in benzyl alcohol containing and free formulations were associated with an initial spike in plasma DCA concentrations within one hour that returned to near baseline 24 hours post-treatment. There are limitations associated with this Phase I study, such as small sample size (12 patients per treatment arm), that preclude us from drawing conclusions from the two study groups. Study design incorporating Hanley’s Rule of Three2 may have resulted in greater understanding regarding interpreting adverse events, especially within categories where there were “zero.†Additionally, it would have been good to have two additional placebo study arms for purposes of comparison evaluating the benzyl alcohol containing and benzyl alcohol-free formulations without the active ingredient ATX-101. These concerns were addressed in two Phase III clinical trials conducted in Europe3-5 and two Phase III clinical trials conducted in North America (unpublished data).
Based upon the safety data,1 ATX-101 appears to be relatively safe with an associated transient increase of plasma DCA. The most common adverse events of erythema, edema and pain, could be termed “anticipated events†due to the frequency of occurrence and are typical sequela of injection site reactions. Furthermore, these common responses are well aligned with the mechanism of action: localized adipocyte cell death followed by resultant inflammation. Publication of ATX-101 Phase I safety and pharmacokinetic data is an important scientific “look behind the curtain†that provides valuable insight into Phase I clinical trial study design and foundational safety data, while “setting the stage†for future Phase II/III studies that precede arrival of new drugs to market. With great enthusiasm I encourage other researchers, pharmaceutical, and device companies to follow suit, and publish Phase I clinical trial results to cultivate and promote research transparency while sharing important safety data.
Disclosure
The author has no financial conflict of interest to declare.
References
- Walker P, Fellmann J, Lizzul PF. A Phase I Safety and Pharmacokinetic Study of ATX-101: Injectable, Synthetic Deoxycholic Acid for Submental Contouring. J Drugs Dermatol. 2015;14(3):279-84.
- Hanley JA, Lippman-Hand A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA. 1983;249(13):1743-5.
- Ascher B, Hoffmann K, Walker P, Lippert S, Wollina U, Havlickova B. Efficacy, patient-reported outcomes and safety profile of ATX-101 (deoxycholic acid), an injectable drug for the reduction of unwanted submental fat: results from a phase III, randomized, placebo-controlled study. J Eur Acad Dermatol Venereol. 2014;28(12):1707-15.
- Rzany B, Griffiths T, Walker P, Lippert S, McDiarmid J, Havlickova B. Reduction of unwanted submental fat with ATX-101 (deoxycholic acid), an adipocytolytic injectable treatment: results from a phase III, randomized, placebo-controlled study. Br J Dermatol. 2014;170(2):445-53.
- McDiarmid J, Ruiz JB, Lee D, Lippert S, Hartisch C, Havlickova B. Results from a pooled analysis of two European, randomized, placebo-controlled, phase 3 studies of ATX-101 for the pharmacologic reduction of excess submental fat. Aesthetic Plast Surg. 2014;38(5):849-60.
