A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study.

BACKGROUND: CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma. METHODS: Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety. RESULTS: Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3+ infiltrates. Surprisingly, the baseline cell density of CD3+CD8- T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (P = 0.0179). CONCLUSIONS: These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment. TRIAL REGISTRATION NUMBER: NCT02565992.

Pharmacokinetic and Pharmacodynamic Properties of a Micro-Dose Nasal Spray Formulation of Desmopressin (AV002) in Healthy Water-Loaded Subjects.

PURPOSE: Antidiuretic therapy with desmopressin for nocturia has been hampered by formulations with high doses, low bioavailability and variable pharmacokinetics. AV002 (SER120), a novel, emulsified, microdose desmopressin nasal spray, with a permeation enhancer (cylcopentadecanolide), was developed to have pharmacokinetic characteristics suitable for nocturia treatment. METHODS: Twelve healthy subjects participated in an open-label, dose-escalating study. Water-loaded subjects were sequentially dosed every 48 h with AV002 0.5, 1.0, 2.0 µg and 0.12 µg desmopressin subcutaneous (SC) bolus injection. RESULTS: AV002 intranasal administration produced a time-to-maximum concentration (Tmax) between 15 and 30 min and a maximum concentration (Cmax) <10 pg/mL. Cmax and area under the curve showed dose proportionality. Coefficient of variation for AV002 was similar to that observed for the SC dose. Bioavailability of AV002 was approximately 8% compared to SC injection. AV002 demonstrated pharmacodynamic effects within 20 min of dosing and showed increasing magnitude and duration with escalating doses. AV002 2.0 µg had maximum median urine osmolality of 629 mOsm/kg and median urine output ≤2 mL/min for 5-6 h. CONCLUSIONS: AV002 demonstrated rapid absorption, high bioavailability, limited duration of action, and low coefficient of variation, suggesting it may be a suitable formulation for nocturia treatment. Trial registration not required (single-center, phase 1).

Efficacy and Safety of SER120 Nasal Spray in Patients with Nocturia: Pooled Analysis of 2 Randomized, Double-Blind, Placebo Controlled, Phase 3 Trials.

PURPOSE: SER120 desmopressin intranasal spray is the first U.S. Food and Drug Administration approved pharmacotherapy for nocturia. We evaluated its efficacy and safety in 2 randomized, double-blind, placebo controlled studies, DB3 and DB4. MATERIALS AND METHODS: A total of 1,333 intent to treat patients 50 years old or older with 2.16 or more nocturic voids per night during a 2-week screening period were randomized equally to SER120 intranasal spray 1.66 or 0.83 mcg, or placebo for a 12-week treatment. Co-primary end points were the mean change from baseline in nocturic episodes per night and the percent of patients with a 50% or greater reduction in mean nocturic episodes per night. Secondary end points were the validated INTU (Impact of Nighttime Urination) quality of life questionnaire in DB4, time to the first nocturic void and the percent of nights with 1 or fewer nocturic voids. RESULTS: Each SER120 dose showed statistical significance vs placebo for the 2 co-primary end points, including the mean nocturic episodes per night (-1.4 with 0.83 mcg and -1.5 with 1.66 mcg vs -1.2 with placebo, each p <0.0001), the percent of patients with a 50% or greater reduction in mean nocturic episodes per night (37.9% with 0.83 mcg and 48.7% with 1.66 mcg vs 30.3% with placebo, p = 0.0227 and <0.0001, respectively) as well as for all secondary end points in the pooled analyses. The 1.66 mcg dose demonstrated significant improvements in the INTU score (p = 0.0255). The incidence of hyponatremia, defined as serum sodium 125 mmol/l or less regardless of symptoms or less than 130 mmol/l with symptoms, was 1.1%, 0% and 0.2% in the 1.66 and 0.83 mcg, and placebo groups, respectively. Other adverse events were similar across treatment groups. CONCLUSIONS: SER120 demonstrated significant improvements over placebo for co-primary and secondary efficacy end points that corresponded with quality of life improvements. SER120 at each dose had an acceptable safety profile.

Development of the Impact of Nighttime Urination (INTU) questionnaire to assess the impact of nocturia on health and functioning.

AIMS: This study describes development of the Impact of Nighttime Urination (INTU) questionnaire to assess nocturia impacts on health and functioning. METHODS: Development of the questionnaire followed an iterative patient-directed process as recommended by current guidance for patient-reported outcome (PRO) measures. An initial 15-item questionnaire was devised based on reviewing the published literature, and then modified through four rounds of semi-structured interviews of 28 individuals with nocturia. In each round, open-ended concept elicitation, followed by cognitive debriefing, was used to assess the questionnaire. Items were modified based on participants' responses and incorporated into the next round of interviews. RESULTS: In all rounds, participants reported that their experiences were easy to recall and report on a daily basis and that the burden of completing the questionnaire was low. The final questionnaire has a same-day recall period. It includes six daytime impact items-having limited concentration, a sense of feeling tired, difficulty getting things done, irritability, not feeling rested, and drowsiness-and four items that measure the nighttime impact of nocturia-patient concern, waking up too early, difficulty getting enough sleep, and feeling bothered by having to get up at night to void. Responses follow a 5- or 4-point scale. The final INTU captures the key concepts associated with nocturia as confirmed by cognitive debriefing. CONCLUSIONS: Development of the 10-item INTU, a nocturia-specific PRO measure, was based on direct input and feedback from patients and has demonstrated that it captures the patient-reported impacts of nocturia.

Development of a new patient-reported outcome (PRO) measure on the Impact of Nighttime Urination (INTU) in patients with nocturia-Psychometric validation.

AIMS: To psychometrically evaluate the Impact of Nighttime Urination (INTU) questionnaire, a new patient-reported outcome measure developed to assess the impact of nocturia on health and functioning in a multicenter, behavioral modification (fluid restriction) study. METHODS: Participants aged 50-95 years with at least two voiding episodes/night for ≥6 months completed voiding diaries and the INTU on 3 consecutive days during weeks 1 and 2 (same day recall) and completed the Pittsburgh Sleep Quality Index (PSQI) and Nocturia Quality of Life Questionnaire (N-QOL) at baseline and days 8 and 15. Psychometric evaluations of the INTU were conducted. RESULTS: Rasch analysis showed the INTU to be a unidimensional construct, with most items located on the severe end of the symptom severity continuum. In addition to an Overall Impact Score (10 items), exploratory factor analysis affirmed by confirmatory factor analysis identified two domains: Daytime (six items) and Nighttime (four items) Impact Scores (comparative fit index = 0.968; root mean square error of approximation = 0.08). Concurrent validity met prespecified hypotheses, indicating similarity of concepts with the PSQI (correlation [r] = 0.627) and N-QOL (r = -0.784) total scores. The INTU differentiated among patients with different nocturic episode frequencies (P < 0.05 for all three summary scores). Statistically significant decreases were observed in mean Overall and Nighttime Impact Scores at week 2 versus week 1 in responders, indicating that the instrument can detect changes in response to symptom improvements. CONCLUSIONS: The INTU questionnaire demonstrated robust measurement properties and is a suitable tool for assessing the patient-reported impact of nocturia on health and functioning.

A comprehensive preclinical study supporting clinical trial of oncolytic chimeric poxvirus CF33-hNIS-anti-PD-L1 to treat breast cancer.

CF33-hNIS-anti-PD-L1 is an oncolytic chimeric poxvirus encoding two transgenes: human sodium iodide symporter and a single-chain variable fragment against PD-L1. Comprehensive preclinical pharmacology studies encompassing primary and secondary pharmacodynamics and biodistribution and safety studies were performed to support the clinical development of CF33-hNIS-anti-PD-L1. Most of the studies were performed in triple-negative breast cancer (TNBC) models, as the phase I trial is planned for patients with TNBC. Biological functions of virus-encoded transgenes were confirmed, and the virus demonstrated anti-tumor efficacy against TNBC models in mice. In a good laboratory practice (GLP) toxicology study, the virus did not produce any observable adverse effects in mice, suggesting that the doses proposed for the clinical trial should be well tolerated in patients. Furthermore, no neurotoxic effects in mice were seen following intracranial injection of the virus. Also, the risk for horizontal transmission of CF33-hNIS-anti-PD-L1 was assessed in mice, and our results suggest that the virus is unlikely to transmit from infected patients to healthy individuals. Finally, the in-use stability and compatibility of CF33-hNIS-anti-PD-L1 tested under different conditions mimicking the clinical scenarios confirmed the suitability of the virus in clinical settings. The results of these preclinical studies support the use of CF33-hNIS-anti-PD-L1 in a first-in-human trial in patients with TNBC.

Comparison of the efficacy and safety of a highly purified human follicle-stimulating hormone (Bravelle) and recombinant follitropin-beta for in vitro fertilization: a prospective, randomized study.

OBJECTIVE: To compare the efficacy and safety of Bravelle s.c., Bravelle i.m., and Follistim s.c. in patients undergoing controlled ovarian hyperstimulation for IVF-ET. DESIGN: Open-label, randomized, parallel group, multicenter study. SETTING: Eleven academic and private fertility clinics with experience in IVF-ET. PATIENT(S): Infertile premenopausal women with regular ovulatory menstrual cycles undergoing IVF-ET. INTERVENTION(S): Down-regulation with leuprolide acetate followed by up to 12 days of Bravelle s.c. (n = 60), Bravelle i.m. (n = 59), or Follistim s.c. (n = 58); hCG administration, oocyte retrieval, and ET. MAIN OUTCOME MEASURE(S): Mean number of oocytes retrieved; patients with ET, chemical, clinical and continuing pregnancies; mean peak serum E2 levels; adverse events and injection site pain scores. RESULT(S): There were no significant differences among treatment groups in mean number of oocytes retrieved, peak serum E2 levels, patients with ET, continuing pregnancies, or live births. There were no significant differences among the treatment groups in the number, nature, or intensity of adverse events. Patients treated with Bravelle s.c. or Bravelle i.m. experienced significantly less injection site pain than patients treated with Follistim s.c. CONCLUSION(S): Bravelle s.c. and Bravelle i.m. are comparable in efficacy and safety to Follistim s.c. in patients undergoing controlled ovarian hyperstimulation for IVF-ET.

Intravenous synthetic secretin reduces the incidence of pancreatitis induced by endoscopic retrograde cholangiopancreatography.

OBJECTIVES: This study aimed to evaluate whether synthetic secretin is effective in reducing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. METHODS: This is a single academic medical center, prospective, randomized, double-blind, placebo-controlled trial using secretin (dose of 16 µg) administered intravenously immediately before ERCP. Patients were evaluated for the primary outcome of post-ERCP pancreatitis as diagnosed by a single investigator. RESULTS: A total of 1100 patients were screened, of whom 869 were randomly assigned to receive secretin (n = 426) or placebo (n = 443) before ERCP and were evaluated after the procedure for efficacy of secretin. The incidence of pancreatitis in the secretin group compared with the placebo group was 36 (8.7%) of 413 patients versus 65 (15.1%) of 431 patients, respectively, P = 0.004. In the subgroup analysis, secretin was highly protective against post-ERCP pancreatitis for patients undergoing biliary sphincterotomy (6/129 vs 32/142, P < 0.001), patients undergoing cannulation of the common bile duct (26/339 vs 56/342, P < 0.001), and patients not undergoing pancreatic sphincterotomy (26/388 vs 57/403, P = 0.001). Analysis of the interaction between these groups reveals that the primary effect of secretin prophylaxis was prevention of post-ERCP pancreatitis in patients undergoing biliary sphincterotomy. CONCLUSIONS: Synthetic secretin reduces the risk of post-ERCP pancreatitis, particularly in patients in undergoing biliary sphincterotomy.

A prospective crossover study comparing secretin-stimulated endoscopic and Dreiling tube pancreatic function testing in patients evaluated for chronic pancreatitis.

BACKGROUND: Direct pancreatic function tests (PFT) are conventionally performed with use of double-lumen "Dreiling" collection tubes. We have developed an endoscopic collection method (ePFT) that eases the performance of these tests. OBJECTIVE: Our aim was to compare the bicarbonate results obtained from the secretin ePFT and Dreiling PFT methods in patients evaluated for chronic pancreatitis. DESIGN: A prospective crossover design was used to compare the PFT methods. SETTING: Tertiary care referral center. PATIENTS AND INTERVENTIONS: Twenty-four patients undergoing an evaluation for chronic pancreatitis underwent the secretin-stimulated ePFT and Dreiling PFT methods on separate days. MAIN OUTCOME MEASUREMENTS: Duodenal fluid bicarbonate concentrations and estimated bicarbonate outputs were compared. RESULTS: The mean difference in peak bicarbonate concentration (Dreiling PFT minus ePFT) was 7 mEq/L (SD 20) and not statistically significant (P = .11). A good correlation in peak bicarbonate concentrations (r = 0.74, 95% CI, 0.48-0.88) and estimated bicarbonate output (r = 0.78, 95% CI, 0.54-0.90) was observed between the two PFT methods. LIMITATION: The sensitivities and specificities of the secretin ePFT and Dreiling PFT could not be compared because of the lack of a histologic gold standard. CONCLUSION: The secretin ePFT yields results similar to those of the Dreiling PFT in patients evaluated for chronic pancreatitis.

Basal-prandial insulin delivery in type 2 diabetes mellitus via the V-Go: a novel continuous subcutaneous infusion device.

BACKGROUND: The V-Go is a once-daily disposable device that allows coverage of basal and prandial insulin requirements over a period of 24 hours. The aim of this proof-of-concept study was to evaluate the clinical functionality, safety, and pharmacodynamics of the V-Go delivering insulin aspart and redistributing a single basal dose of insulin glargine as a constant basal infusion supplemented with prandial insulin in subjects with type 2 diabetes mellitus. METHODS: In six subjects receiving once-daily subcutaneous (SC) injections of insulin glargine (> or =15 U/day) with or without concomitant oral antidiabetic drugs, glargine was discontinued following a 3-day baseline phase. The V-Go was then applied to the lower abdomen of the subjects once daily for 7 days (days 1-3 inpatient, days 4-7 outpatient). Each V-Go provided a continuous 24-hour preset basal infusion rate of insulin aspart (0.6 U/h) and up to three daily prandial doses at mealtimes. Capillary blood glucose concentrations were measured at 11 time points per day during the baseline and inpatient phases and at 4 time points per day during the outpatient phase. Additionally, glucose profiles were measured continuously on all days. RESULTS: The V-Go was well tolerated and operated as anticipated. The mean +/- SEM prestudy daily dose of SC insulin glargine was 33.3 +/- 13.8 U; the mean daily total insulin aspart dose infused with the V-Go was 31.5 +/- 7.5 and 32.3 +/- 7.8 U for the inpatient and outpatient periods, respectively. Fasting blood glucose values were similar to those observed at baseline throughout the study, with nonsignificant (NS) reductions in readings collected during the outpatient phase before lunch (-35 +/- 27 mg/dl) and before dinner (-38 +/- 25 mg/dl). The 2-hour postprandial glucose trended lower from 231 to 195 mg/dl (NS) at breakfast, 234 to 166 mg/dl (NS) at lunch, and 222 to 171 mg/dl (NS) at dinner. Bedtime blood glucose decreased (mean change from baseline -52 +/- 21 mg/dl; P = 0.0313), as did nighttime (3:00 AM) measurements (-20 +/- 9 mg/dl; P = 0.0313). Overall glycemic control tended to improve, as shown by continuous glucose monitoring changing from 173 to 157 mg/dl (P = 0.063, NS) and 156 mg/dl (P = 0.219) during inpatient and outpatient periods, respectively. Glycemic variability assessed by the M value similarly tended to decrease from 33 +/- 9 to 25 +/- 4 (NS) and 21 +/- 4 (NS) for inpatient and outpatient periods, respectively. CONCLUSIONS: These first data suggest that use of the V-Go is an attractive alternative to SC insulin injection therapy because metabolic control appears to be maintained or even improved without increasing daily insulin doses.

Comparison of endoscopic ultrasound chronic pancreatitis criteria to the endoscopic secretin-stimulated pancreatic function test.

Endosonography (EUS) has emerged as a major diagnostic tool in pancreatic imaging. Direct tests of pancreatic function are considered the most sensitive and accurate method to establish a diagnosis of chronic pancreatitis (CP), particularly when imaging studies are inconclusive. The aim of this study was to compare current EUS CP criteria with our newly described, purely endoscopic, secretin-stimulated pancreatic function test (ePFT). Fifty-six patients (25 male, mean age = 44 years) who were referred for evaluation/treatment of chronic abdominal pain with or without CP underwent both EUS and ePFT. The EUS protocol included the following: (1) EUS images were obtained in a standardized fashion from both gastric and duodenal stations, and (2) EUS images were scored independently by one of three therapeutic endoscopists for 0--9 parenchymal/ductal criteria as follows: 0-3 = normal, 4-5 = equivocal, >/=6 = definite CP. Endoscopic pancreatic function test (ePFT) protocol included the following: (1) upper endoscopy, (2) intravenous synthetic porcine secretin (0.2 mcg/kg, ChiRhoClin, Inc.) after test dose, (3) duodenal fluid aspirated every 15 min for 1 h, and (4) autoanalyzed for [HCO3] cutpoint of 80 mEq/L. According to EUS, 33 were normal, 13 equivocal, and 10 definite for CP. The mean peak [HCO3 -] range (in mEq/L) for each group was normal CP (83.7, range = 58-118), equivocal CP (68, range = 30-88), and definite CP (56, range=19-84). Using a peak [HCO3 -] of

A randomized crossover study of secretin-stimulated endoscopic and dreiling tube pancreatic function test methods in healthy subjects.

OBJECTIVES: We have developed an endoscopic method of secretin endoscopic pancreatic function testing (ePFT) to simplify duodenal fluid collection. Validation of the ePFT requires a direct comparison to the traditional PFT using a Dreiling tube (DT). Our aim was to compare bicarbonate concentrations [HCO3-] obtained by the ePFT and DT methods in healthy subjects (HS). METHODS: HS were randomized to either DT or ePFT, then crossed over to the other test after a minimum 1-wk washout. An age/weight-based sedation bolus was used for each test. DT protocol: Endoscopic placement of a DT was confirmed by fluoroscopy. After a baseline 15-min collection and administration of IV synthetic secretin, fluid was continuously collected in 15-min aliquots for an hour. ePFT protocol: Endoscopy was performed using a 6-mm endoscope. After gastric aspiration and discard and IV secretin, duodenal aspirates were obtained every 15-min for an hour. Fluid specimens were auto-analyzed for [HCO3-]. RESULTS: Twelve HS were enrolled (6F, mean age 37 yr). The difference in [HCO3-] between the two methods was not significant at the 0-, 30-, 45-, or 60-min collections. An excellent correlation in peak [HCO3-] was observed (R2 = 0.84, p < 0.001). Using a peak [HCO3-] cutpoint 80 mEq/L, there was 100% agreement between the methods; using cutpoint 90 mEq/L, there was 83% agreement. CONCLUSIONS: The accuracy of the ePFT is similar to DT: There were minimal differences in [HCO3-] at each of the timed collections and at peak. There is an excellent correlation in peak [HCO3-] and high level of diagnostic agreement between the tests.

Facilitation of pancreatic duct cannulation using a new synthetic porcine secretin.

OBJECTIVES: Cannulation of the pancreatic duct at ERCP can represent a technical challenge, even to experienced pancreaticobiliary endoscopists. Secretin is a polypeptide hormone that increases the volume and bicarbonate content of pancreatic secretions. We report our single center experience in the use of a new synthetic porcine secretin (sPS) for the facilitation of cannulation of either the major or minor pancreatic orifice during ERCP. METHODS: Patients presenting for a variety of indications were enrolled. If identification or cannulation of the desired pancreatic duct was difficult, 0.2 microg/kg of sPS was administered i.v. Cannulation success or failure was recorded. RESULTS: Between March, 1999, and May, 2000, a total of 25 patients (seven men and 18 women) were enrolled. The most frequent indication (15 of 25 cases) was facilitation of dorsal pancreatic duct cannulation in patients with pancreas divisum. The overall rate of successful cannulation secretin administration was 24 of 25 cases (96%). No adverse events directly attributable to secretin were observed. CONCLUSIONS: The results of this study show that sPS is safe and efficacious in faciliting cannulation of either the major or minor pancreatic orifice at ERCP in the subset of patients who represent cannulation difficulties. Once commercially available, sPS can be added to the armamentarium of techniques to facilitate ERP.

A new synthetic porcine secretin for facilitation of cannulation of the dorsal pancreatic duct at ERCP in patients with pancreas divisum: a multicenter, randomized, double-blind comparative study.

BACKGROUND: Secretin, a 27 amino acid polypeptide released in response to duodenal luminal acidification, stimulates secretion of water and bicarbonate from pancreatic ductal cells. To date the only secretin available for clinical use has been a biologically derived compound extracted from porcine duodenums. Although used to facilitate pancreatic duct cannulation, secretin has not been approved for this indication. In this study, a new synthetic porcine secretin with an identical amino acid composition was compared with saline solution for the facilitation of minor papilla cannulation in patients with pancreas divisum. METHODS: A multicenter, prospective, randomized, placebo-controlled, double-blind, comparative trial was conducted at 4 centers with expertise in pancreaticobiliary endoscopy. Patients with pancreas divisum in whom minor papilla cannulation initially was unsuccessful were enrolled. Either saline solution (placebo) or synthetic porcine secretin was administered. If the minor papilla orifice and/or pancreatic juice flow was noted, cannulation was attempted and success or failure was documented (phase 1), as well as the time taken for successful cannulation. If cannulation was unsuccessful, no juice flow was noted, or the orifice was not seen, the alternate agent was administered (phase 2). RESULTS: Twenty-nine patients (7 men, 22 women; mean age 51 years, range 21-76 years) were enrolled. In phase 1, cannulation was achieved in 1 of 13 patients (7.7%) after the placebo was given and in 13 of 16 patients (81.3%) after synthetic porcine secretin was given (p < 0.0001). In phase 2, cannulation was achieved in 12 of 12 patients (100%) after synthetic porcine secretin was given and in 0 of 3 patients (0%) after the placebo was given (p = 0.0022). Overall, cannulation was successful in 25 of 28 patients (89.3%) who received synthetic porcine secretin and in 1 of 16 (6.3%) who received the placebo (p < 0.0001). Mean time to cannulation was significantly greater for the placebo than for the synthetic porcine secretin (4.75 min vs. 2.63 min; p = 0.0001). No adverse events directly attributable to synthetic porcine secretin administration were documented. CONCLUSIONS: This study confirmed the use and safety of synthetic porcine secretin in facilitating cannulation of the minor papilla in patients with pancreas divisum in whom cannulation was difficult. Use of this agent has the potential to further increase the cannulation success rate in this group of patients.

Electrolyte composition of endoscopically collected duodenal drainage fluid after synthetic porcine secretin stimulation in healthy subjects.

BACKGROUND: Traditional pancreatic function tests are sensitive for the diagnosis of pancreatic exocrine insufficiency but are cumbersome and difficult to perform. A sedationless endoscopic pancreatic function test that has the potential for wide clinical application was developed by us, but data on the results of this method in healthy subjects are lacking. This study analyzed endoscopically collected duodenal fluid from healthy subjects after synthetic porcine secretin stimulation. METHODS: Healthy subjects underwent the sedationless endoscopic pancreatic function test. After secretin stimulation, duodenal aspirates were obtained every 5 minutes for 1 hour. The collected fluid was analyzed for electrolyte concentrations. RESULTS: Sixteen healthy subjects (8 women, 8 men; median age 34.5 years) underwent the endoscopic pancreatic function test. The concentrations of the sodium ([Na+]) and potassium ([K+]) cations remained constant, similar to normal concentrations in plasma (median [Na+], 155 mEq/L; median [K+], 4.3 mEq/L). The concentrations of the bicarbonate ([HCO 3 - ]) and chloride anions increased and decreased, respectively, in an inverse and reciprocal manner, similar to the previously characterized "secretory curve." The median peak [HCO 3 - ] was 108 mEq/L IQR: 99-110). By the 20-minute collection, the [HCO 3 - ] was greater than 80 mEq/L for 94% (15/16) of subjects, the historic cut point for [HCO 3 - ] in studies based on traditional methods of pancreatic function testing. CONCLUSIONS: Endoscopic collection of pancreatic fluid reproduces the anion-cation secretory curve described by prior studies of pancreatic secretory physiology based on traditional collection methods.