Phase IIB Pilot of Atazanavir + Raltegravir (SPARTAN)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled from sites in Argentina (n=21 randomized), France (n=26 randomized), and the United States (n=47 randomized).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of 167 participants enrolled, 94 were randomized to treatment; 1 withdrew consent after randomization but prior to study dosing. Of the 73 not randomized, 5 withdrew consent, 1 lost to follow up; 1 poor/noncompliance; 61 no longer met study criteria, and 5 for other reasons. The trial was terminated early.

Reporting Groups

	Description
Atazanavir + Raltegravir	Atazanavir 300 mg twice daily plus Raltegravir 400 mg twice daily
Atazanavir + Ritonavir + Tenofovir/Emtricitabine	Atazanavir, 300 mg once daily, plus Ritonavir, 100 mg once daily, plus fixed-dose Tenofovir/emtricitabine, 300 mg/200 mg once daily

Participant Flow for 3 periods

Period 1:   Prior to Week 24

	Atazanavir + Raltegravir	Atazanavir + Ritonavir + Tenofovir/Emtricitabine
STARTED	63	30
COMPLETED	59	27
NOT COMPLETED	4	3
Withdrawal by Subject	1	0
Adverse Event	3	0
Lost to Follow-up	0	1
Protocol Violation	0	2

Period 2:   Week 24 to Prior to Week 36

	Atazanavir + Raltegravir	Atazanavir + Ritonavir + Tenofovir/Emtricitabine
STARTED	59	27
COMPLETED	51	27
NOT COMPLETED	8	0
Adverse Event	1	0
Lack of Efficacy	6	0
Withdrawal by Subject	1	0

Period 3:   On or After Week 36

	Atazanavir + Raltegravir	Atazanavir + Ritonavir + Tenofovir/Emtricitabine
STARTED	51	27
COMPLETED	0	0
NOT COMPLETED	51	27
Lack of Efficacy	1	0
Adverse Event	0	1
Lost to Follow-up	1	0
Poor Compliance	1	0
Protocol Violation	1	0
Did not attend termination visit	2	0
Sponsor Termination	45	26

Reporting Groups

	Description
Atazanavir + Raltegravir	Atazanavir 300 mg twice daily plus Raltegravir 400 mg twice daily
Atazanavir + Ritonavir + Tenofovir/Emtricitabine	Atazanavir, 300 mg once daily, plus Ritonavir, 100 mg once daily, plus fixed-dose Tenofovir/emtricitabine, 300 mg/200 mg once daily
Total	Total of all reporting groups

Baseline Measures

	Atazanavir + Raltegravir	Atazanavir + Ritonavir + Tenofovir/Emtricitabine	Total
Number of Participants   [units: participants]	63	30	93
Age   [units: years] Mean ± Standard Deviation	39.5  ± 10.90	41.6  ± 10.87	40.2  ± 10.88
Gender   [units: participants]
Female	8	2	10
Male	55	28	83
Race (NIH/OMB)   [units: participants]
American Indian or Alaska Native	0	0	0
Asian	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	8	6	14
White	54	23	77
More than one race	0	0	0
Unknown or Not Reported	1	0	1
HIV RNA Level at Baseline   [units: log10 copies/mL] Mean ± Standard Deviation	4.9  ± 0.57	4.9  ± 0.66	4.9  ± 0.60
HIV RNA Distribution at Baseline   [units: Participants]
< 30,000 copies/mL	14	7	21
30,000 to <100,000 copies/mL	15	10	25
100,000 to <500,000 copies/mL	26	10	36
>=500,000 copies/mL	8	3	11
Mean Cluster of Differentiation 4 (CD4) Cell Count at Baseline   [units: cells/mm^3] Mean ± Standard Deviation	256.2  ± 116.79	261.2  ± 134.93	257.8  ± 122.21
CD4 Distribution at Baseline   [units: Participants]
< 50 cells/mm^3	5	4	9
50 to < 100 cells/mm^3	1	1	2
100 to < 200 cells/mm^3	13	3	16
200 to < 350 cells/mm^3	29	13	42
350 to < 500 cells/mm^3	14	9	23
>= 500 cells/mm^3	1	0	1

1.  Primary:

Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) Level <50 Copies/mL at Week 24   [ Time Frame: At Week 24 from Baseline ]

2.  Secondary:

Number of Nonresponders at Week 8   [ Time Frame: At Week 8 from Baseline ]

3.  Secondary:

Number of Participants With HIV RNA Levels <50 Copies/mL at Weeks 48 and 96   [ Time Frame: At Weeks 48 and 96 from Baseline ]

4.  Secondary:

Number of Participants With HIV RNA Levels <400 Copies/mL at Week 24   [ Time Frame: At Week 24 from Baseline ]

5.  Secondary:

Number of Participants With HIV RNA Levels <400 Copies/mL at Week 48   [ Time Frame: At Week 48 from Baseline ]

6.  Secondary:

Number of Participants With HIV RNA Levels <400 Copies/mL at Week 96   [ Time Frame: At Week 96 from Baseline ]

7.  Secondary:

Mean Change From Baseline in Absolute Cluster of Differentiation 4 Cell Count   [ Time Frame: From Baseline to Weeks 2, 4, 8, 12, 16, 20, and 24 ]

8.  Secondary:

Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Death as Outcome, AEs Leading to Discontinuation, SAEs Leading to Discontinuation   [ Time Frame: Week 1 to Week 96, continuously ]

9.  Secondary:

Baseline and Mean Change From Baseline in Total Cholesterol Levels   [ Time Frame: From Baseline to Week 24 and Week 48 ]

10.  Secondary:

Mean Change From Baseline in Total Bilirubin Level   [ Time Frame: From Baseline to Week 24 and Week 48 ]

11.  Secondary:

Mean Change From Baseline in Electrocardiogram Findings   [ Time Frame: From Baseline to Week 24 ]

12.  Secondary:

Atazanavir Maximum Observed Plasma Concentration (Cmax) in 1 Dosing Interval   [ Time Frame: At Week 2 from Baseline ]

13.  Secondary:

Raltegravir Cmax in 1 Dosing Interval   [ Time Frame: At Week 2 from Baseline ]

14.  Secondary:

Atazanavir Time of Maximum Observed Plasma Concentration (Tmax)   [ Time Frame: At Week 2 from Baseline ]

15.  Secondary:

Raltegravir Tmax   [ Time Frame: At Week 2 from Baseline ]

16.  Secondary:

Atazanavir Trough Plasma Concentration (Cmin) 12 Hours Postdose   [ Time Frame: At Week 2 from Baseline ]

17.  Secondary:

Raltegravir Cmin 12 Hours Postdose   [ Time Frame: At Week 2 from Baseline ]

18.  Secondary:

Atazanavir Cmin Prior to the Morning Dose   [ Time Frame: At Week 2 from Baseline ]

19.  Secondary:

Raltegravir Cmin Prior to the Morning Dose   [ Time Frame: At Week 2 from Baseline ]

20.  Secondary:

Atazanavir Area Under the Concentration Curve From Time 0 to 12 Hours (AUC [0-12h]) in 1 Dosing Interval   [ Time Frame: At Week 2 from Baseline ]

21.  Secondary:

Raltegravir AUC (0-12h) in 1 Dosing Interval   [ Time Frame: At Week 2 from Baseline ]

22.  Secondary:

Atazanavir Area Under the Concentration Curve From Time 0 to 24 Hours (AUC [0-24h]) in 1 Dosing Interval   [ Time Frame: At Week 2 from Baseline ]

23.  Secondary:

Atazanavir Individual Inhibitory Quotient (IQ)   [ Time Frame: At Week 2 from Baseline ]

24.  Secondary:

Atazanavir Terminal Elimination Half Life   [ Time Frame: At Week 2 from Baseline ]

25.  Secondary:

Raltegravir Terminal Elimination Half Life   [ Time Frame: At Week 2 from Baseline ]

26.  Secondary:

Number of Participants With Hematology Laboratory Test Results With Worst Toxicity of Grades 1 to 4 Among All Treated Participants   [ Time Frame: While on treatment from Baseline through Week 96 ]

27.  Secondary:

Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4   [ Time Frame: While on treatment from Baseline through Week 96 ]

28.  Secondary:

Number of Participants With Blood Chemistry Laboratory Test Results With Worst Toxicity of Grades 1 to 4 (Continued)   [ Time Frame: While on treatment from Baseline through Week 96 ]

29.  Secondary:

Number of Participants With Enzyme and Urine Laboratory Test Results With Worst Toxicity of Grades 1 to 4   [ Time Frame: While on treatment from Baseline through Week 96 ]