Effect of Gamma-cyclodextrin on the Bioavailability of Ginsenosides

Dissolution and Pharmacokinetic of Ginsenosides Released From Cyclodextrin Based Chewable Tablets: a Comparative, Randomized, Crossover, Open-label Study in Healthy Human Subjects.

Status

Suspended

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04932265

Enrollment

Registered

2021-06-21

Start date

2021-09-01

Completion date

2025-12-26

Last updated

2023-09-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Drug Absorption

Keywords

Ginsenosides Rg5, Ginsenosides Rk1, Compound K (CK)., Red ginseng HRG80, gamma-cyclodextrin, pharmacokinetic, relative bioavailability

Brief summary

This study will evaluate the relative bioavailability of ginsenosides Rg5, Rk1, and Ck of Red ginseng HRG80 preparations containing gamma-cyclodextrin (GCD) in the blood plasma of healthy subjects after oral administration of two different formulations of HRG80: A. Capsules containing red ginseng preparation HRG80 (reference product) B. Chewable tablets containing red ginseng preparation HRG80 and GCD (modified product). Dissolution testing measures the rate and extend water solubility of ginsenosides from the reference (A) and the modified (B) products. The difference of in vitro dissolution profiles between the reference (A) and modified (B) products will be assessed.

Detailed description

A growing body of evidence suggests that gamma-cyclodextrin (GCD) can increase the clinical efficacy of water-insoluble biologically active compounds, which have low bioavailability. GCD is the most bio adaptable and applicable to increase the absorption of many drugs, including ginsenosides of Panax ginseng, by forming inclusion complexes or the form of GCD/drug conjugates. Ginsenosides have absolute bioavailability in the range from 0.2% to 48%, depending on the chemical structure and water solubility. Hypothesis: gamma-cyclodextrin increases absorption and bioavailability of active constituents - Ginsenosides Rg5, Rk1, and Compound K (CK). The study aims to provide experimental evidence supporting or rejecting this hypothesis. Sixteen healthy volunteers will be randomly assigned to receive two formulations, A and B, in two consecutive phases (Phase 1 and Phase) of an open-label study with a crossover design. All patients will provide blood samples in each phase in each phase in 0.5, 0.75, 1, 2, 4, 6, 12, 24, and 48 hours (9 points) after drug administration, following will be a washout period for two weeks. Subjects will be fasting for 10.00 hours before administering the investigational product. They will remain in the clinic post-dose until at least 24.00 hours each period, provided they are not suffering from any adverse event. The concentration of ginsenosides Rg5, Rk1, and Ck in all blood samples will be determined using a validated analytical method (HPLC-MS) with the internal standard - digoxin. Appropriate mathematical methods and Kinetic 4.4.1 software will be used to generate basic pharmacokinetic parameters.

Interventions

DIETARY_SUPPLEMENTHRG80™ Red Ginseng

Capsules containing red ginseng preparation HRG80 capsules, 200 mg - reference product

COMBINATION_PRODUCTHRG80™ Red Ginseng + gamma cyclodextrin

Chewable tablets containing red ginseng preparation HRG80 (100 mg) incorporated in gamma-cyclodextrin (GCD) - experimental modified product

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

A comparative study with the positive control, parallel groups, randomized, crossover design

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

* Healthy volunteers, as determined by medical history, physical examination, and clinical laboratory testing, * Willingness to stay in the unit overnight for the duration of the study, * Provide a signed written informed consent.

Exclusion criteria

* overweight (BMI \>35 kg/m2), * pregnancy, * lactation, * drug abuse, * use of dietary supplements or any form of medication (with the exception of oral contraceptives), * heavy smokers, or ex-smokers with a remote history (\> one pack/day), * frequent alcohol consumption (\>20 g ethanol/d), * adherence to a restrictive dietary regimen, * physical activity of more than 5 h/wk, * respiratory tract infections, or suspicion thereof in the last 14 days before dosing, * history or presence of disease in the kidneys and heart, lungs, liver, the gastrointestinal tract, endocrine organs, or other conditions such as the metabolic disease is known to interfere with the absorption, distribution, metabolism, and excretion of drugs, * malignancy, * autoimmune disorders such as (but not limited to) lupus erythematosus, multiple sclerosis, rheumatoid arthritis, or sarcoidosis, * any other disease or condition, which, in the opinion of the Investigator, would make the subject unsuitable for this study, * currently taking medications known to be CYP2C9 inducers (i.e., carbamazepine and rifampicin).

Design outcomes

Primary

Measure	Time frame	Description
The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rg5.	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The changes from the baseline the concentration (ng/ml) of Rg5 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of ginsenoside Ck	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The changes from the baseline the concentration (ng/ml) of ginsenoside Ck in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rk1.	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The changes from the baseline the concentration (ng/ml) of Rk1 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.

Secondary

Measure	Time frame	Description
The absorption rate constant (Ka, h-1) of Rk1	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The absorption rate constants (Ka, h-1) of Rk1 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
The absorption rate constant (Ka, h-1) of Rg5	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The absorption rate constants (Ka, h-1) of Rg5 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
The absorption rate constant (Ka, h-1) of Ck	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The absorption rate constants (Ka, h-1) of Ck in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Maximum plasma concentration (Cmax, ng/ml), of Rg5	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Maximum plasma concentration (Cmax, ng/ml), of Rg5 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Maximum plasma concentration (Cmax, ng/ml), of Rk1	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Maximum plasma concentration (Cmax, ng/ml), of Rk1 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Maximum plasma concentration (Cmax, ng/ml), of Ck	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Maximum plasma concentration (Cmax, ng/ml), of Ck in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Time to reach maximum plasma concentration, Tmax (h) of Rg5 .	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Time to reach maximum plasma concentration, Tmax (h) of Rg5 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Time to reach maximum plasma concentration, Tmax (h) of Rk1	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Time to reach maximum plasma concentration, Tmax (h) of Rk1 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Time to reach maximum plasma concentration, Tmax (h) of Ck.	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Time to reach maximum plasma concentration, Tmax (h) of Ck in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Mean absorption time MAT (h) of Rg5	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Mean absorption time MAT (h) of Rg5 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Mean absorption time MAT (h) of Rk1	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Mean absorption time MAT (h) of Rk1 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.
Mean absorption time MAT (h) of Ck	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Mean absorption time MAT (h) of Ck in blood plasma obtained after oral administration of the experimental product A or the active comparator B.

Other

Measure	Time frame	Description
Effect of gamma-cyclodextrin on absorption rate constant (Ka, h-1) of Rg5	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the absorption rate constants (Ka, h-1) of Rg5 obtained after oral administration of the experimental product A or the active comparator B.
Effect of gamma-cyclodextrin on absorption rate constant (Ka, h-1) of Rk1	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the absorption rate constants (Ka, h-1) of Rk1 obtained after oral administration of the experimental product A or the active comparator B.
Effect of gamma-cyclodextrin on absorption rate constant (Ka, h-1) of Ck	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the absorption rate constants (Ka, h-1) of Ck obtained after oral administration of the experimental product A or the active comparator B.
Effect of gamma-cyclodextrin on the maximal concentration (ng/ml) of Rg5 in blood	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the maximal concentration (ng/ml) of Rg5 obtained after oral administration of the experimental product A or the active comparator B.
Effect of gamma-cyclodextrin on the maximal concentration (ng/ml) of Rk1 in blood	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the maximal concentration (ng/ml) of Rk1 obtained after oral administration of the experimental product A or the active comparator B.
Effect of gamma-cyclodextrin on the maximal concentration (ng/ml) of Ck in blood	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the maximal concentration (ng/ml) of Ck obtained after oral administration of the experimental product A or the active comparator B.
the dissolution of Rg5	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the dissolution of Rg5 (% of the labeled content, Q) obtained in dissolution testing of the experimental product A or the active comparator B.
the dissolution of Rk1	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the dissolution of Rk1 (% of the labeled content, Q) obtained in dissolution testing of the experimental product A or the active comparator B.
the dissolution of Ck	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	The difference in the dissolution of Ck (% of the labeled content, Q) obtained in dissolution testing of the experimental product A or the active comparator B.
Relative bioavailability (%) of Ck incorporated in gamma-cyclodextrin	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Relative bioavailability (%) of Ck from 0 to 96 hours defined as the ratio of AUC0-96h for the tested formulation (B) to the AUC0-96h obtained for the reference product (A, 100%), given by the same route of administration in the same dose. F= AUCB/AUCA x 100%.
Relative bioavailability (%) of Rg5 incorporated in gamma-cyclodextrin	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Relative bioavailability (%) of Rg5 from 0 to 96 hours defined as the ratio of AUC0-96h for the tested formulation (B) to the AUC0-96h obtained for the reference product (A, 100%), given by the same route of administration in the same dose. F= AUCB/AUCA x 100%.
Relative bioavailability (%) of Rk1 incorporated in gamma-cyclodextrin	0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose	Relative bioavailability (%) of Rk1 from 0 to 96 hours defined as the ratio of AUC0-96h for the tested formulation (B) to the AUC0-96h obtained for the reference product (A, 100%), given by the same route of administration in the same dose. F= AUCB/AUCA x 100%.

Countries

Armenia, Sweden

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026