A Phase 2 evaluation of a new flavored peg and sulfate solution compared to an over-the-counter laxative, peg and sports drink bowel preparation combination.

BACKGROUND: Acceptability and tolerance of bowel preparation is critical to overcome patient hesitancy in undergoing colon cancer screening and surveillance colonoscopy. To improve patient experience, a new sports drink-flavored bowel preparation containing polyethylene glycol (PEG) and sulfate salts (FPSS) was developed to provide a similar experience to a commonly used but not United States Food and Drug Administration (FDA) approved PEG and sports drink bowel preparation (PEG-SD), while also achieving improved cleansing efficacy. METHODS: This FPSS preparation, approved by the FDA in June 2023, was evaluated in a non-randomized Phase 2 study in which 40 patients requiring colonoscopy were prepared with FPSS and 20 with PEG-SD. RESULTS: Overall cleansing success was high with FPSS based on unblinded local endoscopist assessment (93%) and blinded central reading (97%), exceeding PEG-SD which achieved success rates of 84% (local read), 74% and 68% (blinded central reads). Similar differences favoring FPSS were seen for excellent preparations and cleansing success by colon segment as rated by local endoscopists. Both preparations were well-tolerated, with 93% of FPSS patients rating their preparation as Tolerable to Very Easy to consume, compared to 100% of PEG-SD. Patients who had previously taken a preparation for colonoscopy found FPSS and PEG-SD better than their prior preparation (73% and 70%, respectively) and nearly all would request their assigned study preparation again in the future. About two thirds of FPSS patients agreed that the preparation tasted similar to a sports drink. CONCLUSION: The new sports drink-like flavored preparation compares favorably to PEG-SD for bowel cleansing efficacy while achieving similar patient satisfaction. The study was registered at www. CLINICALTRIALS: gov (NCT03328507) on 01/11/2017.

Comparison of a Novel, Flavor-optimized, Polyethylene Glycol and Sulfate Bowel Preparation With Oral Sulfate Solution in Adults Undergoing Colonoscopy.

INTRODUCTION: A new bowel preparation for colonoscopy has been developed containing poorly absorbed sulfate salts and polyethylene glycol 3350, which retain water within the intestinal lumen resulting in copious diarrhea, thereby cleansing the bowel. The product was formulated to be safe and effective with a sports drink-like flavor. This study evaluated the new flavored polyethylene glycol and sulfate solution (FPSS) compared with a Food and Drug Administration-approved bowel preparation containing sulfate salts only [oral sulfate solution (OSS)]. METHODS: Five hundred adults were enrolled in this multicenter, noninferiority study. Subjects were assigned FPSS or OSS administered in split-dose regimens (PM/AM). FPSS subjects took 2 L of the flavored osmotic solution (1 L at night and 1 L in the morning). OSS was taken according to its approved labeling. Colonoscopies were graded globally and segmentally by blinded local investigators using a 4-point scale (excellent, good, fair, and poor), with "good" and "excellent" considered successful. Safety was assessed by adverse events (AEs) and laboratory testing. RESULTS: A high rate of cleansing success was seen with FPSS (94%), which was noninferior to OSS (94%). This conclusion was confirmed by blinded central readers. Segmental success rates were >90% for both preparations, including the right colon. Questionnaire ratings indicated the FPSS experience was preferred over OSS with 87% of FPSS subjects noting their preparation was "tolerable" to "very easy" to consume versus 74% for OSS. The majority of FPSS subjects agreed their preparation tasted like a sports drink. Gastrointestinal symptoms were the most common AEs. There was no difference between preparations for any AE and no clinically significant differences in laboratory parameters. CONCLUSIONS: The new sports drink-like flavored preparation achieved a high level of cleansing in the study, demonstrating noninferiority to OSS. FPSS was well-tolerated with low rates of expected gastrointestinal symptoms. The optimized flavor of FPSS resulted in significantly better acceptance ratings.

A Safety and Efficacy Comparison of a New Sulfate-Based Tablet Bowel Preparation Versus a PEG and Ascorbate Comparator in Adult Subjects Undergoing Colonoscopy.

INTRODUCTION: A new tablet-based bowel prep for colonoscopy has been developed containing poorly absorbed sulfate salts which act to retain water within the intestinal lumen resulting in a copious diarrhea, thereby cleansing the bowel. This study evaluated the safety and efficacy of these oral sulfate tablets (OST) compared with a US FDA-approved bowel prep solution containing PEG3350, electrolytes, and ascorbate (polyethylene glycol and ascorbate [PEG-EA]). METHODS: Five hundred fifteen adult patients (mean 57y) were enrolled in this single-blind, multicenter, noninferiority study. Subjects were assigned either PEG-EA or OST to be administered in a split-dose regimen starting the evening before colonoscopy. PEG-EA was taken according to its approved labeling (1 L of prep solution with 16 oz. of additional water) in the evening and again in the morning. OST patients took a total of 24 tablets. OST patients were administered 12 tablets in the evening, and the following morning. Patients consumed 16 ounces of water with each dose of 12 tablets and drank an additional 32 oz. of water with each dose. Colonoscopies were performed by blinded investigators. Cleansing efficacy was evaluated globally and segmentally using a 4-point scale (Excellent-no more than small bits of feces/fluid which can be suctioned easily; achieves clear visualization of the entire colonic mucosa. Good-feces and fluid requiring washing and suctioning, but still achieves clear visualization of the entire colonic mucosa. Fair-enough feces even after washing and suctioning to prevent clear visualization of the entire colonic mucosa. Poor-large amounts of fecal residue and additional bowel preparation required). Scores of Good or Excellent were considered to be a success. Safety was assessed by spontaneously reported adverse events, solicited ratings of expected prep symptoms, and laboratory testing. RESULTS: A high rate of cleansing success was seen with OST (92%), which was noninferior to PEG-EA (89%). Only a small proportion of subjects rated their expected gastrointestinal symptoms as severe (<5% for both preps). No clinically significant differences were seen between preps for chemistry and hematology parameters. No serious adverse experiences were reported with OST. DISCUSSION: Sulfate tablets achieved a high level of cleansing in the study, comparable with US FDA-approved preps. OST was noninferior to PEG-EA in this study and achieved significantly more Excellent preps overall and in the proximal colon. The OST prep was well-tolerated, with a similar rate of spontaneously reported adverse experiences to PEG-EA and a low rate of severe expected gastrointestinal symptoms.

A Comparative Study of Treatment-Emergent Adverse Events Following Use of Common Bowel Preparations Among a Colonoscopy Screening Population: Results from a Post-Marketing Observational Study.

BACKGROUND: Colonoscopy may be one of the most frequent elective procedures in older adults and is associated with a low occurrence of complications. However, reduction of risks attributable to the bowel preparation may be achieved with the use of effective and safer products. AIM: The aim of this study was to examine the incidence of treatment-emergent adverse events (TEAEs) associated with SUPREP(®) [oral sulfate solution (OSS)] and other common prescription bowel preparations (non-OSS). METHODS: This real-world, observational study used de-identified health insurance claims and laboratory results to identify TEAEs in the 3 months following screening colonoscopy in adults with a prescription for a bowel preparation in the prior 60 days. The unadjusted and adjusted (controlling for patient risk factors) cumulative incidences of TEAEs were estimated using Kaplan-Meier and Poisson regression, respectively. RESULTS: Among patients ≥45 years, the overall cumulative incidence was significantly lower (p < 0.001) in the OSS cohort than in the non-OSS cohort (unadjusted: 2.31 vs. 2.89 %; adjusted: 1.61 vs. 1.95 %), with significantly lower acute cardiac conditions (1.56 vs. 1.90 %; p < 0.001), renal failure/other serious renal diseases (OSS: 0.21 %, non-OSS: 0.32 %; p < 0.001), and serum electrolyte abnormalities (OSS: 0.39 %, non-OSS: 0.49 %; p = 0.017). There were no significant differences between cohorts in death, seizure disorders, aggravation of gout, and ischemic colitis. Results were similar in the adjusted cumulative incidences. CONCLUSIONS: In actual use, the overall cumulative incidence of TEAEs was significantly lower in the OSS cohort, demonstrating that OSS is as safe as, or possibly safer than, non-OSS prescription bowel preparations.

A comparison of oral sulfate solution with sodium picosulfate: magnesium citrate in split doses as bowel preparation for colonoscopy.

BACKGROUND: There are few data comparing U.S. Food and Drug Administration-approved low-volume bowel preparations for colonoscopy. OBJECTIVE: To compare oral sulfate solution (OSS) with sodium picosulfate plus magnesium citrate (SP+MC) for bowel cleansing efficacy. DESIGN: Single-blind, randomized, controlled trial. SETTING: Ten U.S. centers. PATIENTS: Outpatients undergoing colonoscopy for routine indications. INTERVENTIONS: Patients were randomized to undergo bowel preparation with OSS or SP+MC. Both preparations were given in split doses. MAIN OUTCOME MEASUREMENTS: Cleansing efficacy on a 4-point scale from excellent (4) to poor (1). RESULTS: Among 338 randomized patients who took preparation, OSS resulted in a higher rate of successful (excellent or good) preparation (94.7% vs 85.7%; P = .006) and more excellent preparations (54% vs 26%; P < .001) compared with SP+MC. There was no difference between OSS and SP+MC in treatment-emergent adverse events. SP+MC had better scores for nausea, but the differences were small. LIMITATIONS: The preparation grading scale has been used in previous studies and has regulatory acceptance but has not been formally validated. CONCLUSION: The U.S. Food and Drug Administration-approved split-dose regimen of OSS provides superior bowel cleansing compared with the approved split-dose regimen of SP+MC. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01786629.).

A randomized, controlled trial of oral sulfate solution plus polyethylene glycol as a bowel preparation for colonoscopy.

BACKGROUND: No bowel preparation for colonoscopy is optimal with regard to efficacy, safety, and tolerability. New options for bowel preparation are needed. OBJECTIVE: To compare a new hybrid preparation consisting of a reduced dose of oral sulfate solution (OSS) plus 2 L of sulfate-free electrolyte lavage solution (SF-ELS) with 2 low-volume preparations based on polyethylene glycol electrolyte lavage solution (PEG-ELS). DESIGN: Two randomized, controlled trials. SETTING: Twenty-four U.S. centers. PATIENTS: A total of 737 outpatients undergoing colonoscopy. INTERVENTIONS: In study 1, OSS plus SF-ELS was given as a split dose, and in study 2, OSS plus SF-ELS was given in its entirety the evening before colonoscopy. In study 1, the active control was 2 L of PEG-ELS plus ascorbic acid (PEG-EA) given as a split dose. In study 2, the control was 10 mg of bisacodyl plus 2 L of SF-ELS taken the evening before colonoscopy. MAIN OUTCOME MEASUREMENTS: Rates of successful (good or excellent) bowel preparation. RESULTS: In study 1, the rates of successful (excellent or good) preparation with OSS plus SF-ELS and PEG-EA were identical at 93.5% for split-dose preparation. OSS plus SF-ELS was noninferior to PEG-EA (P < .001). In study 2, OSS plus SF-ELS resulted in successful preparation in 89.8% of patients compared with 83.5% with bisacodyl plus SF-ELS in a same-day preparation regimen. OSS plus SF-ELS was noninferior to bisacodyl plus SF-ELS (P <.001). In study 1, vomiting was more frequent with OSS plus SF-ELS (13.5% vs 6.7%; P = .042), and bloating was rated worse with PEG-EA (P = .025). In study 2, overall discomfort was rated worse with OSS plus SF-ELS (mean score 2.1 vs 1.8; P = .032). There were no deaths in either study and no serious adverse events considered related to the preparation. LIMITATIONS: Bowel cleansing was not scored by colon segment. Adenoma detection was not compared between the regimens. CONCLUSION: OSS plus SF-ELS is a new, safe, and effective bowel preparation for colonoscopy.

A pharmacokinetics evaluation of a new, low-volume, oral sulfate colon cleansing preparation in patients with renal or hepatic impairment and healthy volunteers.

The pharmacokinetics (PK) of an oral sulfate solution (OSS) for bowel cleansing preparation was studied. OSS (30 g of sulfate) was split between 2 doses, 12 hours apart. Safety measures included electrocardiography, vital signs, adverse events, hematology, blood chemistry, and urinalysis. Six adult patients with moderate renal disease (MRD), 6 with mild-moderate hepatic disease (M/MHD), and 6 normal healthy volunteers (NHVs) completed the study. Adverse events were mild to moderate in severity and were mainly limited to headache and expected gastrointestinal symptoms. Serum sulfate levels were highly variable at all times, even after adjusting for baseline. Sulfate was higher in MRD in comparison to the other groups. The C(max) and AUC were higher in the patients, but no statistically significant differences emerged. Sulfate levels returned to predose values within 54 hours after dosing. No electrolyte disturbances occurred. Urinary sulfate excretion was approximately 20% of the dose. OSS was well tolerated. The types and severity of adverse events were similar to those seen in large phase III trials. While patients with MRD had elevated sulfate, the levels were less than those in renal failure and did not alter biochemical parameters that are associated with hypersulfatemia.

Safety of oral sulfates in rats and dogs contrasted with phosphate-induced nephropathy in rats.

An oral sulfate salt solution (OSS), under development as a bowel cleansing agent for colonoscopy in humans, is studied in rats and dogs. In rats, amaximumpractical oral OSS dose (5 g/kg/d) is compared with an oral sodium phosphate (OSP) solution, both at about 7 times the clinical dose. OSS induces the intended effects of loose stools and diarrhea. In rats, higher urine sodium and potassium accompany higher clearance rates, considered adaptive to the osmotic load of OSS. OSS for 28 days is well tolerated in rats and dogs. In contrast, OSP causes increased mortality, reduced body weight and food consumption, severe kidney tubular degeneration, and calcium phosphate deposition in rats. These are accompanied by mineralization in the stomach and aorta, along with cardiac and hepatic degeneration and necrosis. The greater safety margin of OSS over OSP at similarmultiples of the clinical dose indicates its suitability for human use.

A randomized, multicenter comparison of polyethylene glycol laxative and tegaserod in treatment of patients with chronic constipation.

OBJECTIVE: Polyethylene glycol (PEG) 3350 (MiraLax) and tegaserod (Zelnorm), a serotonin subtype 4 receptor partial agonist, are currently approved for treatment of constipation. This study was designed to compare the efficacy of each product over a 4-wk treatment period. METHODS: Study patients who met defined criteria for chronic constipation were randomized in this open-labeled, parallel, multicenter study to receive the PEG laxative as a single daily dose of 17 g or tegaserod tablets 6 mg b.i.d., for 28 days. As a primary end point, treatment success was defined for each patient as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were also assessed. An interactive voice response system (IVRS) recorded patient reported daily bowel movement experience and study efficacy and safety information. RESULTS: A total of 237 patients were enrolled and received treatment at one of 25 centers. Successful treatment according to the primary end point was seen in 50.0% of the PEG and 30.8% of tegaserod patients (P= 0.003). By treatment weeks 3 and 4, significantly more PEG patients were successfully treated according to primary and secondary response definitions. PEG patients experienced more bowel movements per week (P= 0.019) and had significantly greater improvement in constipation symptoms (P= 0.016) based on results from a validated patient self-reported questionnaire. Tegaserod patients experienced a significantly higher incidence of headaches. Otherwise, there were no significant differences in adverse events. CONCLUSIONS: While PEG laxative and tegaserod are safe for their intended use in chronic constipation, PEG had superior efficacy, caused fewer headaches, and produced greater improvement of constipation symptoms.

A randomized, multicenter, placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation.

OBJECTIVES: Polyethylene glycol (PEG) 3350 (MiraLAX) is currently approved for the short-term treatment of occasional constipation. This study was designed to compare the safety and efficacy of PEG laxative versus placebo over a 6-month treatment period in patients with chronic constipation. METHODS: Study subjects who met defined criteria for chronic constipation were randomized in this double-blind, placebo-controlled, parallel, multicenter study to receive PEG laxative as a single daily dose of 17 g or placebo for 6 months. Baseline constipation status was confirmed during a 14-day observation period. As a primary efficacy variable, treatment success was defined as relief of modified ROME criteria for constipation for 50% or more of their treatment weeks. Various secondary measures were assessed. An Interactive Voice Response System (IVRS) recorded daily bowel movement experience and study efficacy and safety information. Laboratory testing at baseline and monthly for the study duration was analyzed for hematology, blood chemistry including amylase, GGT, uric acid, lipids, and urinalysis. RESULTS: A total of 304 patients were enrolled and received treatment at one of 50 centers. Successful treatment according to the primary efficacy variable was seen in 52.0% of PEG and 11% of placebo subjects (P < 0.001). Similar efficacy was seen in a subgroup of 75 elderly subjects. According to the primary efficacy definition (based on individual treatment weeks), 61% of PEG treatment weeks versus 22% of the placebo weeks were successful (P < 0.001). There were no significant differences in laboratory findings or adverse events except for the gastrointestinal category where diarrhea, flatulence, and nausea were the most frequent with PEG although they were not individually statistically significant compared with placebo. Similar results were observed when analyzed for differences due to gender, race, or age. CONCLUSIONS: PEG laxative is safe and effective for use in patients with chronic constipation for 6 months.

Comparison of reduced volume versus four liters sulfate-free electrolyte lavage solutions for colonoscopy colon cleansing.

OBJECTIVE: In an attempt to improve patient tolerance for colonoscopy cleansing, a reduced volume lavage regimen with 2 L sulfate-free electrolyte lavage solution (SF-ELS, NuLYTELY, Braintree Laboratories, Braintree, MA) plus 20 mg p.o. bisacodyl (Half Lytely, Braintree Laboratories) was compared with standard 4 L SF-ELS lavage for safety and efficacy. METHODS: At two centers, 200 patients undergoing colonoscopy for routine indications were randomized to receive the reduced volume or standard 4 L method. The day before scheduled colonoscopy, study subjects were allowed a normal breakfast and clear liquids for lunch and dinner. Those randomized to receive the reduced volume method received four 5-mg bisacodyl tablets p.o. at noon. Six hours later, they received 2 L SF-ELS given as 10 oz every 10 min. Subjects randomized to receive 4 L SF-ELS also drank their solution at 6:00 PM in a similar fashion. Colonoscopists, unaware as to the randomized preparation received, rated efficacy of cleansing. Patient tolerance and various hematological and biochemical parameters were assessed. RESULTS: Physician assessment of colon cleansing showed no differences between those patients randomized to receive reduced volume (n = 93) or 4 L (n = 93) SF-ELS cleansing (p = 0.16). There was a profound reduction in preparation side effects. The reduced volume preparation had less fullness (p < 0.01), nausea (p < 0.01), vomiting (p = 0.01), and overall discomfort (p < 0.01). There were no clinically significant changes in hematology or blood chemistry associated with either preparation. CONCLUSIONS: Reduced volume preparation with 2 L SF-ELS and bisacodyl is safe and effective. Clinical symptoms from the reduced volume preparation are significantly reduced compared with traditional 4 L gut lavage.

Overnight efficacy of polyethylene glycol laxative.

OBJECTIVES: Clinical studies in constipated adult patients have shown that a 17- or 34-g daily dose of polyethylene glycol (PEG) 3350 (MiraLax) is safe and effective for the treatment of constipation, with the best efficacy seen in wk 2 of treatment. The purpose of this study was to determine an optimal dose of PEG to provide satisfactory relief of constipation within 24 h. METHODS: A total of 24 adult study subjects who met Rome II criteria for constipation were randomized in a double-blind, parallel pilot study to receive a single dose of placebo or PEG laxative at doses of 51, 68, or 85 g in 500 ml of flavored water. Over a 72-h period, subjects rated bowel movements (BM), completeness of evacuation, and satisfaction. RESULTS: The 68-g dose seemed to be most satisfactory. Five of six subjects had a BM within 24 h. The time to first BM was 14.8 h for 68 g versus 27.3 h for placebo (p = NS). The time to second BM was 19.2 h versus 47.2 h for 68 g and placebo, respectively (p = 0.003). Of the subjects receiving 68 g of PEG, 50% and 100% reported complete evacuation for the first and second BM, respectively. The average number of BMs in 24 h for placebo, 51 g, 68 g, and 84 g were 0.5, 2.2, 2.2, and 4.2, respectively (p = 0.004). There were no adverse reactions, and no patient reported incontinence or complained of cramps or diarrhea at any dose. There were no changes in measured electrolytes, calcium, glucose, BUN, creatinine, or serum osmolality. CONCLUSIONS: A 68-g dose of PEG laxative seems to provide safe and effective relief in constipated adults within a 24-h period.