Pharmacokinetic Interactions Between Buprenorphine and Kaletra (Lopinavir/Ritonavir)

• Status: Completed
• Trial end date: 2008-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The main purpose of this protocol is to study the effect of an HIV medication, Kaletra (lopinavir/ritonavir), on buprenorphine in non-HIV infected people who have been receiving the same dose of buprenorphine for at least 3 weeks.

Study Hypothesis:

Kaletra (lopinavir/ritonavir) will increase buprenorphine plasma levels without any significant clinical effect on the subject or need for dose adjustment.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Yale University
• Collaborator: Abbott
• Treatments: Buprenorphine; Lopinavir; Ritonavir

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.