In addition to SPIRIT, Gilead is evaluating Complera in two post-marketing studies - an open-label Phase 3b head-to-head trial comparing Complera to Atripla ® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) among patients who are new to therapy (Study 110), and a Phase 2b open-label pilot study evaluating the efficacy and safety of switching virologically suppressed Atripla patients to Complera (Study 111). Twenty-four week data from Study 111 were presented at the 18th Annual Conference of the British HIV Association (BHIVA) in April 2012, and 48-week data will be presented at an upcoming medical meeting.

SPIRIT Study

SPIRIT (Study 106) is a randomized (2:1), open-label Phase 3 study of switching virologically suppressed HIV patients from a regimen consisting of a ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (n=159) to Complera (n=317). The primary objective of the study is to evaluate the non-inferiority, at a 12 percent margin, of Complera compared to a protease-based regimen in maintaining HIV RNA levels less than 50 copies/mL through 24 weeks of therapy, based on the FDA snapshot algorithm. Secondary endpoints include changes in serum lipid levels, change in CD4 cell count, and safety and tolerability through 48 weeks of therapy. Patients randomized to the protease-based regimens rolled over to Complera after week 24.

At baseline, patients in the Complera switch arm had mean CD4 cell counts of 576 cells/mm 3 compared to 600 cells/mm 3 in the protease arm. Mean fasting lipids levels at baseline for the Complera and protease arms, respectively, were 192 and 194 mg/dL in total cholesterol, 121 and 124 mg/dL in LDL, 53 and 50 mg/dL in HDL, and 163 and 173 mg/dL in triglycerides. Mean ratios of total cholesterol to HDL at baseline were 3.86 for the Complera arm and 4.08 for the protease arm.

Virologic Outcome at 24 Weeks (FDA Snapshot Algorithm)
    Complera

n=317
 

Protease-Based Regimen

n=159
Virologic response 94% 90%
Virologic failure 0.9% 5.0%
No 24-week data 5.4% 5.0%
Discontinued due to adverse events 1.9% 0
Discontinued due to other reasons 3.5% 3.1%

Missing data during 24-week window but on study drug
  0   1.9%

Changes in CD4 cell counts at 24 weeks of therapy were +20 cells/mm 3 for the Complera arm and +32 cells/mm 3 for the protease-based regimen (p=0.28). Five percent (n=16) and 6.9 percent (n=11) of patients in the Complera and protease-based regimen arms, respectively, experienced a Grade 3 or 4 adverse event.

At 24 weeks Complera patients had greater mean changes in fasting total cholesterol (-25 vs. -1 mg/dL), LDL (-16 vs. 0 mg/dL) and triglycerides (-53 vs. +3 mg/dL) compared to those who remained on protease-based regimens (p<0.001 for all comparisons between treatment groups). Patients in both arms had similar changes in HDL (-4 vs. -1 mg/dL for Complera and protease-based regimen, respectively; p<0.001). Switching to Complera resulted in greater improvements in the 10-year Framingham Risk Score, a measure of cardiovascular risk, at week 24 compared to a protease-based regimen (p=0.001).

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