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

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01232127
• Other study ID #: AI424-398
• Secondary ID: 2009-016981-95
• Status: Completed
• Phase: Phase 4
• First received: October 29, 2010
• Last updated: August 27, 2012
• Start date: February 2011
• Est. completion date: June 2011

Study information

• Verified date: August 2012
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: CHMP: Committee for Medicinal Products for Human UseEMEA: European Medicines Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Atazanavir
Capsule, oral, 300 mg, once daily, 10 days
• Atazanavir
Capsule, oral, 400 mg, once daily, 7 days
• Ritonavir
Capsule, oral, 100 mg, once daily, 10 days
• Ritonavir
Capsule, oral, 100 mg, once daily, 7 days
• Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 10 days
• Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 7 days
• Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 10 days
• Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 7 days
• Famotidine (FAM)
Tablet, oral, 20 mg, twice daily, 7 days
• Famotidine (FAM)
Tablet, oral, 40 mg, twice daily, 7 days

Locations

Country	Name	City	State
Germany	Local Institution	Berlin
United Kingdom	Local Institution	London	Greater London

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Concentration (Cmax) and Trough Observed Plasma Concentration (Ctrough) for Atazanavir and Ritonavir		Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.	No
Primary	Time of Maximum Observed Plasma Concentration (Tmax) for Atazanavir and Ritonavir		Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.	No
Primary	Area Under the Plasma Concentration-time Curve in 1 Dosing Interval (Time 0 to 24 Hours Postdose) (AUC[TAU]) for Atazanavir and Ritonavir		Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.	No
Secondary	Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, AES, and AEs of Clinical Interest	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.	Yes
Secondary	Number of Participants With Abnormalities in Vital Signs	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.	Yes
Secondary	Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings	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.	Yes
Secondary	Number of Participants With Abnormalities in Laboratory Test Results	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.	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form