Short Term Safety and Efficacy of Lubiprostone in Adults With Cystic Fibrosis

The purpose of this study is to determine the short term safety and effectiveness of lubiprostone when used for constipation in adults with cystic fibrosis.

Study Overview

• Status: Completed
• Conditions: Constipation; Cystic Fibrosis
• Intervention / Treatment: Drug: lubiprostone

Detailed Description

Cystic fibrosis (CF) affects about 30,000 people in the United States. It is caused by an absent or dysfunctional protein called CF transmembrane conductance regulator (CFTR) which functions as a chloride channel. Lubiprostone is a medication indicated for constipation that activates type 2 chloride channels (ClC-2) and has the potential to be an effective treatment for constipation in adults with CF. It has the potential to correct the underlying disorder by utilizing a chloride channel whose activity does not depend on CFTR. This project is a prospective open-label pilot study to examine the safety and effectiveness of lubiprostone when used in adults with CF with constipation. The specific aims are as follows: 1) Determine the effectiveness of lubiprostone for constipation in participants with CF, and 2) Determine the short term safety of lubiprostone in adults with CF. Data will also be collected to generate further information about the effect of lubiprostone on nutritional status.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women of all races
• 18 years of age or older at time of enrollment
• Diagnosis of cystic fibrosis
• History of constipation, as defined by the Rome III criteria, OR the requirement of chronic scheduled doses of a laxative, OR a score ≥1.5 on the Patient assessment of constipation symptoms (PAC-SYM)15 survey administered during the screening visit, OR a score of less than 3 on the Bristol Stool Scale (BSS) at the screening visit.

Exclusion Criteria:

• Current gastrointestinal (GI) obstruction
• History of GI obstruction requiring hospitalization within six months of enrollment
• Pregnancy or breastfeeding
• Hypersensitivity to lubiprostone or any of its components
• Serum creatinine >1.8 mg/dL at last annual visit
• Clinically significant liver disease, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3X upper limit of normal
• History of frequent hospital admissions for CF exacerbations (≥4 in the last 6 months)
• Currently registered on a lung transplant waiting list
• Women of capable of child-bearing who either refuse a pregnancy test, or are incapable or unwilling to use contraception during the protocol, or both.
• Any other condition, in the opinion of the investigators, that interferes with the ability of the participant to comply with study requirements, confers significant risk to the participant, or limits the ability of the participant to complete the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Spontaneous Bowel Movements Per Week	2-week run-in period, 2-weeks of treatment, 4-weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Assessment of Constipation Symptoms	The Patient Assessment of Constipation - Symptom (PAC-SYM) survey is a 1-page 12-item tool that measures a patient's assessment of constipation symptoms. The items are in Likert scale format and address the severity of stool, rectal and abdominal symptoms over the past 2 weeks. Items are scored on a scale of 0 to 4, with 4 indicating the most severe. To compute the overall score, the scores of the non-missing items are summed and this is divided by the total number of non-missing items (overall score range, 0 to 4).	2-week run-in period, 2 weeks of treatment, 4 weeks of treatment
Bristol Stool Scale Score	The Bristol Stool Scale is a scale used to rate the consistency of stool. Stool types are accompanied by a written description. There are seven types of stool that are scored from 1 to 7. A score of 1 or 2 indicates constipation; a score of 6 or 7, diarrhea.	2-week run-in period, 2 weeks of treatment, 4 weeks of treatment
Body Mass Index		baseline, 2 weeks of treatment, 4 weeks of treatment
Self Reported Adverse Effects at Each Study Visit	Adverse effects are problems reported by each study subject that they experienced during this clinical trial. Examples are headache and nausea. Study subjects were asked at each visit while on study drug to report any adverse affects that had occurred since the last visit.	During entire study period
Serum Sodium		baseline, 4 weeks
Serum Chloride		baseline and 4 weeks
Serum Potassium		baseline and 4 weeks
Serum Bicarb		baseline and 4 weeks
Serum BUN		baseline and 4 weeks
Serum Creatinine		baseline and 4 weeks
AST		baseline and 4 weeks
ALT		baseline and 4 weeks
Serum Calcium		baseline and 4 weeks
Serum Magnesium		baseline and 4 weeks
Serum Phosphate		baseline and 4 weeks
Serum Glucose		baseline and 4 weeks
Serum Vitamin D		baseline and 4 weeks
Serum Vitamin A		baseline and 4 weeks
Serum Vitamin E		baseline and 4 weeks
Serum Prealbumin		baseline and 4 weeks
Serum Albumin		baseline and 4 weeks

Collaborators and Investigators

• Sponsor: University of Arkansas
• Collaborators: Takeda Pharmaceuticals North America, Inc.
• Investigators: Principal Investigator: Catherine E. O'Brien, Pharm.D., University of Arkansas

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: June 25, 2008
• First Submitted That Met QC Criteria: June 26, 2008
• First Posted (Estimate): June 27, 2008

Study Record Updates

• Last Update Posted (Estimate): April 18, 2011
• Last Update Submitted That Met QC Criteria: March 14, 2011
• Last Verified: March 1, 2011

More Information

Terms related to this study

• Keywords: cystic fibrosis; constipation; lubiprostone; Constipation in adults with cystic fibrosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Signs and Symptoms, Digestive; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Constipation; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Lubiprostone
• Other Study ID Numbers: 76992