rpad (not included) (see figure 1 ). 1. open the administration set and close the pinch clamp by pushing the clamp until it is fully closed (see figure 2 ). 2. remove the tab from the spike port of the bag containing thawed rebyota and remove the cap from the administration tube spike. insert the administration tube spike through the spike port of the bag containing thawed rebyota (see figure 3 ). do not remove air from the administration tube prior to insertion to avoid loss of rebyota. figure 1 figure 2 figure 3 2.3 administration administer rebyota 24 to 72 hours after the last dose of antibiotics for cdi. 1. prepare the patient for administration by requesting they empty their bladder and bowel, if possible. place the patient in the left-side position or the knee-chest position with a disposable underpad beneath the patient (see figures 4 and 5 ). 2. apply water-soluble lubricant to the administration tube tip. gently insert the administration tube tip into the rectum about 12 cm (5 inches) in a direction pointed slightly toward the navel (umbilicus) (see figure 6 ). 3. hold the administration tube in place with one hand for the entire procedure to maintain the tube position in the rectum. with the other hand, open the pinch clamp on the administration tube, and then gradually raise the bag to allow delivery of rebyota via gravity flow (see figure 7 and 8 ). do not allow the administration tube to sag or loop as this will prevent the entire dose from being delivered. do not squeeze the bag to deliver rebyota as this could be uncomfortable for the patient. do not hang the bag from an iv stand. 4. when the entire dose has been delivered, close the pinch clamp and then slowly withdraw the tube. take care to prevent any residual rebyota remaining in the tube from leaking out. note: some rebyota will remain in the tube after administration. 5. keep the patient in the left-side position or the knee-chest position for up to 15 minutes to minimize any cramping that may occur (see figure 9 and 10 ). there are no restrictions on the patient's use of the restroom. dispose of all components in medical waste. figure 4 and figure 5 figure 6 figure 7 and figure 8 figure 9 and figure 10

ble-blind clinical studies (study 1: nct03244644 and study 2: nct02299570) and 3 open-label clinical studies (nct01925417, nct02589847, nct03931941) conducted in the united states and canada. a total of 978 adults 18 years of age and older with a history of 1 or more recurrences of clostridioides difficile (cdi) infection and whose symptoms were controlled 24 – 72 hours post-antibiotic treatment were enrolled and received 1 or more doses of rebyota; 595 of whom received a single dose of rebyota. in the 2 randomized, double-blind clinical studies, 131 adults were originally randomized to receive placebo and 48 crossed over to receive an open-label dose of rebyota after additional cdi recurrence. overall, across the 5 studies, the median age of participants was 64 years and 67.2 % were female. the racial and ethnic distribution was as follows: 93.8% were white, and 2.4% were of hispanic or latino ethnicity. no meaningful differences in demographic characteristics occurred across the treatment groups. study 1 and study 2 excluded individuals with celiac disease, inflammatory bowel disease, irritable bowel syndrome, and chronic diarrhea. individuals with these conditions were not excluded from one of the open-label studies (nct03931941), and individuals with food allergies were not excluded from any of the 5 clinical studies. adverse reactions across the 5 clinical studies, participants recorded solicited adverse events in a diary for the first 7 days after each dose of rebyota or placebo. participants were monitored for all other adverse events by queries during scheduled visits, with duration of follow-up ranging from 6 to 24 months after the last dose. in study 1, a multi-center, double-blind randomized (2:1), placebo-controlled trial conducted in the united states and canada, 180 adults 18 years of age and older received a single dose of rebyota and 87 received placebo. participants with a recurrence of cdi (rcdi) during the first 8 weeks after receipt of rebyota or placebo were censored from analysis at the time of rcdi . during the first two weeks following a dose of rebyota or placebo, 34 participants (18.9%) and 24 participants (27.6%) respectively, were censored. overall, during the 8 week follow up period, 47 rebyota recipients (26.1%) and 30 placebo recipients (34.5%) were censored from analysis. in an analysis of solicited and unsolicited adverse events reported in study 1, the most common adverse reactions (defined as adverse events assessed as definitely, possibly, or probably related to investigational product by the investigator) reported by ≥3% of rebyota recipients, and at a rate greater than that reported by placebo recipients, were abdominal pain, (8.9%), diarrhea (7.2%), abdominal distention (3.9%), flatulence (3.3%), and nausea (3.3%) (table 1). table 1: adverse reactions adverse reactions were defined as solicited and unsolicited adverse events that were assessed as definitely, possibly or probably related to treatment by the study investigator. reported by ≥3% of rebyota recipients, and at a rate greater than that reported by placebo recipients, within 8 weeks after receipt of rebyota or placebo (study 1). adverse reaction rebyota n=180 n (%) placebo n=87 n (%) abdominal pain 16 (8.9) 6 (6.9) diarrhea 13 (7.2) 3 (3.4) abdominal distension 7 (3.9) 2 (2.3) flatulence 6 (3.3) 0 nausea 6 (3.3) 1 (1.1) most adverse reactions occurred during the first 2 weeks after treatment. after this, the proportion of patients with adverse reactions declined in subsequent 2-week intervals. beyond 2 weeks after treatment only a few single adverse reactions were reported. most adverse drug reactions were mild to moderate in severity. no life-threatening adverse reaction was reported. serious adverse reactions in a pooled analysis of the 5 clinical studies, 10.1% (60/595) of rebyota recipients (1 dose only) and 7.2% (6/83) of placebo recipients reported a serious adverse event within 6 months post last dose of investigational product. none of these events were considered related to the investigational product.

rs to a maximum of 72 hours (study 1) or 24 hours to a maximum of 48 hours (study 2) antibiotic washout period was required prior to administration of the assigned study treatment. in study 1, enrolled adults were randomized 2:1 to a single dose of rebyota or placebo respectively. in study 2, randomization was 1:1:1 to receive two doses of rebyota, two doses of placebo, or one dose of rebyota and one dose of placebo, administered 7±2 days apart. only data from the rebyota one-dose group and the placebo group are described below and were integrated in the bayesian analysis. in the integrated efficacy analysis set, the demographic profile and baseline recurrent cdi characteristics of treated adults were similar in the rebyota and placebo groups. in study 1, a total of 262 adults were randomized and treated, of which 177 adults received rebyota and 85 received placebo. adults had a mean age of 60.1 years with 45.4% of adults 65 years of age or older, were mainly white (92.0%) and female (69.1%). in this study, 32.8% of adults received rebyota or placebo for their first recurrence of cdi. in study 1, 87.4% of adults had received vancomycin alone prior to treatment. in study 2, 39 adults received one dose of rebyota and one dose of placebo and 43 adults received two doses of placebo. adults in these two groups had a mean age of 59.8 years with 42.7% of adults 65 years of age or older, were mainly white (97.6%) and female (63.4%). in this study, 89.0% of adults had received vancomycin prior to treatment. treatment success was defined as the absence of cdi diarrhea within 8 weeks of blinded treatment. cdi diarrhea was defined as the passage of ≥ 3 unformed/loose stools in ≤ 24 hours for at least 2 consecutive days and a positive stool test for the presence of c difficile toxin at the time of the diarrhea. in the bayesian analysis, the estimated rate of treatment success was significantly higher in the rebyota group (70.6%) than in the placebo group (57.5%) through 8 weeks after completing blinded treatment, resulting in a difference of 13.1 percentage points (95% credible interval: 2.3, 24.0) which corresponds to a 99.1% posterior probability that rebyota is superior to placebo (table 2). table 2: efficacy results: treatment success at 8 weeks post-treatment (mitt population mitt includes all randomized subjects excluding: 1) those who withdrew prior to treatment; 2) those in whom treatment was attempted but not completed; 3) those who discontinued from the study prior to evaluation of treatment outcome for the primary endpoint if the reason for exit was not related to cdi symptoms. ) parameter rebyota mean (95% cri) placebo mean (95% cri) treatment effect (rebyota – placebo) mean (95% cri) cri=credible interval model-estimated treatment success (%) 70.6 (64.1, 76.8) 57.5 (48.1, 67.1) 13.1 (2.3, 24.0) posterior probability of superiority - - 0.991 pre-defined threshold was 0.975 study 1 evaluated sustained clinical response which was defined as treatment success at 8 weeks and no cdi event through 6 months after the last dose during the blinded period. the difference in sustained clinical response rate (9.1%; 95% ci: -3.6%, 21.7%) was not statistically significant between the rebyota (65.5%) and the placebo groups (56.5%).

medical waste.