Lubiprostone for the Treatment of Chronic Idiopathic Constipation

A Phase 3, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lubiprostone for the Treatment of Chronic Idiopathic Constipation

The purpose of this study is to evaluate the efficacy and safety of oral administration of lubiprostone 24 μg twice daily (BID) for 4 weeks in participants with chronic idiopathic constipation (CIC) compared with placebo.

The drug being tested in this study is called lubiprostone. Lubiprostone is being tested to treat people who have chronic idiopathic constipation. This study will look at the frequency of spontaneous bowel movements (SBMs) in people who take lubiprostone compared to placebo.

The study will enroll approximately 204 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups, such that equal numbers of subjects will be in each treatment group-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

• Lubiprostone 24 μg
• Placebo (dummy inactive pill) - this is a capsule that looks like the study drug but has no active ingredient

All participants will be asked to take one capsule with breakfast and one capsule with dinner each day throughout the study. All participants will be asked to record each time they have a SBM and all details of each SBM (including the consistency of the stool and the difficulty they have in passing it) in a diary.

This multi-center trial will be conducted in Russia. The overall time to participate in this study is 8 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Inclusion Criteria:

1. In the opinion of the investigator, is capable of understanding and complying with protocol requirements.

2. The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. Has a history of constipation defined as having spontaneous bowel movement (SBM) frequency of less than 3 times per week on average for 6 months or longer and for whom the same SBM frequency is observed during the Screening Period.

4. Has had 1 or more of the symptoms associated with SBM (described below) for 6 months or longer at the start of Screening:

   1. Scybalum stool or hard feces in at least 1 out of every4 bowel movements.
   2. Sensation of incomplete evacuation in at least 1 out of every 4 bowel movements.
   3. Straining in at least 1 out of every 4 bowel movements.

5. Rarely has loose stools without the use of laxatives.

6. Is willing and able to keep a diary on his/her own and willing and able to complete a questionnaire.

7. Is male or female and aged 18 years or older, at the time of signing an informed consent.

8. A female participant of childbearing potential who is sexually active agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and 14 days after the last dose of study drug.

Exclusion Criteria:

1. Has received any investigational compound within 30 days prior to Screening.
2. Has received lubiprostone in a previous clinical study or as a therapeutic agent.
3. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
4. Has, in the judgment of the investigator, clinically significant abnormal hematological parameters of hemoglobin, hematocrit, or erythrocytes at Screening.
5. Has a history or clinical manifestations of significant mechanical obstruction (intestinal obstruction due to tumor, hernia etc).
6. Has a history of hypersensitivity or allergies to lubiprostone or any of its excipients.
7. Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the Screening Visit.
8. Is required to take excluded medications.
9. If female, is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
10. Participant whose constipation is considered to be due to drugs or to whom a prohibited concomitant medication has been administered.
11. Is having chronic constipation due to a secondary cause (medications, diabetes mellitus, hypothyroidism, depression, etc.)
12. Has sufficient criteria for irritable bowel syndrome (IBS) or functional defecation disorder.
13. SBM frequency is 3 or more per week.
14. SBM frequency has been less than 3 times per week for less than 6 months in duration or whose symptoms associated with SBM have been present for less than 6 months (hard feces, sensation of incomplete evacuation, or straining).
15. Received treatment with a rescue medication within 24 hours prior to the first dose on the morning of Day1: bisacodyl suppository, which is a standard laxative, glycerin enema, or any other rescue medication.
16. Has megacolon/megarectum or has received a diagnosis of intestinal pseudo-obstruction.
17. Has confirmed or suspected organic disorders of the large intestine (obstruction, stenosis, carcinoma, or inflammatory bowel disease). Organic disorders of the large intestine can be confirmed or ruled out using the results of enema X-ray examination or total colonoscopy performed in the previous 2 years. If the participant has no history or shows no current evidence of weight loss, anemia, or rectal bleeding, organic disorders may be ruled out based on the results of such testing performed in the past 3 years. Any participant in whom total colonoscopy has detected a polyp requiring treatment is excluded from this study .Note: Participant should not be screened unless at least 7 days have passed since an enema X-ray examination, total colonoscopy or sigmoidoscopy have been performed.
18. Has been hospitalized for gastrointestinal or abdominal surgery within 3 months prior to Screening.
19. Has a significant cardiovascular, liver, lung, kidney, neurological, or mental disease (including existing alcohol or drug abuse problem) or a systemic disease.
20. Has significant clinical findings or in whom a significant abnormality has been found in hematology test, serum chemistry, or urinalysis.
21. Participant in whom noncompliance with the study protocol (administration schedule, visit schedule, diary completion or other study procedure) is expected.
22. Has a history of malignant disease (except basal cell carcinoma) within 5 years prior to Screening.
23. Has any screening abnormal laboratory value that suggests a clinically significant underlying disease or condition that may prevent the participant from entering the study; or the participant has: creatinine >1.5 mg/dL, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN), or total bilirubin >2.0 mg/dL with AST/ALT elevated above the limits of normal values.
24. Participant who the investigator/subinvestigator has determined ineligible to participate in this study for any reason other than the above.