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Drug AbsorptionPhase 1NCT04932265

Effect of Gamma-cyclodextrin on the Bioavailability of Ginsenosides

A Phase 1 study testing HRG80™ Red Ginseng and HRG80™ Red Ginseng + gamma cyclodextrin in people with Drug Absorption, run by EuroPharma, Inc. at 4 sites in 2 countries.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Drug Absorption
What is being tested?
HRG80™ Red Ginseng and HRG80™ Red Ginseng + gamma cyclodextrin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
4 sitesin 2 countries
Study dates
1 Sep 2021to 26 Dec 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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),
Show all 15Show fewer
  • 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 locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

Armenia3 sites
  • CARDIOMED Family Health Center, LLC of the Ministry of Health of the Republic of Armenia

    Yerevan

  • Institute of Fine Organic Chemistry of the National Academy of Science

    Yerevan

  • Scientific Center of Drug and Medical Technologies Expertise

    Yerevan

Other trials in Armenia

Sweden1 site
  • Phytomed AB

    Våxtorp, HL, 31275

Other trials in Sweden

About this study

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

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:

  1. 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.

Read the 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.

Conditions
Drug Absorption
Being tested
HRG80™ Red Ginseng, HRG80™ Red Ginseng + gamma cyclodextrin
Keywords
Ginsenosides Rg5, Ginsenosides Rk1, Compound K (CK)., Red ginseng HRG80, gamma-cyclodextrin, pharmacokinetic, relative bioavailability

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HRG80™ Red GinsengDietary supplement

    Also called HRG80™ Red Ginseng Energy

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

  • HRG80™ Red Ginseng + gamma cyclodextrinCombination product

    Also called HRG80™ Red Ginseng Energy Chewable

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

Study groups in NCT04932265
Study groupRoleWhat they receive
Red ginseng HRG80Active comparator16 subjects will receive 200 mg of red ginseng preparation HRG80 in one capsule
Receives: Dietary Supplement: HRG80™ Red Ginseng
Red ginseng HRG80 incorporated in gamma-cyclodextrinExperimental16 subjects will receive 200 mg of red ginseng preparation HRG80 incorporated in gamma-cyclodextrin in two chewable tablets
Receives: Combination Product: HRG80™ Red Ginseng + gamma cyclodextrin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

Secondary outcomes (12)
  1. The absorption rate constant (Ka, h-1) of Rg5

    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.

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

  2. The absorption rate constant (Ka, h-1) of Rk1

    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.

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

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

    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.

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

  4. Maximum plasma concentration (Cmax, ng/ml), of Rg5

    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.

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

  5. Maximum plasma concentration (Cmax, ng/ml), of Rk1

    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.

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

  6. Maximum plasma concentration (Cmax, ng/ml), of Ck

    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.

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

  7. Time to reach maximum plasma concentration, Tmax (h) of Rg5 .

    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.

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

  8. Time to reach maximum plasma concentration, Tmax (h) of Rk1

    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.

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

  9. Time to reach maximum plasma concentration, Tmax (h) of Ck.

    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.

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

  10. Mean absorption time MAT (h) of Rg5

    Mean absorption time MAT (h) of Rg5 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.

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

  11. Mean absorption time MAT (h) of Rk1

    Mean absorption time MAT (h) of Rk1 in blood plasma obtained after oral administration of the experimental product A or the active comparator B.

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

  12. Mean absorption time MAT (h) of Ck

    Mean absorption time MAT (h) of Ck in blood plasma obtained after oral administration of the experimental product A or the active comparator B.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2021
  2. Study start1 Sep 2021
  3. Primary completion20 Dec 2024 (estimated)
  4. Study completion26 Dec 2025 (estimated)

Why it stopped: Technical Problems with sensitivity of mass spectral detector

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
A comparative study with the positive control, parallel groups, randomized, crossover design
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04932265
Sponsor's protocol ID
EP-1008
Status last verified
Sep 2023
First submitted
1 Jun 2021
Last updated
14 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 33918329
  • 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.

    PubMed 28086165
  • 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.

    PubMed 29158964
  • 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.

    PubMed 24235859
  • 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.

    PubMed 29883635
  • 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.

    PubMed 22717707
  • 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.

    PubMed 33113141
  • 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.

    PubMed 33333914
  • 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.

    PubMed 17891389

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HRG80™ Red Ginseng and HRG80™ Red Ginseng + gamma cyclodextrin in people with Drug Absorption, run by EuroPharma, Inc. at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 14 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Armenia, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of Rg5. (time frame: 0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04932265, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2023.

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