Ignite Creation Date:
2025-12-25 @ 12:33 AM
Ignite Modification Date:
2025-12-30 @ 5:29 PM
Study NCT ID:
NCT04940767
Status:
COMPLETED
Last Update Posted:
2023-06-22
First Post:
2021-06-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Companion Treatment Study for Patients With Moderate to Severe Acne Vulgaris
Sponsor:
Edward Lain, MD
Organization:
Study Overview
Official Title:
A Prospective, Multicenter, Randomized, Evaluator-Blinded, Study to Evaluate the Safety and Efficacy of AMZEEQ® Companion Treatment With Oral Isotretinoin Therapy in Patients With Moderate to Severe Acne Vulgaris
Status:
COMPLETED
Status Verified Date:
2023-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Acne vulgaris is a common disease of both males and females, usually manifesting initially during adolescence. The use of retinoic acid analogues such as adapalene, tazarotene and isotretinoin are also commonly prescribed to treat inflammation; dysregulated sebum production and comedonal acne. This study seeks to evaluate the efficacy and safety of concomitant use of both AMZEEQ® and oral isotretinoin compared to oral isotretinoin only use and to explore sequence dosing of both products as part of a long-term management protocol for acne vulgaris.
Detailed Description:
Acne vulgaris is a common disease of both males and females, usually manifesting initially during adolescence. The primary pathologic events are initiated in the pilosebaceous units, especially of sebaceous-gland-bearing areas of the face, chest, and back as a result of increased androgen stimulation initiated at adrenarche or puberty. As a result of both abnormal keratinization of the infra-infundibular portion of the pilosebaceous follicle and increased sebum produced in the gland, a blockage of the duct results in the unapparent clinical lesion of the microcomedone. Continued blockage, colonization of the follicle by Cutibacterium acnes (C. acnes), and generation of multiple chemoattractant and proinflammatory moieties may result in non-inflammatory clinical lesions, comedones, and inflammatory lesions: papules, pustules, nodules, and cysts.
Acne treatments vary widely and frequently involve therapy combination approaches to achieve the objectives of initial disease control and long-term maintenance of effect. Antibiotics, especially clindamycin, minocycline, and doxycycline, have been prescribed as acne treatments for many years. These antibiotics effectively control the signs of inflammatory acne while patients continue to use them. Equally, the use of retinoic acid analogues such as adapalene, tazarotene and isotretinoin are also commonly prescribed to treat inflammation; dysregulated sebum production and comedonal acne.
AMZEEQ® is a topical lipophilic foam containing 4% minocycline that was approved in the US for the treatment of acne vulgaris in 2019 although minocycline containing products have been available in the US since the early 1970s. Minocycline is a semi-synthetic, second-generation tetracycline that imparts both a bacteriostatic and anti-inflammatory effect in the treatment of inflammatory acne. In addition, AMZEEQ® has been previously shown in clinical studies to positively impact comedonal acne.
Adverse events relating to oral minocycline use include tissue depigmentation primarily related to the ability of minocycline to complex with metals such as calcium and sequester into a variety of tissues e.g. bone, teeth and skin; CNS effects affecting the vestibular system e.g. dizziness, blurred vision and rare episodes of intracranial hypertension. Oral minocycline has also been implicated in rare but serious reactions such as anaphylaxis, erythema multiforme and DRESS syndrome. Interestingly, these findings do not appear to have much applicability to topically applied minocycline (as AMZEEQ®), likely due to significantly lower systemic exposure to minocycline when dosed by the topical route.
Isotretinoin is a retinoic acid analogue (13-cis-retinoic acid) supplied as oral capsules. and was approved in the US for the treatment of severe acne vulgaris in 1982 under the brand name Accutane®. Isotretinoin is the only therapy that impacts on all of the major aetiological factors implicated in acne. It achieves this by influencing cell-cycle progression, cellular differentiation, cell survival and apoptosis which results in a significant reduction in sebum production, influences comedogenesis, lowers surface and ductal C. acnes and has anti-inflammatory properties.
Although isotretinoin can ameliorate all four of the primary drivers of disease pathology, resulting in impressive clinical outcomes for severe and/or recalcitrant patients, the safety of isotretinoin continues to be a focal point for prescribers. As a teratogen, isotretinoin impacts the function of Hox genes that disrupts genetic control of axial patterning during embryo development. This can lead to developmental defects of the heart, spinal cord, palate, mandible, and other skeletal and neurological disorders such as hydrocephalus, microcephaly, and mental retardation. As such, careful monitoring of patients of both sexes via a risk evaluation and mitigation program (REMS) such as iPledge is a prerequisite for the safe use of the isotretinoin-containing products. Consequently, prescribers seek to discontinue oral isotretinoin use when it is appropriate to do so and to introduce other products with the goal of achieving a sustained long term clinical benefit for the patient.
The combination of these two, well-characterized acne treatments with two separate administration routes presents an intriguing, combined proposition of achieving rapid control of disease coupled with long-term disease management possibilities. As such this study seeks to evaluate the efficacy and safety of concomitant use of both AMZEEQ® and oral isotretinoin compared to oral isotretinoin only use and to explore sequence dosing of both products as part of a long-term management protocol for acne vulgaris.
Acne treatments vary widely and frequently involve therapy combination approaches to achieve the objectives of initial disease control and long-term maintenance of effect. Antibiotics, especially clindamycin, minocycline, and doxycycline, have been prescribed as acne treatments for many years. These antibiotics effectively control the signs of inflammatory acne while patients continue to use them. Equally, the use of retinoic acid analogues such as adapalene, tazarotene and isotretinoin are also commonly prescribed to treat inflammation; dysregulated sebum production and comedonal acne.
AMZEEQ® is a topical lipophilic foam containing 4% minocycline that was approved in the US for the treatment of acne vulgaris in 2019 although minocycline containing products have been available in the US since the early 1970s. Minocycline is a semi-synthetic, second-generation tetracycline that imparts both a bacteriostatic and anti-inflammatory effect in the treatment of inflammatory acne. In addition, AMZEEQ® has been previously shown in clinical studies to positively impact comedonal acne.
Adverse events relating to oral minocycline use include tissue depigmentation primarily related to the ability of minocycline to complex with metals such as calcium and sequester into a variety of tissues e.g. bone, teeth and skin; CNS effects affecting the vestibular system e.g. dizziness, blurred vision and rare episodes of intracranial hypertension. Oral minocycline has also been implicated in rare but serious reactions such as anaphylaxis, erythema multiforme and DRESS syndrome. Interestingly, these findings do not appear to have much applicability to topically applied minocycline (as AMZEEQ®), likely due to significantly lower systemic exposure to minocycline when dosed by the topical route.
Isotretinoin is a retinoic acid analogue (13-cis-retinoic acid) supplied as oral capsules. and was approved in the US for the treatment of severe acne vulgaris in 1982 under the brand name Accutane®. Isotretinoin is the only therapy that impacts on all of the major aetiological factors implicated in acne. It achieves this by influencing cell-cycle progression, cellular differentiation, cell survival and apoptosis which results in a significant reduction in sebum production, influences comedogenesis, lowers surface and ductal C. acnes and has anti-inflammatory properties.
Although isotretinoin can ameliorate all four of the primary drivers of disease pathology, resulting in impressive clinical outcomes for severe and/or recalcitrant patients, the safety of isotretinoin continues to be a focal point for prescribers. As a teratogen, isotretinoin impacts the function of Hox genes that disrupts genetic control of axial patterning during embryo development. This can lead to developmental defects of the heart, spinal cord, palate, mandible, and other skeletal and neurological disorders such as hydrocephalus, microcephaly, and mental retardation. As such, careful monitoring of patients of both sexes via a risk evaluation and mitigation program (REMS) such as iPledge is a prerequisite for the safe use of the isotretinoin-containing products. Consequently, prescribers seek to discontinue oral isotretinoin use when it is appropriate to do so and to introduce other products with the goal of achieving a sustained long term clinical benefit for the patient.
The combination of these two, well-characterized acne treatments with two separate administration routes presents an intriguing, combined proposition of achieving rapid control of disease coupled with long-term disease management possibilities. As such this study seeks to evaluate the efficacy and safety of concomitant use of both AMZEEQ® and oral isotretinoin compared to oral isotretinoin only use and to explore sequence dosing of both products as part of a long-term management protocol for acne vulgaris.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?: