Table 4.
Characteristics of randomized controlled trials of alosetron in irritable bowel syndrome and efficacy outcomes
| Study | Treatment | Study duration | N | Population | Relief of abdominal pain | Relief of bloating | Global/overall IBS improvement | Stool frequency | Stool consistency | Urgency | Other efficacy assessments |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Alosetron vs placebo | |||||||||||
| Camilleri et al66 | 1, 2, 4, or 8 mg bid | 12 wk | 370 | Adults with IBS-D or -A (Rome I) | |||||||
| Women | 1 mg: + | NA/NR | NA/NR | All doses: + | All doses: + | All doses: + | NA/NR | ||||
| 2 mg: + | |||||||||||
| 4 mg: 0 | |||||||||||
| 8 mg: 0 | |||||||||||
| Men | All doses: 0 | NA/NR | NA/NR | All doses: 0 | All doses: 0 | All doses: 0 | NA/NR | ||||
| Bardhan et al67 | 0.1, 0.5, or 2 mg bid | 12 wk | 462 | Adults with IBS-D, -A, -C, or other IBS (Rome I) | |||||||
| All patients | 0.1 mg: 0 | NA/NR | NA/NR | 0.1 mg: 0 | NA/NR | NA/NR | 2 mg: + for diarrhea | ||||
| 0.5 mg: 0 | 0.5 mg: + in wk 1–2, 9–12 | ||||||||||
| 2 mg: + in wk 5–8, 9–12 | 2 mg: + 1 in wk 1–2, 9–12 | ||||||||||
| Women | 0.1 mg: 0 | NA/NR | NA/NR | 0.1 mg: 0 | 0.1 mg: ++ | NA/NR | 2 mg: + for diarrhea | ||||
| 0.5 mg: 0 | 0.5 mg: + in wk 1–2 | 0.5 mg: ++ | |||||||||
| 2 mg: + in wk 9–12 | 2 mg: + in wk 1–2 | 2 mg: ++; all at wk 1–2, 9–12 | |||||||||
| Men | All doses: 0 | NA/NR | NA/NR | 0.1 mg: 0 | 0.1 mg: 0 | NA/NR | All doses: 0 for diarrhea | ||||
| 0.5 mg: 0 | 0.5 mg: ++ in wk 1–2, 9–12 | ||||||||||
| 2 mg: + in wk 1–2 | 2 mg: ++ in wk 1–2, 9–12 | ||||||||||
| Camilleri et al68 | 1 mg bid | 12 wk | 647 | Women with IBS-D or -A (Rome I) | |||||||
| All patients | + overall and weekly in wk 2–12 | NA/NR | NA/NR | +++ weekly in wk 1–12 | +++ weekly in wk 1–12 | +++ weekly in wk 1–12 | NA/NR | ||||
| IBS-D | + overall | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | ||||
| IBS-A | 0 | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | ||||
| Camilleri et al69 | 1 mg bid | 12 wk | 626 | Nonconstipated womenwith IBS-D or -A (Rome I) | |||||||
| All patients | +++ overall | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | ||||
| IBS-D | +++ overall | 0 | NA/NR | +++ in wk 1–12 | +++ in wk 1–12 | ++ in wk 1–2; +++ in wk 3–12 | + for reduction of days with sensation of incomplete evacuation in mo 2, ++ at mo 3 | ||||
| Watson et al71,* | 1 mg bid | 12 wk | 1273 | Women with IBS-D or -A (Rome I) | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | + in IBS-D on all QOL subscales† in both studies* (except mental health subscale in Camilleri69) |
| Lembo et al70 | 1 mg bid | 12 wk | 801 | Nonconstipated women without satisfactory control of bowel urgency (Rome II) | NA/NR | NA/NR | +++ in wk 4, 8, and 12 | +++ | +++ | +++ | +++ for reduction of days with sensation of incomplete evacuation |
| Olden et al73 (Same cohort as Lembo et al70) | 1 mg bid | 12 wk | 801 | Nonconstipated women without satisfactory control of bowel urgency (Rome II) | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | NA/NR | +++ for overall satisfaction with treatment at 12 wk |
| Chey et al74 | 1 mg bid | 48 wk | 714 | Women with IBS-D or -A (Rome I) | |||||||
| IBS-D | ++ for 48 wk average | 0 | NA/NR | ++ | + | +++ | NA/NR | ||||
| IBS-D with greater urgency | ++ for 48 wk average | NA/NR | ++ | + | +++ | NA/NR | |||||
| Lembo et al75,‡ | 1 mg bid | 12 wk | 492 | Women with severe IBS-D (Rome II) | NA/NR | NA/NR | +++ at wk 4, 8, 12 | +++ | +++ | +++ | + for reduction of days with sensation of incomplete evacuation for 11 of 12 wk |
| 711 | Women with IBS-D without satisfactory control of bowel urgency (Rome II) | NA/NR | NA/NR | +++ at wk 4, 8, 12 | +++ | +++ | +++ | ++ for the % of subjects with ≤1 d of uncontrolled urgency at wk 1–2; +++ for wk 3–12 | |||
| Chang et al76 | 0.5, 1, 2, or 4 mg bid | 12 wk | 662 | Men with IBS-D (Rome I) | 0.5 mg: 0 1 mg: + at wk 5–12 2 mg: 0 4 mg: 0 |
All doses: 0 | NA/NR | All doses: 0 | All doses: +++ | All doses: 0 | 0 for reduction of days with sensation of incomplete evacuation |
| Krause et al (efficacy and safety)77 | 0.5 mg qd, 1 mg qd, or 1 mg bid | 12 wk | 705 | Women with severe IBS-D who had failed conventional therapy (Rome II) | All doses: + at each 4 wk interval (1–4, 5–8, 9–12) | NA/NR | All doses: + at wk 12 | All doses: ++ at each 4 wk interval (1–4, 5–8, 9–12) | All doses: +++ at each 4 wk interval (1–4, 5–8, 9–12) | 0.5 mg: + at wk 9–12 1 mg qd: + at wk 9–12 1 mg bid: 0 | All doses: ++ at each 4 wk interval (1–4, 5–8, 9–12) for normalization of bowel patterns |
| Nicandro et al (QOL)78 (same cohort as Krause et al77) | 0.5 mg qd, 1 mg qd, or 1 mg bid | 12 wk | 705 | Women with severe IBS-D who had failed conventional therapy (Rome II) | NA/NR | NA/NR | ++ all alosetron-treated subjects on overall treatment satisfaction | NA/NR | NA/NR | NA/NR | IBS-QOL 0.5 mg qd: + in 8/9 domains 1 mg qd: + in 5/9 domains 1 mg bid: + in 7/9 domains Reduction in lost work productivity 0.5 mg qd: + 1 mg qd: 0 1 mg bid: ++++ |
Notes:
†
QOL subscales: emotional health, sleep, energy, physical and social functioning, food/diet, role-physical, sexual relations, and mental health.
‡
Counted as a reanalysis of Lembo et al.70 Positive signs indicate significant improvement over placebo: + for P ≤ 0.05; ++ for P ≤ 0.01; +++ for P ≤ 0.001; ++++ for P ≤ 0.0001; 0 represents no statistically significant difference between active treatment and placebo.
Abbreviations: IBS, irritable bowel syndrome; IBS-A, irritable bowel syndrome with alternating diarrhea and constipation symptom predominance; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; NA/NR, not assessed or not reported; IBS-QOL, Irritable Bowel Syndrome Quality of Life Questionnaire; QOL, quality of life.