During Period 2, dialysis will occu

During Period 2, dialysis will occur prior to study drug administration on Period 2, Day 1, and the HD subjects will remain in the clinical center until completion of all study assessments on Period 2, Day 3.[2]The Washout Period will occur between the 2 periods regardless of the sequence of periods.The Washout Period will be scheduled to ensure that study drug administration is at least 6 days apart.[4]Plasma samples will be collected for PK assessments at:predose, 1.5 h(mid-infusion), 3 h(end-of-infusion), 3 h 15 min, 3 h 30 min, 3 h 45 min, 4, 5, 6, 8, 10, 12, 24, and 4B h after dosing[5]Collect a pre-spert dialysate sample priorto initiating HD and then hourly dialysate samples(with aliquots)during dialysis and through the end of dialysis[6]Complete this assessment if Day 3 is the final, end-of-study visit for a subject.Because Periods 1 and 2 do not have to occur in sequence, the Day 3 may be a subject's end of study visit.Plasma Pharmacokinetic AssessmentsFor Groups 1 through 5, serial venous blood samples were collected for PK analysis at predose(0 hrs), 1.5 hrs(mid-infusion), 3 hrs(end of infusion), 3 hrs 15 min, 3 hrs 30 min, 3 hrs 45 min, 4 hrs, 5 hrs 6 hrs, 8 hrs, 10 hrs, 12 hrs, 24 hrs, and 48 hrs for all subjects as described in the Study Event Flow Charts(Table 9-1 and Table 9-2).All sample times for PK blood collections were relative to the start of study drug infusion.For the PK blood samples, the following deviation windows from the actual sampling times were permitted:> 4 hrs to 48 hrs,±5 minAfter collection of the blood samples for PK analyses, blood was centrifuged, and the plasma was collected.Plasma was diluted 1:1 with 3-(-N-morpholino)propanesulfonic acid(MOPS)buffer, thoroughly mixed, and frozen until samples were shipped to the bioanalytical laboratory.For Groups 1 through 4, serial urine samples for PK analysis were collected predose(0 hrs)and then post-dose over the intervals 0-4 hrs, 4-8 hrs, 8-12 hrs, 12-24 hrs, and 24-48 hrs. On Day 1, a single predose morning void was collected prior to dosing.Then, to begin the 0-4 hrs collection interval, subjects voided completely within 15 minutes prior to dosing.Subjects were encouraged to void at the end of each collection interval.If they voided at any time during the collection interval, the time was documented.For the urine samples at the end of each interval, the following deviation windows from the actual sampling times were permitted:After collection of urine samples for PK analysis, urine was refrigerated during the collection intervals.At the end of each interval, total urine volume was measured using a graduated cylinder and recorded.Within 30 minutes of urine collection, the urine was diluted 1:1 with MOPS buffer, thoroughly mixed, and frozen until samples were shipped to the bioanalytical laboratory.Dialysate Pharmacokinetic AssessmentsFor Group 5, dialysate aliquots were collected prior to HD initiation and then hourly during HD for the intervals 0-1 hrs, 1-2 hrs, 2-3 hrs, and 3 hrs-end of dialysis.At the end of each collection period, the dialysate sample was thoroughly mixed and weighed.Within 30 minutes of the collection period, a 10-mL aliquot was diluted 1:1 with MOPS buffer and frozen until samples were shipped to the bioanalytical laboratory.The outcome variables which assess the safety and tolerability of single-dose, meropenem and RPX7009 were AEs, SAEs, vital sign measurements, ECGs, physical examinations, and clinical laboratory tests.Assessment of AEs occurred from admission to the clinic center(Day -1)through the Follow