Linaclotide
An exciting new medication near approval
These last few years have been exciting for patients with gastrointestinal disorders. There have been many new constipation medications under development or under intense investigation to treat constipation. Lubiprostone (trade name Amitiza) is a recent and first FDA approved treatment for chronic constipation and also a form of irritable bowel syndrome.
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Likewise, linaclotide is a drug that is undergoing serious tests in patients to see if it can relieve constipation. As of early 2009, a phase 2 clinical trial was completed in a small population showing benefits for patients with constipation. Clinical trials are the standard by which medications are approved or not approved under the Federal Drug Administration (FDA). There are 3 phases in order of increasing difficulty from 1 to 3. A phase 2 trial is conducted small populations of patients.
A positive Phase II study
The phase 2 study that was completed enrolled 42 adults with chronic constipation. Each adult received either a regular drug or a placebo (a non-active substance) without knowing ahead of time which one was which. The 8 days followng administration of constipation medication, data was collected on patients regarding the frequency and volume of bowel movements. Results showed that patients who had taken linaclotide had a statistically significant increase in number of bowel movements. Moreover, these patients reported less straining and softer stools. The positive effects of the medication seemed to increase with dosage also.
Upcoming Phase III
Linaclotide is a constipation medication that has not only completed several phase 2 studies, but has also been evaluated in a phase 3 trial, as well as several other phase 2 trials. Since linaclotide has only completed phase 2 trials, it is not yet ready for the average consumer.
A compound with a novel mode of action
Is there a reason consumers should be very excited about linaclotide? Yes, there is a good scientific reason. Linaclotide is a very novel constipation medication that acts on the gut in a unique way when compared to existing laxatives or even lubiprostone. Any constipation medication has what is called a "mode of action". For example, osmotic agents draw water out by virtue of their physical properties, whereas lubiprostone activates calcium channels in gut cells. Linaclotide is a stimulator of yet another cellular sensor called a guanylate cyclase c receptor. The short story is that stimulation of this sensor causes water to be secreted into the gut, which lubricates and stimulates intestinal movement of stool.
Hope for patients
The reason why physicians and patients are excited is because a drug with a new mode of action means a new way to attack constipation. Perhaps patients who don't respond to traditional laxatives and lubiprostone will response to this entirely new drug. Perhaps the clinical trials will reveal that dosing with two kinds of constipation medications will be even more effective. These are speculative thoughts, but reflect the underlying reason for the kind of excitement many scientists and doctors feel about drugs with novel modes of action.
Sources:
Fox-Orenstein et al, Update on constipation: One treatment does not fit all, Cleveland Clinic Journal of Medicine, 2008; 75(11):813-824
Muller-Lissner, The Pathophysiology, Diagnosis, and Treatment of Constipation, Deutsches Arzteblatt International, 2009; 106(25):424-32