Phase III Randomized Non-Inferiority Study of OSS Versus PEG + Electrolyte Colonoscopy Preparation in Adolescents.

OBJECTIVES: Many protocols and preparations are used for bowel cleansing before pediatric colonoscopy but few are based on scientific evidence. We evaluated efficacy, safety, tolerability, and patient preference of oral sulfate solution (OSS) at 75% of the adult dose versus polyethylene glycol (PEG)-electrolyte solution in adolescents presenting for diagnostic colonoscopy. METHODS: Phase III, randomized, evaluator-blinded, non-inferiority study of OSS and PEG in adolescents aged 12-17 years. OSS and PEG were administered in 2 doses on the day before colonoscopy. Primary endpoint included proportion of patients with successful overall preparation (4-point scale). Secondary endpoints included overall and segmental bowel cleansing (Boston Bowel Preparation Scale; BBPS), completed colonoscopies, duration of examination, time to cecal intubation, proportion of nasogastric tubes (NGTs), adverse events (AEs) and acceptability. RESULTS: Successful cleansing was achieved in 71.4% and 79.0% of patients receiving OSS and PEG, respectively [adjusted difference -7.61 (95% confidence interval, CI, -18.45 to 3.24); P = 0.0907]. Segmental BBPS score for the left and transverse colon were similar between treatment groups, but better for the right colon with PEG than OSS [2.2 (95% CI, 2.0-2.4) and 1.9 (95% CI, 1.7-2.1), respectively; P = 0.0015]. Significantly fewer OSS patients needed NGT placement to ingest the whole solution [9/125 (7.2%)] than PEG patients [36/116 (31.0%); P < 0.0001]. Treatment acceptability was significantly higher with OSS than PEG ( P < 0.0001). Duration of examination, completed colonoscopies, and time to cecal intubation were similar between preparations. Gastrointestinal AEs including nausea, vomiting, abdominal pain, and distension were similar in both groups but more patients receiving PEG had AEs assessed as incapacitating. CONCLUSIONS: Non-inferiority of OSS to PEG was not demonstrated, but OSS was associated with a lower requirement for NGT, better acceptability, and less frequent severe AEs than with PEG.

A European, multicentre, observational, post-authorisation safety study of oral sulphate solution: compliance and safety.

Background and study aims Oral sulphate solution (OSS) is a sulphate-based, low-volume bowel cleansing preparation taken in two doses of 500 mL, each followed by 1000mL of water or clear liquid. The primary objective of this observational study was to document compliance with the recommended hydration guidelines in a representative sample of the European population. Patients and methods Prospective, non-interventional, multicentre study (NCT02630680, EUPAS9361) in patients prescribed OSS for colonoscopy preparation in routine clinical practice in Europe. Patients were included according to pre-agreed consecutive enrolment rules. Patients recorded the volume of OSS and water or clear liquid intake, and occurrence of adverse events (AEs). Compliance with hydration was calculated as a ratio of actual volume of water/clear liquid taken versus prescribed 2,000 mL, and non-compliance defined as < 75 % intake. Colon cleansing level was assessed on a 4-point scale. Results Between October 2015 and January 2017, 1,281 patients were recruited in 16 centres in four European countries (safety population n = 1,206; registry population n = 1,177). Of patients, 94.5 % were ≥ 75 % and 86.8 % 100 % compliant with hydration guidelines. Patients took an average of 96.8 % of the recommended OSS volume; 46 patients (3.9 %) were non-compliant. Colon cleansing levels were good-to-excellent in 87.6 % of patients. Three hundred and twenty-nine patients (27.3 %) experienced 758 treatment-related AEs, mostly gastrointestinal (82.9 %), all were mild-to-moderate. Non-compliant patients had no AEs suggestive of dehydration. Conclusion In this non-interventional study in a real-life setting, treatment compliance with hydration guidelines was good-to-excellent in 94.5 % of patients receiving OSS. The safety profile of OSS was similar to the prescribing information.

A phase I dose escalation study to determine the optimal biological dose of irosustat, an oral steroid sulfatase inhibitor, in postmenopausal women with estrogen receptor-positive breast cancer.

Steroid sulfatase (STS) inhibition may have a therapeutic role in suppression of endocrine-responsive breast cancer. This study aimed to determine the optimal biological dose and recommended dose (RD) of the STS inhibitor irosustat. A three-part, open-label, multicenter, dose escalation study of irosustat in estrogen receptor-positive breast cancer patients involved administration of a single dose of irosustat with a 7-day observation period; followed by a daily oral dose of irosustat for 28 days; and an extension phase, in which the daily oral dose of irosustat was continued at the discretion of the investigator and as long as the patient was benefitting from the treatment. Five doses of irosustat were tested (1, 5, 20, 40, and 80 mg) in 50 patients. After 28 days of daily administration of irosustat, all the evaluated patients in the 5, 20, 40, and 80 mg cohorts achieved ≥95 % STS inhibition in peripheral blood mononuclear cells and corresponding endocrine suppression. The maximum tolerated dose was not reached, and the 40 mg dose was established as the RD. The median time to disease progression in the 40 mg cohort was 11.2 weeks. Disease stabilization was achieved in 10 % of patients potentially indicative of drug activity. Dry skin was the most frequent adverse event. The RD of irosustat is 40 mg. Disease stabilization occurred in 10 % of this heavily pretreated patient population. A larger study is required to define an accurate response rate to irosustat as a single agent and whether co-administration with an aromatase inhibitor is needed.