Effects of Famotidine on the Pharmacokinetics of Atazanavir When Coadministered to Participants With HIV Infection

August 27, 2012 updated by: Bristol-Myers Squibb

Open-Label, Multiple-Dose, Drug Interaction Study to Assess the Effect of Famotidine on the Pharmacokinetics of Atazanavir in HIV-Infected Subjects Receiving Atazanavir With Ritonavir and Tenofovir

The purpose of this study is to assess the effects of famotidine, given twice daily, on atazanavir administered with ritonavir and tenofovir in HIV-infected participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This protocol was designed to compare the pharmacokinetic parameters of atazanavir administered as atazanavir/ritonavir, 400/100 mg once daily (QD), plus famotidine, 20 mg and 40 mg twice daily, with the parameters found at the usual clinical dose of atazanavir/ritonavir, 300/100 mg QD, without famotidine in HIV-infected participants receiving tenofovir disoproxil fumarate and at least 1 other nucleoside reverse transcriptase inhibitor.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 14050
        • Local Institution
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, SW10 9NH
        • Local Institution

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Key inclusion criteria:

  • Males and females, 18 to 65 years of age, with HIV infection and a body mass index of 18.0 to 35.0 kg/m^2
  • HIV-infected participants receiving a treatment regimen containing only atazanavir/ritonavir, 300/100 mg once daily (QD) + tenofovir, 300 mg QD + at least 1 other nucleotide reverse transcriptase inhibitor continuously for at least 3 months prior to study day 1
  • Plasma HIV RNA levels of <50 copies/mL and a CD4 count >200 cells/mm^3.
  • No history of virologic failure on a protease inhibitor (PI), documented phenotypic PI resistance, or primary PI mutations, according to International AIDS Society recommendations
  • No documented phenotypic resistance to atazanavir or primary genotypic mutations causing resistance to atazanavir
  • Women of childbearing potential who were not nursing or pregnant and were using an acceptable method of contraception for at least 4 weeks before dosing, during the study, and for 8 weeks from the last dose of study drug.
  • Women with a negative pregnancy test result within 24 hours prior to dosing with study medication
  • Women not breastfeeding
  • Men willing or able to agree to practice barrier contraception for the duration of the study and at least 3 months after dosing.

Key exclusion criteria:

  • Any history of CD4 cell count <50 cells/mm^3
  • Previously documented phenotypic or genotypic resistance to any of the currently prescribed NRTIs
  • Any significant acute illness within 6 months of study day 1 or chronic medical illness unless stable or controlled by a nonprohibited medication
  • Any major surgery within 4 weeks of study day 1
  • Any gastrointestinal surgery that could impact upon the absorption of any study drug
  • Inability to be venipunctured and/or tolerate venous access
  • History of Gilbert's syndrome, hemophilia, chronic pancreatitis, hypochlorhydria, achlorhydria, clinically relevant gastroesophageal reflux disease, hiatal hernia, or peptic/gastric ulcer disease
  • Intractable diarrhea (≥ 6 loose stools/day for at least 7 consecutive days) within 30 days prior to study day 1
  • Recent (within 6 months prior to study day 1) drug or alcohol abuse
  • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, electrocardiogram (ECG)
  • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations, which would not be expected for the extent of HIV disease
  • Any of the following on 12-lead ECG prior to dosing on study day 1, confirmed by repeat: PR ≥ 210 msec; QRS ≥ 120 msec; QT ≥ 500 msec; QTcF ≥ 450 msec
  • Second- or third-degree A-V block or clinically relevant ECG abnormalities
  • Positive urine screen for drugs of abuse at screening or prior to dosing without a valid prescription. Positive urine drug screen for cannabinoids with or without a prescription is not exclusionary
  • Creatinine clearance, as estimated by method of Cockcroft and Gault, less than 60 mL/min
  • Liver enzyme levels > 3* the upper limit of normal (ULN) prior to dosing on study day 1
  • Total bilirubin level >10*ULN prior to study day 1
  • Positive blood screen for hepatitis B surface antigen or hepatitis C antibody.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Atazanavir/ritonavir (300/100 mg) + TDF + ≥ 1 NRTI
The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Drug: Atazanavir
Capsule, oral, 300 mg, once daily, 10 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Atazanavir
Capsule, oral, 400 mg, once daily, 7 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 10 days
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 7 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 10 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 7 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 10 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 7 days
Other: Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (20)
FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Drug: Atazanavir
Capsule, oral, 300 mg, once daily, 10 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Atazanavir
Capsule, oral, 400 mg, once daily, 7 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 10 days
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 7 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 10 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 7 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 10 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 7 days
Drug: Famotidine (FAM)
Tablet, oral, 20 mg, twice daily, 7 days
Drug: Famotidine (FAM)
Tablet, oral, 40 mg, twice daily, 7 days
Other: Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (40)
FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Drug: Atazanavir
Capsule, oral, 300 mg, once daily, 10 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Atazanavir
Capsule, oral, 400 mg, once daily, 7 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 10 days
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 7 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 10 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 7 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 10 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 7 days
Drug: Famotidine (FAM)
Tablet, oral, 20 mg, twice daily, 7 days
Drug: Famotidine (FAM)
Tablet, oral, 40 mg, twice daily, 7 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Maximum Observed Plasma Concentration (Cmax) and Trough Observed Plasma Concentration (Ctrough) for Atazanavir and Ritonavir
Time Frame: Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Time of Maximum Observed Plasma Concentration (Tmax) for Atazanavir and Ritonavir
Time Frame: Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Area Under the Plasma Concentration-time Curve in 1 Dosing Interval (Time 0 to 24 Hours Postdose) (AUC[TAU]) for Atazanavir and Ritonavir
Time Frame: Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, AES, and AEs of Clinical Interest
Time Frame: Days 1 through 25 (end of study), continuously, and at study discharge for those who discontinued prematurely.
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Days 1 through 25 (end of study), continuously, and at study discharge for those who discontinued prematurely.
Number of Participants With Abnormalities in Vital Signs
Time Frame: Days 1, 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Vital signs include temperature, respiratory rate, seated blood pressure, and heart rate.
Days 1, 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
Time Frame: Days 1 and 25 (end of study) and at study discharge for those who discontinued prematurely.
ECG findings include heart rate, ECG intervals (including PR, QRS, QT, and corrections to QT using both Bazett's and Fridericia's formulae), and Investigator-identified ECG abnormalities.
Days 1 and 25 (end of study) and at study discharge for those who discontinued prematurely.
Number of Participants With Abnormalities in Laboratory Test Results
Time Frame: Days 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.
PreRX=pretreatment; ULN=upper limit of normal. Neutrophils, (absolute), low (10*3 c/uL): <0.85*PreRx, if PreRx <1.5; <1.5 if PreRx ≥1.5. Alanine aminotransferase, high (U/L): >1.25*PreRx if PreRx >ULN; >1.25*ULN if PreRx ≤ULN. Bilirubin, direct (mg/dL), high: >1.1*ULN if PreRx ≤ULN;> 1.1*ULN if PreRx is missing; >1.25*PreRx if PreRx >ULN. Bilirubin, total (mg/dL), high: >1.1*ULN if PreRx ≤ULN;> 1.1*ULN if PreRx is missing; >1.25*PreRx if PreRx >ULN.
Days 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bristol-Myers Squibb

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 29, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 1, 2010

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 2, 2010

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 31, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 27, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AI424-398
  • 2009-016981-95 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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