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Trial record 11 of 36 for:    " January 07, 2009":" February 06, 2009"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]
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Drug Interactions Between Voriconazole and Atazanavir Coadministered as Atazanavir/Ritonavir in Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00833482
First received: January 30, 2009
Last updated: September 24, 2012
Last verified: September 2012
History of Changes
  Purpose

This study assesses the effects of voriconazole, 200 mg, administered twice daily (BID), on the steady-state pharmacokinetics of atazanavir administered as atazanavir/ritonavir, 300/100 mg once daily (QD), in healthy participants with functional CYP2C19 alleles. The study also reviews the effects of atazanavir/ritonavir, 300/100 mg QD, on the pharmacokinetics of voriconazole, 200 mg, BID in healthy participants with functional CYP2C19 alleles.


Condition Intervention Phase
Human Immunodeficiency Virus Type 1 (HIV-1)
HIV Infections
 Drug: Voriconazole
Drug: Atazanavir
Drug: Ritonavir
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Study to Assess the Pharmacokinetic Drug - Drug Interactions Between Atazanavir Plus Ritonavir Coadministered With Voriconazole in Healthy Subjects

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in Participants Who Are Extensive Metabolizers (EM) [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    EM participants are those with functional CYP2C19 alleles.

  • Time to Maximum Concentration (Tmax) of Atazanavir, Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  • Area Under the Plasma Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] of Atazanavir Administered as Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  • Tmax of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    Tmax=time to maximum concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  • Cmax and Cmin of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    Cmax=maximum observed plasma concentration; Cmin=minimum observed plasma concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  • AUC(TAU)of Voriconazole, Administered With and Without Atazanavir/Ritonavir, in EM Participants [ Time Frame: Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdoseDays 3 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    AUC(TAU)=area under the plasma concentration-time curve in 1 dosing interval; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.


Secondary Outcome Measures:
  • Cmax and Cmin of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    Cmax=maximum observed plasma concentration; Cmin=minimum observed plasma concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  • Tmax of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    Tmax=time to maximum concentration; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  • AUC(TAU) of Ritonavir, Administered As Atazanavir/Ritonavir With and Without Voriconazole, in EM Participants [ Time Frame: Predose and at 1, 2, 3, 4, 5, 7, 9,13, and 24 hours postdose on Days 20 and 30 of a 30-day cycle ] [ Designated as safety issue: No ]
    AUC(TAU)=area under the plasma concentration-time curve in 1 dosing interval; EM=extensive metabolizers, or participants with functional CYP2C19 alleles.

  • Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, and Any AE [ Time Frame: Days 1 to 31 (discharge), continuously ] [ Designated as safety issue: No ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.

  • Number of Participants With Marked Abnormalities in Serum Chemistry Test Results [ Time Frame: Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge) ] [ Designated as safety issue: No ]
    LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Safety criteria: AST and ALT: If >1.25*ULN, or if preRX>ULN, use >1.25*preRX. Total and direct bilirubin: If >1.1*ULN or if preRX>ULN, use >1.25*preRX. Creatinine: If >1.33*preRX. Serum glucose, fasting: If preRX<LLN, use <.8*preRX or >ULN; if preRX>ULN, use >2*preRX or <LLN. Creatinine kinase: If >1.5*ULN or preRX>ULN, use >1.5*or preRX. Lactose dehydrogenase: If >1.25*ULN or preRX>ULN, use >1.5*preRX.

  • Number of Participants With Marked Abnormalities in Hematology Laboratory Test and Urinalysis Results [ Time Frame: Within 21 days of Day 1 and on Days 3, 10, 20, 26, and 31 (at discharge) ] [ Designated as safety issue: No ]
    LLN=lower limit of normal; ULN=upper limit of normal; preRX=pretreatment. Safety criteria: Neutrophils + bands: If <.85*LLN or >1.15*ULN or ULN or if preRX<LLN, use <0.85*preRX or >ULN; if preRX>ULN, use >1.15*preRX or <LLN. Lymphocytes, relative: If <0.85*LLN or >1.15*ULN, or if preRX <LLN, use <0.85*preRX or >ULN; if preRX >ULN, use >1.15*preRX or <LLN. Blood, urine: If >= 2+, or if preRX >=1+, use >=2*preRX. White blood cells, urine: If >=2+, or if preRX >=2+, use >=4+. Red blood cells, urine: If >=2+ or if preRX >=2+, use >=4+. Not all categories were evaluated for each arm.

  • Number of Participants With Investigator-identified Abnormalities in Electrocardiogram Results Not Present Prior to Administration of Study Drug and Considered Not Relevant and Not AEs by Investigator [ Time Frame: Within 21 days of Day 1 and on Days -1, 21, and 31 (at discharge) ] [ Designated as safety issue: No ]
    volt=voltage; LVH=left ventricular hypertrophy

  • Number of Participants With Abnormalities in Vital Signs [ Time Frame: Within 21 days of Day 1 and on Days -1, 1, 3, 11, 21, and 31 (at discharge) ] [ Designated as safety issue: No ]

Enrollment: 185
Study Start Date: September 2009
Study Completion Date: February 2011
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Voriconazole, 200 mg BID (EM) Drug: Voriconazole
Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.
Active Comparator: Atazanavir/Ritonavir, 300/100 QD (EM & PM) Drug: Atazanavir
Treatment B in EM participants: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Treatment B in participants who were poor metabolizers of CYP2C19 (PMs): PM participants received oral tablets of atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir

Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.
Active Comparator: Atazanavir/Ritonavir, 300/100mgQD + Voriconazole, 200mgBID(EM) Drug: Voriconazole
Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.
Drug: Atazanavir
Treatment B in EM participants: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Treatment B in participants who were poor metabolizers of CYP2C19 (PMs): PM participants received oral tablets of atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir

Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.
Active Comparator: Voriconazole, 50 mg BID (PM) Drug: Voriconazole
Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.
Active Comparator: Atazanavir/ritonavir, 300/100mgQD+voriconazole, 50mgBID (PM) Drug: Voriconazole
Treatment A: Participants with functional CYP2C19 alleles (EM) received oral tablets of voriconazole, 400 mg, twice daily (BID), on Day 1, then 200 mg BID on Days 2 and 3. Voriconazole dose was given at least 1 hour after a light meal. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.
Drug: Atazanavir
Treatment B in EM participants: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Treatment B in participants who were poor metabolizers of CYP2C19 (PMs): PM participants received oral tablets of atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30.
Other Names:
  • Reyataz
  • BMS-232632
Drug: Ritonavir

Treatment B: EM participants received atazanavir/ritonavir, 300/100 mg once daily (QD), on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

Treatment C: EM participants received atazanavir/ritonavir, 300/100 mg QD, plus voriconazole, 400 mg BID on Day 21 then 200 mg BID on Days 22-30. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal, and 1 hour before voriconazole morning dose.Treatment E: PM participants received atazanavir/ritonavir, 300/100 mg QD plus voriconazole, 100 mg BID, on Day 21, then 50 mg BID on Days 22-30. Treatment B in PM participants: PM participants received atazanavir/ritonavir, 300/100 mg QD, on Days 11 through 20. Atazanavir/ritonavir dose was administered in the morning within 5 minutes of completing a light meal.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy participants as determined by no clinically significant deviation from normal
  • Body Mass Index (BMI) of 18 to 32 kg/m^2, inclusive. BMI=weight(kg)/height (m)^2
  • Women who are not of childbearing potential (WOCBP)(ie, who are postmenopausal or surgically sterile) and men, ages 18 to 45 years, inclusive

Exclusion Criteria:

  • WOCBP
  • Sexually active fertile men not using effective birth control if their partners are WOCBP
  • Proven or suspected acute hepatitis (within 12 months prior to the 1st dose)
  • Any significant acute or chronic medical illness
  • Any gastrointestinal surgery that could impact on the absorption of study drug
  • Smoking more than 5 cigarettes per day
  • History of any hemolytic disorders (including drug-induced hemolysis)
  • History of acute or chronic pancreatitis
  • History of hypochlorhydria or achlorhydria
  • Men and women weighing <40 kg
  • Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or HIV-2 antibody
  • Patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00833482

Locations
United States, California
West Coast Clinical Trials, Llc
Cypress, California, United States, 90630
Netherlands
Local Institution
Nijmegen, Netherlands, 6425 GA
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

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

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00833482     History of Changes
Other Study ID Numbers: AI424-383, 2009-009095-13
Study First Received: January 30, 2009
Results First Received: July 23, 2012
Last Updated: September 24, 2012
Health Authority: United States: Food and Drug Administration
Europe, Middle East, Africa: Committee for Medicinal Products for Human Use

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Ritonavir
Atazanavir
 Voriconazole
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antifungal Agents
14-alpha Demethylase Inhibitors

ClinicalTrials.gov processed this record on May 21, 2013