Pharmacokinetics of Efavirenz in HIV-1 Infected Subjects With Hepatic Impairment
This study has been completed.
Sponsor:
Bristol-Myers Squibb
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00162097
First received: September 9, 2005
Last updated: September 7, 2010
Last verified: September 2010
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections Hepatic Impairment |
Drug: efavirenz containing antiretroviral regimen |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Pharmacokinetics of Efavirenz During Treatment of HIV-1 Infected Subjects With Hepatic Impairment. |
Resource links provided by NLM:
Genetics Home Reference related topics:
complement factor I deficiency
MedlinePlus related topics:
HIV/AIDS
Drug Information available for:
Efavirenz
U.S. FDA Resources
Further study details as provided by Bristol-Myers Squibb:
Primary Outcome Measures:
- 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. ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: No ]Tmax was obtained directly from the concentration-time data.
Secondary Outcome Measures:
- 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. ] [ Designated as safety issue: Yes ]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.
- 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). ] [ Designated as safety issue: Yes ]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.
- 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). ] [ Designated as safety issue: Yes ]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.
- 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. ] [ Designated as safety issue: Yes ]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.
- Number of Participants With Serum Chemistry MAs [ Time Frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. ] [ Designated as safety issue: Yes ]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.
- Number of Participants With Urinalysis MAs [ Time Frame: Throughout study, from screening (within 21 days of Day 1 dosing) through Day 3. ] [ Designated as safety issue: Yes ]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+).
- 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) ] [ Designated as safety issue: Yes ]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.
- 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) ] [ Designated as safety issue: Yes ]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.
- 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) ] [ Designated as safety issue: Yes ]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
| Enrollment: | 21 |
| Study Start Date: | November 2004 |
| Study Completion Date: | March 2008 |
| Primary Completion Date: | March 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: EFV600mg Participants With Mild Hepatic Impairment |
Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
|
| Experimental: EFV600mg Participants With Moderate Hepatic Impairment |
Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
|
| Experimental: EFV600mg Participants With Severe Hepatic Impairment |
Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
|
| Active Comparator: EFV600mg Participants With Normal Hepatic Function |
Drug: efavirenz containing antiretroviral regimen
Capsule or Tablet, Oral, once daily for 2 days
Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00162097
Locations
| United States, Maryland | |
| Johns Hopkins University School Of Medicine | |
| Baltimore, Maryland, United States, 21287 | |
| United States, Texas | |
| Uthscsa | |
| San Antonio, Texas, United States, 78229 | |
| United States, Virginia | |
| Virginia Commonwealth University Health Systems | |
| Richmond, Virginia, United States, 23298 | |
| Italy | |
| Local Institution | |
| Milano, Italy, 20127 | |
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
More Information
Additional Information:
No publications provided
| Responsible Party: | Study Director, Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT00162097 History of Changes |
| Other Study ID Numbers: | AI266-917 |
| Study First Received: | September 9, 2005 |
| Results First Received: | July 28, 2010 |
| Last Updated: | September 7, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
HIV Infections Acquired Immunodeficiency Syndrome Liver Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases |
Digestive System Diseases Efavirenz Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Therapeutic Uses Anti-HIV Agents |
ClinicalTrials.gov processed this record on May 16, 2013