Drug Interactions of Echinacea, Ginseng, and Ginkgo Biloba Taken With Lopinavir/Ritonavir in Healthy Volunteers

NCT00103012 | Completed Phase 4 Results

• 2 other identifiers: 05008205-CC-0082
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine the interaction of the HIV combination medication lopinavir/ritonavir with the herbal products echinacea, ginseng, and ginkgo biloba. Patients with HIV infection often take herbal products and dietary supplements in addition to their doctor-prescribed medicines to treat the disease, lessen the side effects of anti-viral drugs, and improve their overall well being. Alternative medicines such as these may, however, interfere with the elimination of lopinavir/ritonavir from the body, causing either higher or lower blood levels of these drugs than would be expected. This study will assess in healthy subjects any potential harms of taking echinacea, ginseng, or ginkgo biloba together with lopinavir/ritonavir. Healthy normal volunteers between 18 and 50 years of age may be eligible for this study. Candidates are screened with a history, physical examination, and blood tests, including an HIV test and a pregnancy test for women. Pregnant women are excluded from the study. Participants come to the NIH Clinical Center after fasting overnight for the following procedures: Visits 1 and 2: A catheter (plastic tube) is placed in an arm vein to collect blood samples. After the first sample is drawn, the subject takes 8 mg of midazolam syrup and two fexofenadine tablets. Midazolam is a sedative, and fexofenadine (Allegra) is a medicine used to treat allergies. Subjects are given breakfast an hour after taking the drugs. Blood samples are collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8 and 24 hours after taking the drugs to measure blood levels of fexofenadine. An extra sample is collected at the 4-hour mark to measure the midazolam level. The catheter is removed after the 8-hour blood draw and subjects are dismissed home. They return the following morning (visit 2) for the 24-hour blood draw. Visit 3: From 7 to 28 days after visit 1, subjects begin taking lopinavir/ritonavir capsules twice a day by mouth for a total of 29.5 days. On day 15 they return to the clinic for lopinavir/ritonavir blood levels as were done for fexofenadine, except that samples are collected once before breakfast and then at 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after the lopinavir/ritonavir dose. An extra sample is collected for routine tests. The catheter is removed after the 12-hour draw and the subject is dismissed home. The next morning, subjects begin taking one of the following: echinacea 500 mg 3 times a day; ginkgo biloba 120 mg twice a day; or ginseng 500 mg 3 times a day for 28 days. Visit 4: On the last day of taking lopinavir/ritonavir, subjects return to the clinic again for blood level measurements of these drugs as on visit 3, except that the catheter is removed and the subject dismissed home after the 8-hour blood draw. Visits 5 and 6: On the last day of taking the herbal supplement, subjects return to the clinic for repeat measurement of fexofenadine and midazolam levels, as described in visits 1 and 2. At the final visit (visit 6) an additional blood sample is collected for repeat laboratory testing. ...

Conditions

Healthy

Keywords

Antiretrovirals; Protease Inhibitors; Herbal Supplements; Drug Interactions; Metabolism; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• Lopinavir Pharmacokinetics When Administered Alone and in Combination With Three Different Herbal Supplements: Ginkgo Biloba, Panax Ginsing, and Echinacea Purpurea.

  The outcome measurement for each study arm is the change in lopinavir area under the concentration versus time curve (AUC) after two weeks administration of an herbal preparation (Ginkgo Biloba, Echinacea purpurea, or Panax Ginseng).

  2 weeks

Study Arms (3)

Effect of G. Biloba on LPV disposition

EXPERIMENTAL

The primary outcome measurement for each study arm is the change in lopinavir area under the concentration versus time curve (AUC) after two weeks administration of an herbal preparation (Ginkgo Biloba).

Drug: Gingko Biloba

Effect of Echinacea on LPV disposition

EXPERIMENTAL

The primary outcome measurement for each study arm is the change in lopinavir area under the concentration versus time curve (AUC) after two weeks administration of an herbal preparation (Echinacea purpurea).

Drug: Echinacea purpurea

Effect of P. ginseng on LPV disposition

EXPERIMENTAL

The primary outcome measurement for each study arm is the change in lopinavir area under the concentration versus time curve (AUC) after two weeks administration of an herbal preparation (Panax ginseng).

Drug: Panax ginseng

Interventions

Gingko Biloba DRUG

Ginkgo Biloba 120 mg twice daily for 14 days

Effect of G. Biloba on LPV disposition

Echinacea purpurea DRUG

Echinacea purpurea 500 mg three times daily for 14 days

Effect of Echinacea on LPV disposition

Panax ginseng DRUG

Panax ginseng 500 mg twice daily

Effect of P. ginseng on LPV disposition

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females between the ages of 18 and 50 years.
• Healthy by medical history and physical exam.
• Laboratory values within established guidelines for participation in clinical studies: AST less than or equal to 2 times the ULN; SCr less than or equal to ULN; hemoglobin equal to or greater than 11 g/dL (for both males and females).
• Ability to abstain from ingesting fruit juice during pharmacokinetic sampling periods (a total of 2 study days), and abstain from eating grapefruit or drinking grapefruit juice during the entire study period.
• Negative serum or urine pregnancy test for females of child-bearing potential.
• Females of child-bearing potential who are able and willing to practice abstinence or use non-hormonal effective methods of birth control during the study, such as condoms or diaphragms.

You may not qualify if:

• Concomitant routine therapy with any prescription, over-the-counter, herbal, or holistic medications, including oral contraceptives, for 30 days prior to study participation. Intermittent use of any medication within 30 days prior to screening will be considered case by case by the principal investigator and the medically accountable investigator.
• Concomitant therapy (chronic or intermittent) with any prescription, over-the-counter, or herbal drugs (including tinctures, foods, beverages, and gum) will not be allowed during the study duration, including any intermittent use of allergy medication.
• Intermittent use of acetaminophen, non-steroidal anti-inflammatory medications (i.e. ibuprofen), and loperamide will be allowed during the study, but should not be taken on the days of pharmacokinetic blood sampling.
• A daily multivitamin with minerals will be allowed during the study.
• Inability to obtain venous access for blood sample collection.
• The presence or history of any of the following: diabetes mellitus (clinical diagnosis based on current guidelines, HIV infection, active tuberculosis, cardiac disease (eg. Hypertension \[SBP greater than 140 mmHG or DBP greater than 90 mmHG\], heart failure, arrhythmia, etc.), renal disease, hepatitis or hepatic impairment, pancreatitis, bleeding disorders, internal bleeding (such as gastrointestinal or intracranial), respiratory disease (eg. asthma requiring maintenance pharmacologic therapy, chronic obstructive pulmonary disease, etc.), peptic ulcer disease, osteoporosis, osteonecrosis, atopy or atopic dermatitis, hormone sensitive cancers or conditions, organ transplant, seizure disorders, schizophrenia or other psychiatric illnesses that may interfere with the subject's ability to participate in the study, or any other condition that may interfere with the interpretation of the study results or not be in the best interest of the subject in the opinion of the investigators.
• Plans for elective surgery during the investigation or within 1 month following completion for subjects in the gingko biloba arm of the study.
• Positive serum or urine pregnancy test or breastfeeding female.
• The presence of persistent diarrhea or malabsorption that would interfere with the subject's ability to absorb drugs.
• Drug or alcohol abuse that may impair safety or adherence (more than 3 alcoholic drinks per day, on a daily basis).
• History of intolerance or allergic reaction to any products containing echinacea, ginkgo biloba extract, or ginseng (including pills, tinctures, foods, beverages, and gum).
• History of intolerance or allergic reaction to lopinavir, ritonavir, midazolam, or fexofenadine.
• History of atopy including atopic dermatitis, bronchial asthma, multiple food allergies, or severe recurring allergic rhinitis.
• Fasting total cholesterol greater than 240 mg/dL or fasting triglycerides greater than 400 mg/dL.
• Use of nicotine-containing tobacco products, including cigarettes and chewing tobacco.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Fairfield KM, Eisenberg DM, Davis RB, Libman H, Phillips RS. Patterns of use, expenditures, and perceived efficacy of complementary and alternative therapies in HIV-infected patients. Arch Intern Med. 1998 Nov 9;158(20):2257-64. doi: 10.1001/archinte.158.20.2257.

  PMID: 9818806 BACKGROUND

• Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey S, Van Rompay M, Kessler RC. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey. JAMA. 1998 Nov 11;280(18):1569-75. doi: 10.1001/jama.280.18.1569.

  PMID: 9820257 BACKGROUND

• Risa KJ, Nepon L, Justis JC, Panwalker A, Berman SM, Cinti S, Wagener MM, Singh N. Alternative therapy use in HIV-infected patients receiving highly active antiretroviral therapy. Int J STD AIDS. 2002 Oct;13(10):706-13. doi: 10.1258/095646202760326471.

  PMID: 12396542 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Ginkgo Extract; Echinacea extract; Asian ginseng

Intervention Hierarchy (Ancestors)

Plant Extracts; Plant Preparations; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Scott Penzak
• Organization: National Institutes of Health, Clinical Center, Department of Pharmacy

spenzak@cc.nih.gov

301-496-2997

Study Officials

• Scott R Penzak, Pharm.D.

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2005
• First Posted: February 7, 2005
• Study Start: January 1, 2005
• Primary Completion: January 1, 2011
• Study Completion: June 1, 2011
• Last Updated: April 16, 2012
• Results First Posted: April 16, 2012

Record last verified: 2012-03

Locations

US (1)