Healthy VolunteersPhase 1NCT01136928
Pharmacokinetic Interaction Study of Efavirenz and American Ginseng in Healthy Volunteers
A Phase 1 study testing American ginseng in people with Healthy Volunteers, run by Johns Hopkins University at 1 site in United States.
Trial summary
This is a 4-week sequential drug interaction study to measure the effects of American ginseng on efavirenz pharmacokinetics using steady-state 24-hour Area Under the Curve (AUC) and Cmax as the primary comparison measures in healthy male volunteers. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- American ginseng
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Sep 2010to 14 Mar 2011
- 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 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All enrollees will be healthy volunteers, ≥18 years of age with
- Negative HIV-1 serology, documented by any licensed ELISA test kit
- Ability and willingness to provide a signed informed consent and comply with study requirements
- Males only because efavirenz has been reported to have teratogenic properties
- Estimated creatinine clearance ≥50 mL/minute, as calculated by the Cockcroft-Gault method
- Normal laboratory and physical examination, as judged by the Principal Investigator
- Good peripheral venous access
- Willingness and ability to take oral medications.
Who cannot join
- Known or suspected hypersensitivity to American Ginseng (AG) or efavirenz
- Taking any prescription, over-the-counter medication, or Complementary and alternative medicine (CAM) agents within 30 days of study enrolment
- Evidence of active drug or alcohol abuse
- Any other medical or psychological condition that might, in the opinion of the investigator, interfere with participation in the study or put subjects at undue risk
- Hospitalization or therapy for serious illness within 30 days prior to study entry, as judged by the investigator
- Participation in any investigational drug trials within 30 days prior to study entry that, in the opinion of the investigator, would preclude study participation.
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins University
Baltimore, Maryland, 21287-5554
About this study
Official title: Phase I Pharmacokinetic Interaction Study of Efavirenz and American Ginseng in Healthy Volunteers
This is a 4-week sequential drug interaction study to measure the effects of American ginseng on efavirenz pharmacokinetics using steady-state 24-hour Area Under the Curve (AUC) and Cmax as the primary comparison measures in healthy male volunteers. Efavirenz Cmin, T1/2, tmax, and clearance will also be assessed as secondary outcome measures. This study is a phase I, prospective, within-subject, fixed-order, two-period, multiple dose, open label, drug interaction study, to determine the stead-state plasma pharmacokinetic profile of efavirenz before and after concurrent treatment with American ginseng. The investigators hypothesis is that concurrent oral administration of American ginseng for up to 14 days will not significantly alter the steady-state plasma pharmacokinetic of efavirenz.
Read the detailed description
This study is supported by R01AT005526-01 grant awarded by National Center for Complementary and. Alternative Medicine (NCCAM) to evaluate the safety, efficacy, and mechanism of American ginseng in HIV-related fatigue. This is a 4-week sequential drug interaction study to measure the effects of American ginseng on efavirenz pharmacokinetics using steady-state 24-hour AUC and Cmax as the primary comparison measures in healthy male volunteers. Efavirenz Cmin, T1/2, tmax, and clearance will also be assessed as secondary outcome measures. This study is a phase I, prospective, within-subject, fixed-order, two-period, multiple dose, open label, drug interaction study, to determine the stead-state plasma pharmacokinetic profile of efavirenz before and after concurrent treatment with American ginseng. Therefore, this study will evaluate the effects of American ginseng on efavirenz plasma concentrations. Only efavirenz plasma concentrations will be measured in this study. American ginseng plasma concentrations will not be assessed in this study. Efavirenz plasma concentrations will be measured on study Days 14 and 28 (corresponding to weeks 2 and 4, respectively).
This is an important study because although American ginseng is a popular dietary supplement, the safety and efficacy of this agent in HIV-infected patients has not yet been established. A major concern regarding the safety of American ginseng in HIV-infected patients is the potential for herb-drug interactions that could alter the metabolism of antiretroviral drugs. Induction of drug metabolizing enzymes by dietary supplements such as American ginseng, could lead to a reduction in the therapeutic concentrations of these drugs and treatment failure. Inhibition of these drug metabolizing enzymes, on the other hand, could result in higher plasma concentrations of antiretroviral agents and potentially lead to increased toxicity.
Most antiretroviral drugs are metabolized by the cytochrome P450 (CYP450) isoenzyme CYP3A4. Our preliminary data suggest that American ginseng does not significantly affect CYP3A4 activity in vivo. A recent study has also reported that the American ginseng-mediated induction of Uridyl dipohsphate (UDP)-glucuronosyltransferase enzyme involved in the metabolism of the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine and abacavir, and the integrase inhibitor raltegravir, does not significantly alter zidoduvine pharmacokinetics. However, data are not available concerning the effect of American ginseng on other major CYP 450 isoforms involved in the metabolism of antiretroviral drugs. For instance, the non- nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is also metabolized by CYP2B6 and only to a lesser extent by the CYP3A4 isoform. Therefore, a potential drug interaction between American ginseng and this popular NNRTI must be excluded before this herb can be safely used in HIV-infected patients. This study will complete the work that has been currently done characterizing the effects of American ginseng on major drug metabolizing enzymes.
DURATION:
The total duration of this study is five weeks. Participants will receive study medications during the first four weeks of the study. On week 5 participants will complete their final post treatment safety study visit.
POPULATION AND SAMPLE SIZE:
Fifteen adult healthy male volunteers will be enrolled in this study.
REGIMEN:
Period 1 Days 0-14 Daily efavirenz monotherapy 600 mg orally Efavirenz pharmacokinetic sampling on Day 14
Period 2 Days 15-28 Daily efavirenz 600 mg orally PLUS American ginseng 3000 mg orally Efavirenz pharmacokinetic sampling on Day 28
Because efavirenz is a Category D drug with positive evidence of fetal risk, only male healthy volunteers will be enrolled in this study. Our hypothesis is that concurrent oral administration of American ginseng for up to 14 days will not significantly alter the steady-state plasma pharmacokinetic of efavirenz.
- Conditions
- Healthy Volunteers
- Being tested
- American ginseng
- Keywords
- Antiretroviral therapy, American ginseng, Efavirenz, Cytochrome P450 enzymes, Complementary and Alternative Medicine, Herbal, Pharmacikinetics, Healthy volunteers
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
American ginsengDrug
Also called Efavienz (Sustiva)
Healthy volunteers will ge given efavirnez 600 mg daily monotherapy for 14 days followed by efavirenz 600 mg PLUS American ginseng 3000 mg daily for an additional 14 days.
| Study group | Role | What they receive |
|---|---|---|
| American ginseng and efavirenz | Experimental | This is a sequential study. Healthy volunteers will receive efavirenz alone for 14 days followed by efavirenz plus American ginseng for an additional 14 days. Receives: Drug: American ginseng |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare efavirenz AUC0-24 and Cmax when dosed alone to steady-state efavirenz AUC0-24 and Cmax given concurrently with American ginseng. Efavirenz AUC0-24 with and without American ginseng
Compare efavirenz AUC0-24 and Cmax when dosed alone at 600 mg daily, to steady-state efavirenz AUC0-24 and Cmax dosed at 600 mg daily and given concurrently with American ginseng 3000 mg daily.
Measured: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Secondary outcomes (4)
Efavirenz tmax with and without American ginseng
To compare efavirenz tmax at steady-state when dosed alone as 600 mg daily, to steady-state efavirenz tmax dosed at 600 mg daily and given concurrently with American ginseng 3000 mg daily in HIV-seronegative healthy male volunteers.
Measured: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Efavirenz Cmin with and without American ginseng
To compare efavirenz Cmin at steady-state when dosed alone as 600 mg daily, to steady-state efavirenz Cmin dosed at 600 mg daily and given concurrently with American ginseng 3000 mg daily in HIV-seronegative healthy male volunteers.
Measured: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Efavirenz Clearance with and without American ginseng
To compare efavirenz Clearance at steady-state when dosed alone as 600 mg daily, to steady-state efavirenz Clearance dosed at 600 mg daily and given concurrently with American ginseng 3000 mg daily in HIV-seronegative healthy male volunteers
Measured: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Efavirenz T1/2 with and without American ginseng
To compare efavirenz T1/2 at steady-state when dosed alone as 600 mg daily, to steady-state efavirenz T1/2 dosed at 600 mg daily and given concurrently with American ginseng 3000 mg daily in HIV-seronegative healthy male volunteers
Measured: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2010 (estimated)
- Study start28 Sep 2010
- Primary completion14 Mar 2011
- Study completion14 Mar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Sponsor
- Investigators
- Adriana Andrade, MD, MPH, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01136928
- Sponsor's protocol ID
- NA_00038067
- Other IDs
- R01AT005526-01
- Status last verified
- Jun 2018
- First submitted
- 2 Jun 2010
- Last updated
- 15 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Pharmacokinetic Interaction Study of Efavirenz and American Ginseng in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01136928
- Acronym / sponsor ID
- NA_00038067
- Conditions
- Healthy Volunteers
- Keywords
- Antiretroviral therapy, American ginseng, Efavirenz, Cytochrome P450 enzymes, Complementary and Alternative Medicine, Herbal, Pharmacikinetics, Healthy volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 28 Sep 2010 (actual)
- Primary completion
- 14 Mar 2011 (actual)
- Study completion
- 14 Mar 2011 (actual)
- First posted
- 4 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 4-week sequential drug interaction study to measure the effects of American ginseng on efavirenz pharmacokinetics using steady-state 24-hour Area Under the Curve (AUC) and Cmax as the primary comparison measures in healthy male volunteers. Efavirenz Cmin, T1/2, tmax, and clearance will also be assessed as secondary outcome measures. This study is a phase I, prospective, within-subject, fixed-order, two-period, multiple dose, open label, drug interaction study, to determine the stead-state plasma pharmacokinetic profile of efavirenz before and after concurrent treatment with American ginseng. The investigators hypothesis is that concurrent oral administration of American ginseng for up to 14 days will not significantly alter the steady-state plasma pharmacokinetic of efavirenz.
Detailed description
This study is supported by R01AT005526-01 grant awarded by National Center for Complementary and. Alternative Medicine (NCCAM) to evaluate the safety, efficacy, and mechanism of American ginseng in HIV-related fatigue. This is a 4-week sequential drug interaction study to measure the effects of American ginseng on efavirenz pharmacokinetics using steady-state 24-hour AUC and Cmax as the primary comparison measures in healthy male volunteers. Efavirenz Cmin, T1/2, tmax, and clearance will also be assessed as secondary outcome measures. This study is a phase I, prospective, within-subject, fixed-order, two-period, multiple dose, open label, drug interaction study, to determine the stead-state plasma pharmacokinetic profile of efavirenz before and after concurrent treatment with American ginseng. Therefore, this study will evaluate the effects of American ginseng on efavirenz plasma concentrations. Only efavirenz plasma concentrations will be measured in this study. American ginseng plasma concentrations will not be assessed in this study. Efavirenz plasma concentrations will be measured on study Days 14 and 28 (corresponding to weeks 2 and 4, respectively).
This is an important study because although American ginseng is a popular dietary supplement, the safety and efficacy of this agent in HIV-infected patients has not yet been established. A major concern regarding the safety of American ginseng in HIV-infected patients is the potential for herb-drug interactions that could alter the metabolism of antiretroviral drugs. Induction of drug metabolizing enzymes by dietary supplements such as American ginseng, could lead to a reduction in the therapeutic concentrations of these drugs and treatment failure. Inhibition of these drug metabolizing enzymes, on the other hand, could result in higher plasma concentrations of antiretroviral agents and potentially lead to increased toxicity.
Most antiretroviral drugs are metabolized by the cytochrome P450 (CYP450) isoenzyme CYP3A4. Our preliminary data suggest that American ginseng does not significantly affect CYP3A4 activity in vivo. A recent study has also reported that the American ginseng-mediated induction of Uridyl dipohsphate (UDP)-glucuronosyltransferase enzyme involved in the metabolism of the nucleoside reverse transcriptase inhibitors (NRTIs) zidovudine and abacavir, and the integrase inhibitor raltegravir, does not significantly alter zidoduvine pharmacokinetics. However, data are not available concerning the effect of American ginseng on other major CYP 450 isoforms involved in the metabolism of antiretroviral drugs. For instance, the non- nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is also metabolized by CYP2B6 and only to a lesser extent by the CYP3A4 isoform. Therefore, a potential drug interaction between American ginseng and this popular NNRTI must be excluded before this herb can be safely used in HIV-infected patients. This study will complete the work that has been currently done characterizing the effects of American ginseng on major drug metabolizing enzymes.
DURATION:
The total duration of this study is five weeks. Participants will receive study medications during the first four weeks of the study. On week 5 participants will complete their final post treatment safety study visit.
POPULATION AND SAMPLE SIZE:
Fifteen adult healthy male volunteers will be enrolled in this study.
REGIMEN:
Period 1 Days 0-14 Daily efavirenz monotherapy 600 mg orally Efavirenz pharmacokinetic sampling on Day 14
Period 2 Days 15-28 Daily efavirenz 600 mg orally PLUS American ginseng 3000 mg orally Efavirenz pharmacokinetic sampling on Day 28
Because efavirenz is a Category D drug with positive evidence of fetal risk, only male healthy volunteers will be enrolled in this study. Our hypothesis is that concurrent oral administration of American ginseng for up to 14 days will not significantly alter the steady-state plasma pharmacokinetic of efavirenz.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| American ginseng and efavirenz | Experimental | Drug: American ginsengThis is a sequential study. Healthy volunteers will receive efavirenz alone for 14 days followed by efavirenz plus American ginseng for an additional 14 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- All enrollees will be healthy volunteers, ≥18 years of age with
- Negative HIV-1 serology, documented by any licensed ELISA test kit
- Ability and willingness to provide a signed informed consent and comply with study requirements
- Males only because efavirenz has been reported to have teratogenic properties
- Estimated creatinine clearance ≥50 mL/minute, as calculated by the Cockcroft-Gault method
Key exclusion criteria (6 listed)
- Known or suspected hypersensitivity to American Ginseng (AG) or efavirenz
- Taking any prescription, over-the-counter medication, or Complementary and alternative medicine (CAM) agents within 30 days of study enrolment
- Evidence of active drug or alcohol abuse
- Any other medical or psychological condition that might, in the opinion of the investigator, interfere with participation in the study or put subjects at undue risk
- Hospitalization or therapy for serious illness within 30 days prior to study entry, as judged by the investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| American ginsengAlso: Efavienz (Sustiva)Healthy volunteers will ge given efavirnez 600 mg daily monotherapy for 14 days followed by efavirenz 600 mg PLUS American ginseng 3000 mg daily for an additional 14 days. | Drug | American ginseng and efavirenz |
Primary outcome
To compare efavirenz AUC0-24 and Cmax when dosed alone to steady-state efavirenz AUC0-24 and Cmax given concurrently with American ginseng. Efavirenz AUC0-24 with and without American ginseng
Time frame: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Compare efavirenz AUC0-24 and Cmax when dosed alone at 600 mg daily, to steady-state efavirenz AUC0-24 and Cmax dosed at 600 mg daily and given concurrently with American ginseng 3000 mg daily.
4 secondary outcomes
Efavirenz tmax with and without American ginseng
Time frame: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Efavirenz Cmin with and without American ginseng
Time frame: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Efavirenz Clearance with and without American ginseng
Time frame: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Efavirenz T1/2 with and without American ginseng
Time frame: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adriana Andrade, MD, MPH principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing American ginseng in people with Healthy Volunteers, run by Johns Hopkins University at 1 site in United States.
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 8 inclusion and 6 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: finished, as of the sponsor's last update on 15 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To compare efavirenz AUC0-24 and Cmax when dosed alone to steady-state efavirenz AUC0-24 and Cmax given concurrently with American ginseng. Efavirenz AUC0-24 with and without American ginseng (time frame: 14 days of efavirenz alone, followed by 14 days of concurrent administration of efavirenz and American ginseng). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jun 2018.