Pharmacokinetic Interactions Between Buprenorphine and Kaletra (Lopinavir/Ritonavir)

NCT00571961 | Completed Results

• 2 other identifiers: 0511000791M118687
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

HIV Infections

Keywords

HIV; Pharmacokinetics; Buprenorphine; Kaletra; HIV Seronegativity

Outcome Measures

Primary Outcomes (1)

• Buprenorphine Area Under the Curve With LPV/r (ng/mL*hr)

  Pharmacokinetic parameters were determined by use of non compartmental methods. The area under the plasma concentration versus time curve was determined by use of the trapezoidal rule and measured over a 24-hr time period.

  15 days

Study Arms (1)

1

EXPERIMENTAL

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.

Drug: Kaletra (lopinavir/ritonavir); Drug: buprenorphine; Other: Clinical evaluations/Blood draws

Interventions

Kaletra (lopinavir/ritonavir) DRUG

4 tablets, once a day (800 mg/dose) on Days 2 through 14 of this study

1

buprenorphine DRUG

Buprenorphine will be obtained through prescription at the subject's drug treatment program.

1

Clinical evaluations/Blood draws OTHER

Physical examinations, vital sign measurements, 12-lead electrocardiogram (ECG), clinical laboratory evaluations (blood chemistry and blood counts), PK blood draws.

1

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• Abbott: collaborator

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Related Publications (1)

• Bruce RD, Altice FL, Moody DE, Morse GD, Andrews L, Lin SN, Fang WB, Ma Q, Friedland GH. Pharmacokinetic interactions between buprenorphine/naloxone and once-daily lopinavir/ritonavir. J Acquir Immune Defic Syndr. 2010 Aug;54(5):511-4. doi: 10.1097/qai.0b013e3181d3cad3.

  PMID: 20672450 RESULT

MeSH Terms

Conditions

HIV Infections

Interventions

lopinavir-ritonavir drug combination; Lopinavir; Ritonavir; Buprenorphine; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: R. Douglas Bruce, MD, MA, MSc
• Organization: Yale University AIDS Program

robert.bruce@yale.edu

(203) 737-6133

Study Officials

• Robert D Bruce, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 11, 2007
• First Posted: December 12, 2007
• Study Start: January 1, 2007
• Primary Completion: August 1, 2008
• Study Completion: August 1, 2008
• Last Updated: November 21, 2012
• Results First Posted: November 21, 2012

Record last verified: 2012-10

Locations

US (1)