Pharmacokinetic Interactions Between Buprenorphine and Kaletra (Lopinavir/Ritonavir)
HIV Infections
About this trial
This is an interventional basic science trial for HIV Infections focused on measuring HIV, Pharmacokinetics, Buprenorphine, Kaletra, HIV Seronegativity
Eligibility Criteria
Inclusion Criteria:
- Chronic BUP users enrolled in BUP program, receiving BUP for at least 3 months and on a stable BUP dose for at least 3 weeks.
- Acceptable medical history, physical examination, 12 lead electrocardiogram, and clinical laboratory evaluations consistent with BUP maintenance
- Subjects who meet the criteria of opiate dependence, are enrolled in long-term BUP maintenance therapy, and have been on a stable dose of BUP for at least 3 weeks.
- Body weight >60 kg for males and >40 kg for females
- Body Mass Index (BMI) of 18 to 30 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2.
- Male or females, ages 18 to 65 years.
- Women of childbearing potential (WOCBP) must not be nursing, pregnant and on adequate non-hormonal contraception to avoid pregnancy. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of Study Day 1.
Exclusion Criteria:
Sex and Reproductive Status Exceptions
- WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 4 weeks before and after the study.
- WOCBP using a prohibited contraceptive method (oral, injectable, or implantable hormonal agents)
- Women who are pregnant or breastfeeding
- Women with a positive pregnancy test on enrollment or prior to study drug administration.
Medical History and Concurrent Diseases
- History or current evidence of any significant acute or chronic medical illness that, within the investigator's discretion, would interfere with the conduct or interpretation of the study.
- History of nephrolithiasis
- History of acute or chronic pancreatitis.
- History of uncontrolled chronic medical illness which could adversely affect the subject's adherence to study protocol or affect patient safety in the opinion of the investigator
- Use of any medication thought to significantly alter the metabolism of Kaletra, Buprenorphine or naloxone.
- History of any hemolytic disorders (including drug-induced hemolysis).
- Proven or suspected acute hepatitis at the time of study entry.
- Current or recent (within 3 months) gastrointestinal disease which would interfere with the conduct or interpretation of the study.
- Any major surgery within 4 weeks of enrollment. Minor surgical procedures requiring local anesthesia are exceptions.
- Any gastrointestinal surgery that could impact upon the absorption of study drug.
- Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of enrollment.
- Blood transfusion within 4 weeks of enrollment.
- Inability to tolerate oral medication.
- Inability to tolerate venipuncture and/or absence of secure venous access.
- Inability to refrain from smoking during in-patient period
- Known or suspected HIV infection (subjects who are found to be positive upon screen for HIV will be excluded).
- Known active drug or alcohol abuse, which in the opinion of the investigator makes study participation to completion unlikely.
- Any other sound medical, psychiatric and/or social reason as determined by the Investigator.
Physical and Laboratory Test Findings
- Evidence of organ dysfunction or any clinically relevant deviations from the norms observed in a buprenorphine treated population in physical examination, vital signs, ECG or clinical laboratory determinations.
- Ingestion of alcohol within 24 hours prior to the dose of study medication
- Positive breathalyzer alcohol test, or positive urine screen for barbiturates, benzodiazepines, amphetamines or opiates other than buprenorphine.
- Positive blood screen for HIV antibody.
- QTc interval >450 msec for males or >470 msec for females.
- Second or third-degree AV block.
- Creatinine clearance(as estimated by method of Cockcroft and Gault) less than 80 mL/min.
- CLcr=0.85(females only)x(140-age)x weight(kg)
- serum creatinine(mg/dL)x 72
- Subjects with bilirubin >2 mg/dL, serum albumin <2.5 g/dL and ascites, AST and ALT >3 times ULN, hemoglobin <9 g/dL, and platelet count <75,000/mm3.
- Positive serum or urine for HCG.
Sites / Locations
- Yale University School of Medicine
Arms of the Study
Arm 1
Experimental
1
HIV negative subjects currently enrolled in a long-term buprenorphine maintenance therapy program for at least 3 months who have been on stable dose of buprenorphine for at least 3 weeks will be admitted to the General Clinical Research Center (GCRC) for pharmacokinetic (PK) blood draws at intervals over a 24-hour period. Subjects will then receive Kaletra and buprenorphine coadministered for 14 days. Subjects will be admitted to the GCRC for a second PK sampling day.