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Asimadoline and its potential for the treatment of diarrhea-predominant irritable bowel syndrome: a review.

Mangel AW, Hicks GA - Clin Exp Gastroenterol (2012)

Bottom Line: The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS.Furthermore, the scientific rationale for the use of asimadoline in the treatment of IBS is reviewed.Considering the high patient and societal burdens of IBS, new treatments for IBS represent therapeutic advances.

View Article: PubMed Central - PubMed

Affiliation: RTI Health Solutions, Research Triangle Park, NC.

ABSTRACT
Irritable bowel syndrome (IBS) is a multifactorial condition with principal symptoms of pain and altered bowel function. The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS. Asimadoline, to date, has shown a good safety profile and the target Phase III population - diarrhea-predominant IBS patients with at least moderate pain - was iteratively determined in a prospective manner from a Phase II dose-ranging study. The clinical data in support of this population are reviewed in this article. Furthermore, the scientific rationale for the use of asimadoline in the treatment of IBS is reviewed. Considering the high patient and societal burdens of IBS, new treatments for IBS represent therapeutic advances.

No MeSH data available.


Related in: MedlinePlus

Effects of asimadoline on pain scores in D-IBS patients with at least moderate pain at baseline: asimadoline (asi) and placebo were administered twice daily for up to 12 weeks. Pain scores were collected daily and averaged numerically on a weekly basis. Week 0 represents the 2-week baseline period. As is apparent, with 0.5 mg and 1.0 mg dose levels, a substantial reduction in pain occurred, compared with placebo. Copyright © 2008. Reproduced with permission from Alimentary Pharmacology & Therapeutics. Mangel AW, Bornstein JD, Hamm LR, et al. Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(2):239–249.Note:aP < 0.05; bP < 0.10.Abbreviation: D-IBS, diarrhea-predominant irritable bowel syndrome.
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f1-ceg-5-001: Effects of asimadoline on pain scores in D-IBS patients with at least moderate pain at baseline: asimadoline (asi) and placebo were administered twice daily for up to 12 weeks. Pain scores were collected daily and averaged numerically on a weekly basis. Week 0 represents the 2-week baseline period. As is apparent, with 0.5 mg and 1.0 mg dose levels, a substantial reduction in pain occurred, compared with placebo. Copyright © 2008. Reproduced with permission from Alimentary Pharmacology & Therapeutics. Mangel AW, Bornstein JD, Hamm LR, et al. Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(2):239–249.Note:aP < 0.05; bP < 0.10.Abbreviation: D-IBS, diarrhea-predominant irritable bowel syndrome.

Mentions: In the intent-to-treat population, asimadoline at doses of 0.15 mg, 0.5 mg, or 1.0 mg was given bid and no dose level distinguished itself from placebo (bid). Following the prospectively planned analysis scheme, numerically and statistically significant benefit was seen with all doses of asimadoline in patients with higher levels of baseline pain.57,69 One-third of the patients who entered the trial with the highest level of baseline pain showed excellent benefit on multiple endpoints. Similar benefit was seen in both genders, but efficacy was driven by D-IBS patients. Thus, the Phase IIb study identified a target population for progression into Phase III of male and female D-IBS patients who had more severe pain at baseline. For ease of recruitment into the Phase III program, the target population became D-IBS patients with at least moderate pain at baseline. Analyses of this population from the Phase IIb data yielded excellent efficacy results on pain scores (Figure 1), stool frequency (Figure 2), pain-free days, urgency, bloating, and adequate relief.57


Asimadoline and its potential for the treatment of diarrhea-predominant irritable bowel syndrome: a review.

Mangel AW, Hicks GA - Clin Exp Gastroenterol (2012)

Effects of asimadoline on pain scores in D-IBS patients with at least moderate pain at baseline: asimadoline (asi) and placebo were administered twice daily for up to 12 weeks. Pain scores were collected daily and averaged numerically on a weekly basis. Week 0 represents the 2-week baseline period. As is apparent, with 0.5 mg and 1.0 mg dose levels, a substantial reduction in pain occurred, compared with placebo. Copyright © 2008. Reproduced with permission from Alimentary Pharmacology & Therapeutics. Mangel AW, Bornstein JD, Hamm LR, et al. Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(2):239–249.Note:aP < 0.05; bP < 0.10.Abbreviation: D-IBS, diarrhea-predominant irritable bowel syndrome.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3278196&req=5

f1-ceg-5-001: Effects of asimadoline on pain scores in D-IBS patients with at least moderate pain at baseline: asimadoline (asi) and placebo were administered twice daily for up to 12 weeks. Pain scores were collected daily and averaged numerically on a weekly basis. Week 0 represents the 2-week baseline period. As is apparent, with 0.5 mg and 1.0 mg dose levels, a substantial reduction in pain occurred, compared with placebo. Copyright © 2008. Reproduced with permission from Alimentary Pharmacology & Therapeutics. Mangel AW, Bornstein JD, Hamm LR, et al. Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther. 2008;28(2):239–249.Note:aP < 0.05; bP < 0.10.Abbreviation: D-IBS, diarrhea-predominant irritable bowel syndrome.
Mentions: In the intent-to-treat population, asimadoline at doses of 0.15 mg, 0.5 mg, or 1.0 mg was given bid and no dose level distinguished itself from placebo (bid). Following the prospectively planned analysis scheme, numerically and statistically significant benefit was seen with all doses of asimadoline in patients with higher levels of baseline pain.57,69 One-third of the patients who entered the trial with the highest level of baseline pain showed excellent benefit on multiple endpoints. Similar benefit was seen in both genders, but efficacy was driven by D-IBS patients. Thus, the Phase IIb study identified a target population for progression into Phase III of male and female D-IBS patients who had more severe pain at baseline. For ease of recruitment into the Phase III program, the target population became D-IBS patients with at least moderate pain at baseline. Analyses of this population from the Phase IIb data yielded excellent efficacy results on pain scores (Figure 1), stool frequency (Figure 2), pain-free days, urgency, bloating, and adequate relief.57

Bottom Line: The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS.Furthermore, the scientific rationale for the use of asimadoline in the treatment of IBS is reviewed.Considering the high patient and societal burdens of IBS, new treatments for IBS represent therapeutic advances.

View Article: PubMed Central - PubMed

Affiliation: RTI Health Solutions, Research Triangle Park, NC.

ABSTRACT
Irritable bowel syndrome (IBS) is a multifactorial condition with principal symptoms of pain and altered bowel function. The kappa-opioid agonist asimadoline is being evaluated in Phase III as a potential treatment for IBS. Asimadoline, to date, has shown a good safety profile and the target Phase III population - diarrhea-predominant IBS patients with at least moderate pain - was iteratively determined in a prospective manner from a Phase II dose-ranging study. The clinical data in support of this population are reviewed in this article. Furthermore, the scientific rationale for the use of asimadoline in the treatment of IBS is reviewed. Considering the high patient and societal burdens of IBS, new treatments for IBS represent therapeutic advances.

No MeSH data available.


Related in: MedlinePlus