Effect of Gamma-cyclodextrin on the Bioavailability of Berberine

NCT04918667 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: EP-1007
• Study Type: interventional
• Target: 16
• Locations: 2 countries
• Sites: 4

Brief Summary

In this study, we will evaluate the relative bioavailability of Berberine (BB) from capsules containing Indian Barberry (Berberis aristate DC.) Bark and Root Extract in the blood plasma of healthy subjects after oral administration of: A. Capsules containing Berberine and GCD (BBA Berberine MetX™ Ultra Absorption, 250 mg) B. Capsules containing Berberine (BB, Berberine MetX™, 500 mg) - (reference product).

Conditions

Drug Absorption

Keywords

Berberine; gamma-cyclodextrin; Pharmacokinetic; Bioavailability; Berberine MetX™ Ultra Absorption

Outcome Measures

Primary Outcomes (2)

• The area under the plasma concentration versus time curve (AUC, expressed in ng x h/mL) of berberine incorporated in gamma-cyclodextrin

  The changes from the baseline the concentration (ng/ml) of berberine in blood plasma obtained after oral administration of the experimental product BBA.

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72 and 96 hours, post-dose

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

  The changes from the baseline the concentration (ng/ml) of berberine in blood plasma obtained after oral administration of the active comparator BB.

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72 and 96 hours, post-dose

Secondary Outcomes (8)

• The absorption rate constants (Ka, h-1) of berberine incorporated in gamma-cyclodextrin

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72 and 96 hours, post-dose

• The absorption rate constants (Ka, h-1) of berberine

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72 and 96 hours, post-dose

• Maximum plasma concentration (Cmax, ng/ml) of Berberine incorporated in gamma-cyclodextrin

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72, and 96 hours, post-dose

• Maximum plasma concentration (Cmax, ng/ml) of Berberine

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72, and 96 hours, post-dose

• Time to reach maximum plasma concentration, Tmax (h) of berberine incorporated in gamma-cyclodextrin

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72, and 96 hours, post-dose

Other Outcomes (5)

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

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72, and 96 hours, post-dose

• Effect of gamma-cyclodextrin on absorption rate constant (Ka, h-1) of berberine

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72, and 96 hours, post-dose

• Effect of gamma-cyclodextrin on the maximal concentration (ng/ml) of berberine in blood

  0.5, 0.75, 1, 2, 4, 6, 12, 24, 48, 72, and 96 hours, post-dose

Study Arms (2)

Berberine MetX™ Ultra Absorption

EXPERIMENTAL

16 healthy subjects will receive orally 500 mg of berberine in two capsules of Berberine MetX™ Ultra Absorption.

Combination Product: Berberine incorporated in gamma cyclodextrin

Berberine MetX™

ACTIVE COMPARATOR

16 healthy subjects will receive orally 500 mg of berberine in one capsule of Berberine MetX™ (reference product).

Dietary Supplement: Berberine

Interventions

Berberine incorporated in gamma cyclodextrin COMBINATION_PRODUCT

Experimental modified product. One capsule contains 250 mg of Berberine from Indian Barberry (Berberis aristate DC.) Bark and Root Extract incorporated in gamma-cyclodextrin

Also known as: Berberine MetX™ Ultra Absorption, 250 mg

Berberine MetX™ Ultra Absorption

Berberine DIETARY_SUPPLEMENT

Active comparator. One capsule contains 500 mg of Berberine from Indian Barberry (Berberis aristate DC.) Bark and Root Extract

Also known as: Berberine MetX™, 500 mg

Berberine MetX™

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, gastrointestinal tract, endocrine organs or other conditions such as metabolic disease 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
• Scientific Center of Drug and Medical Technologies Expertise of the Ministry of Health, Armenia: collaborator
• Cardiomed LLC, Armenia: collaborator
• Institute of Fine Organic Chemistry of the National Academy of Science, Armenia: collaborator
• Phytomed AB, Sweden: 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 (7)

• Liu CS, Zheng YR, Zhang YF, Long XY. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia. 2016 Mar;109:274-82. doi: 10.1016/j.fitote.2016.02.001. Epub 2016 Feb 2.

  PMID: 26851175 BACKGROUND

• Xu X, Yi H, Wu J, Kuang T, Zhang J, Li Q, Du H, Xu T, Jiang G, Fan G. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence. Biomed Pharmacother. 2021 Jan;133:110984. doi: 10.1016/j.biopha.2020.110984. Epub 2020 Nov 10.

  PMID: 33186794 BACKGROUND

• Loftsson T, Moya-Ortega MD, Alvarez-Lorenzo C, Concheiro A. Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes. J Pharm Pharmacol. 2016 May;68(5):544-55. doi: 10.1111/jphp.12427. Epub 2015 Jun 9.

  PMID: 26059798 BACKGROUND

• Kamigauchi M, Kawanishi K, Ohishi H, Ishida T. Inclusion effect and structural basis of cyclodextrins for increased extraction of medicinal alkaloids from natural medicines. Chem Pharm Bull (Tokyo). 2007 May;55(5):729-33. doi: 10.1248/cpb.55.729.

  PMID: 17473458 BACKGROUND

• Hopwood VL, Pathak S. Improved quality of Giemsa banding by the use of trypsin concentrate. Am Biotechnol Lab. 1994 Oct;12(11):52. No abstract available.

  PMID: 7765426 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

• Uekama K. Design and evaluation of cyclodextrin-based drug formulation. Chem Pharm Bull (Tokyo). 2004 Aug;52(8):900-15. doi: 10.1248/cpb.52.900.

  PMID: 15304981 BACKGROUND

MeSH Terms

Interventions

gamma-cyclodextrin; Berberine

Intervention Hierarchy (Ancestors)

Berberine Alkaloids; Benzylisoquinolines; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring

Study Officials

• Aghavni Ginosyan, PhD, MD

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

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

  PRINCIPAL INVESTIGATOR

• Alexander G Panossian, PhD

  Phytomed AB, Sweden

  STUDY DIRECTOR

Central Study Contacts

Alexander G. Panossian, PhD

CONTACT

+46733306226; ap@phytomed.se

Jennifer Hansgate

CONTACT

jhansgate@europharmausa.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 9, 2021
• Study Start: September 1, 2024
• Primary Completion: November 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 14, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1); AR (3)