Atlantia Clinical Trials is a world class provider of human clinical studies, which are composed of well-defined steps necessary for their successful completion. Among them, a pivotal role is played by pharmacokinetic and bioavailability studies. Steve Morrison explains their importance for the industry.
Bioavailability studies
Bioavailability studies and pharmacokinetic studies have their origins in the pharmaceutical sector. Bioavailability studies traditionally look at the amounts and time profile of a bioactive substance in the bloodstream, after single and multiple administrations of a product. Pharmacokinetic studies can have slightly broader aims to look not only at the rate and extent of the absorption of the active constituent (usually a small molecule in the case of a drug), but also at the metabolism and excretion of that bioactive entity once it has entered the systemic circulation.
These types of studies don’t always transfer easily to the functional food setting because it is less common for the bioactive agent(s) within functional foods to exert their physiological affects through that traditional, ‘drug-like’ route of absorption into the bloodstream. Also because there are often groups of bioactive entities within some functional foods which jointly impact on health.
A good example would be polyphenolic compounds that exist in a number of fruit or vegetable extracts. So, many bioactives within functional food ingredients and food supplements act either locally, in the gastrointestinal tract, or through a range of secondary downstream metabolites. For that reason, these types of studies are not included in all of Atlantia’s clinical trials. However, we routinely take blood samples in most of the studies we perform and so retain the capacity to take samples for pharmacokinetic and bioavailability studies, where appropriate.
It is worth noting that another type of study, so called pharmacodynamic studies, where the time-course of the desired physiological effect (e.g. a change in blood sugar levels, feelings of anxiety or perhaps a change in cognitive skills) are measured and related to the timing of the investigational product administration, are more commonly the focus for functional foods.
EFSA Health claims and bioavailability studies
EFSA primarily seeks strong proof of a reproducible cause and effect relationship existing between the consumption of the food (or food ingredient) and the proposed physiological health benefit. This is first and foremost driven by outcomes data from the human studies. However, in reviewing health claim applications, EFSA scientists are also influenced by whether there is a plausible mode of action behind the reported benefits and, where appropriate, whether any kind of dose response relationship exists. That correlation between dose and response is not something that is necessarily as closely correlated for functional foods as it is with drug products. Pharmacokinetic and/or bioavailability studies could, in some cases, be beneficial to health claim applications if there is a relatively simple bioactive profile and where systemic absorption occurs. In such cases the data could be very supportive. However, pharmacodynamic studies remain the mainstay of work in these functional food development programs.
The first EFSA health claim ever approved
Fruitflow was a ground-breaking submission under the Nutrition and Health Claims Regulation (NHCR), EC Regulation No: 1924/2006. It’s regulatory success, in gaining the first endorsement from EFSA’s NDA Panel, hinged on a consistent yet modest package of well-designed clinical studies, using an appropriate target population for functional foods and a consistent clear primary endpoint. The primary endpoint for these clinical studies was a measure of levels of platelet aggregation in the blood samples taken from study volunteers and that created a pharmacodynamic profile. The fruitflow extract contained > 30 bioactives, many of them polyphenolic compounds, which all contributed, to a greater or lesser extent, to the overall effect of the product on blood flow and circulation. It would not have been possible (or practical) to measure all of these compounds in the blood using a traditional pharmacokinetic approach. Instead the talented research team behind Fruitflow were able to carefully identify all these compounds in the extract using chromatographic techniques and to subsequently demonstrate that they had a role to play in the proposed effect through ex-vivo studies. That data was clearly presented in the health claim submission although I think it is important to acknowledge that such a complex profile of bioactives is also not the normal for functional foods either.
How do bioavailability studies work?
Pharmacokinetic and bioavailability studies will probably remain of more core interest to our pharmaceutical clients and pharmacodynamic studies will continue to be the focus of the nutraceutical / functional food clients, but not exclusively. It has been reported for several years that there is a real convergence between these two important health sectors and both sectors are increasingly looking at their health promoting assets to see where they best fit from a clinical and commercial perspective. Sometimes that means targeting both sectors and developing packages of clinical data to suit disease modifying agents in a patient population and the maintenance of health in a more general pre-disease population. We have seen this broader perspective with clients over recent years and can help to design the early studies so that they can be run efficiently and quickly but also keeping all options on the table until the human activity/safety profile is better understood.
Recent advancements in technologies and methods in clinical studies
Advances in technology are driving great changes in the field of clinical trials and especially where the study of free-living subjects are concerned. So called “wearable technology”, such a continuous blood sugar monitors, ambulatory blood pressure monitors, activity meters etc, are revolutionizing the way studies are performed and allowing remote data access. It can be so much more valuable to be able to gather multiple data points while the subjects go about their normal lives, and over a period of many days or weeks, rather than having to only focus on single measures taken at a clinic visit. The use of mobile phone “Apps” to gather subjective data on how subjects are feeling and to monitor any adverse effects is also greatly improving the quality of the data we can gather in the studies and these technologies are so well aligned with the way we live modern lives. Atlantia has developed and continues to work on proprietary Apps and digital tools which allow for better data collection in a more real time setting. Our ability to stay connected with the study participants and being able to remotely monitor compliance, both of study product consumption and completion of daily symptom diaries is a feature that many of our clients value.The advancement in technology also strongly supports the move to decentralized clinical trials, or a hybrid design that minimizes on-site participant visits, without having to sacrifice data collection and endpoints. This further increases the potential to conduct large scale studies, with diverse demographical, cultural, and ethnic populations, that could in turn shorten the timeline on delivering a company’s clinical studies and time to market.