Comparative subchronic toxicity of copper and a tertiary copper mixture to early life stage rainbow trout (Oncorhynchus mykiss): impacts on growth, development, and histopathology.

This research aimed to characterize and compare the subchronic impacts of Cu to a Cu, Cd, and Zn mixture in early life stages of rainbow trout (Oncorhynchus mykiss) by examining uptake, survival, growth, development, and histopathology parameters. To accomplish this, rainbow trout were exposed for 31 days from eyed embryos to the swim-up fry life stage to waterborne Cu (31, 47, 70, and 104 µg/L) individually or as mixture containing Cd (4.1, 6.2, 9.3, and 14 µg/L) and Zn (385, 578, 867, and 1300 µg/L). Exposures elicited pronounced effects on survival when Cu was administered as a mixture (LC25 = 32.9 µg/L Cu) versus individually (LC25 = 46.3 µg/L Cu). Mixtures of Cu, Cd, and Zn also elicited more pronounced sublethal toxicity relative to equivalent Cu treatments with respect to reduced yolk sac resorption and increased incidence and/or severity of gill, liver, and kidney lesions. Our findings of reduced body weight (EC10, Cu = 55.0 µg/L Cu; EC10, Cu+Cd+Zn = 58.9 µg/L Cu), yolk sac resorption (LOECCu = 70 µg/L Cu; LOECCu+Cd+Zn = 70 µg/L Cu), coelomic fat (LOECCu = 47 µg/L Cu; LOECCu+Cd+Zn = 70 µg/L Cu), and increased hepatocellular cytoplasmic vacuolation (LOECCu = 70 µg/L Cu; LOECCu+Cd+Zn = 47 µg/L Cu) collectively indicate a complicated metabolic interference by metals in exposed fish. These lethal and sublethal effects observed in the laboratory could translate to reduced survival and fitness of wild salmonid populations inhabiting waterbodies receiving wastewater or runoff containing multiple metals at elevated concentrations.

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 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.

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.

Clopidogrel-associated acute generalized exanthematous pustulosis.

Acute generalized exanthematous pustulosis (AGEP) is a skin eruption of rapid onset and progression that is characterized by the formation of numerous sterile pustules on an erythematous background. Other features may include fever and leukocytosis, with resolution usually in less than 15 days. We present an 83-year-old woman with an erythematous pustular eruption following placement of a bare metal coronary stent and initiation of anticoagulation with clopidogrel. She was diagnosed with AGEP after a biopsy was performed and other possible causes of a pustular eruption were excluded. Two medications--carvedilol and rosuvastatin--were initially viewed as possible culprits and were temporarily discontinued. However, the patient's rash continued to worsen. Additionally, she had a persistent low-grade fever, leukocytosis, and a slow rise in her creatinine level. Clopidogrel was discontinued and replaced with ticlopidine on day 7 of hospitalization. Within 48 hours her temperature, white blood cell count, and creatinine level began to improve. Her skin subsequently desquamated and she was sent home on day 20. We discuss drug-induced AGEP and a desensitization protocol that has allowed patients to resume use of clopidogrel following a prior cutaneous reaction to this medication.

A randomized clinical study comparing reduced-volume oral sulfate solution with standard 4-liter sulfate-free electrolyte lavage solution as preparation for colonoscopy.

BACKGROUND: Low-volume bowel preparations for colonoscopy improve tolerability. OBJECTIVE: We compared the efficacy, tolerability, and safety of a new low-volume sulfate solution with a standard 4-L polyethylene glycol electrolyte lavage solution as bowel preparation for colonoscopy. DESIGN: Multicenter, single-blind, randomized, noninferiority study. SETTING: Five academic and community endoscopy centers in the United States. PATIENTS: One hundred thirty-six outpatients undergoing colonoscopy. INTERVENTIONS: Patients were randomized to receive 4 L sulfate-free electrolyte lavage solution (SF-ELS) given the night before colonoscopy versus 12 oz oral sulfate solution (OSS) given in equally divided doses the evening before and the morning of colonoscopy. MAIN OUTCOME MEASUREMENTS: Successful (ie, good or excellent) bowel preparation. RESULTS: Successful bowel preparation was more frequent with OSS than with SF-ELS (98.4% vs 89.6%; P = .04). Excellent preparation also was achieved more frequently with OSS (71.4% vs 34.3%; P < .001). Patients receiving OSS had less residual stool in the cecum and ascending colon and less residual fluid in the cecum and ascending, transverse, and descending colon compared with SF-ELS. The percentage of patients with GI side effects and adverse events was not significantly different between the 2 groups. LIMITATIONS: The OSS was administered in split doses, whereas the SF-ELS was administered the evening before (which is its FDA-approved regimen). CONCLUSIONS: Oral sulfate solution is promising as a safe low-volume preparation for colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT00856843.).

A randomized clinical study evaluating the safety and efficacy of a new, reduced-volume, oral sulfate colon-cleansing preparation for colonoscopy.

OBJECTIVES: We sought to evaluate a new, low-volume, oral sulfate solution as a bowel preparation for colonoscopy in adult patients. METHODS: The investigations were designed as two multicenter, single-blind, randomized, non-inferiority studies to show that the sulfate regimen would effect cleansing that is acceptable and equivalent to polyethylene glycol electrolyte solution with ascorbic acid (PEG-EA), and would be suitable for colonoscopy. One study evaluated same-day administration; the other compared the two study preparations given by split-dose administration in which the first portion was taken the evening before colonoscopy and the second portion on the morning of the procedure. The primary efficacy variable was based on bowel cleansing graded by an investigator who was unaware of the preparation method received. RESULTS: Study 1 randomized 408 outpatients scheduled for colonoscopy for routine indications, with 387 subjects taking the preparation. In all, 364 subjects were randomized and took the preparation in study 2. The demographics of the enrolled subjects were similar across both treatment groups in the two studies, including gender, race, and ethnic characteristics. The primary efficacy analysis supports the conclusion that the oral sulfate solution produces the same degree of cleansing as PEG-EA. Successful preparations were seen in 82.4% and 80.3% in study 1 and 97.2% and 95.6% in study 2 for the oral sulfate solution and the PEG-EA regimen, respectively. Although no difference in excellent preparations was seen in the 1-day preparation, split-dose administration resulted in more excellent preparations in the sulfate group than in the PEG-EA group (63.3 vs. 52.5%, P=0.043). Preparation-related symptoms of cramping, bloating, nausea, and vomiting were generally mild and infrequent. Sulfate subjects reported slightly increased gastrointestinal events and higher vomiting scores (P=0.009) in the 1-day preparation but not in the split-dose regimen. There were no other differences for adverse events or clinically significant laboratory findings, including no increased creatinine. CONCLUSIONS: The new 960 -ml oral sulfate solution is effective for colonoscopy cleansing and has an acceptable safety profile.

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.

PEG3350 in the treatment of childhood constipation: a multicenter, double-blinded, placebo-controlled trial.

OBJECTIVE: To establish the efficacy and best starting dose of polyethylene glycol (PEG)3350 in the short-term treatment of children with functional constipation. STUDY DESIGN: Prospective, randomized, multicenter, double-blinded, placebo-controlled, dose-ranging study of PEG3350 in children with functional constipation. Patients were randomly assigned to either placebo or 0.2 g/kg per day, 0.4 g/kg per day, or 0.8 g/kg per day of PEG3350 after a 1 week run-in period, followed by 2 weeks of treatment. All received behavior modification. The primary outcome was the proportion of patients with a successful treatment response: >or=3 bowel movements (BM) in the second week. RESULTS: 103 children (mean, 8.5 +/- 3.1 years) were enrolled. 77%, 74%, and 73% of the 0.2, 0.4, and 0.8 g/kg groups were successfully treated, as compared with 42% receiving placebo (P < .04). There was a significant increase in BM (P < .001) and straining improvement (P < .05) with the different PEG3350 doses. Stool consistency improved significantly for doses 0.4 g/kg or higher (P < .001). There was more abdominal pain and fecal incontinence in patients receiving 0.8 g/kg. PEG3350 was well tolerated. CONCLUSIONS: This placebo-controlled study confirms the efficacy and safety of PEG3350 for the short-term treatment of children with functional constipation. We recommend a starting dose of 0.4 g/kg per day.

Cost-analysis model of colonoscopy preparation using split-dose reduced-volume oral sulfate solution (OSS) and polyethylene glycol with electrolytes solution (PEG-ELS).

OBJECTIVE: The study aimed to (1) develop a cost model for colonoscopy preparation among patients referred for colonoscopy using split-dose reduced-volume oral sulfate solution (OSS) and generic polyethylene glycol with electrolytes solution (PEG-ELS), (2) examine cost savings associated with OSS vs PEG-ELS, and (3) assess the robustness of the cost model. METHODS: Efficacy of each agent was based on the results of a 541-patient clinical trial comparing OSS to PEG-ELS. Cleansing agent and colonoscopy procedure costs were calculated from OptumHealth Reporting & Insights claims data for 2010-Q12013. In the model, patients' colonoscopies were tracked over a 25 or 35 year time period until the patients reached age 75. The difference per patient per year (PPPY) in total cleansing agent and colonoscopy procedure costs over the time horizon between the OSS and PEG-ELS cohort was calculated. One-way sensitivity analyses were conducted to test the robustness of the cost model. RESULTS: The model showed lower cost for OSS patients over the time horizon. Total PPPY costs were $280.34 for the OSS cohort and $296.36 for the PEG-ELS cohort, resulting in a cost saving of $16.01 PPPY for the OSS cohort. This was due primarily to OSS patients having fewer colonoscopies (OSS: 0.158 vs PEG-ELS: 0.170 PPPY). Over the time horizon, cost savings of $4 763 335 were observed among 10, 000 OSS patients. Cost savings switched from OSS to PEG-ELS cohort in four cases: (1) base-case cost of a completed colonoscopy decreased by 75%, (2) base-case cost of OSS increased to over $143 per usage, (3) all non-completers were lost to follow-up, and (4) OSS bowel preparation quality dropped below PEG-ELS to 70%. CONCLUSIONS: From a payer's perspective, the model showed that the use of OSS as the cleansing agent resulted in potential cost savings compared with PEG-ELS. Cost savings under OSS remained under various sensitivity analyses.

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.

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 comparison of polyethylene glycol laxative and placebo for relief of constipation from constipating medications.

OBJECTIVES: Medications often cause constipation and little data are available concerning treatment interventions. This study was designed to evaluate the safety and efficacy of polyethylene glycol (PEG) 3350 laxative (MiraLax) for relief of constipation from medicines associated with symptoms of constipation. METHODS: Study subjects were enrolled who met defined criteria for chronic constipation and were also taking medications that were associated with a reported side effect incidence of more than 3% constipation. Subjects were randomized into a double-blind, parallel, multicenter study where they received 17 g per day of PEG laxative or placebo for 28 days. The primary efficacy variable, "Treatment Success," was defined as relief of ROME II criteria for constipation over the last 7 days of the treatment period. Various secondary measures were also assessed. Daily bowel movement experience, patient perception of efficacy, and safety information were recorded in a diary. Laboratory testing was performed at baseline and at end of study for hematology and blood chemistry, including BUN, calcium, electrolytes, and TSH. RESULTS: One hundred patients were enrolled at 4 study centers. Successful treatment according to the primary efficacy variable was seen in 78.3% of PEG and 39.1% of placebo subjects (P < 0.001). Similar results were observed in a subgroup of 28 elderly subjects. Secondary measures of number of bowel movements, complete bowel movements, satisfactory bowel movements, straining at stool and stool consistency also showed statistically significant results in favor of PEG compared with placebo (P < or = 0.01) after the first week of treatment. There were no differences inpatient reported scores for gas, cramping, or bloating between PEG and placebo. No significant differences in laboratory findings or adverse events, including the gastrointestinal category, were observed. Diarrhea and flatulence occurred more frequently with PEG treatment, although they were not individually statistically different from placebo. Similar results were observed when these symptoms were analyzed for differences due to gender, race, or age. CONCLUSIONS: PEG laxative is safe and effective for use in treating constipation in patients taking constipating medications.

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.