HIV InfectionsPhase 1NCT00162097
Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment
A Phase 1 study testing efavirenz containing antiretroviral regimen in people with HIV Infections and Hepatic Impairment, run by Bristol-Myers Squibb at 4 sites in 2 countries.
Trial summary
The purpose of the study was to assess the steady-state pharmacokinetics (PK) of efavirenz (EFV) in human immunodeficiency virus type 1 (HIV-1) infected subjects on stable antiretroviral regimens containing EFV, and having selected degrees of hepatic impairment or normal hepatic function. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections, Hepatic Impairment
- What is being tested?
- efavirenz containing antiretroviral regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Nov 2004to Mar 2008
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 infection with or without Hepatitis B or C infection
- Stable antiretroviral regimen containing efavirenz and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) for at least 1 month
- Mild, moderate or severe hepatic impairment with hepatic cirrhosis
Who cannot join
- Acute flare of hepatitis
- Positive pregnancy test for a female
- Significant acute medical illness in past 2 months
- Use of agents known to significantly affect liver metabolism
- Change in medications to treat a chronic disease in the past 2 months
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
Johns Hopkins University School Of Medicine
Baltimore, Maryland, 21287
Virginia Commonwealth University Health Systems
Richmond, Virginia, 23298
Uthscsa
San Antonio, Texas, 78229
About this study
Official title: Pharmacokinetics of Efavirenz During Treatment of HIV-1 Infected Subjects With Hepatic Impairment.
The purpose of the study was to assess the steady-state pharmacokinetics (PK) of efavirenz (EFV) in human immunodeficiency virus type 1 (HIV-1) infected subjects on stable antiretroviral regimens containing EFV, and having selected degrees of hepatic impairment or normal hepatic function.
- Conditions
- HIV Infections, Hepatic Impairment
- Being tested
- efavirenz containing antiretroviral regimen
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
efavirenz containing antiretroviral regimenDrug
Also called Sustiva, BMS-561525
Capsule or Tablet, Oral, once daily for 2 days
efavirenz containing antiretroviral regimenDrug
Also called Sustiva, BMS-561525
Capsule or Tablet, Oral, once daily for 2 days
efavirenz containing antiretroviral regimenDrug
Also called Sustiva, BMS-561525
Capsule or Tablet, Oral, once daily for 2 days
efavirenz containing antiretroviral regimenDrug
Also called Sustiva, BMS-561525
Capsule or Tablet, Oral, once daily for 2 days
| Study group | Role | What they receive |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Experimental | Not described Receives: Drug: efavirenz containing antiretroviral regimen |
| EFV600mg Participants With Moderate Hepatic Impairment | Experimental | Not described Receives: Drug: efavirenz containing antiretroviral regimen |
| EFV600mg Participants With Severe Hepatic Impairment | Experimental | Not described Receives: Drug: efavirenz containing antiretroviral regimen |
| EFV600mg Participants With Normal Hepatic Function | Active comparator | Not described Receives: Drug: efavirenz containing antiretroviral regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax)
Cmax was obtained directly from the concentration-time data.
Measured: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
Minimum Plasma Concentration (Cmin)
Cmin was obtained directly from the concentration-time data.
Measured: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])
The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.
Measured: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Tmax was obtained directly from the concentration-time data.
Measured: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
Secondary outcomes (9)
Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)
An SAE was defined as any adverse event (AE) occurring at any dose that; resulted in death; was life threatening; resulted in a persistent or significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; was a cancer; or was an overdose.
Measured: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing). Participants were monitored for SAEs up to 30 days after study discharge.
Number of Participants Who Experienced AEs
AEs were defined as any new untoward medical occurrences or worsening of a pre-existing medical condition in a participant administered a medicinal product, whether or not considered related to the medicinal product.
Measured: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing).
Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation
AEs were defined as any new untoward medical occurrences or worsening of a pre-existing medical condition in a participant administered a medicinal product, whether or not considered related to the medicinal product. Participants who discontinued the study due to an AE were recorded.
Measured: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing).
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Low platelet count: <0.85 x lower limit of normal (LLN) (or if pre-treatment value <LLN, then <0.85 x pre-treatment value). Low leukocytes: <0.9 x LLN (or if pre-treatment value <LLN, then <0.85 x pre-treatment value. If pre-treatment value >upper limit of normal [ULN], then <LLN). Low neutrophils+bands (absolute): <=1.500 10^3 cells/microliter (uL). Low lymphocytes (absolute): <0.750 10^3 cells/uL.
Measured: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.
Number of Participants With Serum Chemistry MAs
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify the criteria for MAs in the data presented. High bilirubin (total): >1.1 x ULN (or if pre-treatment value >ULN, then >1.25 x pre-treatment value). High creatinine: >1.33 x pre-treatment value. Low albumin: <0.9 x LLN (or if pre-treatment value <LLN, then <0.9 x pre-treatment value). High amylase (total): >2 x pre-treatment value.
Measured: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.
Number of Participants With Urinalysis MAs
MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following urinalysis MA definitions specify the criteria for MAs in the data presented. The presence of white blood cells (WBCs) and red blood cells (RBCs) in the urine was graded on a scale: 0 = no cells present (negative); trace =a small number of cells present; then 1+, 2+, 3+ and 4+, denoting increasingly "positive" urine results (ie, WBCs/RBCs present in the urine). The MA for both WBCs and RBCs was >= 2+ (or, if pre-treatment value >=2+, then >= 4+).
Measured: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
ECG abnormalities are findings that are clinically meaningful by the judgment of the investigator. A 12-lead ECG was performed and all ECG recordings were evaluated by the investigator. Abnormalities, if present at any study time point, were listed.
Measured: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing)
Number of Participants With Clinically Meaningful Vital Signs Measures
Vital signs were recorded throughout the study and included investigations related to body temperature, respiratory rate, seated blood pressure (systolic and diastolic), and heart rate. The investigator used his/her clinical judgement to decide whether or not abnormalities in vital signs were clinically meaningful.
Measured: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing)
Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)
The physical examination included an evaluation of the participant's height and body mass index (BMI) (at screening only), and weight. Abnormal physical examination are findings that are clinically meaningful by the judgment of the investigator
Measured: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2005 (estimated)
- Study startNov 2004
- Primary completionMar 2008
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00162097
- Sponsor's protocol ID
- AI266-917
- Status last verified
- Sep 2010
- First submitted
- 9 Sep 2005
- Last updated
- 14 Sep 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Efavirenz During Treatment of HIV-1 Infected Subjects With Hepatic Impairment.
- ClinicalTrials.gov ID
- NCT00162097
- Acronym / sponsor ID
- AI266-917
- Conditions
- HIV Infections, Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Nov 2004
- Primary completion
- Mar 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 13 Sep 2005 (estimated)
- Results
- Posted 25 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study was to assess the steady-state pharmacokinetics (PK) of efavirenz (EFV) in human immunodeficiency virus type 1 (HIV-1) infected subjects on stable antiretroviral regimens containing EFV, and having selected degrees of hepatic impairment or normal hepatic function.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| EFV600mg Participants With Mild Hepatic Impairment | Experimental | Drug: efavirenz containing antiretroviral regimen |
| EFV600mg Participants With Moderate Hepatic Impairment | Experimental | Drug: efavirenz containing antiretroviral regimen |
| EFV600mg Participants With Severe Hepatic Impairment | Experimental | Drug: efavirenz containing antiretroviral regimen |
| EFV600mg Participants With Normal Hepatic Function | Active comparator | Drug: efavirenz containing antiretroviral regimen |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HIV-1 infection with or without Hepatitis B or C infection
- Stable antiretroviral regimen containing efavirenz and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) for at least 1 month
- Mild, moderate or severe hepatic impairment with hepatic cirrhosis
Key exclusion criteria (5 listed)
- Acute flare of hepatitis
- Positive pregnancy test for a female
- Significant acute medical illness in past 2 months
- Use of agents known to significantly affect liver metabolism
- Change in medications to treat a chronic disease in the past 2 months
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 |
|---|---|---|
| efavirenz containing antiretroviral regimenAlso: Sustiva, BMS-561525Capsule or Tablet, Oral, once daily for 2 days | Drug | EFV600mg Participants With Mild Hepatic Impairment |
| efavirenz containing antiretroviral regimenAlso: Sustiva, BMS-561525Capsule or Tablet, Oral, once daily for 2 days | Drug | EFV600mg Participants With Moderate Hepatic Impairment |
| efavirenz containing antiretroviral regimenAlso: Sustiva, BMS-561525Capsule or Tablet, Oral, once daily for 2 days | Drug | EFV600mg Participants With Severe Hepatic Impairment |
| efavirenz containing antiretroviral regimenAlso: Sustiva, BMS-561525Capsule or Tablet, Oral, once daily for 2 days | Drug | EFV600mg Participants With Normal Hepatic Function |
Primary outcome
Maximum Plasma Concentration (Cmax)
Time frame: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
Cmax was obtained directly from the concentration-time data.
Minimum Plasma Concentration (Cmin)
Time frame: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
Cmin was obtained directly from the concentration-time data.
Area Under the Plasma Concentration-time Curve Over the Dosing Interval of 24 Hours (AUC[TAU])
Time frame: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
The AUC(TAU), from time 0 to the time of the last measurable concentration (t), was calculated by the linear trapezoidal rule.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.
Tmax was obtained directly from the concentration-time data.
9 secondary outcomes
Number of Participants Who Died or Experienced Other Serious Adverse Events (SAEs)
Time frame: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing). Participants were monitored for SAEs up to 30 days after study discharge.
Number of Participants Who Experienced AEs
Time frame: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing).
Number of Participants Who Experienced AEs Leading to Study Drug Discontinuation
Time frame: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing).
Number of Participants With Marked Abnormalities (MAs) in Hematology Measurements
Time frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.
Number of Participants With Serum Chemistry MAs
Time frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.
Number of Participants With Urinalysis MAs
Time frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3.
Number of Participants With Identified Electrocardiogram (ECG) Abnormalities
Time frame: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing)
Number of Participants With Clinically Meaningful Vital Signs Measures
Time frame: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing)
Number of Participants With Abnormal Physical Examination Findings at Baseline (Screening and/or Day 1)
Time frame: From screening (within 21 days of Day 1 dosing) to the study discharge day (Day 2 for AM dosing or Day 3 for PM dosing)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing efavirenz containing antiretroviral regimen in people with HIV Infections and Hepatic Impairment, run by Bristol-Myers Squibb at 4 sites in 2 countries.
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 3 inclusion and 5 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 14 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Italy. 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?
Yes. Results are posted in the registry (first posted 25 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Plasma Concentration (Cmax) (time frame: Blood samples were collected at time 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose, relative to administration of PM or AM dose.). The study lists 4 primary outcomes in all. 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 14 Sep 2010.