Clinical trial NCT00486330: Pharmacokinetic Interactions Between Buprenorphine and Tipranavir/Ritonavir
Official title: Pharmacokinetic Interactions Between Buprenorphine/Naloxone and Tipranavir/Ritonavir in HIV-Negative Subjects Chronically Receiving Buprenorphine/Naloxone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: HIV
Pharmacokinetics
Buprenorphine
Tipranavir
HIV Seronegativity
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2007-06-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to examine the effect of tipranavir combined with ritonavir, medications for the treatment of HIV-infection, on buprenorphine/naloxone (BUP) in people who have been receiving the same dose of buprenorphine/naloxone for at least 3 weeks before study entry.

Detailed description: A large number of people with HIV-infection obtained HIV through injection drug use. Some of these people are currently being treated with buprenorphine/naloxone (BUP) for their addiction and with medications for HIV infection. Tipranavir is a medication that was recently approved by the Food and Drug Administration (FDA) for the treatment of HIV-infection. Tipranavir is given in combination with another HIV medication, ritonavir. Tipranavir acts by making it more difficult for the virus that causes AIDS to multiply and cause more damage to the immune system. Ritonavir acts by increasing the amount of tipranavir available to fight HIV.

Earlier studies looking at the combination of BUP and HIV medications have shown that BUP and some HIV medications act differently when taken together. It is important to learn if taking BUP and HIV medications together results in changes in the blood level of either medication. If the HIV medication decreases the level of BUP in the blood, an individual taking BUP and HIV medications may experience symptoms of withdrawal ("dope sickness"), even while taking their usual dose of BUP. On the other hand, if BUP decreases the amount of HIV medication in the blood, then the HIV medication may be less effective in controlling HIV infection. It is therefore important to learn if tipranavir/ritonavir and BUP will affect each other when taken together.

In order to learn about the effects of BUP on tipranavir/ritonavir, we will need to measure the amount of BUP in your blood for 24 hours after you have taken tipranavir/ritonavir and BUP together and then compare that to the amount of BUP in your blood when you are not taking tipranavir/ritonavir.

Eligibility criteria: Inclusion Criteria:

* Buprenorphine/naloxone (BUP/NAL) users (taking 16/4 mg sublingually daily) for at least 3 weeks deemed by the investigator to have acceptable medical history, physical examination, 12 lead electrocardiogram, and clinical laboratory evaluations consistent with BUP maintenance will be eligible to participate in the study.
* 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/NAL 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 \< 60 years.
* Women of childbearing potential (WOCBP) must not be nursing or pregnant and must be 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:

* 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 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 tipranavir, ritonavir, Buprenorphine or naloxone.
* History of any hemolytic disorders (including drug-induced hemolysis).
* Proven or suspected acute hepatitis at the time of study entry.
* Chronic liver disease with Childs-Pugh Class B or C staging
* 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-residence 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.
* Evidence of organ dysfunction or any clinically relevant (as determined by the investigator) deviations from the norms observed in a buprenorphine/naloxone 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, benzo-diazepines, amphetamines, THC, cocaine or opiates other than buprenorphine/naloxone.
* Positive blood screen for HIV antibody.
* Subjects with AST, ALT or bilirubin \> 2.5X the upper limit of normal.
* Hemoglobin \< 9 g/dL, and platelet count \< 75, 000/mm3.
* Positive serum or urine for HCG.
* History of any significant drug allergy, drug rash or sensitivity to any class of drugs relevant to the study drugs.

Primary outcomes:
measure: Area Under the Curve of BUP/NLX With TPV/r (h*ng/mL)
timeFrame: 10 days
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University School of Medicine AIDS Program
state: Connecticut
Study officials:
affiliation: Yale University
name: Robert D Bruce, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bruce RD, Altice FL, Moody DE, Lin SN, Fang WB, Sabo JP, Wruck JM, Piliero PJ, Conner C, Andrews L, Friedland GH. Pharmacokinetic interactions between buprenorphine/naloxone and tipranavir/ritonavir in HIV-negative subjects chronically receiving buprenorphine/naloxone. Drug Alcohol Depend. 2009 Dec 1;105(3):234-9. doi: 10.1016/j.drugalcdep.2009.07.007. Epub 2009 Sep 1.