Clinical trial NCT01232127: Effects of Famotidine on the Pharmacokinetics of Atazanavir When Coadministered to Participants With HIV Infection
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2010-11-02
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) and Trough Observed Plasma Concentration (Ctrough) for Atazanavir and Ritonavir
timeFrame: Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
measure: Time of Maximum Observed Plasma Concentration (Tmax) for Atazanavir and Ritonavir
timeFrame: Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
measure: Area Under the Plasma Concentration-time Curve in 1 Dosing Interval (Time 0 to 24 Hours Postdose) (AUC[TAU]) for Atazanavir and Ritonavir
timeFrame: Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Secondary outcomes:
measure: Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, AES, and AEs of Clinical Interest
timeFrame: Days 1 through 25 (end of study), continuously, and at study discharge for those who discontinued prematurely.
measure: Number of Participants With Abnormalities in Vital Signs
timeFrame: Days 1, 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.
measure: Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
timeFrame: Days 1 and 25 (end of study) and at study discharge for those who discontinued prematurely.
measure: Number of Participants With Abnormalities in Laboratory Test Results
timeFrame: Days 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: