Clinical Project Manager Braintree Laboratories, Inc. Braintree, MA
Matthew L. Walker, PhD1, Cynthia A. Zamora, MD2, Mark Cleveland, PhD3, Kathleen Hague1, Sue Hall, PhD4, John McGowan, MPH1; 1Braintree Laboratories, Inc., Braintree, MA; 2Worldwide Clinical Trials, San Antonio, TX; 3Mark Cleveland, Norwell, MA; 4Braintree Laboratories, Inc., Roswell, GA
Introduction: Properly formulated bowel preps induce copious amounts of diarrhea sufficient for colonoscopy (2.5-3.5L with stool clarity of 0-5.0) while minimizing electrolyte and fluid shifts. These criteria were used to evaluate a new oral sulfate tablet (OST) preparation. Methods: 25 healthy males (18-50 yoa) were enrolled in a Phase 1 study of OST formulations. Tablets were administered using a split-dose (PM/AM) regimen. Subjects consumed 12 tablets per dose, along with 473 mL of water. Another 946 mL of water was consumed over the next one hour. All stool was collected, weighed and analyzed for clarity and electrolyte composition (Patel et al 2010). Blood samples were collected prior to dosing and at 4 and 6 hours post-dose for serum chemistry analyses. Gastric water balance was calculated by subtracting the total fecal output from the total water consumption. Subtracting urine output from gastric balance yielded the fluid output. Fecal electrolyte balance was determined by the difference between electrolytes in preparation and in the total stool output. Results: Subjects given OST produced mean stool output of 2.7 L (±0.4) with clarity of 3.7% (±6.0). Gastric water balance was positive (2.5±1.1 L) and overall fluid balance (-0.2 ±0.5 L) was effectively neutral, indicating a net zero movement of water. Fecal electrolyte balances for Na (14.2 ± 116.1 mEq), Cl (-0.8 ±24.7 mEq), K (-1.2±15.8 mEq) and Mg (-6.4±18.0 mEq), were not significantly different from 0, indicating no net movement. Mean serum electrolytes remained relatively constant, with only small transient and inconsistent changes observed. Increases were seen in Ca, Cl, K, Mg and anion gap, and decreases in HCO3, Na, and PO4. Abnormal shifts were infrequent and considered not clinically significant. Increases in serum sulfate occurred immediately following Dose 1 and 2 and began to decrease 4 hours after dosing (similar to what has previously been observed with oral sodium sulfate solutions). No adverse events related to the increase in serum sulfate were observed. Discussion: The fecal profile of the OST prep was well within the generally accepted ranges for fecal output and clarity established by currently approved preparations. These findings indicate that the osmotic activity of the OST prep is sufficient to provide adequate cleansing of the bowel, without inducing dehydration. The OST prep was well tolerated, as the preparation composition was sufficiently balanced to minimize serum electrolyte shifts.
Disclosures: Matthew Walker: Braintree Laboratories Inc. – Employee. Cynthia Zamora: Braintree – Other Financial or Material Support, Worldwide Clinical Trials conducted the research protocol. Braintree Laboratories Inc. – Grant/Research Support. Mark Cleveland: Braintree Laboratories Inc. – Consultant. Kathleen Hague: Braintree Laboratories Inc. – Employee. Sue Hall: Braintree Laboratories Inc. – Employee. John McGowan: Braintree Laboratories Inc. – Employee.