- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04932265
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.
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Yerevan, Armenia
- CARDIOMED Family Health Center, LLC of the Ministry of Health of the Republic of Armenia
-
Yerevan, Armenia
- Institute of Fine Organic Chemistry of the National Academy of Science
-
Yerevan, Armenia
- Scientific Center of Drug and Medical Technologies Expertise
-
-
-
-
HL
-
Vaxtorp, HL, Sweden, 31275
- Phytomed AB
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Red ginseng HRG80
16 subjects will receive 200 mg of red ginseng preparation HRG80 in one capsule
|
Capsules containing red ginseng preparation HRG80 capsules, 200 mg - reference product
Other Names:
|
Experimental: 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
|
Chewable tablets containing red ginseng preparation HRG80 (100 mg) incorporated in gamma-cyclodextrin (GCD) - experimental modified product
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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 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.
Time Frame: 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.
|
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
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The absorption rate constant (Ka, h-1) of Rg5
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
The absorption rate constant (Ka, h-1) of Rk1
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
The absorption rate constant (Ka, h-1) of Ck
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Maximum plasma concentration (Cmax, ng/ml), of Rg5
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Maximum plasma concentration (Cmax, ng/ml), of Rk1
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Maximum plasma concentration (Cmax, ng/ml), of Ck
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Time to reach maximum plasma concentration, Tmax (h) of Rg5 .
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Time to reach maximum plasma concentration, Tmax (h) of Rk1
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Time to reach maximum plasma concentration, Tmax (h) of Ck.
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Mean absorption time MAT (h) of Rg5
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Mean absorption time MAT (h) of Rk1
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Mean absorption time MAT (h) of Ck
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relative bioavailability (%) of Rg5 incorporated in gamma-cyclodextrin
Time Frame: 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%.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Relative bioavailability (%) of Rk1 incorporated in gamma-cyclodextrin
Time Frame: 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%.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Relative bioavailability (%) of Ck incorporated in gamma-cyclodextrin
Time Frame: 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%.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Effect of gamma-cyclodextrin on absorption rate constant (Ka, h-1) of Rg5
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Effect of gamma-cyclodextrin on absorption rate constant (Ka, h-1) of Rk1
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Effect of gamma-cyclodextrin on absorption rate constant (Ka, h-1) of Ck
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Effect of gamma-cyclodextrin on the maximal concentration (ng/ml) of Rg5 in blood
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Effect of gamma-cyclodextrin on the maximal concentration (ng/ml) of Rk1 in blood
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Effect of gamma-cyclodextrin on the maximal concentration (ng/ml) of Ck in blood
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
the dissolution of Rg5
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
the dissolution of Rk1
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
the dissolution of Ck
Time Frame: 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.
|
0.5, 0.75, 1, 2, 4, 6, 12 and 24 hours, post-dose
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Samvel Hairumyan, PhD, MD, CARDIOMED Family Health Center, LLC of the Ministry of Health of the Republic of Armenia
- Principal Investigator: Aghavni T Ginosyan, PhD, MD, Scientific Center of Drug and Medical Technologies Expertise of the Ministry of Health of the Republic of Armenia
- Study Director: Areg Hovhannisyan PhD of A Hovhannisyan, Institute of Fine Organic Chemistry of the National Academy of Science, Armenia
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- EP-1008
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Drug Absorption
-
EuroPharma, Inc.Scientific Center of Drug and Medical Technologies Expertise of the Ministry... and other collaboratorsNot yet recruiting
-
University of California, San FranciscoFood and Drug Administration (FDA)RecruitingThe Impact of Excipients on Drug AbsorptionUnited States
-
Astellas Pharma Europe B.V.Cubist Pharmaceuticals LLCCompletedHealthy Subjects | Drug-Drug Interaction (DDI) | Intestinal Absorption | Pharmacokinetics of Rosuvastatin | Pharmacokinetics of FidaxomicinGermany
-
Kuopio University HospitalUnknownDrug AbsorptionFinland
-
University of California, DavisNot yet recruitingIron Absorption | Zinc AbsorptionUnited States
-
KU LeuvenNot yet recruitingIron Absorption | Zinc Absorption
-
Malaysia Palm Oil BoardUniversity of MalayaCompleted
-
King's College LondonCompletedAbsorption; ChemicalsUnited Kingdom
-
Gaia Herbs Inc.Appalachian College of PharmacyCompleted
-
Texas Tech UniversityNutraceutical CorporationCompletedMineral AbsorptionUnited States
Clinical Trials on HRG80™ Red Ginseng
-
EuroPharma, Inc.Completed
-
EuroPharma, Inc.Botalys SACompleted
-
Unity Health TorontoHeart and Stroke Foundation of CanadaCompletedHypertension | Blood Pressure | Endothelial FunctionCanada
-
Chuncheon Sacred Heart HospitalCompleted
-
Shanghai Jiao Tong University School of MedicineRenJi Hospital; Beijing Obstetrics and Gynecology Hospital; Foshan Fuxing Changcheng... and other collaboratorsRecruitingAntioxidative Stress | Healthy AgeingChina
-
The Korean Society of GinsengCompleted
-
Daegu Catholic University Medical CenterThe Korean Society of GinsengCompletedHypertensionKorea, Republic of
-
The Korean Society of GinsengCompleted
-
Korea Ginseng CorporationNutrasource Pharmaceutical and Nutraceutical Services, Inc.RecruitingCardiovascular Diseases | Platelet Aggregation | Vasodilation | Blood Pressure DisordersUnited States
-
Chuncheon Sacred Heart HospitalCompleted