Original article
Safety and Tolerability of Tegaserod in Patients With Chronic Constipation: Pooled Data From Two Phase III Studies

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Background & Aims: Studies show that tegaserod effectively relieves the symptoms of chronic constipation/idiopathic constipation (CC). This pooled analysis assessed the safety and tolerability of tegaserod in a large dataset of CC patients. Methods: Adverse event (AE) data were pooled from 2 double-blind, placebo-controlled phase III trials of 12 weeks’ duration. Post hoc analysis was conducted for the most frequent AEs (incidence, ≥3%). Results: Eight hundred eighty-one, 861, and 861 patients received tegaserod 6 mg twice a day, 2 mg twice a day, or placebo, respectively. Most AEs were mild/moderately severe. AE incidence was similar for the tegaserod 6 mg and 2 mg twice a day (57.1% and 56.3%, respectively) and placebo groups (59.6%) and most frequent in the gastrointestinal system (tegaserod 6 mg twice a day, 25.8%; 2 mg twice a day, 22.5%; placebo, 24.6%). Headache, the most common AE, was slightly more frequent in the placebo group (tegaserod 6 mg twice a day, 11.0%; 2 mg twice a day, 10.1%; placebo, 13.2%). Diarrhea (generally transient and resolved with continued treatment) was the only AE with a statistically significant difference between groups (tegaserod 6 mg twice a day 6.6% vs placebo 3.0%, P = .0005). Serious AE incidence (1.4% overall) was comparable across treatment groups, although abdominal surgery was less common in the combined tegaserod (0.5%) than the placebo group (1.0%). Discontinuation as a result of AEs was slightly higher in tegaserod 6 mg twice a day patients (5.7%; 2 mg twice a day, 3.3%; placebo, 3.7%), mainly because of diarrhea. Laboratory and electrocardiogram parameters were comparable across groups. Conclusions: Tegaserod is well tolerated by patients with CC during 12 weeks of treatment.

Section snippets

Study Design and Patient Characteristics

Two phase III double-blind, randomized, placebo-controlled studies have been described extensively in the primary reports.30, 31 Both studies were performed in accordance with the Declaration of Helsinki and the US21 Code of Federal Regulations regarding patient consent and after institutional review board approval. Because the 2 studies were almost identical in design and inclusion criteria, pooling the data at the patient level was considered appropriate. The evaluations reported here were

Patient Demographics

A total of 3587 patients were screened for participation in the 2 phase III trials, and 2612 were randomized. Of the patients who received study medication, 881 received tegaserod 6 mg twice a day, 861 received tegaserod 2 mg twice a day, and 861 received placebo (Figure 2). The demographic characteristics of the patients were similar across the treatment groups (Table 1). Approximately 88% of patients were women, 91% were white, and the mean age was 47 years. All groups were comparable in

Discussion

This pooled analysis of safety and tolerability data from 2 randomized, placebo-controlled trials in patients with CC provided a large dataset (2603 patients), enabling a thorough investigation of the safety and tolerability of tegaserod. A high proportion of patients (83.2%) completed the studies, and this rate is consistent with that observed with tegaserod in IBS-C trials (ranging between 76%–93%).33, 35, 39

The overall incidences of AEs and SAEs were comparable for the placebo and both

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