A microdose is 100 times below the level calculated to yield a pharmacological effect or 100 micrograms, whichever is the lower
Phase 0/I/IIa clinical development specialist Pharmaceutical Profiles reports the completion of a microdosing study.
The company believes it is the start of a new era in drug development in which human Adme (absorption, distribution, metabolism and excretion) data plays an increasing role in candidate selection or deselection.
The study was carried out for Tripep, a Swedish biotech research company that develops and commercialises candidate drugs based on patented and patent-pending technologies.
Tripep is active in several areas, including the research and development of alphaHGA, an HIV-inhibiting drug and it is in this field of research that the microdosing study was utilised.
The sophisticated human microdosing study took less than six months from inception to completion and examined the pharmacokinetics (PK) of the HIV inhibiting molecule in healthy subjects, following dosing with sub-pharmacological, microgram quantities of drug candidate.
The microdosing approach has provided Tripep with pivotal early human PK data on the performance of their candidate drug much more quickly and accurately than would have been possible using conventional development strategies.
Encouragingly for the development of alphaHGA, the microdose study has shown 100% oral bioavailability for the candidate allowing fast-tracking of the molecule into proof-of-concept studies with an enhanced chance of success and significantly reduced risk.
Tripep's Anders Vahlne, acting CEO and head of research, is in no doubt of the benefits of a microdosing study at this stage of development of the peptide, explaining: "the results were very encouraging for the future development work on alphaHGA and helps us design the clinical study on HIV infected individuals expected to start by the end of this year or early next year".
Through its cutting-edge human microdosing service, Pharmaceutical Profiles is combining its own early clinical development capabilities and expertise with ultra-sensitive accelerator mass spectrometry (AMS).
"Microdosing studies provide a 'smarter' way to develop drugs by providing very early human data," explained Ian Wilding, executive chairman of Pharmaceutical Profiles.
"Tripep utilised the microdosing study approach and now with early human data they can clearly see the benefits of undertaking a microdosing study early in the development of their alphaHGA product.
"Many other biotechs and major pharmaceutical companies are actively discussing human microdosing studies with Pharmaceutical Profiles.
"We believe these studies will create a much greater understanding and awareness of the importance of PK and ADME issues in early phase drug development.
"Up to 40% of new drugs currently fail during Phase I trials and human microdosing offers the promise of selecting the best drug candidates before advancing into full development, thereby increasing the chance of success".
AMS is one of the most precise bioanalytical approaches currently available - up to 100,000 times more sensitive than LC-MS/MS and 1,000,000 times more sensitive than liquid scintillation counting (LSC).
A key biomedical application of AMS technology is in the area of human microdosing (also known as 'human Phase 0') studies.
In these studies, one or more drug candidates is administered to humans in single, sub-pharmacological (microgram) levels to obtain early PK and ADME data in order to select the candidate with the optimal PK characteristics.
Microdosing studies have been endorsed by the EMEA, which has determined that a microdose is 100 times below the level calculated to yield a pharmacological effect or 100 micrograms, whichever is the lower.
Human microdosing studies provide the opportunity to terminate drug development programmes early, thus allowing improved compound selection and reduced attrition rates in early clinical development.
