Effect of Gamma-cyclodextrin on the Bioavailability of Ginsenosides

NCT04932265 | Suspended Phase 1 DMC

• 1 other identifier: EP-1008
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 4

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.

Conditions

Drug Absorption

Keywords

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

Outcome Measures

Primary Outcomes (3)

• The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rg5.

  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.

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

• The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rk1.

  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.

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

• The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of ginsenoside Ck

  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.

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

Secondary Outcomes (12)

• 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 constant (Ka, h-1) of Rk1

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

• The absorption rate constant (Ka, h-1) of Ck

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

• 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 Rk1

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

Other Outcomes (12)

• 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 Rk1 incorporated in gamma-cyclodextrin

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

• Relative bioavailability (%) of Ck incorporated in gamma-cyclodextrin

  0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose

Study Arms (2)

Red ginseng HRG80

ACTIVE COMPARATOR

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

Dietary Supplement: HRG80™ Red Ginseng

Red ginseng HRG80 incorporated in gamma-cyclodextrin

EXPERIMENTAL

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

Combination Product: HRG80™ Red Ginseng + gamma cyclodextrin

Interventions

HRG80™ Red Ginseng DIETARY_SUPPLEMENT

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

Also known as: HRG80™ Red Ginseng Energy

Red ginseng HRG80

HRG80™ Red Ginseng + gamma cyclodextrin COMBINATION_PRODUCT

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

Also known as: HRG80™ Red Ginseng Energy Chewable

Red ginseng HRG80 incorporated in gamma-cyclodextrin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• EuroPharma, Inc.: lead
• Phytomed AB, Sweden: collaborator
• Scientific Center of Drug and Medical Technologies Expertise of the Ministry of Health, Armenia: collaborator
• CARDIOMED Family Health Center, LLC of the Ministry of Health of Armenia: collaborator
• Institute of Fine Organic Chemistry of the National Academy of Science Yerevan, Armenia: collaborator

Study Sites (4)

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

Yerevan, Armenia

Location

Institute of Fine Organic Chemistry of the National Academy of Science

Yerevan, Armenia

Location

Scientific Center of Drug and Medical Technologies Expertise

Yerevan, Armenia

Location

Phytomed AB

Våxtorp, HL, 31275, Sweden

Location

Related Publications (9)

• 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.

  PMID: 33918329 BACKGROUND

• 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.

  PMID: 28086165 BACKGROUND

• 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.

  PMID: 29158964 BACKGROUND

• 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.

  PMID: 24235859 BACKGROUND

• 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.

  PMID: 29883635 BACKGROUND

• 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.

  PMID: 22717707 BACKGROUND

• 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.

  PMID: 33113141 BACKGROUND

• 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.

  PMID: 33333914 BACKGROUND

• 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.

  PMID: 17891389 BACKGROUND

MeSH Terms

Interventions

gamma-cyclodextrin

Study Officials

• Aghavni T Ginosyan, PhD, MD

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

  PRINCIPAL INVESTIGATOR

• Samvel Hairumyan, PhD, MD

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

  PRINCIPAL INVESTIGATOR

• Areg Hovhannisyan PhD of A Hovhannisyan

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 21, 2021
• Study Start: September 1, 2021
• Primary Completion: December 20, 2024
• Study Completion: December 26, 2025
• Last Updated: September 14, 2023

Record last verified: 2023-09

Locations

AR (3); SE (1)