Table 2.
Summary of randomized, controlled studies of asimadoline in patients with IBS.
| Study design and patient population | Treatment | Primary efficacy outcomes | Secondary efficacy outcomes | Safety |
|---|---|---|---|---|
| R, DB, PBO-C, CO [Delvaux et al. 2004] IBS (Rome II criteria) with pain threshold ⩽32 mmHg during first colonic distension attempt |
Asimadoline 0.5 mg 1 h prior to colonic distension attempt on Day 1 or 2, alternating with PBO (n = 20) | Pain intensity significantly decreased with asimadoline versus PBO (p = 0.04) Pain thresholds and compliance following colonic distension did not differ between groups (p = 0.2) |
Not evaluated | |
| R, DB, PBO-C [Szarka et al. 2007] Women with IBS (Rome II criteria) |
Asimadoline 0.5 mg prn up to 1.0 mg qid (n = 60) or PBO (n = 40) for 4 weeks | Mean decrease in pain severity from first daily dose to 2 h post-dose when patient had pain level ⩾30 mm on VAS did not differ between groups | Percentage of daily adequate relief of IBS pain and discomforta did not differ between groups and percentage of patients with adequate relief >50% of days with pain was comparable | AEs comparable between groups, except greater percentage of GI-related AEs with PBO |
| R, DB, PBO-C [Mangel et al. 2008] IBS-D, IBS-C, IBS-M (Rome II criteria) with a mean abdominal pain/discomfort severity score ⩾1.5 |
Asimadoline 0.15 mg (n = 149), 0.5 mg (n = 152), 1.0 mg (n = 144) bid, or PBO (n = 151) for 12 weeks |
Asimadoline 0.15, 0.5, 1.0 mg, versus PBO Total months patients had adequate relief of IBS pain or discomfortb during 3 months of tx: 33%, 37%, 37%, 33%, respectively Moderate pain or greater (score ⩾2.0): Asimadoline 0.5 mg and 1.0 mg versus PBO, 40% and 40% versus 23%, respectively (p = 0.006 and p = 0.005 versus PBO, respectively) Subgroups: IBS-D: 47% and 37% versus 20%, respectively (p = 0.01 and p = 0.05 versus PBO, respectively) IBS-M: 50% versus 28%, respectively (p = 0.02) IBS-C: no benefit with asimadoline |
Abdominal pain or discomfort scoresc: Increase from baseline in pain/discomfort-free days, asimadoline 0.5 mg versus PBO, 42.9% versus 18% (p = 0.001) in patients with IBS-D Stool consistency (Bristol Stool Scale) not improved from baseline in patients with IBS-D or IBS-M Daily stool frequency decreased from baseline to 3 months: asimadoline 0.5 mg versus PBO: 2.3 versus 0.3, p < 0.05 Sense of urgencyd decreased in patients with IBS-D during 3 months of tx Straininge not affected by asimadoline in patients with IBS-D or IBS-M Bloatingf significantly improved from baseline in patients with IBS-D with asimadoline 0.5 mg and 1.0 mg only during Month 2 |
Asimadoline 0.15, 0.5, 1.0 mg, versus PBO: Diarrhea: 13.4%, 5.9%, 11.1%, versus 7.9% Constipation: 12.8%, 10.5%, 7.6%, versus 4.6% Headache: 9.4%, 4.6%, 5.6%, versus 7.3% Nausea: 5.4%, 8.6%, 2.8%, versus 3.3% Sinusitis: 4.7%, 2.6%, 6.3%, versus 1.3% Abdominal pain: 5.4%, 4.6%, 4.2%, versus 4.0% |
Seven-point scale.
Adequate relief of IBS pain or discomfort evaluated by a weekly answer to the question, ‘In the past 7 days have you had adequate relief of your IBS pain or discomfort?’. Patients were considered to have adequate relief on a monthly basis if they answered ‘yes’ ⩾3 of 4 weeks per month. The total number of months that patients had adequate relief was calculated as a percentage of 3 months.
Scoring determined by answer to question, ‘Have you experienced abdominal pain or discomfort in the past 24 hours? If yes, how would you rate the maximum severity of abdominal pain or discomfort you have experienced in the past 24 hours? Mild, 1; Moderate, 2; Severe, 3.’.
Evaluated by the answer to the question, ‘Have you felt or experienced a sense of urgency in the past 24 hours?’.
Rating determined by the answer to the question, ‘Please rate the amount of straining you experienced with your stool in the past 24 hours. 1, no straining; 2, acceptable straining; 3, too much straining.’.
Evaluated by the answer to the question ‘Have you experienced bloating or abdominal distension in the past 24 hours?’.
AE, adverse event; bid, twice daily; CO, crossover; DB, double-blind; GI, gastrointestinal; IBS, irritable bowel syndrome; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; IBS-M, IBS alternating between constipation and diarrhea; IBS-QOL, Irritable Bowel Syndrome - Quality Of Life questionnaire; PBO, placebo; PBO-C, placebo-controlled; prn, as needed; qid, 4 times a day; R, randomized; tx, treatment; VAS, visual analogue scale.