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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01232127
First received: October 29, 2010
Last updated: August 27, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
HIV
Drug: Atazanavir
Drug: Ritonavir
Drug: Tenofovir (TDF)
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug: Famotidine (FAM)
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Days 1, 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely. ] [ Designated as safety issue: Yes ]
    Vital signs include temperature, respiratory rate, seated blood pressure, and heart rate.

  • 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. ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Days 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 25
Study Start Date: February 2011
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Ritonavir
Capsule, oral, 100 mg, once daily, 7 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 10 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 10 days
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, 400 mg, once daily, 7 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 10 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 7 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 7 days
Drug: Famotidine (FAM)
Tablet, oral, 20 mg, twice daily, 7 days
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, 400 mg, once daily, 7 days
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir
Capsule, oral, 100 mg, once daily, 10 days
Drug: Tenofovir (TDF)
Capsule, oral, 300 mg, once daily, 7 days
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Oral, 7 days
Drug: Famotidine (FAM)
Tablet, oral, 40 mg, twice daily, 7 days

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01232127

Locations
Germany
Local Institution
Berlin, Germany, 14050
United Kingdom
Local Institution
London, Greater London, United Kingdom, SW10 9NH
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01232127     History of Changes
Other Study ID Numbers: AI424-398, 2009-016981-95
Study First Received: October 29, 2010
Results First Received: July 23, 2012
Last Updated: August 27, 2012
Health Authority: CHMP: Committee for Medicinal Products for Human Use
EMEA: European Medicines Agency

Additional relevant MeSH terms:
Famotidine
Reverse Transcriptase Inhibitors
Tenofovir
Tenofovir disoproxil
Ritonavir
Atazanavir
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 20, 2014