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

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ClinicalTrials.gov Identifier: NCT01232127
Recruitment Status : Completed
First Posted : November 2, 2010
Results First Posted : August 28, 2012
Last Update Posted : August 31, 2012
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label)
Condition HIV
Interventions Drug: Atazanavir
Drug: Ritonavir
Drug: Tenofovir (TDF)
Drug: Nucleoside Reverse Transcriptase Inhibitor (NRTI)
Drug: Famotidine (FAM)
Enrollment 25
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Hide Arm/Group Description Participants received atazanavir/ritonavir, 300/100 mg QD, plus tenofovir (TDF), 300 mg QD, and at least 1 nucleoside reverse transcriptase inhibitor (NRTI). Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF. Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 20 mg BID. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF. Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 40 mg BID. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Period Title: Period 1: Days 1-10
Started 25 [1] 0 0
Completed 24 0 0
Not Completed 1 0 0
Reason Not Completed
Discontinued due to dosing error             1             0             0
[1]
Participants who received treatment.
Period Title: Period 2: Days 11-17
Started 0 24 [1] 0
Completed 0 24 0
Not Completed 0 0 0
[1]
Participants who received treatment.
Period Title: Period 3: Days 18-24
Started 0 0 24 [1]
Completed 0 0 24
Not Completed 0 0 0
[1]
Participants who received treatment.
Arm/Group Title All Treated
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 25
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 25 participants
Younger than 65 years 25
65 years and older 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
Female
1
   4.0%
Male
24
  96.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
5
  20.0%
White
20
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Age  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 25 participants
39.8
(23 to 62)
CD4 Absolute Count   [1] 
Mean (Standard Deviation)
Unit of measure:  Cells/μL
Number Analyzed 25 participants
584.8  (194.09)
[1]
Measure Description: n=23 (n=evaluable participants)
CD4 Percent of Total   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent of participants
Number Analyzed 25 participants
32.1  (7.10)
[1]
Measure Description: n=23 (n=evaluable participants)For 2 participants, baseline CD4 percent total and absolute count were performed as an unscheduled visit after the initial screening visit and thus, are not included in this summary.
1.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax) and Trough Observed Plasma Concentration (Ctrough) for Atazanavir and Ritonavir
Hide Description [Not Specified]
Time Frame Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study drug and had adequate PK profiles.
Arm/Group Title Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Hide Arm/Group Description:
Participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus tenofovir (TDF), 300 mg QD, and at least 1 nucleoside reverse transcriptase inhibitor (NRTI)on Days 1 through 10. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 20 mg twice daily (BID) on Days 11 through 17. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 40 mg BID on Days 18 through 24. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Overall Number of Participants Analyzed 25 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Atazanavir Cmax
3512
(35.4%)
4131
(37.7%)
3322
(45.2%)
Atazanavir Ctrough
496
(50.9%)
602
(60.3%)
494
(59.4%)
Ritonavir Cmax
1141
(30.5%)
1148
(29.8%)
1096
(36.1%)
Ritonavir Ctrough
45.8
(58.7%)
49.2
(66.8%)
47.3
(53.4%)
2.Primary Outcome
Title Time of Maximum Observed Plasma Concentration (Tmax) for Atazanavir and Ritonavir
Hide Description [Not Specified]
Time Frame Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study drug and had adequate PK profiles.
Arm/Group Title Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Hide Arm/Group Description:
Participants received atazanavir/ritonavir, 300/100 mg QD, plus TDF, 300 mg QD, and at least 1 NRTI on Days 1 through 10. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 20 mg BID on Days 11 through 17. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 40 mg BID on Days 18 through 24. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Overall Number of Participants Analyzed 25 24 24
Median (Full Range)
Unit of Measure: Hours
Atazanavir Tmax
3.0
(2.0 to 4.0)
3.0
(2.0 to 4.0)
3.0
(2.0 to 4.10)
Ritonavir Tmax
4.0
(2.0 to 4.2)
4.00
(2.0 to 6.0)
4.0
(2.0 to 6.0)
3.Primary Outcome
Title Area Under the Plasma Concentration-time Curve in 1 Dosing Interval (Time 0 to 24 Hours Postdose) (AUC[TAU]) for Atazanavir and Ritonavir
Hide Description [Not Specified]
Time Frame Days 10, 11, 17, 18, 24, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study drug and had adequate PK profiles.
Arm/Group Title Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Hide Arm/Group Description:
Participants received atazanavir/ritonavir, 300/100 mg QD, plus tenofovir (TDF), 300 mg QD, and at least 1 nucleoside reverse transcriptase inhibitor (NRTI) on Days 1 through 10. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 20 mg BID on Days 11 through 17. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 40 mg BID on Days 18 through 24. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Overall Number of Participants Analyzed 25 24 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
Atazanavir AUC
32562
(37.7%)
37894
(40.7%)
31481
(48.8%)
Ritonavir AUC
7317
(35.6%)
7430
(32.4%)
7052
(36.7%)
4.Secondary Outcome
Title Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, AES, and AEs of Clinical Interest
Hide Description 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.
Time Frame Days 1 through 25 (end of study), continuously, and at study discharge for those who discontinued prematurely.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study drug and were evaluable.
Arm/Group Title Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Hide Arm/Group Description:
Participants received atazanavir/ritonavir, 300/100 mg QD, plus tenofovir (TDF), 300 mg QD, and at least 1 nucleoside reverse transcriptase inhibitor (NRTI) on Days 1 through 10. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 20 mg BID on Days 11 through 17. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 40 mg BID on Days 18 through 24. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Overall Number of Participants Analyzed 25 25 24
Measure Type: Number
Unit of Measure: Participants
Deaths 0 0 0
SAEs 0 0 0
AEs leading to discontinuation 0 0 0
AEs 6 7 5
AEs of clinical interest: Nausea 0 2 0
AEs of clinical interest: Diarrhea 0 3 0
5.Secondary Outcome
Title Number of Participants With Abnormalities in Vital Signs
Hide Description Vital signs include temperature, respiratory rate, seated blood pressure, and heart rate.
Time Frame Days 1, 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study drug and were evaluable.
Arm/Group Title All Treated
Hide Arm/Group Description:
All participants who received at least 1 dose of atazanavir with ritonavir and tenofovir and with or without famotidine.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: Participants
Isolated decrease in heart rate 2
Sporadic respiration rate >16 bpm 11
6.Secondary Outcome
Title Number of Participants With Abnormalities in Electrocardiogram (ECG) Findings
Hide Description 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.
Time Frame Days 1 and 25 (end of study) and at study discharge for those who discontinued prematurely.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study drug and were evaluable.
Arm/Group Title All Treated
Hide Arm/Group Description:
All participants who received at least 1 dose of atazanavir with ritonavir and tenofovir and with or without famotidine.
Overall Number of Participants Analyzed 25
Measure Type: Number
Unit of Measure: Participants
Nonspecific ST/T wave abnormality 1
Short PR interval 1
7.Secondary Outcome
Title Number of Participants With Abnormalities in Laboratory Test Results
Hide Description 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.
Time Frame Days 11, 18, and 25 (end of study) and at study discharge for those who discontinued prematurely.
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study drug and were evaluable.
Arm/Group Title Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Hide Arm/Group Description:
Participants received atazanavir/ritonavir, 300/100 mg QD, plus tenofovir (TDF), 300 mg QD, and at least 1 nucleoside reverse transcriptase inhibitor (NRTI) on Days 1 through 10. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 20 mg BID on Days 11 through 17. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 40 mg BID on Days 18 through 24. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF.
Overall Number of Participants Analyzed 25 24 23
Measure Type: Number
Unit of Measure: Participants
WBC differential count (low) 1 0 0
Neutrophils (absolute) (low) 0 1 0
Alanine aminotransferase (high) 0 1 0
Aspartate aminotransferase (high) 0 0 1
Bilirubin, direct (high) 1 0 0
Bilirubin, total (high) 3 7 5
Time Frame Days 1 through 25 (end of study), continuously, and at study discharge for those who discontinued prematurely.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Hide Arm/Group Description Participants received atazanavir/ritonavir, 300/100 mg once daily (QD), plus tenofovir (TDF), 300 mg QD, and at least 1 nucleoside reverse transcriptase inhibitor (NRTI) on Days 1 through 10. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF. Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 20 mg twice daily (BID) on Days 11 through 17. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF. Participants received atazanavir/ritonavir, 400/100 mg QD, plus TDF, 300 mg QD, plus at least 1 NRTI, plus famotidine, 40 mg BID on Days 18 through 24. Atazanavir/ritonavir and TDF were administered with food. The AM dose of famotidine was administered simultaneously with atazanavir/ritonavir/TDF
All-Cause Mortality
Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/25 (0.00%)   0/25 (0.00%)   0/24 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atazanavir/Ritonavir (300/100) + TDF + ≥NRTI Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (20) Atazanavir/Ritonavir (400/100) + TDF + ≥NRTI + Famotidine (40)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/25 (16.00%)   6/25 (24.00%)   1/24 (4.17%) 
Gastrointestinal disorders       
Diarrhoea  1  0/25 (0.00%)  3/25 (12.00%)  0/24 (0.00%) 
Nausea  1  0/25 (0.00%)  2/25 (8.00%)  0/24 (0.00%) 
Nervous system disorders       
Headache  1  4/25 (16.00%)  1/25 (4.00%)  1/24 (4.17%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01232127    
Other Study ID Numbers: AI424-398
2009-016981-95 ( EudraCT Number )
First Submitted: October 29, 2010
First Posted: November 2, 2010
Results First Submitted: July 23, 2012
Results First Posted: August 28, 2012
Last Update Posted: August 31, 2012