This is a single dose, randomized, cross-over pharmacokinetic study in healthy volunteers
(n=12) of two dietary supplement formulations. The Product B® IsaGenesis® formulation
represents a newer reformulation of an existing product known simply as IsaGenesis®. Beyond
some changes in the relative abundance of some of the constituents of the earlier IsaGenesis®
formulation, the Product B® IsaGenesis® product has been formulated as a liquid-gel
formulation (rather than a dried powder extract) which is theorized to enhance the absorption
and bioavailability of the contained botanical constituents. The purpose of this study is to
compare the two dietary supplement formulations relative to the absorption of two compounds
contained within the supplement known as the flavonolignans silybin A and silybin B into the
bloodstream after oral administration of capsules.
The study involves a total of five (5) visits to the University of Florida Shands CRC located
in the Clinical Translational Research Building in Gainesville, and is expected to last
approximately 6 weeks.
Screening / Informed Consent:
The Screening Visit will be conducted in the CRC and is expected to last approximately 1
After obtaining written Informed Consent, study subjects will be interviewed about their
medical history and the protocol's Inclusion/Exclusion criteria will be discussed. All
potential participants must be nonsmokers, not taking prescription or over-the-counter
medications or botanical/nutritional supplements (inclusive of vitamins). Additionally,
participants are requested to abstain from alcohol use 24 hours prior to the study health
screen lab work or any scheduled study visit should they participate fully in the study.
During this initial visit, interested subjects will have blood samples drawn for health
screening purposes including baseline serum chemistries, complete blood count, urinalysis,
and a urine pregnancy test (women) which will precede a subsequently scheduled physical exam
and possible study participation. Copies of the laboratory results will be made available to
study subjects at their request. Lastly, a 12-lead electrocardiogram will be obtained.
Study Visits The following section describes the study procedures for the two major study
visits at the CRC following Informed Consent and a satisfactory medical screening.
Following an overnight fast (abstention from eating any food items after 9 pm in the evening
prior to the scheduled visit), subjects will arrive at the CRC the morning of the active
Study Days where they will remain for approximately 8 hours on each day. After checking in,
and under medical supervision, skilled CRC staff will place an indwelling venous catheter in
each subject's arm to facilitate serial blood sampling. Female subjects will provide a urine
sample for a pregnancy test. At approximately 8:00 AM subjects will be administered 2
capsules of either Product B® IsaGenesis® (2 capsules; 1280 mg per capsule) or IsaGenesis® (2
capsules; 1070 mg per capsule) depending on the randomization sequence assigned by the
Investigational Pharmacy Services. Capsules will be administered with 240 ml of room
temperature water which the subjects will be asked to drink in its entirety. Subjects will
remain in a fasted state for 4 additional hours following administration of either
formulation to eliminate any potential effect of food on absorption. Standard meals will be
served to all subjects at least 4 hours post-dosing. The composition and amount of food eaten
throughout the day will be recorded.
Blood sample collection and processing will be done by an indwelling venous catheter to
facilitate serial blood sampling, a total of 9 blood samples (~10 ml each) will be taken over
an 8-hour period during each of the two primary study days. Specific time points of blood
collection will be immediately prior to the dose (0 time point), of either Product B®
IsaGenesis® (2 capsules; 1280 mg per capsule) or IsaGenesis® (2 capsules; 1070 mg per
capsule) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours.
This single dose assessment of the Product B® IsaGenesis® (2 capsules; 1280 mg per capsule)
or IsaGenesis® (2 capsules; 1070 mg per capsule) pharmacokinetics will be conducted with each
of the two described formulations as a single dose assessment in a randomized crossover
fashion. Following the completion of the initially product administration and sample
collection, a minimum 7-day wash-out period will occur prior to scheduling each subject's
return for the assessment of the alternate product (under identical study conditions and
Study Exit Visit The investigators will have the subjects return within 7 days of completing
the second study formulation pharmacokinetics assessment to have "exit" follow-up lab work
consisting of a basic serum chemistry panel and CBC as well as urinalysis.
- Signed Informed Consent
- Race or ethnicity: no restrictions
- Body Mass Index (BMI) between 18.5 to 28 kg/m2 (inclusive)
- Satisfactory completion of the screening medical history, physical exam, and
- Females of child-bearing potential must have a negative urine pregnancy test prior to
enrollment and avoid pregnancy during study participation.
- With the exception of oral contraceptives, subjects must not be taking prescription or
over the counter medication for the duration of study participation
- Subjects must have no ongoing use of any botanical/nutritional supplement, vitamin, or
energy drink for the duration of study participation
- The presence of a known allergy to ragweed and related plants from the
Asteraceae/Compositae plant family. Members of this family include ragweed,
chrysanthemums, marigolds, daisies, and some others. Milk thistle may cause an
allergic reaction in people who are sensitive to these plants.
- A history (within the past year) or presence of clinically significant cardiovascular,
cerebrovascular, renal, hepatic, gastrointestinal, pulmonary, immunological,
hematological, endocrine, or neurologic disease will render subjects ineligible for
- The presence of any surgical or medical condition (active or chronic) that may
interfere with drug absorption, distribution, metabolism, or excretion including;
- Gastric bezoar
- Swallowing disorders
- GI obstruction
- Severe dysphagia
- Crohn's disease
- A positive urine pregnancy test.
- Any concomitant prescription medication, over-the-counter medication, herbal or other
supplements, and vitamins during the study period.