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. 2012 May 25;5:69–100. doi: 10.2147/CEG.S29023

Table 3.

Randomized controlled trials of alosetron in irritable bowel syndrome: study characteristics and efficacy outcomes

Study Diagnostic criteria Sample size, type of IBS,* dosage; analysis population Study type and duration Relief of abdominal pain with or without discomfort Relief of bloating and/or distension Effect on stool frequency Effect on stool consistency Effect on urgency Global or overall IBS improvement Other efficacy assessments
Camilleri et al18 Rome I Patients:
370 adults aged ≥ 18 yr with IBS-D or IBS-A; 67% women
Treatment: alosetron 1, 2, 4, 8 mg bid vs placebo
Analysis population:

  1. Women

  2. Men

 Randomized, DB, PC, dose-ranging, PG design; 12 wk treatment Relief of pain and discomfort

  1. +, for 1 mg bid (P = 0.015) and 2 mg bid (P = 0.023) in women; 0 for 4 or 8 mg bid in women

  2. 0, for all dosage strengths in men

 NA/NR

  1. All doses: +, P < 0.05

  2. 0

  1. All doses: +, P < 0.05

  2. 0

  1. All doses: +, P < 0.05

  2. 0

 NA/NR NA/NR
Bardhan et al19 Rome I Patients:
462 adults aged >18 yr with IBS-D (32.9%), IBS-A (32.3%), IBS-C (31.3%), or IBS other (3.5%), 73% women
Treatment: alosetron 0.1, 0.5, 2 mg bid vs placebo
Analysis population:

  1. Total

  2. Women

  3. Men

 Randomized, DB, PC, PG, design; 12 wk treatment Mean % of pain-free days (diary cards):
1. 2 mg bid:
+, P < 0.05 in wk 5–8 and 9–12 2. 2 mg bid:
+, P < 0.05 in wk 9–12 3. 0; VAS for pain and discomfort:

  1. + for 2 mg bid, P = 0.04

  2. 0

  3. 0

 NA/NR Diary cards:

  1. 0.5 and 2 mg bid: +, P < 0.05 in wk 1–2 and 9–12

  2. 0.5 and 2 mg bid: +, P < 0.05 in wk 1–2

  3. 2 mg bid: +, P < 0.05 in wk 1–2

  1. and

  2. 0.1, 0.5, and 2 mg bid: +, P < 0.002 in wk 1–2 and 9–12

  3. 0.5 and 2 mg bid: +, P < 0.002 in wk 1–2 and 9–12

 NA/NR NA/NR VAS for diarrhea:

  1. 2 mg bid: +, P = 0.03

  2. 2 mg bid: +, P = 0.033

  3. 0
Camilleri et al20 Rome I for last 6 mo Patients:
647 women aged ≥ 18 yr with IBS-D (71%), IBS-A (28%) for ≥ 6 mo; IBS-C (1%) although exclusionary
Treatment: alosetron 1 mg bid vs placebo		 Randomized, DB, PC, PG design; 12 wk treatment Proportion with adequate relief of pain and discomfort:
Overall: +, 41% alosetron, 29% placebo, CI 4.7–19.2;
IBS-D +; IBS-A 0;
Weekly results: +, P < 0.05 from wk 2–12;
Change in pain severity scores: +, P < 0.05 at mo 2 and 3		 NA/NR +, P < 0.001 each wk, wk 1–12 +, P < 0.001 each wk, wk 1–12 +, P < 0.001 each wk, wk 1–12 NA/NR NA/NR
Camilleri et al21 Rome I for last 6 mo Patients:
626 nonconstipated women aged ≥ 18 yr with IBS-D (71%), IBS-A (27%) for ≥ 6 mo; IBS-C (2%) although exclusionary
Treatment: alosetron 1 mg bid vs placebo
Analysis population:

  1. All patients

  2. IBS-D patients

 Randomized, DB, PC, PG, design; 12 wk treatment Proportion with adequate relief of pain and discomfort:

  1. Overall: 41% alosetron vs 26% placebo, P < 0.001; CI 7.8–22.5

  2. Overall: 43% alosetron vs 26% placebo, patients were responders for all 3 mo, P < 0.001; For each mo: +, P < 0.05; Weekly with significant benefit achieved by wk 4–12 +, P < 0.01

  1. NA/NR

  2. 0

 Weekly from wk 1–12

  1. NA/NR

  2. +; P < 0.001

 Weekly from wk 1–12

  1. NA/NR

  2. +, P < 0.001

 Weekly from wk 1–12

  1. NA/NR

  2. +, P < 0.01

  1. NA/NR

  2. NA/NR

 No significant differences in alosetron efficacy between IBS-D and IBS-A incomplete evacuation:

  1. NA/NR

  2. For mo 1: 0; For mo 2: +, P = 0.02; For mo 3: +, P = 0.009
Watson et al22 Rome I Patients:
1273 women aged ≥ 18 yr with IBS-D (71%) or IBS-A (27%) for ≥ 6 mo; IBS-C (2%) although exclusionary
Treatment: alosetron 1 mg bid vs placebo
*Primary efficacy reported in Camilleri et al, 2000 and 2001		 Randomized, DB, PC, PG design; 12 wk treatment See individual trials (Camilleri et al, 2000 and 2001) above See individual trials (Camilleri et al, 2000 and 2001) above See individual trials (Camilleri et al, 2000 and 2001) above See individual trials (Camilleri et al, 2000 and 2001) above See individual trials (Camilleri et al, 2000 and 2001) above NA/NR QOL: across both studies, alosetron resulted in significant improvement in IBS-D +, P < 0.05 on all scales (emotional health, sleep, energy, physical and social functioning, food/ diet, role-physical, and sexual relations), except mental health was improved for Camilleri et al, 2001 only
Lembo et al23 Rome II Patients:
801 women aged ≥ 18 yr, nonconstipated with IBS-D (98%) or IBS-A (2%), with lack of satisfactory control of bowel urgency (required to occur on ≥ 50% of days during 2 wk screening)
Treatment:
alosetron 1 mg bid vs placebo Randomized (2:1 ratio), DB, PC design; 12 wk treatment		 NA/NR NA/NR Median stool frequency: +, P < 0.001 Median stool consistency: +, P < 0.001 Median proportion of days with satisfactory control of urgency: +, P < 0.001 Proportion of responders: +, P < 0.001 at wk 4, 8, 12 Percentage of days with incomplete evacuation (lower): +, P < 0.001
Wolfe et al24 Rome I for at least 6 mo Patients:
859, aged ≥ 18 yr, with IBS-D or IBS-A for ≥ 6 mo, 74% women
Treatment:
alosetron 1 mg bid vs placebo		 Randomized (3:1 ratio), DB, PC design; 48 wk treatment NA/NR NA/NR NA/NR NA/NR NA/NR NA/NR Safety only
Olden et al25 Rome II Patients:
801 women aged ≥ 18 yr nonconstipated with IBS-D (98%) or IBS-A (2%) with lack of satisfactory control of bowel urgency (required to occur on ≥ 50% of days during 2 wk screening)
Treatment:
alosetron 1 mg bid vs placebo		 Randomized (2:1 ratio), DB, PC design; 12 wk treatment See Lembo et al, 2001 above See Lembo et al, 2001 above See Lembo et al, 2001 above See Lembo et al, 2001 above See Lembo et al, 2001 above See Lembo et al, 2001 above Overall satisfaction with treatment 12 wk: 69% alosetron, 45% placebo +, P < 0.001; significantly more patients taking alosetron were satisfied or very satisfied across 11 distinct medication attributes +, P < 0.001
Chey et al26 Rome I Patients:
714 women aged ≥ 18 yr with IBS-D (80%) or IBS-A (20%); same patients in Lembo et al, 2001
Treatment: alosetron 1 mg bid vs placebo
Analysis population:
1. IBS-D subgroup (n = 569) 2. IBS-D with more frequent urgency (urgency on ≥ 10 d of 14 d screening; n = 417)		 Randomized, DB, PC, PG design; 48 wk treatment 48 wk adequate pain and discomfort relief:

  1. +, P = 0.01

  2. +, P = 0.005

  1. 0

  2. NA/NR

 Rate of satisfactory control of stool frequency:

  1. +, P = 0.004

  2. +, P = 0.009

 Rates of satisfactory control of stool consistency:

  1. +, P < 0.014

  2. +, P < 0.012

 48 wk average satisfactory control of urgency:

  1. +, P < 0.001

  2. +, P < 0.001

 NA/NR NA/NR
Lembo et al27†

  1. Population A: Rome II

  2. Population B: Rome II

 Patients:

  1. Population A:

    492 women aged >18 yr with severe IBS-D (>3 mo of IBS symptoms); 89% IBS-D and 11% IBS-A

  2. Population B:

    711 women aged >18 yr (257 from Population A and 454 from Lembo et al, 2001) with IBS-D who lacked satisfactory control of bowel urgency ≥ 71% of the time during screening (≥ 10 of 14 d); 95% IBS-D and 5% IBS-A

Treatment: alosetron 1 mg bid vs placebo		 1. and 2.
Randomized, DB, PC design; 12 wk treatment		 NA/NR NA/NR

  1. +, P < 0.001

  2. +, P < 0.001

  1. +; P < 0.001

  2. +, P < 0.001

 Satisfactory control of urgency:

  1. +, P < 0.001

  2. +, P < 0.001

 GIS responders:

  1. +, P < 0.001 at wk 4, 8, 12

  2. +, P < 0.001 at wk 4, 8, 12

 Sense of incomplete evacuation improved:

  1. At 12 wk: +, P = 0.018

  2. For 11 of 12 wk: +; Diarrhea: Similar between treatment groups
Chang et al28 Rome I Patients:
662 men aged >18 yr with IBS-D (≥ 6 mo of IBS symptoms)
Treatment: alosetron 0.5, 1, 2, or 4 mg bid vs placebo		 Randomized, DB, PC, dose-ranging study; 12 wk treatment Average adequate relief of pain and discomfort in wk 5–12: +, P = 0.04 for alosetron 1 mg bid; 0 for other doses All doses:
0		 All doses:
0		 All doses: +, P < 0.001 All doses:
0		 NA/NR Incomplete evacuation:
0 Pain-free days: 0

  1. Krause et al (efficacy and safety)29

  2. Nicandro et al (QOL)30

 Rome II Patients:
705 women aged ≥ 18 yr with severe IBS-D (≥ 6 mo of symptoms of IBS) who had failed conventional therapy
Treatment: alosetron 0.5 mg qd, 1 mg qd, and 1 mg bid vs placebo		 Randomized, DB, PC design; 12 wk treatment

  1. Average adequate relief of pain and discomfort: +, for all 3 alosetron doses at each 4 wk interval (1–4, 5–8, and 9–12), P ≤ 0.038)

  2. NA/NR

  1. NA/NR

  2. NA/NR

  1. All alosetron doses: +, P ≤ 0.006 for each dose at each 4 wk assessment

  2. NA/NR

  1. All alosetron doses: +, P ≤ 0.001 for each dose at each 4 wk assessment

  2. NA/NR

  1. At wk 9–12: + for alosetron 0.5 and 1 mg qd, P < 0.05

  2. NA/NR

  1. Proportion of responders for IBS-GIS + for all 3 alosetron doses at wk 12: P ≤ 0.02; at wk 4: P ≤ 0.028; at wk 8: P ≤ 0.009

  2. Overall treatment satisfaction: +, P ≤ 0.003

  1. Normalization of bowel patterns: +, P ≤ 0.004 for all alosetron doses at each 4 wk assessment

  2. IBS-QOL questionnaire (9 symptom domains): improvements: +, except for domains of emotional and sleep with alosetron 1 mg qd; physical functioning with alosetron 1 mg qd and 1 mg bid; and sexual relations all alosetron groups; Work productivity time reductions: +, for alosetron 0.5 mg qd (P = 0.02) and 1 mg bid (P = 0.0001)

Notes:

*

According to predominant stool pattern, if available.

†

Counted as a reanalysis of Lembo et al, 2001. + Indicates significant improvement over placebo; 0 represents no statistically significant difference between active treatment and placebo.

If a study did not report on a particular assessment, it was noted as “not assessed.” If more than one population is assessed for a particular parameter, the populations are numbered (see sample size, type of IBS, dosage, analysis population column); subsequent efficacy values are presented to correspond to the population so designated.

Abbreviations: CI, confidence interval; DB, double-blind; GIS, global improvement scale; 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; PC, placebo-controlled; PG, parallel group; QOL, quality of life; VAS, visual analog scale.