Solar Lentigines Treatment With the Triple Combination Cream

Solar Lentigines Treatment With the Triple Combination Cream (Hydroquinone 4%, Tretinoin 0.05%, and Fluocinolone Acetonide 0.01%). Randomized, Double Blind, Controlled Trial.

Background

• Lentigines are usually the first sign of photoaging and may produce a significant impact on patients' quality of life.
• There is no a treatment of choice for this condition.
• Solar lentigines and melasma share similar physiopathologic characteristics.
• The triple combination (TC) cream (hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%) has been effective and safe for the treatment of melasma and other hyperpigmented lesions.

Hypothesis

* The TC cream will be effective and safe for the treatment of solar lentigines on the back of the hands.

Patients and methods

• 22 patients with solar lentigines were selected and their right hand or left hand were selected at random to be treated with either TC cream or tretinoin 0.05% cream once daily for up 12 weeks.
• Patients were instructed to apply both creams on the whole back of the hand and not only in the lentigines, and to use a broad-spectrum sunscreen (SPF 50+, UVA-PF 28) daily in both hands.
• Clinical assessments of Target Lesion Pigmentation, Physician's Global Assessment of Improvement and a Subject's Self-Assessment questionnaire were collected for data analysis at weeks 4, 8, and 12 after starting the treatment and 3 month post-treatment.
• Statistical methods: The ordinally scaled efficacy measures underwent rank transformation and were analyzed by analysis of variance to test the null hypothesis of no differences among treatments. We performed Mann-Whitney and Wilcoxon tests and the XLSTAT 2009 software was used.

Study Overview

• Status: Completed
• Conditions: Lentigo
• Intervention / Treatment: Drug: Triple combination cream; Drug: Tretinoin 0.05%

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Santiago, Chile, 6904413
    • Pontificia Universidad Catolica de Chile

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects of both sexes of 30 - 80 years of age.
• Phototype II-V.
• Postmenopausal women of childbearing age or users of any contraception method with negative pregnancy test (beta subunit chorionic gonadotropin in the blood) at baseline and that maintain the contraceptive treatment during the investigation.
• Subjects with more than 10 solar lentigines on the back of each hand wich were no treated in the last 6 months

Exclusion Criteria:

• Patients under 30 or over 80 years of age.
• Skin types I and VI.
• Less than 10 solar lentigines on the back of each hand.
• Patients who have received or are receiving any other treatment for lentigines of the back of hands.
• Women of childbearing age without contraceptive therapy.
• Pregnancy or lactation.
• History of hypersensitivity to any component of the drugs.
• Simultaneous use of other topical skin lightening.
• Patient refusal to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triple combination cream; The triple combination cream (hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%) was applied on the whole back of one hand.	Drug: Triple combination cream; The triple combination cream (hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%) was applied on the whole back of one hand once daily for up 12 weeks.; Other Names: Tri-luma; Drug: Tretinoin 0.05%; Tretinoin 0.05% cream was applied on the whole back of the other hand once daily for up 12 weeks.; Other Names: Retacnyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Target lesion pigmentation becomes equal or slightly darker than the surrounding skin	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Improvement in physician's global assessment	3 months

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Collaborators: Galderma R&D
• Investigators: Principal Investigator: William A Romero, MD, Pontificia Universidad Catolica de Chile; Study Chair: Emilia M Zegpi, MD, Pontificia Universidad Catolica de Chile

Publications and helpful links

General Publications

• Gupta AK, Gover MD, Nouri K, Taylor S. The treatment of melasma: a review of clinical trials. J Am Acad Dermatol. 2006 Dec;55(6):1048-65. doi: 10.1016/j.jaad.2006.02.009. Epub 2006 Sep 28.
• Rendon M, Berneburg M, Arellano I, Picardo M. Treatment of melasma. J Am Acad Dermatol. 2006 May;54(5 Suppl 2):S272-81. doi: 10.1016/j.jaad.2005.12.039.
• Fleischer AB Jr, Schwartzel EH, Colby SI, Altman DJ. The combination of 2% 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented lesions in two double-blind multicenter clinical studies. J Am Acad Dermatol. 2000 Mar;42(3):459-67. doi: 10.1016/s0190-9622(00)90219-6.
• Draelos ZD. The combination of 2% 4-hydroxyanisole (mequinol) and 0.01% tretinoin effectively improves the appearance of solar lentigines in ethnic groups. J Cosmet Dermatol. 2006 Sep;5(3):239-44. doi: 10.1111/j.1473-2165.2006.00260.x.
• Palumbo A, d'Ischia M, Misuraca G, Prota G. Mechanism of inhibition of melanogenesis by hydroquinone. Biochim Biophys Acta. 1991 Jan 23;1073(1):85-90. doi: 10.1016/0304-4165(91)90186-k.
• Petit L, Pierard GE. Analytic quantification of solar lentigines lightening by a 2% hydroquinone-cyclodextrin formulation. J Eur Acad Dermatol Venereol. 2003 Sep;17(5):546-9. doi: 10.1046/j.1468-3083.2003.00808.x.
• Weinstein GD, Nigra TP, Pochi PE, Savin RC, Allan A, Benik K, Jeffes E, Lufrano L, Thorne EG. Topical tretinoin for treatment of photodamaged skin. A multicenter study. Arch Dermatol. 1991 May;127(5):659-65.
• Taylor SC, Torok H, Jones T, Lowe N, Rich P, Tschen E, Menter A, Baumann L, Wieder JJ, Jarratt MM, Pariser D, Martin D, Weiss J, Shavin J, Ramirez N. Efficacy and safety of a new triple-combination agent for the treatment of facial melasma. Cutis. 2003 Jul;72(1):67-72.
• Ferreira Cestari T, Hassun K, Sittart A, de Lourdes Viegas M. A comparison of triple combination cream and hydroquinone 4% cream for the treatment of moderate to severe facial melasma. J Cosmet Dermatol. 2007 Mar;6(1):36-9. doi: 10.1111/j.1473-2165.2007.00288.x.
• Torok H, Taylor S, Baumann L, Jones T, Wieder J, Lowe N, Jarret M, Rich P, Pariser D, Tschen E, Martin D, Menter A, Weiss J. A large 12-month extension study of an 8-week trial to evaluate the safety and efficacy of triple combination (TC) cream in melasma patients previously treated with TC cream or one of its dyads. J Drugs Dermatol. 2005 Sep-Oct;4(5):592-7.
• Ortonne JP, Pandya AG, Lui H, Hexsel D. Treatment of solar lentigines. J Am Acad Dermatol. 2006 May;54(5 Suppl 2):S262-71. doi: 10.1016/j.jaad.2005.12.043.

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: September 10, 2009
• First Submitted That Met QC Criteria: September 10, 2009
• First Posted (Estimate): September 11, 2009

Study Record Updates

• Last Update Posted (Estimate): September 11, 2009
• Last Update Submitted That Met QC Criteria: September 10, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: hydroquinone; tretinoin; lentigo; fluocinolone acetonide
• Additional Relevant MeSH Terms: Skin Diseases; Hyperpigmentation; Pigmentation Disorders; Melanosis; Lentigo; Antineoplastic Agents; Dermatologic Agents; Keratolytic Agents; Tretinoin
• Other Study ID Numbers: LEN-TriC-001