randomized 2 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 2: Placebo for 3 days treatment

Placebo Comparator group

Description:

Randomized 3 days treatment

Treatment:

Drug: placebo

Part 2: Placebo for 2 days treatment

Placebo Comparator group

Description:

Randomized 2 days treatment

Treatment:

Drug: placebo

Part 1A: Ingenol mebutate gel 0.008%

Experimental group

Description:

Open-label, dose escalation, 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.012%

Experimental group

Description:

Open-label, dose escalation, 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.027%

Experimental group

Description:

Open-label, dose escalation, 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.04%

Experimental group

Description:

Open-label, dose escalation, 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 1B: Ingenol mebutate gel 0.06%

Experimental group

Description:

Open-label, dose escalation, 2 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 1A: Ingenol mebutate gel 0.018%

Experimental group

Description:

Open-label, dose escalation, 3 days treatment

Treatment:

Drug: Ingenol mebutate gel

Part 1B: Ingenol mebutate gel 0.04%

Experimental group

Description:

Open-label, dose escalation, 2 days treatment

Treatment:

Drug: Ingenol mebutate gel