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

Phase 4

Completed

Conditions: HIV

Interventions: Drug: Atazanavir
Drug: Ritonavir
Drug: Tenofovir (TDF)
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug: Famotidine (FAM)

Registration Number: NCT01232127

Lead Sponsor: Bristol-Myers Squibb

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Atazanavir/ritonavir (300/100 mg) + TDF + ≥ 1 NRTI	Tenofovir (TDF)	The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (300/100 mg) + TDF + ≥ 1 NRTI	Nucleoside Reverse Transcriptase Inhibitor (NRTI)	The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (20)	Nucleoside Reverse Transcriptase Inhibitor (NRTI)	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (20)	Famotidine (FAM)	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (20)	Tenofovir (TDF)	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (40)	Tenofovir (TDF)	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (40)	Nucleoside Reverse Transcriptase Inhibitor (NRTI)	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (40)	Famotidine (FAM)	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (300/100 mg) + TDF + ≥ 1 NRTI	Atazanavir	The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (300/100 mg) + TDF + ≥ 1 NRTI	Ritonavir	The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (20)	Atazanavir	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (20)	Ritonavir	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (40)	Atazanavir	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.
Atazanavir/ritonavir (400/100) + TDF + ≥1 NRTI + FAM (40)	Ritonavir	FAM=famotidine. The protocol required that participants enrolled in this study already be receiving atazanavir, ritonavir, TDF, and 1 or more NRTIs.

Primary Outcome Measures

Name	Time	Method
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.
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.
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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, AES, and AEs of Clinical Interest	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.
Number of Participants With Abnormalities in Vital Signs	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.
Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings	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.
Number of Participants With Abnormalities in Laboratory Test Results	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.