HIV infected Subjects MedDRA version: 8.1 Level: LLT Classification code 10020161 Term: HIV infection
Conditions
Interventions
Trade Name: Reyataz
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Atazanavir Sulfate
CAS Number: 229975-97-7
Current Sponsor code: BMS-232632-05
Other descriptive name: ATV
Concentration uni
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: * Signed written informed consent * Either: i) For Cohort 1, are receiving an ARV treatment regimen containing ATV/RTV 300/100 mg + at least 2 NRTIs (dosing per USPI or SmPC)(not TDF) continuously for at least 5 months prior to enrollment, or ii) For Cohort 2, are receiving an ARV treatment regimen containing ATV/RTV 300/100 mg + at least 1 NRTI + TDF continuously for at least 5 months prior to enrollment iii) Have had plasma HIV RNA 200 cells/mm³ * Have no history of virologic failure on a protease inhibitor (PI) or documented phenotypic PI resistance or primary PI mutations (according to IAS recommendations). * Have no documented phenotypic resistance to ATV or primary genotypic mutations causing resistance to ATV. * Body Mass Index (BMI) of 18 to 35 kg/m², inclusive. BMI = weight (kg)/[height (m)]² * Men and women, ages 18 to 65 inclusive * WOCBP must use effective barrier contraception. Other methods of oral contraception, in addition to barrier methods, are permitted (see Protocol Section 6.4.3; Precautions for details regarding potential interactions with ATV and some oral contraceptives). WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: *WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for entire study period & for up to 8 weeks after study; acceptable method must include practice of barrier contraception *WOCBP using oral contraceptives without a barrier method. Caution is warranted with co-administration of oral contraceptives(ethinyl estradiol & norethindrone) *Pregnant or breastfeeding women *Women with positive pregnancy test on enrollment or prior to study drug administration *Men unwilling or unable to agree to practice barrier contraception for duration of study & at least 3 months after dosing *Any history of CD4 cell count 400 copies/mL) while being administered a PI *Any significant acute illness within 6 months of Study Day 1 or chronic medical illness unless stable or controlled by non-prohibited medication *History of gastroesophageal reflux disease, hiatal hernia, or peptic/gastric ulcer disease *Any major surgery within 4 weeks of Day 1 of on-study ATV *Any gastrointestinal surgery that could impact upon the absorption of study drug (ATV/RTV +/- FAM) *Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks of Day 1 of on-study ATV *Blood transfusion within 4 weeks of Day 1 of on-study ATV *Inability to tolerate oral medication *Inability to tolerate venipuncture and/or venous access *Subjects with history of Gilbert’s syndrome *Intractable diarrhea (= 6 loose stools/day for at least 7 consecutive days) within 30 days prior to Day 1 of on-study ATV *History of hemophilia *History of chronic pancreatitis *History of hypochlorhydria or achlorhydria *Recent (=6 months prior to enrollment) drug or alcohol abuse as defined in DSM IV, Diagnostic Criteria for Drug & Alcohol Abuse *Any other sound medical, psychiatric &/or social reason as determined by Investigator *Evidence of organ dysfunction or any clinically significant deviation in physical examination, vital signs, ECG or clinical laboratory determinations, not expected for the extent of HIV disease *Positive urine screen for drugs of abuse at screening or Day -2 without valid prescription (except for cannabinoids) *Creatinine clearance, estimated by method of Cockcroft & Gault 3X upper limit of normal *Total bilirubin > 10X upper limit of normal (due to ARV regimen containing ATV/RTV) *2nd- or 3rd-degree A-V block or clinically relevant ECG abnormalities *Positive pregnancy test for females only(minimum sensitivity of 25 IU/L equivalent units of HCG) *Previously documented phenotypic PI resistance or Primary PI mutations *Previously documented phenotypic or genotypic resistance to currently prescribed nucleoside/nucleotide reverse transcriptase inhibitors such that subjects are being treated with < 3 active antiretrovirals *History of allergy to HIV protease inhibitors (ATV, RTV), HIV nucleoside or nucleotide reverse transcriptase inhibitors or H2-receptor antagonists which the patient will be administered during the study *History of significant drug allergy or adverse drug reaction related to any study drug (ATV/RTV +/- FAM) class in the study *Prior exposure to any investigational drug or placebo within 4 weeks of Day 1 of on-study ATV, except protocol-required pre-study minimum 5 month regimen (ATV/RTV, = 2NRTIs) *Use of any prescription or nonprescription drugs within 4 weeks prior to Day 1 of on-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of multiple-dose FAM BID on the multiple-dose PK of ATV/RTV in HIV-infected subjects when FAM is administered simultaneously (without TDF) or temporally separated (with TDF).;Secondary Objective: • To assess the PK of RTV co-administered with ATV in the presence and absence of FAM • To assess the safety and tolerability of ATV/RTV when co-administered with FAM in the presence of at least 2 NRTIs.;Primary end point(s): * Pharmacokinetic Measures: PK for ATV and RTV will be derived from plasma concentration versus time data. The PK parameters to be assessed include: - Atazanavir and Ritonavir: • Cmax: Maximum observed plasma concentration on Days 10, 17 and 24 • Tmax: Time to reach Cmax on Days 10, 17 and 24 • Cmin: Trough plasma concentration 24-hours post-dose administration on Days 10, 17 and 24 (Days 11, 18 and 25, respectively) • AUC(TAU): Area under the concentration-time curve, in one dosing interval from time zero to 24-hours on Days 10, 17 and 24 • T-HALF: Terminal elimination half life on Days 10, 17 and 24 (RTV only) - Famotidine plasma samples will be collected and stored for possible future analysis of FAM levels. * Primary Safety Outcome Measures: Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests. The incidence of adverse events will be tabulated and reviewed for potential significance and clinical importance. | — |
Countries
United Kingdom
Outcome results
None listed