Amitiza (lubiprostone)
Company: Sucampo/Takeda
Approval Status: Approved January 2006
Treatment for: Constipation
Areas: Gastroenterology
| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |
General Information
Amitiza (lubiprostone) is an orally available, locally acting ClC-2 chloride channel activator, designed to increase the production of chloride-rich intestinal fluid without significantly affecting serum sodium or potassium concentrations. Increased intestinal fluid production has been shown to promote gastrointestinal motility.
Amitiza is specifically indicated for the treatment of adults with chronic idiopathic constipation, defined as low frequency or difficulty in stool passage potentially related to poor colonic motility.
Amitiza is supplied as a gelatin capsule for oral administration. Recommended initial dosing is 24 mcg twice daily, with food. Need for maintained dosing should be periodically assessed by patients and physicians.
Clinical Results
FDA Approval
Approval of Amitiza was based on 6 clinical trials: a phase II
trial, a pair of double-blind, placebo-controlled studies, and
three long term safety studies.
Phase II Trial
This dose-finding, double-blind, placebo-controlled, parallel-group
study was designed to investigate the efficacy of the drug in
promoting spontaneous bowel movements (SBMs). The trial enrolled
127 patients, who went through a 2 week drug-free baseline washout
and were than randomized to receive one of 3 regimens of the drug
(24 mcg once, twice, or thrice daily) or placebo for 3 weeks with
meals. Trial data indicated that all three regimens of the drug
significantly increased frequency of SBMs from baseline; there was
no significant difference in response between the treatment
groups.
Double Blind Trials
These identical-design, double blind, placebo controlled studies
were designed to investigate the efficacy of the drug in increasing
SBM frequency. A total of 479 patients went through a 2 week
drug-free washout/baseline, followed by randomization to receive
either 24 mcg Amitiza or placebo twice daily for 4 weeks. Trial
data indicated that subjects receiving the drug experienced
significantly more SBMs at the end of week 1 than placebo. Similar
results were observed for weeks 2-4, and no significant
"rebound-effect" relapse was noted following the
conclusion of treatment. Further, patients receiving the drug were
more likely to experience their first SBM within 24 hours of dosing
than placebo (56.7% vs. 36.9% for study 1; 62.9% vs. 31.9% for
study 2), and time to first SBM was reduced. Signs and symptoms of
constipation (including bloating, discomfort, poor stool
consistency and straining) were also reduced for subjects receiving
Amitiza.
Long-Term Safety Studies
Three long term open-label safety studies enrolled a combined 871
patients, who received 24 mcg Amitiza twice daily. The drug was
shown to significantly reduce abdominal bloating, abdominal
discomfort, and constipation severity over treatment periods
lasting 6-12 months.
Ongoing Study Commitments
- Deferred pediatric studies under PREA for the treatment of
chronic idiopathic constipation in pediatric patients ages 0 to 17
years.
Protocol Submission: by July 31, 2006
Study Start: by January 31, 2007
Final Report Submission: by January 31, 2008 - Perform a Phase IV study to assess the need for potential dose
adjustment in patients with renal impairment
Protocol Submission: by July 31, 2006
Study Start: by January 31, 2007
Final Report Submission: by January 31, 2008 - Perform a Phase IV study to assess the need for potential dose
adjustment in patients with hepatic impairment.
Protocol Submission: by July 31, 2006
Study Start: by January 31, 2007
Final Report Submission: by January 31, 2008
Side Effects
Adverse events associated with the use of Amitiza may include, but are not limited to, the following:
- Nausea
- Diarrhea
- Headache
- Abdominal Distension
- Abdominal Pain
- Flatulence
- Sinusitis
Mechanism of Action
Amitiza activates CIC-2, a chloride channel present in the apical membrane of the intestine in a protein kinase A-independent fashion, thereby increasing secretion of chloride-rich intestinal fluid. This in turn increases intestinal motility, reducing symptoms of chronic constipation and increasing stool passage. The drug has low systemic availability (below 10 pg/ml), limiting potential side effects.
Literature References
Lubiprostone: RU 0211, SPI 0211. Drugs in R&D 2005;6(4):245-8
Cuppoletti J, Malinowska DH, Tewari KP, Li QJ, Sherry AM, Patchen ML, Ueno R SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents. American Journal of Physiology: Cell Physiology 2004 Nov;287(5):C1173-83. Epub 2004 Jun 22
Additional Information
For additional information regarding Amitiza or Chronic Idiopathic Constipation, please visit the Amitiza web page.
The FDA drug information shown here is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.
