gms | German Medical Science

16. Jahreskongress für Klinische Pharmakologie

Verbund Klinische Pharmakologie in Deutschland

09. - 10. Oktober 2014, Köln

Safety requirements and timing of safety studies throughout the clinical program for topical products [invited speaker]

Meeting Abstract

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  • presenting/speaker B. Hughes-Formella - bioskin GmbH – Hamburg, Deutschland

16. Jahreskongress für Klinische Pharmakologie. Köln, 09.-10.10.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc14vklipha31

doi: 10.3205/14vklipha31, urn:nbn:de:0183-14vklipha314

Veröffentlicht: 25. September 2014

© 2014 Hughes-Formella.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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Aim: Factors influencing health authority requirements and timing of safety studies during topical development programs will be presented.

Conclusion: The rationale for developing a locally acting, locally applied drug for treatment of skin disease is often the need to restrict the drug to the diseased area of the skin and avoid absorption into the systemic circulation. Because the drug levels at the site of action are generally not correlated with systemic blood levels, the classical schemes for entry into the clinic (single ascending dose, multiple ascending dose) do not apply for topical drugs. Rather, identification of safety issues related to dermal tolerability and systemic exposure resulting from accumulation following repeated applications dictate the safety program requirements.

The timing of safety studies in a topical program depends on the availability of the final formulations. In many cases, modifications of the formulation are made following proof of concept studies. This means that Phase I studiesin earlydevelopment are often supporting studies designed to facilitate subsequent early efficacy and dose-finding studies but are not intended to meet licensing requirements. For example, the first safety study may be necessary to assess dermal safety and PK in order to allow patients to treat with the medication at home but may notprovide the data required for licensing.

The Phase Icutaneous safety studies required for licensingmust beconducted withthe final formulation and may be done in parallel with Phase IIb and III studies. These studies include 21-day cumulative dermal irritation (n=30–35), sensitization potential (n=200), and phototoxic (n=30–35) and photoallergenic potential (n=50) if the formulation absorbs between 290–700 nm.

Maximalexposure PK in patients is a general requirement for new drug developments. Drug must be applied to the maximal body surface area intendedto be treateduntil maximal concentrations and steady state arereached. This data may be obtained in subgroups of patients during Phase III or separately in dedicated Phase I studies. In addition, depending on the safetyprofile of the drug and expected systemic exposure, additional studies such as drug-drug interaction or thorough QT/QTc may also be required.

Foresight and strategic planning are essential to avoid unnecessary and costly studies.