Constipation, Cystic Fibrosis
Conditions
Keywords
constipation, cystic fibrosis, lubiprostone, Constipation in adults with cystic fibrosis
Brief summary
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.
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.
Interventions
DRUGlubiprostone
lubiprostone 24 microgram capsule taken twice daily for 4 weeks
Sponsors
Takeda Pharmaceuticals North America, Inc.
University of Arkansas
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Spontaneous Bowel Movements Per Week | 2-week run-in period, 2-weeks of treatment, 4-weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bristol Stool Scale Score | 2-week run-in period, 2 weeks of treatment, 4 weeks of treatment | 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. |
| Body Mass Index | baseline, 2 weeks of treatment, 4 weeks of treatment | — |
| Self Reported Adverse Effects at Each Study Visit | During entire study period | 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. |
| 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 | — |
| Patient Assessment of Constipation Symptoms | 2-week run-in period, 2 weeks of treatment, 4 weeks of treatment | 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). |
| 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 | — |
| ALT | baseline and 4 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lubiprostone 24 micrograms twice daily | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Did not meet eligibility criteria | 2 |
Baseline characteristics
| Characteristic | Lubiprostone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Age Continuous | 26 years STANDARD_DEVIATION 5.4 |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Number of Spontaneous Bowel Movements Per Week
Time frame: 2-week run-in period, 2-weeks of treatment, 4-weeks of treatment
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Number of Spontaneous Bowel Movements Per Week | Baseline period | 9.7 bowel movements | Standard Deviation 5.7 |
| Lubiprostone 24 Mcg Twice Daily | Number of Spontaneous Bowel Movements Per Week | 2 weeks | 10.8 bowel movements | Standard Deviation 5.1 |
| Lubiprostone 24 Mcg Twice Daily | Number of Spontaneous Bowel Movements Per Week | 4 weeks | 8.8 bowel movements | Standard Deviation 2.9 |
Secondary
ALT
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | ALT | Baseline | 25.1 U/L | Standard Deviation 16.7 |
| Lubiprostone 24 Mcg Twice Daily | ALT | 4 weeks | 23.8 U/L | Standard Deviation 14.5 |
Secondary
AST
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | AST | Baseline | 20.6 U/L | Standard Deviation 11.1 |
| Lubiprostone 24 Mcg Twice Daily | AST | 4 weeks | 17.5 U/L | Standard Deviation 3.9 |
Secondary
Body Mass Index
Time frame: baseline, 2 weeks of treatment, 4 weeks of treatment
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Body Mass Index | Baseline | 24.0 kg/m^2 | Standard Deviation 2.8 |
| Lubiprostone 24 Mcg Twice Daily | Body Mass Index | 2 weeks | 24.0 kg/m^2 | Standard Deviation 2.5 |
| Lubiprostone 24 Mcg Twice Daily | Body Mass Index | 4 weeks | 24.3 kg/m^2 | Standard Deviation 2.5 |
Secondary
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.
Time frame: 2-week run-in period, 2 weeks of treatment, 4 weeks of treatment
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Bristol Stool Scale Score | Baseline | 3.4 scores on a scale | Standard Deviation 1.1 |
| Lubiprostone 24 Mcg Twice Daily | Bristol Stool Scale Score | 2 weeks | 3.6 scores on a scale | Standard Deviation 0.8 |
| Lubiprostone 24 Mcg Twice Daily | Bristol Stool Scale Score | 4 weeks | 3.3 scores on a scale | Standard Deviation 1.1 |
Secondary
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).
Time frame: 2-week run-in period, 2 weeks of treatment, 4 weeks of treatment
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Patient Assessment of Constipation Symptoms | Baseline | 1.18 scores on a scale | Standard Deviation 0.56 |
| Lubiprostone 24 Mcg Twice Daily | Patient Assessment of Constipation Symptoms | 2 weeks | 0.54 scores on a scale | Standard Deviation 0.27 |
| Lubiprostone 24 Mcg Twice Daily | Patient Assessment of Constipation Symptoms | 4 weeks | 0.44 scores on a scale | Standard Deviation 0.36 |
Secondary
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.
Time frame: During entire study period
Population: Participants who completed the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Self Reported Adverse Effects at Each Study Visit | 2 weeks | 5 participants |
| Lubiprostone 24 Mcg Twice Daily | Self Reported Adverse Effects at Each Study Visit | 4 weeks | 3 participants |
Secondary
Serum Albumin
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Albumin | Baseline | 4.3 g/dL | Standard Deviation 0.3 |
| Lubiprostone 24 Mcg Twice Daily | Serum Albumin | 4 weeks | 4.3 g/dL | Standard Deviation 0.2 |
Secondary
Serum Bicarb
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Bicarb | Baseline | 23.8 nmol/L | Standard Deviation 4 |
| Lubiprostone 24 Mcg Twice Daily | Serum Bicarb | 4 weeks | 25.2 nmol/L | Standard Deviation 3.3 |
Secondary
Serum BUN
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum BUN | Baseline | 13.0 mg/dL | Standard Deviation 4.6 |
| Lubiprostone 24 Mcg Twice Daily | Serum BUN | 4 weeks | 12.7 mg/dL | Standard Deviation 3.3 |
Secondary
Serum Calcium
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Calcium | Baseline | 9.3 mg/dL | Standard Deviation 0.3 |
| Lubiprostone 24 Mcg Twice Daily | Serum Calcium | 4 weeks | 9.3 mg/dL | Standard Deviation 0.2 |
Secondary
Serum Chloride
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Chloride | Baseline | 103.0 nmol/L | Standard Deviation 3.9 |
| Lubiprostone 24 Mcg Twice Daily | Serum Chloride | 4 weeks | 104.3 nmol/L | Standard Deviation 3.4 |
Secondary
Serum Creatinine
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Creatinine | Baseline | 0.79 mg/dL | Standard Deviation 0.15 |
| Lubiprostone 24 Mcg Twice Daily | Serum Creatinine | 4 weeks | 0.84 mg/dL | Standard Deviation 0.1 |
Secondary
Serum Glucose
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Glucose | Baseline | 150.3 mg/dL | Standard Deviation 101.9 |
| Lubiprostone 24 Mcg Twice Daily | Serum Glucose | 4 weeks | 131.8 mg/dL | Standard Deviation 83.3 |
Secondary
Serum Magnesium
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Magnesium | Baseline | 2.0 mg/dL | Standard Deviation 0.3 |
| Lubiprostone 24 Mcg Twice Daily | Serum Magnesium | 4 weeks | 2.0 mg/dL | Standard Deviation 0.2 |
Secondary
Serum Phosphate
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Phosphate | Baseline | 3.8 mg/dL | Standard Deviation 0.6 |
| Lubiprostone 24 Mcg Twice Daily | Serum Phosphate | 4 weeks | 3.7 mg/dL | Standard Deviation 0.5 |
Secondary
Serum Potassium
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Potassium | Baseline | 4.4 nmol/L | Standard Deviation 0.4 |
| Lubiprostone 24 Mcg Twice Daily | Serum Potassium | 4 weeks | 4.4 nmol/L | Standard Deviation 0.2 |
Secondary
Serum Prealbumin
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Prealbumin | Baseline | 22.6 mg/dL | Standard Deviation 3.3 |
| Lubiprostone 24 Mcg Twice Daily | Serum Prealbumin | 4 weeks | 21.5 mg/dL | Standard Deviation 6.1 |
Secondary
Serum Sodium
Time frame: baseline, 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Sodium | Baseline | 137.4 nmol/L | Standard Deviation 2.8 |
| Lubiprostone 24 Mcg Twice Daily | Serum Sodium | 4 weeks | 139.2 nmol/L | Standard Deviation 3.6 |
Secondary
Serum Vitamin A
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Vitamin A | 4 weeks | 42.7 ug/dL | Standard Deviation 23.3 |
| Lubiprostone 24 Mcg Twice Daily | Serum Vitamin A | Baseline | 41.3 ug/dL | Standard Deviation 14.6 |
Secondary
Serum Vitamin D
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Vitamin D | Baseline | 25.3 ng/mL | Standard Deviation 15.9 |
| Lubiprostone 24 Mcg Twice Daily | Serum Vitamin D | 4 weeks | 25.3 ng/mL | Standard Deviation 18.4 |
Secondary
Serum Vitamin E
Time frame: baseline and 4 weeks
Population: Participants who completed the study
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lubiprostone 24 Mcg Twice Daily | Serum Vitamin E | Baseline | 6.6 mg/L | Standard Deviation 3.4 |
| Lubiprostone 24 Mcg Twice Daily | Serum Vitamin E | 4 weeks | 7.7 mg/L | Standard Deviation 6.1 |