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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01232127
• Date of registration: 29/10/2010
• Primary sponsor: Bristol-Myers Squibb
• Public title: Effects of Famotidine on the Pharmacokinetics of Atazanavir When Coadministered to Participants With HIV Infection
• Scientific 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
• Date of first enrolment: February 2011
• Target sample size: 25
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT01232127
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Countries of recruitment

Germany, United Kingdom

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

HIV

Intervention(s)

Drug: Atazanavir

Drug: Famotidine (FAM)

Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)

Drug: Ritonavir

Drug: Tenofovir (TDF)

Primary Outcome(s)

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.]

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.]

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.]

Secondary Outcome(s)

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.]

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.]

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.]

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.]

Secondary ID(s)

2009-016981-95

AI424-398

Source(s) of Monetary Support

Please refer to primary and secondary sponsors