Amitiza in Constipation Associated With PD (Parkinson's Disease)

Parkinson's disease (PD) affects about one million people in the United States. It is a
common neurological condition that is clinically defined by rigidity (muscle stiffness),
bradykinesia (slowness of movement) and tremor. Parkinson's Disease , however, reveals
numerous non-motor symptoms that have been underemphasized. Problematic symptoms include
varying degrees of dementia, psychosis, diminished assertiveness and confidence, general
fatigue, excessive daytime sleepiness, problems with blood pressure, sweating, and bladder,
and a common yet difficult to define sense of "not feeling well".

A commonly missed symptom in Parkinson's patients is constipation. Constipation can be
difficult to treat with current medications available and many are ineffective. Levodopa and
dopamine agonists drugs are useful for motor symptoms in Parkinson's Disease but have no
effect on constipation. Laxatives and enemas provide limited relief with bothersome side
effects. Even fewer drugs have been studied targeting the constipation problem specifically
in the Parkinson's Disease population. Lubiprostone (AMITIZA) is a new medication that has
been studied in the general population for the treatment of chronic constipation. It has been
shown to be a safe and effective medication with few side effects. Lubiprostone has not yet
been studied in the Parkinson's Disease population. We hope to show that this medication can
be safe and effective for constipation in PD patients as well.

Inclusion Criteria:

- 1. Subjects must be diagnosed with PD according to conventional criteria.

- 2. Subjects must report having constipation and fulfill Rome III criteria19 for
chronic constipation: at least 3 months, in the last 6 months with two or more of the
following: i. Less than 3 SBM's per week ii. Straining with defecation more than 25%
of the time iii. Lumpy or hard stools with defecation more than 25% of the time iv.
Sensation of incomplete evacuation with defecation more than 25% of the time v.
Sensation of anorectal obstruction or blockage with defecation more than 25% of the
time vi. Use of manual maneuvers to facilitate defecation more than 25% of the time

- 3. Patients will be encouraged to use only lubiprostone for constipation. If they use
any other agents they will need to record this use in their diary; any BM that occurs
within 24 hours of the other agent used will be recorded, but not be counted as a SBM.

- 4. Patients or patients' caretaker(s)/ legal guardian must be able to read,
understand, and accurately record data into the diary to guarantee full participation
in the study.

- 5. Patients over the age of 50 must have had a colonoscopy or sigmoidoscopy within 5
years.

- 6. Patients or patient's caretaker(s)/legal guardian must be willing and able to
provide informed consent before beginning the study.

Exclusion Criteria:

- Evidence of structural abnormality of the gastrointestinal tract or
diseases/conditions that affect bowel transit including gastric, small bowel or
colonic resection (appendectomy, cholecystectomy, benign polypectomy are allowed);
history of colon cancer, history of inflammatory bowel disease (Crohn's disease or
ulcerative colitis); insulin-dependent diabetes mellitus, history of Hirschsprung's
disease, progressive systemic sclerosis (scleroderma), anorexia nervosa; other
diseases or conditions that in the opinion of the investigator significantly affect
bowel transit. Subjects with constipation secondary to any other documented cause.

- Planned use of drugs or agents during pretreatment phase onward that affect
gastrointestinal motility and/ or prescription including laxatives including stool
softeners (patients experiencing significant constipation may use a laxative as rescue
medication if needed); antidiarrheals (in case of significant diarrhea loperamide may
be used if needed); antacids containing magnesium or aluminum salts (only calcium
containing ones are allowed); anticholinergics, antispasmodic agents (e.g., Librax,
Donnatal, dicyclomine); erythromycin and other macrolides; octreotide; ondansetron or
other 5-HT3 antagonists; opioids/narcotic analgesics; prokinetics (metoclopramide);
serotonin re-uptake inhibitors or tricyclic antidepressants (allowed if constant doses
for at least 1 month before treatment); calcium antagonists (allowed if constant doses
for at least 1 month before treatment).

- Subjects with any significant cardiovascular, liver, lung, renal, psychiatric or
neurological diseases (not including PD).

- Patients with previous allergic reaction or lack of tolerability to lubiprostone.

- Current or recent history (within 12 months) of drug or alcohol abuse.

- Pregnancy or breast feeding.

- Fertile women (defined as those who are not surgically sterile, are not >1 year
post-menopausal or who are not currently using or complying with a medically approved
method of contraception). Lubiprostone has not been studied in pregnant women and
should only be used during a pregnancy if the potential benefits justify the potential
risk to the fetus. Women should have a negative pregnancy test before beginning
treatment with lubiprostone and need to practice effective contraceptive measures