Professor of Medicine Kansas City VA Medical Center Kansas City, MO
Prateek Sharma, MD, FACG1, Philip S. Schoenfeld, MD, MSEd, MSc (Epi)2, Christopher Allen, MS3, Brooks D. Cash, MD, FACG4; 1Kansas City VA Medical Center, Kansas City, MO; 2John D. Dingell VA Medical Center, Detroit, MI; 3Salix Pharmaceuticals, Bridgewater, NJ; 4University of Texas Health Science Center, Houston, TX
Introduction: NER1006, a 1 L PEG-based bowel preparation, was approved in the US in 2018 for colon cleansing in preparation for colonoscopy in adults. In patients with decreased renal function, bowel preparations may increase the risk of electrolyte imbalances or worsen renal function. The current aim was to evaluate the safety profile of NER1006 in adults undergoing colonoscopy, subgrouped by renal insufficiency. Methods: Data were pooled from two phase 3, randomized studies (NOCT/MORA) of patients (aged 18-85 y) undergoing colonoscopy. Patients were randomized to NER1006 as a 2-day evening/morning (pm/am) or 1-day morning/morning (am/am) split dosing regimen. Per protocol, mild renal insufficiency was defined as creatinine clearance (CrCl) ≥60 to < 90 mL/min/1.73 m2 and moderate as CrCl, ≥30 to < 60 mL/min/1.73m2. Moderate renal insufficiency was an exclusion criterion in NOCT, and severe disease (CrCl < 30 mL/min/1.73 m2) was an exclusion criterion in both trials. Safety (adverse events [AEs] and clinical lab testing) was assessed, per protocol, through 7 ± 1 days post-colonoscopy. Worsening renal function (increase from baseline in creatinine >0.3 mg/dL or decrease from baseline in calculated CrCl of >25%) definition was derived from RIFLE (risk, injury, failure, loss, end-stage kidney disease) criteria. Results: 524 adults who received pm/am regimen of NER1006 (renal insufficiency: mild [n=340; 64.9%], moderate [n=14; 2.7%], none [n=166; 31.7%], or unknown [n=4; 0.8%]) and 269 adults who received am/am regimen (renal insufficiency: mild [n=184; 68.4%], moderate [n=14; 5.2%], none [n=68; 25.3%], or unknown [n=3; 1.1%]) were included. The most common AEs in the study were GI-related, regardless of renal function status (Table 1). To assess a risk of worsening renal function, patients who showed an increase from baseline in creatinine >0.3 mg/dL or a decrease from baseline in calculated CrCl of >25% were identified. The number of patients, subgrouped by renal insufficiency, meeting 1 or both of these criteria was low, with no signal of renal injury related to NER1006 observed (Table 2). In addition, these changes did not persist; only 1 patient (baseline mild renal insufficiency; am/am split dose) with a change in renal function at Day 2 ± post-colonoscopy (Table 2) met the same criteria (for CrCl) at 7 ± 1 days post-colonoscopy. Discussion: Data support the overall safety profile of 1 L PEG-based NER1006 as a bowel preparation, including in patients with mild-to-moderate renal insufficiency.
Disclosures: Prateek Sharma: Boston Scientific – Consultant. Olympus Inc. – Consultant. Philip Schoenfeld: Salix Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Christopher Allen: Salix Pharmaceuticals – Employee. Brooks Cash: Salix Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speaker's Bureau.