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Atazanavir/Ritonavir, Once Daily + Raltegravir, Twice Daily, Switch Study in HIV-1—Infected Patients (SPARTAN)

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ClinicalTrials.gov Identifier: NCT01332227
Recruitment Status : Completed
First Posted : April 11, 2011
Results First Posted : October 16, 2014
Last Update Posted : February 19, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV, Combination Therapy
Interventions Drug: Atazanavir
Drug: Ritonavir (heat-stable)
Drug: Raltegravir
Drug: Tenofovir/Emtricitabine
Enrollment 132
Recruitment Details  
Pre-assignment Details Of 132 patients enrolled, 109 were randomized to receive treatment, and 23 patients were not randomized for the following reasons: 10 did not meet study criteria; 5 withdrew consent; 3 were lost to follow-up, and 5 withdrew for other reasons.
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks. Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Period Title: Overall Study
Started 72 [1] 37 [1]
Completed 56 32
Not Completed 16 5
Reason Not Completed
Adverse Event             4             1
Withdrawal by Subject             5             1
Lost to Follow-up             2             0
Lack of Efficacy             3             1
Poor compliance/noncompliance             1             1
Patient moved from area             1             0
Patient began prohibited medication             0             1
[1]
Participants who received treatment
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine Total
Hide Arm/Group Description Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks. Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks. Total of all reporting groups
Overall Number of Baseline Participants 72 37 109
Hide Baseline Analysis Population Description
All participants who received study drug
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 72 participants 37 participants 109 participants
43.1  (9.26) 44.0  (10.38) 43.4  (9.62)
[1]
Measure Description: Mean age
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 72 participants 37 participants 109 participants
44.0
(25 to 67)
44.0
(25 to 69)
44.0
(25 to 69)
[1]
Measure Description: Median age
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 37 participants 109 participants
< 65 years 69 36 105
65-85 years 3 1 4
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 37 participants 109 participants
Female
14
  19.4%
6
  16.2%
20
  18.3%
Male
58
  80.6%
31
  83.8%
89
  81.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 37 participants 109 participants
Hispanic or Latino
5
   6.9%
1
   2.7%
6
   5.5%
Not Hispanic or Latino
29
  40.3%
13
  35.1%
42
  38.5%
Unknown or Not Reported
38
  52.8%
23
  62.2%
61
  56.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 37 participants 109 participants
White 54 24 78
Black or African American 8 6 14
Hispanic 2 0 2
Unknown 8 7 15
Mean CD4 count  
Mean (Standard Deviation)
Unit of measure:  Cells/mm^3
Number Analyzed 72 participants 37 participants 109 participants
587.7  (252.09) 630.9  (270.02) 601.5  (257.48)
Median CD4 count  
Median (Full Range)
Unit of measure:  Cells/mm^3
Number Analyzed 72 participants 37 participants 109 participants
588.5
(10 to 1511)
639.5
(159 to 1395)
593.0
(10 to 1511)
Cardiovascular disease risk factors   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 72 participants 37 participants 109 participants
Hypertension 5 6 11
Diabetes mellitus 3 1 4
Current smoker 27 11 38
Previous smoker 7 8 15
Family history of premature coronary heart disease 4 0 4
[1]
Measure Description: Hypertension=systolic blood pressure/diastolic blood pressure >140/90 mm Hg or patient was taking antihypertensive medication; family history of coronary heart disease=father, mother, or sibling (male <55 years of age, and mother <65 years of age).
1.Primary Outcome
Title Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 24
Hide Description HIV-1 RNA level was measured with the Abbott m2000rt® polymerase chain reaction assay. Response rates were assessed using an intent-to-treat algorithm, with numerator representing patients meeting the response criteria, and denominator representing all randomized patients. Randomized patients not meeting the criteria for treatment failure (eg, discontinuation of study therapy or virologic rebound at or before Week 24) were considered responders. Virologic rebound was defined as 2 consecutive on-treatment HIV-1 RNA levels ≥40 c/mL or the last on-treatment HIV-1 RNA level ≥40 c/mL followed by discontinuation. Patients who experienced treatment failure or had missing Week 24 HIV-1 RNA levels were considered failures. RNA=ribonucleic acid; HIV=human immunodeficiency virus.
Time Frame From Day 1 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received study drug and who had an HIV-1 RNA measurement at the analysis week.
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description:
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Number of Participants Analyzed 72 37
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
80.6
(69.5 to 88.9)
94.6
(81.8 to 99.3)
2.Secondary Outcome
Title Percentage of Participants With HIV-1 RNA Level <40 c/mL at Week 48
Hide Description Percentages of patients with HIV-1 RNA levels <40 c/mL were summarized at each scheduled visit. Longitudinal plots were created to display proportion versus visit week through Weeks 24 and 48 with error bars representing 95% confidence intervals.
Time Frame From Day 1 to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received study drug and who had an HIV-1 RNA measurement at the analysis week.
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description:
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Number of Participants Analyzed 72 37
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
69.4
(57.5 to 79.8)
86.5
(71.2 to 95.5)
3.Secondary Outcome
Title Number of Participants With Virologic Rebound at Weeks 24 and 48
Hide Description Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates.
Time Frame Day 1 to Weeks 28 and 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients who received study drug and who had an HIV-1 RNA measurement at the analysis week.
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description:
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Number of Participants Analyzed 72 37
Measure Type: Number
Unit of Measure: Participants
Week 24: Virologic rebound 7 1
Week 48: Virologic rebound 9 1
4.Secondary Outcome
Title Number of Participants With Genotypable/Phenotypable Isolates, Emergent Genotypic Substitutions in Patients With Genotypable Isolates, and Phenotypic Resistance in Patients With Phenotypable Isolates at Week 24
Hide Description Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts=patients
Time Frame Day 1 to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Patients who received study drug, who had an HIV-1 RNA measurement at the analysis week and who experienced virologic rebound.
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description:
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Number of Participants Analyzed 7 1
Measure Type: Number
Unit of Measure: Participants
Genotypable (GI)/phenotypable isolates (PI) 4 0
Emergent genotypic substitutions in GI pts (n=4,0) 4 0
Phenotypic resistance in PI pts (n=4,0) 1 0
5.Secondary Outcome
Title Number of Participants With Genotypable/Phenotypable Isolates, Emergent Genotypic Substitutions in Patients With Genotypable Isolates, and Phenotypic Resistance in Patients With Phenotypable Isolates at Week 48
Hide Description Viral genotypic and phenotypic resistance profiles were assessed for virologic rebound (HIV-1 RNA level ≥40 c/mL). Only patients with HIV-1 RNA levels ≥500 c/mL met the criteria for resistance testing. Genotypic substitutions at baseline were summarized for virologic rebound. The genotypic resistance profile presented patients with genotypable isolates, those with protease inhibitor substitutions from genotypable isolates, those with integrase substitutions from genotypable isolates, and those with selected reverse transcriptase substitutions from genotypable isolates using the most current version of the International AIDS Society-USA list and Stanford HIV Drug Resistance Database. Newly emergent genotypic substitutions were summarized analogously for virologic rebound without baseline phenotypic resistance to atazanavir, ritonavir, or raltegravir, using all on-treatment isolates. pts=patients
Time Frame Day 1 to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with virologic rebound
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description:
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Number of Participants Analyzed 9 1
Measure Type: Number
Unit of Measure: Participants
Genotypable (GI)/phenotypable isolates (PI) 5 0
Emergent genotypic substitutions in GI pts (n=5,0) 5 0
Phenotypic resistance in PI pts (n=5,0) 1 0
6.Secondary Outcome
Title Number of Patients With Death as Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, Treatment-emergent Adverse Events (AEs) Leading to Discontinuation, and Treatment-emergent AEs
Hide Description 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. Related=having certain, probable, possible, or unknown relationship to study drug.
Time Frame Day 1 to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received study drug
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description:
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Number of Participants Analyzed 72 37
Measure Type: Number
Unit of Measure: Particpants
Deaths 0 0
SAEs 4 1
Related SAEs 1 0
Treatment-emergent AEs leading to discontinuation 3 1
Treatment-emergent AEs 51 28
7.Secondary Outcome
Title Mean Changes in Fasting Lipid Levels From Baseline to Week 48
Hide Description LD=low-density lipoprotein; HDL=high-density lipoprotein.
Time Frame From Baseline to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received study drug
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description:
Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks.
Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
Overall Number of Participants Analyzed 72 37
Mean (Standard Error)
Unit of Measure: mg/dL
Fasting total cholesterol 11.7  (5.239) -10.2  (4.769)
Fasting LDL cholesterol 7.7  (3.986) -5.4  (4.691)
Fasting HDL cholesterol 2.7  (2.055) -0.3  (1.915)
Fasting non-HDL cholesterol 9.0  (4.983) -9.8  (4.430)
Fasting triglycerides 14.7  (16.667) -17.6  (16.994)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Hide Arm/Group Description Patients received atazanavir, 300-mg capsules, and ritonavir, 100-mg tablets, orally once daily and raltegravir, 400-mg tablets, twice daily for 48 weeks. Patients received atazanavir, 300-mg capsules, plus ritonavir, 100-mg tablets, and tenofovir/emtricitabine, 300/200-mg tablets, orally once daily for 48 weeks.
All-Cause Mortality
Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   4/72 (5.56%)   1/37 (2.70%) 
Gastrointestinal disorders     
Gastrooesophageal reflux disease  1  1/72 (1.39%)  0/37 (0.00%) 
General disorders     
Non-cardiac chest pain  1  1/72 (1.39%)  0/37 (0.00%) 
Infections and infestations     
Device related infection  1  1/72 (1.39%)  0/37 (0.00%) 
Pneumonia legionella  1  1/72 (1.39%)  0/37 (0.00%) 
Injury, poisoning and procedural complications     
Accidental overdose  1  0/72 (0.00%)  1/37 (2.70%) 
Metabolism and nutrition disorders     
Cachexia  1  1/72 (1.39%)  0/37 (0.00%) 
Renal and urinary disorders     
Calculus urinary  1  1/72 (1.39%)  0/37 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atazanavir/Ritonavir + Raltegravir Atazanavir/Ritonavir + Tenofovir/Emtricitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   27/72 (37.50%)   23/37 (62.16%) 
Eye disorders     
Ocular icterus  1  6/72 (8.33%)  3/37 (8.11%) 
Gastrointestinal disorders     
Abdominal distension  1  1/72 (1.39%)  2/37 (5.41%) 
Diarrhoea  1  3/72 (4.17%)  4/37 (10.81%) 
Hepatobiliary disorders     
Jaundice  1  4/72 (5.56%)  4/37 (10.81%) 
Hyperbilirubinaemia  1  6/72 (8.33%)  4/37 (10.81%) 
Infections and infestations     
Gonorrhoea  1  1/72 (1.39%)  2/37 (5.41%) 
Nasopharyngitis  1  4/72 (5.56%)  2/37 (5.41%) 
Bronchitis  1  4/72 (5.56%)  1/37 (2.70%) 
Metabolism and nutrition disorders     
Hyperlactacidaemia  1  0/72 (0.00%)  2/37 (5.41%) 
Musculoskeletal and connective tissue disorders     
Musculoskeletal pain  1  0/72 (0.00%)  2/37 (5.41%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma  1  0/72 (0.00%)  2/37 (5.41%) 
Nervous system disorders     
Headache  1  4/72 (5.56%)  2/37 (5.41%) 
Psychiatric disorders     
Insomnia  1  4/72 (5.56%)  0/37 (0.00%) 
Renal and urinary disorders     
Proteinuria  1  1/72 (1.39%)  3/37 (8.11%) 
Skin and subcutaneous tissue disorders     
Dry skin  1  1/72 (1.39%)  2/37 (5.41%) 
Rash  1  0/72 (0.00%)  2/37 (5.41%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
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
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01332227     History of Changes
Other Study ID Numbers: AI424-402
2009-017032-41 ( EudraCT Number )
First Submitted: April 7, 2011
First Posted: April 11, 2011
Results First Submitted: September 19, 2014
Results First Posted: October 16, 2014
Last Update Posted: February 19, 2015