Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00103012
Status:
COMPLETED
Last Update Posted:
2012-04-16
First Post:
2005-02-05
Brief Title:
Drug Interactions of Echinacea Ginseng and Ginkgo Biloba Taken With LopinavirRitonavir in Healthy Volunteers
Sponsor:
National Institutes of Health Clinical Center CC
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
The Influence of Concurrent Administration of Echinacea Purpurea Ginkgo Biloba or Panax Ginseng on the Steady State Pharmacokinetic Profile of LopinavirRitonavir in Healthy Volunteers
Status:
COMPLETED
Status Verified Date:
2012-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will examine the interaction of the HIV combination medication lopinavirritonavir 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 lopinavirritonavir 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 lopinavirritonavir
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 05 1 15 2 25 3 35 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 lopinavirritonavir capsules twice a day by mouth for a total of 295 days On day 15 they return to the clinic for lopinavirritonavir blood levels as were done for fexofenadine except that samples are collected once before breakfast and then at 05 1 2 3 4 6 8 and 12 hours after the lopinavirritonavir 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 lopinavirritonavir 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
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 05 1 15 2 25 3 35 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 lopinavirritonavir capsules twice a day by mouth for a total of 295 days On day 15 they return to the clinic for lopinavirritonavir blood levels as were done for fexofenadine except that samples are collected once before breakfast and then at 05 1 2 3 4 6 8 and 12 hours after the lopinavirritonavir 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 lopinavirritonavir 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
Detailed Description:
Patients with HIV commonly use herbal products and dietary supplements in addition to medications prescribed by their physicians Up to 73 of patients with HIV have reported using some form of complementary or alternative medicine As such the potential for clinically significant drug interactions between herbs and antiretrovirals is becoming increasingly appreciated Despite this awareness little is known about the effect of commonly used herbal products such as echinacea ginkgo biloba and ginseng on antiretroviral pharmacokinetics Interacting herbal supplements have the potential to alter protease inhibitor PI plasma concentrations as has been shown with St Johns Wort and garlic Drug interactions may potentially increase antiretroviral concentrations putting patients at risk for toxicities or lower drug concentrations below the threshold of viral susceptibility putting patients in jeopardy of antiretroviral failure The protease inhibitors lopinavir and ritonavir both rely principally on cytochrome P450 CYP 3A4 metabolism for their elimination In addition both drugs are substrates for the transport protein p-glycoprotein P-gp which may also contribute to their distribution and elimination
The primary purpose of this investigation is to determine whether the herbal supplements Echinacea purpurea ginkgo biloba and Panax ginseng alter the pharmacokinetic properties of the HIV protease inhibitor PI lopinavir administered as the PI combination lopinavirritonavir LPVr This is an open label pharmacokinetic study that will be performed on an outpatient basis A total of 42 study participants who have met inclusion criteria will be sequentially divided into one of 3 groups such that 14 subjects each will receive LPVr alone and in combination with either E purpurea G biloba or P ginseng
Subjects will begin taking LPVr 400mg100mg twice daily x 295 days returning to the NIH on Day 15 of dosing for post-dose plasma collection and determination of lopinavir and ritonavir concentrations On Day 16 participants will begin taking either E purpurea 500mg three times daily G biloba extract 120 mg twice daily or P ginseng 500 mg twice daily for 28 days On the 30th day of LPVr Day 15 of the herb subjects will return to the NIH where they will take their final LPVr dose and then have their plasma collected for determination of lopinavir concentrations Data from this investigation will determine whether echinacea ginseng or ginkgo biloba supplements alter the pharmacokinetics of lopinavir
The primary purpose of this investigation is to determine whether the herbal supplements Echinacea purpurea ginkgo biloba and Panax ginseng alter the pharmacokinetic properties of the HIV protease inhibitor PI lopinavir administered as the PI combination lopinavirritonavir LPVr This is an open label pharmacokinetic study that will be performed on an outpatient basis A total of 42 study participants who have met inclusion criteria will be sequentially divided into one of 3 groups such that 14 subjects each will receive LPVr alone and in combination with either E purpurea G biloba or P ginseng
Subjects will begin taking LPVr 400mg100mg twice daily x 295 days returning to the NIH on Day 15 of dosing for post-dose plasma collection and determination of lopinavir and ritonavir concentrations On Day 16 participants will begin taking either E purpurea 500mg three times daily G biloba extract 120 mg twice daily or P ginseng 500 mg twice daily for 28 days On the 30th day of LPVr Day 15 of the herb subjects will return to the NIH where they will take their final LPVr dose and then have their plasma collected for determination of lopinavir concentrations Data from this investigation will determine whether echinacea ginseng or ginkgo biloba supplements alter the pharmacokinetics of lopinavir
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-CC-0082 | None | None | None |