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A statistically significant change of estimated creatinine clearance from baseline was observed after 7 days of treatment with cobicistat 150 mg among subjects with an estimated creatinine clearance of at least 80 mL per minute (-9.9 13.1 mL/min) and subjects with an estimated creatinine clearance between 50 and 79 mL per minute (-11.9 7.0 mL per minute)

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Once when the ingredients are sourced, secondly when they get to the mixing center, and thirdly when the product is done being created