Buprenorphine/Raltegravir Pharmacokinetic Interaction Study

This study has been completed.
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
R. Douglas Bruce, MD, MA, Yale University
ClinicalTrials.gov Identifier:
NCT00858962
First received: March 6, 2009
Last updated: October 19, 2012
Last verified: October 2012
  Purpose

The main purpose of this protocol is to study the effect of an HIV medication known as Raltegravir on Buprenorphine in people who have been receiving the same dose of Buprenorphine for at least 3 weeks before study entry. This will be determined by giving Raltegravir along with Buprenorphine and by measuring the amount of Raltegravir and Buprenorphine in the blood. The investigators will also learn about the effects of Buprenorphine on Raltegravir and about the safety of taking these two medications together.


Condition Intervention
HIV Infection
HIV Infections
Drug: Raltegravir

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of the Pharmacokinetic and Pharmacodynamic Interactions Between Raltegravir (Isentress) and Buprenorphine

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Area Under the Curve (AUC) of BUP/NLX With Raltegravir (hr*ng/mL) [ Time Frame: 6-14 days after beginning co-administration of drugs ] [ Designated as safety issue: No ]
    PK parameters of BUP were determined by non-compartmental methods. AUC of BUP was determined by use of the trapezoidal rule.


Enrollment: 12
Study Start Date: March 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bup/Ral
Buprenorphine and Raltegravir co-administration
Drug: Raltegravir
400 mg of raltegravir orally twice daily together with normally prescribed stable dose of buprenorphine for a minimum of 4 days and up to 14 days.
Other Name: Isentress

Detailed Description:

A large number of people who are infected with HIV have acquired it through injection drug use. Some of these people are currently being treated with Buprenorphine for their addiction and with medications for HIV infection. Raltegravir is a medication that was approved by the Food and Drug Administration (FDA) for the treatment of HIV infection. Raltegravir acts by making it more difficult for the virus that causes AIDS to multiply and cause more damage to the immune system in someone who is HIV infected.

Earlier studies looking at the effect of Buprenorphine and HIV medications have shown that Buprenorphine and some HIV medications act differently when taken together. It is important to learn if taking Buprenorphine and HIV medications together results in changes in the blood level of either medication. If the HIV medication affects the level of Buprenorphine in the blood, an individual taking Buprenorphine and HIV medications may experience symptoms of withdrawal, even while taking their usual dose of Buprenorphine. On the other hand, if Buprenorphine 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 Raltegravir and Buprenorphine will affect each other when taken together.

In order to learn about the effects of Buprenorphine and Raltegravir, we will need to measure the amount of Buprenorphine in your blood for 24 hours before you have taken Raltegravir and then compare that to the amount of Buprenorphine in your blood after you have taken Buprenorphine and Raltegravir together .

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients who are opioid dependent on long-term buprenorphine/naloxone (BUP/NLX) maintenance (minimum of 4 weeks) and who must remain at a stable dose of buprenorphine for at least 3 weeks deemed by the investigator to have acceptable medical history, physical examination and clinical laboratory evaluations consistent with BUP maintenance will be eligible to participate in the study.
  • Body weight >60 kg for males and >40 kg for females
  • Male or females, ages > 21 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:

  • 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.
  • Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of enrollment and throughout the study.
  • Women who are currently pregnant or breastfeeding.
  • 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.
  • Proven or suspected acute hepatitis at the time of study entry
  • Any major surgery within 4 weeks of enrollment. Minor surgical procedures requiring local anesthesia are exceptions.
  • 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
  • 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, or clinical laboratory determinations.
  • Positive breathalyzer alcohol test, or positive urine screen for barbiturates, benzodiazepines, amphetamines, cocaine or opioids other than buprenorphine/naloxone.
  • Subjects with AST, ALT or bilirubin > 3.0X 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.
  • HIV antibody positive
  • Exposure to any investigational drug within 4 weeks of enrollment and throughout the study.
  • Prior exposure to Raltegravir.
  • Use of any agent (prescribed or otherwise) within 2 weeks of dosing, that is known or suspected to induce or inhibit drug metabolizing enzymes (e.g., cimetidine and compounds in the barbiturate and phenothiazine classes), affect renal tubular secretion (e.g., probenecid, beta-lactam antibiotics), gastrointestinal motility (e.g., metoclopramide, propantheline, loperamide, or narcotic analgesics or opioids other than buprenorphine/naloxone), or uric acid metabolism (e.g., allopurinol) or gastrointestinal pH (including antacids, H2-receptor antagonists, proton pump inhibitors etc.).
  • Use of over-the-counter medications and herbal preparations, within 1 week prior to enrollment and throughout the study.
  • Use of St. John's Wort (Hypericum) within four weeks prior to study enrollment and throughout the study.
  • Consumption of grapefruit or grapefruit juice within 1 week of study entry and throughout the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00858962

Locations
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Yale University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Robert D Bruce, MD Yale University
  More Information

No publications provided

Responsible Party: R. Douglas Bruce, MD, MA, Investigator, Yale University
ClinicalTrials.gov Identifier: NCT00858962     History of Changes
Other Study ID Numbers: 0811004456, R01DA025932
Study First Received: March 6, 2009
Results First Received: May 31, 2012
Last Updated: October 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
HIV
Pharmacokinetics
Pharmacodynamics
Buprenorphine
Raltegravir
HIV seronegativity
Interaction

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
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
Buprenorphine
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Narcotic Antagonists

ClinicalTrials.gov processed this record on September 30, 2014