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Completed

NCT Number: NCT01837719

Bioequivalence Study of Individual Atazanavir and Cobicistat Compared With Atazanavir in Fixed-dose Combination With Cobicistat

The purpose of the study is to compare the pharmacokinetics and bioequivalence of atazanavir in a fixed-dose combination with cobicistat with that of atazanavir coadministered with cobicistat as single agents.

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Key information

Conditions

Human Immunodeficiency Virus Type 1 (HIV-1) Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year–49 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Ppd Development, Inc.

Austin, Texas, 78744, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • Healthy men and women, ages 18 to 49 years
  • Body mass index 18 to 32 kg/m^2, inclusive
  • Women of childbearing potential (WOCBP) who were not pregnant or breastfeeding
  • WOCBP and men who are sexually active with WOCBP must use acceptable contraceptive methods

Key Exclusion Criteria:

  • Any significant acute or chronic medical illness
  • Current or recent (within 3 months of study drug administration) gastrointestinal tract disease
  • Any major surgery within 4 weeks of study drug administration
  • Any gastrointestinal tract surgery (including cholecystectomy) that could have an impact on the absorption of study drug
  • Donation of blood to a blood bank or in a clinical study (except a screening visit) within 4 weeks of study drug administration (within 2 weeks for plasma only)
  • Blood transfusion within 4 weeks of study drug administration
  • Inability to tolerate oral medication, to be venipunctured, or to tolerate venous access
  • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination or electrocardiogram (ECG) findings, vital sign measurements, or results of clinical laboratory tests, beyond what is consistent with the target population
  • Any of the following 12-lead ECG findings prior to study drug administration, confirmed by repeat testing
  • PR ≥210 msec
  • QRS ≥120 msec
  • QT ≥500 msec
  • QTcF ≥450 msec
  • 2nd- or 3rd-degree A-V block or clinically relevant abnormalities in ECG findings
  • Positive result on urine screening for drugs of abuse
  • Positive result on blood screening for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or -2 antibody
  • Laboratory test results indicating levels outside of the ranges specified below:
  • Alanine aminotransferase >upper limit of normal (ULN)
  • Aspartate aminotransferase >ULN
  • Total bilirubin >ULN
  • Serum creatinine >ULN

Treatment and study plan

Atazanavir

Drug

300-mg capsule

Other names: BMS-232632

Cobicistat

Drug

150-mg tablet

Atazanavir/Cobicistat FDC

Drug

Atazanavir 300-mg/cobicistat 150-mg FDC tablet

Primary outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of Atazanavir

    Time frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

    Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. Cmax was derived from plasma concentration versus time data.

  2. Area Under the Plasma Concentration-time Curve (AUC) From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and From Time 0 to Infinity (AUC[INF]) for Atazanavir

    Time frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

    Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. AUC(0-T) and AUC(INF) were derived from plasma concentration versus time data.

Secondary outcomes

  1. Number of Participants Who Died and With Serious Adverse Events (SAEs)

    Time frame: On Day 24 or 31

    An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant who receives an investigational product and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product. An SAE is any untoward medical occurrence that at any dose results in death; is life-threatening; or requires or prolongs inpatient hospitalization.

  2. Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests

    Time frame: At Screening and on Days -1,4, 11, 18, and 31 (study discharge)

    LLN=lower limit of normal; ULN=upper limit of normal; preRx=pretreatment; h=high; hpf=high power field. Abnormal criteria: Leukocytes, low (*10^3 c/uL): <0.85*preRx if preRx<LLN; <0.9*LLN if LLN≤preRx≤ULN;< 0.9*LLN if preRx=missing;<LLN if preRX>ULN. Neutrophils, low (*10^3 c/uL): <0.85*preRx if preRx<1.5; <1.5 if preRx=missing; <1.5 if preRx ≥1.5. Bilirubin, h (mg/dL): >1.1* ULN if preRx≤ULN; >1.1*ULN if preRx=missing; >1.25*preRx if preRx>ULN. Bilirubin, h (mg/dL): >1.1* ULN if preRx≤ULN; >1.1*ULN if preRx=missing; >1.25*preRx if preRx>ULN. Blood, urine, h: ≥2*preRx if preRx≥1; ≥2 if preRx <1; ≥2 if preRx=missing. RBCs/WBCs, h (hpf): ≥2 if preRx=missing ≥2 if preRx<2 ≥4 if preRx ≥2. Creatine kinase, h (U/L): >1.5*preRx if preRx>ULN; >1.5*ULN if preRx≤ULN; >1.5*ULN if preRx=missing; AST, h (U/L): >1.25* preRx if preRx>ULN; >1.25*ULN if preRx≤ULN; >1.25*ULN if preRx=missing. Lactate dehydrogenase, h (U/L): >1.25*ULN if preRx≤ULN; >1.25*ULN if preRx=missing; >1.5*preRx if preRx>ULN.

  3. Number of Participants With Out-of-range Intervals on Electrocardiogram (ECG) Findings

    Time frame: At screening; on Day -1; predose and 4 hours postdose on Days 1, 18, 15, 22, and 29; and at study discharge (Day 31)

    A 12-lead ECG was recorded at predose and 4 hours post dose at screening, Days -1, 1, 8 15, 22, 29 and study discharge. ECGs were recorded after the patient had been supine for at least 5 minutes. All ECG readings post dosing (including unscheduled) were included.

  4. Time of Maximum Observed Concentration (Tmax) of Atazanavir

    Time frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

    Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. Tmax was derived from plasma concentration versus time data.

  5. Observed Concentration at 24 Hours (C24) of Atazanavir

    Time frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

    Blood samples for plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. C24 was derived from plasma concentration versus time data.

  6. Apparent Terminal Half-life (T-HALF) of Atazanavir

    Time frame: Days 1, 8, 15, 22, and 29 (predose and at 1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24, 30, and 36 hours postdose); Days 3, 10, 17, 24, and 31 (48 hours postdose)

    Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. T-HALF was derived from plasma concentration versus time data.

  7. Maximum Observed Plasma Concentration (Cmax) of Cobicistat

    Time frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)

    Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. Cmax was derived from plasma concentration versus time data.

  8. Time of Maximum Observed Concentration (Tmax) of Cobicistat

    Time frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)

    Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. Tmax was derived from plasma concentration versus time data.

  9. Area Under the Concentration Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-T]) and Area Under the Concentration Curve From Time 0 to Infinity (AUC[INF]) of Cobicistat

    Time frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)

    Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. AUC(0-T) and AUC(INF) were derived from plasma concentration versus time data.

  10. T-HALF of Cobicistat

    Time frame: Days 1, 8, 15, 22, and 29 (1,2, 2.5, 3, 4, 5, 6, 8, 12, and 16 hours postdose); Days 2, 9, 16, 23, and 30 (24 hours postdose)

    Blood samples for testing plasma concentrations were obtained at predose and at specific timepoints up to 48 hours after dosing on Days 1, 8, 15, 22, and 29. T-HALF was derived from plasma concentration versus time data.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study title

A Randomized, 5-Period, Crossover Study in Healthy Subjects to Assess the Bioequivalence of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Following a Light Meal, the Relative Bioavailability of Atazanavir When Co-Administered With Cobicistat as a Fixed Dose Combination Relative to the Single Agents Under Fasted Conditions, and the Effect of Food on the Bioavailability of Atazanavir in the Fixed Dose Combination

Acronym: Atazanavir

Important dates

Study start
2013
Primary completion
2013
Study completion
2013
First posted
Apr 23, 2013
Registry last updated
Aug 29, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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