Safety and Dose Finding Study of New Vehicle Formulations Containing Ingenol Mebutate to Treat Actinic Keratosis on the Forearm

A Seamless Phase 1/2 Exploratory Multi-centre, Investigator-blind, Dose Escalation Study (Study Part 1), Followed by a Randomised, Intra-subject, Active Controlled Efficacy Study of Different Ingenol Mebutate Formulations Applied to the Forearm for 2 Consecutive Days (Study Part 2)

The purpose of this study is to determine if the new vehicle formulations containing ingenol mebutate are as safe and effective as Picato® gel 0.05% (it's current vehicle formulation) when applied to AK lesions on the forearm for two consecutive days.

Study Overview

• Status: Completed
• Conditions: Actinic Keratosis
• Intervention / Treatment: Drug: once daily for two consecutive days (Picato)

Detailed Description

This study will be run in 2 parts. The first part involves applying escalating concentrations of the new vehicle formulations containing ingenol mebutate to AKs on the forearms. Reactions and safety will be compared to Picato® (a registered and marketed ingenol mebutate gel) to ascertain if the new vehicle formulations are at least as safe and effective as Picato® . The purpose of part 2 is to select the concentration in the "new formulation" that produces this same, if not better response, as Picato® and with a similar or better safety profile.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Dermatology department
    • Woolloongabba, Queensland, Australia, 4102
      • Specialist Connect

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be male or female and at least 18 years of age.
• Female patients must be of non-childbearing potential or if of childbearing potential then negative serum and urine pregnancy test and using effective contraception.
• Ability to provide informed consent.

Exclusion Criteria:

• location of the selected treatment area within 5cm of an incompletely healed wound or within 5cm of a suspected basal cell carcinoma or squamous cell carcinoma
• undergone Cosmetic or therapeutic procedures within 2cm of the selected treatment area in the 2 weeks prior to the treatment visit
• presence of sunburn within the selected treatment areas
• use of acid-containing therapeutic products within 2cm of the selected treatment area in the 2 weeks prior to the treatment visit
• previous enrolment in this clinical trial
• prior treatment with ingenol mebutate on the forearms
• use of topical moisturisers/creams/lotions, artificial tanners or topical steroids within 2cm of the selected treatment areas in the 2 weeks prior to the treatment visit
• treatment with immunomodulators, or interferon/interferon inducers or systemic medications that suppress the immune system within 4 weeks of the treatment visit
• treatment with 5-FU, imiquimod, diclofenac,or photodynamic therapy within 2 cm of the treatment area in the 8 weeks prior to the treatment visit
• use of systemic retinoids
• those who are currently participating in any other clinical trial
• females who are pregnant or are breastfeeding
• those known or suspected or not being able to comply with the requirements of the protocol or provide consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Picato® 0.05% gel; once daily for two consecutive days	Drug: once daily for two consecutive days (Picato); Other Names: Picato® 0.05% gel; escalating doses of ingenol mebutate vehicle formulation 1; escalating doses of ingenol mebutate vehicle formulation 2; escalating doses of ingenol mebutate vehicle formulation 3
Experimental: ingenol mebutate vehicle formulation 1; once daily for two consecutive days	Drug: once daily for two consecutive days (Picato); Other Names: Picato® 0.05% gel; escalating doses of ingenol mebutate vehicle formulation 1; escalating doses of ingenol mebutate vehicle formulation 2; escalating doses of ingenol mebutate vehicle formulation 3
Experimental: ingenol mebutate vehicle formulation 2; once daily for two consecutive days	Drug: once daily for two consecutive days (Picato); Other Names: Picato® 0.05% gel; escalating doses of ingenol mebutate vehicle formulation 1; escalating doses of ingenol mebutate vehicle formulation 2; escalating doses of ingenol mebutate vehicle formulation 3
Experimental: ingenol mebutate vehicle formulation 3; once daily for two consecutive days	Drug: once daily for two consecutive days (Picato); Other Names: Picato® 0.05% gel; escalating doses of ingenol mebutate vehicle formulation 1; escalating doses of ingenol mebutate vehicle formulation 2; escalating doses of ingenol mebutate vehicle formulation 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of 3 new vehicle formulations containing ingenol mebutate compared to Picato® gel applied topically once daily for two consecutive days to four separate treatment areas containing actinic keratosis on the forearm	Safety data to be collected via CRF entries of AEs/SAEs and photographs. Relative skin reactions for comparison to Picato®.	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate treatment responses on AK of selected concentration of ingenol mebutate containing vehicle formulation from Part 1 compared to Picato® gel as assessed by reduction in the number of selected AK lesions 2 months after treatment	Assessed by visible and imaged lesion count	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of the new ingenol mebutate vehicle formulation (ascertained in Part 1) compared to Picato® gel applied topically once daily for 2 consecutive days to 4 separate treatment areas containing actinic keratosis on the forearm	Safety data to be collected via CRF entries of AEs/SAEs and photographs. Treatment responses assessed by Reflective confocal microscopy scoring of visible selected AK lesions	8 weeks

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Principal Investigator: Lynda Spelman, MD, Specialist Connect; Principal Investigator: Hans P Soyer, MD, Dermatology Department, Princess Alexandra Hospital

Publications and helpful links

Helpful Links

• Therapeutic Goods Administration
• LEO Pharma

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: February 28, 2013
• First Submitted That Met QC Criteria: March 1, 2013
• First Posted (Estimate): March 4, 2013

Study Record Updates

• Last Update Posted (Estimate): September 10, 2014
• Last Update Submitted That Met QC Criteria: September 8, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Precancerous Conditions; Keratosis, Actinic; Keratosis
• Other Study ID Numbers: LP0085-1000