Hans Graffner

Treatment of joint pain in Crohn's patients with budesonide controlled ileal release

1. Joint pain is a frequent manifestation of Crohn’s disease. Budesonide controlled ileal release (CIR) is a predominantly topically acting glucocorticosteroid, which is effective in treating active ileal or ileocaecal Crohn’s disease.

A3309, an Ileal Bile Acid Transport (IBAT /ASBT) Inhibitor, Significantly Improved Stool Frequency and Other Constipation-Related Complaints in Adults With Chronic Constipation: Data From an 8-Week, Randomized, Double-Blind, Placebo-Controlled Study

and symptoms while subjects were at their highest dose (last 7 days of treatment period) versus placebo, adjusting for corresponding baseline values. Results. All 30 patients completed the study. 15 pts (7P, 8 PLA) had moderately severe autonomic neuropathy. P was well tolerated; mild-moderate, predominantly cholinergic side effects, were more common (p = 0.07) with P (11pt) than placebo (5pt). Compared to placebo, P accelerated colonic transit (GC24, p = 0.004), increased stool frequency (p = 0.02), reduced stool consistency (p= 0.004), and improved ease of passage (p=0.04). However, no significant treatment effects relative to placebo were detected in gastric emptying or small intestinal transit. Conclusions. P accelerated colonic transit and improved bowel symptoms in constipated patients with diabetes mellitus. Longer studies evaluating the effects of P on symptoms in DM and constipation are necessary. Supported by PO1 DK68055.

Effects of A3309, an Ileal Bile Acid Transporter Inhibitor, on Colonic Transit and Symptoms in Patients with Functional Constipation

3OBJECTIVES: Delivery of bile acid (BA) to the colon stimulates propulsive motility and fl uid secretion. The objective of this study was to examine gastrointestinal (GI) transit effects of A3309, a small molecule inhibitor of the ileal BA transporter, in patients with functional constipation (FC). METHODS: In a double-blind, placebo-controlled study of 36 female FC patients randomized to placebo, 15 mg A3309, or 20 mg A3309 administered orally once daily for 14 consecutive days, we assessed GI and colonic transit, stool characteristics, symptoms of constipation, fasting serum C4 (7 α -hydroxy4-cholesten-3-one) (surrogate of BA synthesis and malabsorption), and fasting serum total and low-density lipoprotein (LDL) cholesterol (surrogates of inhibition of BA absorption). Following the intention-to-treat paradigm, we used analysis of covariance to assess the overall treatment effects and Dunnett ’ s test for pairwise comparisons. RESULTS: Overall colonic transit (geometric center at 24 h) was signifi cantly accelerated with 20 mg A3309 compared with placebo (overall effect, P = 0.059; A3309 15 mg, P = 0.18; and A3309 20 mg, P = 0.04). Colonic transit at 48 h was signifi cantly accelerated with both A3309 dosages (overall effect, P < 0.001; A3309 15 mg, P = 0.002; and A3309 20 mg, P < 0.001). Signifi cantly looser stool consistency was noted with both A3309 dosages compared with placebo ( P < 0.005). Signifi cant effects of A3309 on constipation rating, ease of stool passage, and reduction of straining were also detected. The most common side effect was lower abdominal cramping / pain. A3309 treatment signifi cantly and reversibly increased fasting C4 (A3309 15 mg, P = 0.05; A3309 20 mg, P < 0.01) but did not affect fasting total and LDL cholesterol. CONCLUSIONS: A3309 accelerates colonic transit and loosens stool consistency in FC patients.