Abdominal Discomfort Score Research Articles

A randomized double-blind trial of 3 aspirin regimens to optimize antiplatelet therapy in essential thrombocythemia

AbstractEssential thrombocythemia (ET) is characterized by abnormal megakaryopoiesis and enhanced thrombotic risk. Once-daily low-dose aspirin is the recommended antithrombotic regimen, but accelerated platelet generation may reduce the duration of platelet cyclooxygenase-1 (COX-1) inhibition. We performed a multicenter double-blind trial to investigate the efficacy of 3 aspirin regimens in optimizing platelet COX-1 inhibition while preserving COX-2–dependent vascular thromboresistance. Patients on chronic once-daily low-dose aspirin (n = 245) were randomized (1:1:1) to receive 100 mg of aspirin 1, 2, or 3 times daily for 2 weeks. Serum thromboxane B2 (sTXB2), a validated biomarker of platelet COX-1 activity, and urinary prostacyclin metabolite (PGIM) excretion were measured at randomization and after 2 weeks, as primary surrogate end points of efficacy and safety, respectively. Urinary TX metabolite (TXM) excretion, gastrointestinal tolerance, and ET-related symptoms were also investigated. Evaluable patients assigned to the twice-daily and thrice-daily regimens showed substantially reduced interindividual variability and lower median (interquartile range) values for sTXB2 (ng/mL) compared with the once-daily arm: 4 (2.1-6.7; n = 79), 2.5 (1.4-5.65, n = 79), and 19.3 (9.7-40; n = 85), respectively. Urinary PGIM was comparable in the 3 arms. Urinary TXM was reduced by 35% in both experimental arms. Patients in the thrice-daily arm reported a higher abdominal discomfort score. In conclusion, the currently recommended aspirin regimen of 75 to 100 once daily for cardiovascular prophylaxis appears to be largely inadequate in reducing platelet activation in the vast majority of patients with ET. The antiplatelet response to low-dose aspirin can be markedly improved by shortening the dosing interval to 12 hours, with no improvement with further reductions (EudraCT 2016-002885-30).

Efficacy and safety of Gelidium elegans intake on bowel symptoms in obese adults: A 12-week randomized double-blind placebo-controlled trial.

Background/aims:Gelidium elegans (GE) is known to have antiobesity effects and beneficial effects on functional bowel symptoms in preclinical studies. The aim of this study was to determine the efficacy and safety of GE intake on bowel symptoms in obese human adults.Methods:This 12-week single-center randomized double-blind placebo-controlled study was performed from September 2016 to May 2017. Consecutive obese subjects were randomly assigned (1:1) to either GE (1 g) or placebo (1 g) once daily group for 12 weeks. Patients’ bowel symptoms were evaluated using the Bristol Stool Form Scale, Constipation Scoring System (CSS), and Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire.Results:The stool symptom score of PAC-SYM significantly improved in the GE group compared with the placebo group after the 12-week treatment (P = .041). Abdominal discomfort score of CSS significantly decreased at 12 weeks compared to that at baseline in the GE group (P = .003), but not in the placebo group (P = .398). In addition, abdominal discomfort score of CSS slightly decreased in the GE group compared with the placebo group after the 12-week treatment (P = .060). However, stool consistency, total CSS score, and PAC-SYM score did not change significantly in both GE group and the placebo group over the 12-week treatment period.Conclusions:GE treatment for 12 weeks improved the stool symptom score on the PAC-SYM and abdominal discomfort score on the CSS in obese adults. However, further research is needed in large-scale human studies.

A clinical research of Lingshao-Zaoren granule for the female with overactive bladder symptom: a randomized, double-blind, placebo-controlled trial

Objective To evaluate the effectiveness of Lingshao-Zaoren granule in the treatment of female overactive bladder. Methods A total of 60 female OAB patients who met the inclusion criteria were randomly divided into 2 groups, 30 cases in each group. The control group recieved the Tolterodine Tartrate Sustained Release Tablets and the Lingshao-Zaoren granule placebo, and the treatment group used the Tolterodine Tartrate Sustained Release Tablets and the true Lingshao-Zaoren granule treatment. Both groups were treated for 4 weeks. Overactive bladder symptom scale (OABSS) was used to determine the severity of OAB. Results After treatment 14, 28 d, OABSS scores of the treatment group (5.3 ± 2.3, 1.4 ± 1.2 vs. 8.4 ± 2.4, F=137.209), and control group (7.8 ± 1.9, 6.8 ± 1.4 vs. 8.6 ± 2.6, F=8.927), were significantly lower than the baseline of each group respectively (P<0.01). Besides, OABSS scores of the treatment group after 14 and 28 d were significantly lower than the control group (t=4.668, 15.678, P<0.01). The pain scores (5.9 ± 1.9, 2.7 ± 1.1 vs. 9.5 ± 2.3, F=108.819) of treatment group at 14 and 28 d were significantly lower than the baseline (P<0.01); and the pain scores of treatment group at 14 and 28 d were significantly lower than the control group (t=6.342, 14.812, P<0.01). The lower abdomen discomfort scores at 14, 28 d in treatment group (1.9 ± 1.4, 1.1 ± 1.0 vs. 3.3 ± 1.1, F=28.762), and control group (2.7 ± 1.0, 2.4 ± 0.8 vs. 3.4 ± 1.2, F=12.103) were significantly lower than the baseline of each group (P<0.01); and the abdominal discomfort scores of treatment group at 14, 28 d were significantly lower than the control group (t=2.521, 5.041, P<0.05 or P<0.01). Conclusions The Lingshao-Zaoren granule could decrease OABSS score, pain score, abdominal discomfort symptoms, improve clinical symptoms of the female patients with OAB. Key words: Urinary bladder, overactive; Female; Lingshao-Zaoren granule; Integrated Chinese traditional and western medicine therapy; Overactive bladder symptom scale

Saccharomyces cerevisiae CNCM I-3856 in irritable bowel syndrome: An individual subject meta-analysis.

AIMTo confirm previous conclusions on Saccharomyces cerevisiae (S. cerevisiae) CNCM I-3856 for irritable bowel syndrome (IBS) management.METHODSAn individual patient data meta-analysis was performed on two randomized clinical trials studying the effect of S. cerevisiae CNCM I-3856 supplementation on gastrointestinal (GI) symptoms in IBS subjects. A total of 579 IBS subjects were included. Outcomes were the daily Likert scale scores of abdominal pain/discomfort and bloating [area under the curve (AUC) and weekly means], responder status, and bowel movements (stool frequency and consistency). Statistical analyses were conducted in Intent to Treat (ITT) population, IBS-C subjects and IBS-C subjects with an abdominal pain/discomfort score higher than or equal to 2 at baseline (“IBS-C ≥ 2 subpopulation”).RESULTSS. cerevisiae CNCM I-3856 significantly improved abdominal pain/discomfort and bloating during the second month of supplementation [AUC (W5-W8)] with improvement up to the minimal clinically relevant threshold of 10%: a 12.3% reduction of abdominal pain/discomfort in the ITT population compared to the Placebo group (P = 0.0134) has been observed. In the IBS-C ≥ 2 subpopulation, there were a 13.1% reduction of abdominal pain/discomfort and a 14.9% reduction of bloating compared to the Placebo group (P = 0.0194 and P = 0.0145, respectively). GI symptoms significantly decreased during supplementation but no statistical differences were reported between groups at the end of the supplementation period. Responder status was defined as a subject who experienced a decrease of 1 arbitrary unit (a.u.) or 50% of the abdominal discomfort score from baseline for at least 2 wk out of the last 4 wk of the study. A significant difference between groups was reported in the ITT population, when considering the first definition: subjects in the Active group had 1.510 higher odds to be a responder (reduction of 1 a.u. of abdominal pain/discomfort) compared with subjects in the Placebo group (P = 0.0240). At the end of supplementation period, stool consistency in the Active group of the ITT population was significantly improved and classified as “normal” compared to Placebo (respectively 3.13 ± 1.197 a.u. vs 2.58 ± 1.020 a.u., P = 0.0003). Similar results were seen in the IBS-C ≥ 2 subpopulation (Active group: 3.14 ± 1.219 a.u. vs Placebo group: 2.59 ± 1.017 a.u., P = 0.0009).CONCLUSIONThis meta-analysis supports previous data linking S. cerevisiae I-3856 and improvement of GI symptoms, in IBS overall population and in the IBS-C and IBS-C ≥ 2 subpopulations.

PTU-133 Effect of Eluxadoline on Abdominal and Bowel Symptoms Over Time in Phase 3 Clinical Trials in Patients with Irritable Bowel Syndrome with Diarrhoea (IBS-D)

Introduction Eluxadoline (ELX) is a mixed µ- and κ-opioid receptor (OR) agonist and δ-OR antagonist. It is locally active and approved for the treatment of IBS-D. Effects of ELX on abdominal pain and stool consistency have been reported based on a composite response; effects on other abdominal and bowel symptoms were evaluated over time. Methods Two double-blind, placebo (PBO)-controlled, Phase 3 trials (IBS-3001 and IBS-3002) randomised patients (pts) meeting Rome III criteria for IBS-D to twice-daily treatment with ELX 75 or 100 mg or PBO. Pts completed an electronic diary and rated daily IBS symptoms of abdominal discomfort and bloating (both on a 0–10 scale), and recorded numbers of bowel movements (BMs) and episodes of urgency and fincontinence daily through 26 weeks (wks). To assess trajectories of treatment effects over time, daily symptom scores and counts of BMs and episodes of urgency and incontinence were mwith longitudinal analyses. Treatment effect estimates from the models were evaluated at Wks 4, 8, 12, 16, 20, and 24 based on estimated least squares (LS) mean differences (symptom scores) and risk ratios (frequency data). Results 2428 pts with IBS-D were enrolled across both trials. In both studies, daily abdominal discomfort and bloating scores decreased from baseline within the first wk, with greater reductions seen for ELX. Abdominal discomfort scores were significantly lower (p Conclusion ELX significantly improves abdominal discomfort and bloating, and significantly reduces BM frequency and episodes of urgency and incontinence; effects are sustained through 6 months of treatment. Reference 1 Previously presented at ACG 2015. Abstract #1761. Am J Gastroenterol 2015; 110 :S739–S766. doi:10.1038/ajg.2015.275. Disclosure of Interest L. Harris Grant/research support from: Alvine, Rhythm Pharmaceuticals, Consultant for: Allergan plc, QoL, Ironwood, Conflict with: Ironwood, Allergan plc, S. Lucak Consultant for: Allergan plc, Takeda, Salix, Ironwood, Prometheus, Speaker bureau with: Allergan plc, Takeda, Salix, Ironwood, Conflict with: Allergan plc, Takeda, Salix, Ironwood, L. Chang Conflict with: Ironwood, Allergan plc, Valeant, QOL Medical, Takeda, Ardelyx, Commonwealth Laboratories, AstraZeneca, Synergy, L. Dove Consultant for: Allergan plc, P. Covington: None Declared

PTU-186 Baseline characteristics as a predictor of response to linaclotide (constella®) in patients with irritable bowel syndrome with constipation: a pooled analysis of 2 phase 3 trials: Abstract PTU-186 Table 1

<h3>Introduction</h3> In 2 Phase 3 trials in irritable bowel syndrome with constipation (IBS-C) (Trial 31, Trial 302), linaclotide 290 μg once-daily (Constella^®; LIN) treatment was superior to placebo (PBO) based on European Medicines Agency co-primary endpoints (rate of abdominal pain/discomfort responders [Trial 31: 54.8% vs 41.8%; Trial 302: 54.1% vs 38.5%; <i>P &lt; </i>0.001]; IBS degree-of-relief responders [Trial 31: 37.0% vs 18.5%; Trial 302: 39.4% vs 16.6%; <i>P &lt; </i>0.0001]). A potential association between baseline patient characteristics and likelihood of therapeutic response to LIN is unclear. <h3>Method</h3> This pooled analysis evaluated potential predictive value of baseline characteristics in 2 pivotal Phase 3 trials in IBS-C by comparing demographics and baseline symptoms (Table) for LIN 12-week non-responders vs responders, defined as: 1) abdominal pain/discomfort responders (≥30% reduction in abdominal pain and/or discomfort score [11-point scales], with neither worsening from baseline, for ≥6/12 weeks) and 2) IBS degree-of-relief responders (symptoms ‘considerably’ or ‘completely’ relieved for ≥6/12 weeks). <h3>Results</h3> The pooled analysis included 1602 patients (LIN, n = 805; PBO, n = 797). Baseline characteristics were similar for responders and non-responders in the LIN and PBO groups for both endpoints (Table 1). Abdominal discomfort scores and body mass index were also similar for responders and non-responders (not shown). <h3>Conclusion</h3> The baseline demographics and disease characteristics analysed did not predict treatment response to LIN or PBO in patients with IBS-C in the Phase 3 pivotal trials. <h3>Disclosure of interest</h3> C. Díaz Employee of: Almirall S. A., M. Falques Employee of: Almirall S. A., D. Vilardell Employee of: Almirall S. A., J. Fortea Employee of: Almirall S. A., J. Johnston Employee of: Ironwood Pharmaceuticals.

Carbon dioxide insufflation can significantly reduce toilet use after colonoscopy: a double-blind randomized controlled trial

Carbon dioxide (CO2) insufflation during colonoscopy can significantly decrease abdominal pain and bloating after the procedure, but its impact on the frequency and duration of toilet use remains unknown. The aim of this study was to assess the impact of CO2 insufflation on toilet use after screening colonoscopy. From 138 average-risk individuals who underwent screening colonoscopy during March to August 2013, 120 were enrolled and randomized to receive either CO2 or air insufflation at colonoscopy. Both the colonoscopist and participant were blinded to the type of gas used. Abdominal pain and distension were assessed using a visual analog scoring system. The frequency and duration of toilet visits during a 2-hour postcolonoscopy period were recorded using a radiofrequency identification system. Baseline characteristics were similar in both groups in terms of age, sex, and procedure time. In the 2 hours after colonoscopy, 50 participants (83 %) in the air group and 18 participants (30 %) in the CO2 group (P < 0.001) used the toilet at least once. The mean (± SD) duration of each toilet visit was 5.93 ± 4.65 minutes in the air group and 1.53 ± 2.84 minutes in the CO2 group (P < 0.001). The abdominal discomfort score was lower in the CO2 group than in the air group both at the end of the colonoscopy (P < 0.001) and 2 hours later (P < 0.001). Insufflation with CO2 can significantly reduce abdominal discomfort and toilet use after colonoscopy. Use of this technique may help reduce patient burden and allow more efficient use of space in the endoscopy unit.

Inhibition of gastric perception of mild distention by omeprazole in volunteers

To evaluate the effects of omeprazole on gastric mechanosensitivity in humans. A double lumen polyvinyl tube with a plastic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure (MDP) was determined after a 30-min adaptation period. Isobaric distensions were performed in stepwise increments of 2 mmHg (2 min each) starting from the MDP. Subjects were instructed to score feelings at the end of every step using a graphic rating scale: 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but significant; 5, severe discomfort; and 6, unbearable pain. After this first test, subjects received omeprazole (20 mg, after dinner) once daily for 1 wk. A second test was performed on the last day of treatment. No adverse effects were observed. Mean MDP before and after treatment was 6.3 ± 0.3 mmHg and 6.2 ± 0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pressure required to reach scores of 1 (P = 0.019) and 2 (P = 0.017) as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling < 1 at MDP, and mean (± SE) abdominal discomfort scores at MDP were 0.13 ± 0.09 and 0.04 ± 0.04, respectively. Mean scores induced by each MDP + 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 (mmHg) were 1.1 ± 0.3, 2.0 ± 0.4, 2.9 ± 0.5, 3.3 ± 0.4, 4.6 ± 0.3, 5.2 ± 0.3, 5.5 ± 0.2, 5.5 ± 0.3, 5.7 ± 0.3, and 5.4, respectively. After omeprazole, abdominal feeling scores for the same incremental pressures over MDP were 0.3 ± 0.1, 0.8 ± 0.1, 2.0 ± 0.4, 2.8 ± 0.4, 3.8 ± 0.4, 4.6 ± 0.4, 4.9 ± 0.3, 5.4 ± 0.4, 5.2 ± 0.6, and 5.0 ± 1.0, respectively. A significant decrease in feeling score was observed at intrabag pressures of MDP + 2 mmHg (P = 0.028) and + 4 mmHg (P = 0.013), respectively, after omeprazole. No significant score changes were observed at pressures ≥ MDP + 6 mmHg. Although the precise mechanisms are undetermined, the present study demonstrated that omeprazole decreases mechanosensitivity to mild gastric distension.

Probiotics and the irritable bowel syndrome: authors’ reply

Sirs, We appreciate that doctors Chassany and Matuchansky comment1 on our publication about probiotic supplementation in the irritable bowel syndrome (IBS).2 This study strengthens the findings from an earlier study showing that a multispecies probiotic significantly alleviates symptoms of IBS.3 We agree that complete validity for the health-related quality of life (HRQOL) questionnaire remains to be achieved. We do not, on the other hand, agree that the slight difference between the groups in baseline symptom severity creates a methodological concern, as baseline-correction (analysis of covariance with baseline as covariate) was used in the statistical analyses. Despite proper randomisation, it may, in clinical trials, unwittingly happen that groups differ for some variables, and it is a recommended and accepted procedure to correct for this by using appropriate statistics. Concerning end points, current recommendations on trial design recommend that trials should be based on one, or at most two, primary end points,4, 5 and that the primary efficacy end point should combine, in a global assessment, the key symptoms of IBS. A summary score, as the one used in our study, is one advocated outcome measure. A classification of patients into responders and non-responders based on the primary end point may additionally be done if the definition of a responder has been decided a priori. If this has not been done, it is not correct to analyse the proportion of responders. We are criticized for not citing the recent trial by Guyonnet et al.6 in the HRQL part of the Discussion: the results in that trial showed that the HRQL score improved similarly in both the probiotic group and the placebo group (P < 0.001), but no difference between the groups could be observed. As the placebo response in IBS is estimated to be up to 70%,7 within-group analysis cannot, in our opinion, be considered an appropriate method to evaluate the effect of a treatment in this syndrome. In the responder rate analysis, Guyonnet et al. saw a significant difference between the groups in the HRQOL abdominal discomfort score only half-way through the trial, but not at the end. The effect on HRQOL was consequently not particularly obvious, as the beneficial effect was noticed at 3 weeks, but it did not remain at the end of the study at 6 weeks. With reference to the magnitude of the improvement of the HRQOL bowel symptoms domain in our trial, the median change in the score was 0.62 in the probiotic group, and 0.37 in the placebo group (P for difference between groups = 0.045). The authors of the questionnaire8 suggest that a mean change of 0.5 on the 1–7 scale approximates the minimal important difference in questionnaire score, but we agree that the actual clinical significance of HRQOL improvements in general is a demanding question. Because of the lack of a biological marker, clinical trials in IBS remain challenging to plan, conduct and interpret. We thus see all debates that aim to improve methodological issues in IBS trials as welcome and valuable. Declaration of personal interests: K. Kajander and R. Korpela are employees of Valio Ltd, Finland. Declaration of funding interests: The study by Kajander et al. was funded by Valio Ltd and the Finnish Funding Agency for Technology and Innovation. The preparation of the manuscript of the study was funded in part by the Academy of Finland.

Baseline quality of life (QOL) as a predictor of tolerance to intraperitoneal (IP) chemotherapy for advanced epithelial ovarian cancer (EOC): A Gynecologic Oncology Group (GOG) study

5007 Background: A recent GOG randomized phase III trial demonstrated a 16 month improvement in survival for women with optimally debulked stage III EOC. Patients on the IP chemotherapy arm experienced a survival advantage but significantly worse toxicities, worse QOL during treatment, and more neurotoxicity (NTX) one year later, compared to those on the IV arm. We sought to determine whether baseline QOL and NTX and abdominal discomfort (AD) predict severity of IP treatment-related adverse effects and number of cycles completed. Methods: Three self-report QOL measures were utilized: the FACT-O (39 items), and FACT/GOG-NTX (11 items) and FACT/GOG-AD (4 items) subscales. Scoring was on a 5-point scale, with higher scores representing better QOL (FACT-O) whereas higher scores indicated worse symptoms (-NTX and -AD subscales). In addition to NTX and AD, we explored associations with fatigue. A logistic regression model was used for the analyses. Results: Of 205 patients randomly assigned to receive IP chemotherapy, 198 (97%) completed baseline QOL assessments, of whom 83 (42%) completed all 6 cycles and 16 (8%) completed none. Adjusting for age, performance status and residual disease, patients reporting higher baseline FACT-O and lower -NTX and -AD scores were more likely to complete more IP cycles. Categorizing FACT-O scores by quartiles (≤92, 93 to ≤108.8, 109 to ≤121.1, and &gt;121.1), patients in the lowest quartile were significantly less likely to complete 6 cycles of IP therapy (odds ratio [OR] = 4.46; 95% CI: 1.95–10.21, p &lt; 0.001). Higher FACT-O scores were also associated with less grade 3–4 fatigue (OR = 0.81 per 10 points; 95% CI: 0.67–0.99; p = 0.037); however, there was no relationship between baseline NTX and AD subscale scores and severity of physician-rated NTX and AD. Conclusions: Baseline patient-reported QOL and NTX and AD symptoms predict tolerance to IP chemotherapy. Patients with the poorest baseline QOL (FACT-O score &lt;92) were least likely to complete IP therapy. No significant financial relationships to disclose.

Is Carbon Dioxide as an Insufflation Agent for Double Contrast Barium Enema Still Worthwhile After a Same-day Flexible Sigmoidoscopy?

PURPOSE: The aim of the study was to evaluate the efficacy of a double-contrast barium enema (DCBE) with CO2 as a distending gas after a screening flexible sigmoidoscopy for reducing abdominal distension after an examination. PATIENTS AND METHODS: A total of 165 DCBEs for patients with positive faecal occult blood tests were randomly allocated to a CO2 group (n=83) and a control group (n=82) using air. Abdominal radiograph were taken before the DCBE, immediately following it, and 30 minutes later to determine residual bowel gas. The degree of abdominal discomfort was recorded using a scoring system. RESULTS: The patients in the CO2 group had significantly smaller amounts of residual gas 30 minutes after the DCBE than did the control group, both in the colon (P<0.02) and in the small intestine (P<0.001). There was significantly less abdominal distension after the DCBE in the CO2 group compared to the control group (P<0.001). The abdominal discomfort score at 30 minutes after CO2 correlated with the residual gas in the small intestine(r=0.390,P=0.003) but not in the colon(r=0.155,P=0.15). The quality of the images and the number of polyps detected did not differ between two groups. CONCLUSIONS: We concluded that using CO2 when administering a DCBE after a screening sigmoidoscopy was useful for relieving abdominal discomfort following the examination; furthermore, it did not impair the diagnostic ability of the DCBE. Asao, T. (2002). Clinical Radiology57, 488–491.

Effects of single oral dose administration of a hydantoin prostaglandin analogue BW 245C in man

Following an open pilot study, BW 245C, a hydantoin prostaglandin analogue, was given by mouth in an aqueous solution to six healthy volunteers. The subjects received BW 245C 50 and 150 μg and placebo on separate occasions according to a double blind randomised design. Heart rate, blood pressure and, using visual analogue scales, facial flushing, abdominal discomfort and headache, were measured before dosing, at 15 minute intervals after dosing for 2 hours and at 30 minute intervals for a further 2 hours. Platelet aggregation responses to ADP and to collagen were measured before dosing and at 15 minutes, 45 minutes, 2 hours and 4 hours after dosing. Cutaneous bleeding time was measured before and 45 minutes after dosing. 150 μg BW 245C produced significant (p < 0.05) facial flushing over the period from 15 to 120 minutes after dosing. Heart rate increased slightly but significantly (p < 0.05) in response to both doses of 245C only at 75 minutes after dosing. Systolic and diastolic blood pressures were unchanged by either dose of BW 245C. Platelet aggregation response to ADP were significantly (p < 0.05) inhibited only at 120 minutes after 150 μg BW 245C. Aggregation responses to collagen were significantly (p < 0.05) inhibited 45 and 120 minutes after 150 μg BW 245C and also at 120 minutes after 50 μg BW 245C. Bleeding time was unchanged in response to either dose of BW 245C. There was no change in headache or abdominal discomfort scores following either dose of BW 245C. Nausea was reported after 7 out of 12 administrations of BW245C but not after placebo. Nasal congestion was experienced by two subjects receiving 150 μg BW 245C and muscle tension and stiffness, especially of the jaw muscles, was also reported following administration of BW 245C but not of placebo. BW 245C is active when given by mouth and has similar pharmacodynamic effects to prostacyclin in man.