Effect of Gamma-cyclodextrin on the Bioavailability of Ginsenosides

NCT ID: NCT04932265

Last Updated: 2023-09-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-01

Study Completion Date

2025-12-26

Brief Summary

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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

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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.

Conditions

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Drug Absorption

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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

TREATMENT

Blinding Strategy

NONE

Study Groups

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Red ginseng HRG80

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

Group Type ACTIVE_COMPARATOR

HRG80™ Red Ginseng

Intervention Type DIETARY_SUPPLEMENT

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

Red ginseng HRG80 incorporated in gamma-cyclodextrin

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

Group Type EXPERIMENTAL

HRG80™ Red Ginseng + gamma cyclodextrin

Intervention Type COMBINATION_PRODUCT

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

Interventions

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HRG80™ Red Ginseng

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

Intervention Type DIETARY_SUPPLEMENT

HRG80™ Red Ginseng + gamma cyclodextrin

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

Intervention Type COMBINATION_PRODUCT

Other Intervention Names

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HRG80™ Red Ginseng Energy HRG80™ Red Ginseng Energy Chewable

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Phytomed AB, Sweden

UNKNOWN

Sponsor Role collaborator

Scientific Center of Drug and Medical Technologies Expertise of the Ministry of Health, Armenia

UNKNOWN

Sponsor Role collaborator

CARDIOMED Family Health Center, LLC of the Ministry of Health of Armenia

UNKNOWN

Sponsor Role collaborator

Institute of Fine Organic Chemistry of the National Academy of Science Yerevan, Armenia

UNKNOWN

Sponsor Role collaborator

EuroPharma, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aghavni T Ginosyan, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Scientific Center of Drug and Medical Technologies Expertise of the Ministry of Health of the Republic of Armenia

Samvel Hairumyan, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

CARDIOMED Family Health Center, LLC of the Ministry of Health of the Republic of Armenia

Areg Hovhannisyan PhD of A Hovhannisyan

Role: STUDY_DIRECTOR

Institute of Fine Organic Chemistry of the National Academy of Science, Armenia

Locations

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CARDIOMED Family Health Center, LLC of the Ministry of Health of the Republic of Armenia

Yerevan, , Armenia

Site Status

Institute of Fine Organic Chemistry of the National Academy of Science

Yerevan, , Armenia

Site Status

Scientific Center of Drug and Medical Technologies Expertise

Yerevan, , Armenia

Site Status

Phytomed AB

Våxtorp, HL, Sweden

Site Status

Countries

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Armenia Sweden

References

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Yoo S, Park BI, Kim DH, Lee S, Lee SH, Shim WS, Seo YK, Kang K, Lee KT, Yim SV, Soung DY, Kim BH. Ginsenoside Absorption Rate and Extent Enhancement of Black Ginseng (CJ EnerG) over Red Ginseng in Healthy Adults. Pharmaceutics. 2021 Apr 2;13(4):487. doi: 10.3390/pharmaceutics13040487.

Reference Type BACKGROUND
PMID: 33918329 (View on PubMed)

Zhou QL, Zhu DN, Yang YF, Xu W, Yang XW. Simultaneous quantification of twenty-one ginsenosides and their three aglycones in rat plasma by a developed UFLC-MS/MS assay: Application to a pharmacokinetic study of red ginseng. J Pharm Biomed Anal. 2017 Apr 15;137:1-12. doi: 10.1016/j.jpba.2017.01.009. Epub 2017 Jan 6.

Reference Type BACKGROUND
PMID: 28086165 (View on PubMed)

Elshafay A, Tinh NX, Salman S, Shaheen YS, Othman EB, Elhady MT, Kansakar AR, Tran L, Van L, Hirayama K, Huy NT. Ginsenoside Rk1 bioactivity: a systematic review. PeerJ. 2017 Nov 17;5:e3993. doi: 10.7717/peerj.3993. eCollection 2017.

Reference Type BACKGROUND
PMID: 29158964 (View on PubMed)

Kim HK. Pharmacokinetics of ginsenoside Rb1 and its metabolite compound K after oral administration of Korean Red Ginseng extract. J Ginseng Res. 2013 Oct;37(4):451-6. doi: 10.5142/jgr.2013.37.451.

Reference Type BACKGROUND
PMID: 24235859 (View on PubMed)

Pan W, Xue B, Yang C, Miao L, Zhou L, Chen Q, Cai Q, Liu Y, Liu D, He H, Zhang Y, Yin T, Tang X. Biopharmaceutical characters and bioavailability improving strategies of ginsenosides. Fitoterapia. 2018 Sep;129:272-282. doi: 10.1016/j.fitote.2018.06.001. Epub 2018 Jun 5.

Reference Type BACKGROUND
PMID: 29883635 (View on PubMed)

Quan LH, Jin Y, Wang C, Min JW, Kim YJ, Yang DC. Enzymatic transformation of the major ginsenoside Rb2 to minor compound Y and compound K by a ginsenoside-hydrolyzing beta-glycosidase from Microbacterium esteraromaticum. J Ind Microbiol Biotechnol. 2012 Oct;39(10):1557-62. doi: 10.1007/s10295-012-1158-1. Epub 2012 Jun 21.

Reference Type BACKGROUND
PMID: 22717707 (View on PubMed)

Tannous M, Caldera F, Hoti G, Dianzani U, Cavalli R, Trotta F. Drug-Encapsulated Cyclodextrin Nanosponges. Methods Mol Biol. 2021;2207:247-283. doi: 10.1007/978-1-0716-0920-0_19.

Reference Type BACKGROUND
PMID: 33113141 (View on PubMed)

Rivero-Barbarroja G, Benito JM, Ortiz Mellet C, Garcia Fernandez JM. Cyclodextrin-Based Functional Glyconanomaterials. Nanomaterials (Basel). 2020 Dec 15;10(12):2517. doi: 10.3390/nano10122517.

Reference Type BACKGROUND
PMID: 33333914 (View on PubMed)

Li Z, Wang M, Wang F, Gu Z, Du G, Wu J, Chen J. gamma-Cyclodextrin: a review on enzymatic production and applications. Appl Microbiol Biotechnol. 2007 Nov;77(2):245-55. doi: 10.1007/s00253-007-1166-7. Epub 2007 Sep 22.

Reference Type BACKGROUND
PMID: 17891389 (View on PubMed)

Other Identifiers

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EP-1008

Identifier Type: -

Identifier Source: org_study_id

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