Effect of Gamma-cyclodextrin on the Bioavailability of Ginsenosides

EuroPharma

Status and phase: Suspended; Phase 1

Conditions: Drug Absorption

Treatments: Combination Product: HRG80™ Red Ginseng + gamma cyclodextrin; Dietary Supplement: HRG80™ Red Ginseng

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT04932265

EP-1008

Details and patient eligibility

About

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.

Full 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.

Enrollment: 3 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

3 participants in 2 patient groups

Red ginseng HRG80

Active Comparator group

Description:

16 subjects will receive 200 mg of red ginseng preparation HRG80 in one capsule

Treatment:

Dietary Supplement: HRG80™ Red Ginseng

Red ginseng HRG80 incorporated in gamma-cyclodextrin

Experimental group

Description:

16 subjects will receive 200 mg of red ginseng preparation HRG80 incorporated in gamma-cyclodextrin in two chewable tablets

Treatment:

Combination Product: HRG80™ Red Ginseng + gamma cyclodextrin