Cystic Fibrosis
Conditions
Keywords
digitoxin, inflammatory markers, cytokines, gene expression
Brief summary
This study will measure the inflammatory effects of digitoxin on IL-8 and neutrophil counts in induced sputum in stable Cystic Fibrosis (CF) patients and the pharmacokinetics of digitoxin in serum. Funding Source-FDA OOPD
Detailed description
The study will be conducted as a randomized, double blind, placebo-controlled, repeat dosing trial evaluating the effects of 28 days of digitoxin on IL-8 and neutrophil concentrations in induced sputum in subjects with mild to moderate cystic fibrosis lung disease. Twenty-four total patients will be randomized into 3 groups of 8 subjects each (0.05 mg or 0.1 mg digitoxin or a placebo).
Interventions
DRUGdigitoxin
0.05mg tabs, once daily for 28 days
OTHERplacebo
pill taken once daily for 28 days
Sponsors
National Jewish Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Male or female 18-45 years of age * Confirmed diagnosis of CF based on the following criteria:positive sweat chloride \> or = 60 mEq/liter (by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF * FEV1 \> or = 40% predicted value at screening * Weight \> 45 kg at Screening and Visit 1 (dosing) * Clinically stable with no evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation (see Appendix II) or treatment of a pulmonary exacerbation within the 14 days prior to Screen Visit. Subject may rescreen 14 days after they complete treatment for a pulmonary exacerbation, if healthy at that time. * Ability to perform Spirometry. * Ability to understand and sign a written informed consent and comply with the requirements of the study.
Exclusion criteria
* Use of an investigational agent within the 4-week period prior to Screen visit. * Use of a medication with anti-neutrophil or anti-inflammatory effect or those known to have an effect on inflammatory outcomes \[azithromycin, gentamicin, amikacin, colistin, ibuprofen, celecoxib, or other NSAIDs, prednisone or other corticosteroids(systemic or inhaled), such as Advair, cromolyn (Intal®), montelukast (Singulair®), zafirlukast (Accolate®), zileuton (Zyflo®), and any immunosuppressive agent within the 4 weeks prior to Visit #1, Day 1 and until their participation in the study ends (after Visit 6). See NOTE at end of exclusionary criteria for subjects on oral antibiotic therapy. * Use of topical nasal steroid products for at least 2 weeks prior to study drug administration and discontinued use until after the nasal cell collection at Day 28. * Inability or unwillingness to stop macrolide antibiotics 4 weeks prior to Day 1 until their participation in the study ends. Prior use of macrolide antibiotics, including those for maintenance therapy will not exclude the subject from participation. * History of significant cardiac disease or cardiac arrhythmia * Presence of an arrhythmia identified on screening ECG or 24 hour holter monitor * Pulmonary hypertension * History of significant cardiac disease or cardiac arrhythmia * Presence of a clinically significant arrhythmia identified on screening ECG or 24 hour holter monitor. * Pulmonary hypertension * Burkholderia species in sputum within 2 years or at Screen visit * Drugs known to interact with digitoxin including phenobarbital, amphotericin B, rifampicin, diltiazem, and verapamil or drugs that would potentiate potassium loss (certain diuretics or excessive laxative use, defined as more than twice daily use of miralax). * Unwillingness to use beta-agonists (or levalbuterol) prior to induced sputum procedures. * Oxygen saturation \< 92% on room air at Screen visit * Pregnant, breastfeeding, or unwilling to use an effective form of birth control for the duration of the study * History of significant hemoptysis \> or = 60cc per episode during the 30 days prior to Screening visit * Significant history of hepatic, cardiovascular, renal, neurological, hematologic, or peptic ulcer disease * SGOT (ALT) or SGPT (AST) \> 3 times the upper limit of normal at Screen, documented biliary cirrhosis, or portal hypertension * Creatinine \> 1.8 mg/dL at Screen * Inability to swallow pills * Potassium, serum \<3.3 mEq/L at screening * Known inability to produce sputum (if unable to expectorate, must be able to produce an induced sputum sample at screening). * Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the subject or the quality of the data NOTE: For subjects on continuous antibiotic therapy for at least 6 months one continuous antibiotic or alternating two different antibiotics, they can maintain their current therapy. If the subject is alternating between two different inhaled antibiotics each month, Visit 1 should coincide with the on cycle of one of the inhaled antibiotics for consistency during the treatment period. For subjects on alternate month TOBI®, colistin or Cayston therapy, the off cycle must coincide with the Treatment Phase of the study. Subjects should be scheduled for Screening Visit during their one-month on period, and may resume taking TOBI®, colistin or Cayston after completion of Visit 6 (Day 42) or early termination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | 42 days (Day 1 to Day 42) | The Il-8 measurements of sputum digitoxin levels for each group is shown for 5 days (Days 1, 14, 21, 28 and 42). |
| Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period). | 28 days (Day 28 minus Day 1) | Change in Il-8 values are expressed as a change in log 10 Il-8 pg/mL from Day 28 minus Day 1. |
| Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | 42 days (Day 1- Day 42) | The neutrophil counts were measured in the induced sputum of participants in each group on study 5 days (Days 1, 14, 21, 28 and 42). |
| Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period). | 28 days (Day 28 minus Day 1) | The change in log 10 neutrophil cell count from Day 28 minus Day 1 (during the treatment period) expressed as log (10\^4 neutrophil/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in C Reactive Protein (CRP) During Treatment. | Baseline and Day 28 | Median changes in CRP and IQR were assessed from serum samples collected at Visits 1,3, 4 and 5. |
| Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period. | Baseline and Day 28 | Median change in serum ESR (mm/hr) and IQR was calculated from Treatment Period (28 days). |
| Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42 | Digitoxin serum levels were drawn on Days 1 (pre-dose), 7, 14, 21 and 42. The range of digitoxin levels for each visit is listed and the number of subjects who had that level are marked by group (placebo, low dose and high dose). |
| Clinically Significant Alterations in ECG Readings | 28 days | Safety indices included an assessment for the number of clinically significant alterations in the subjects ECG readings from Day 1 to Day 28. |
| Clinically Significant Changes in the Microbiology of Sputum in Subjects | 28 days | Count of clinically significant changes in sputum microbiology during the Treatment phase (Day 1 to Day 28) to include any new acquisition of B. cepacia or new acquisition of any multiple resistant organism. |
| Number of CF Subjects With Microarray Results From Nasal Epithelial Cells to Measure the Effect of Digitoxin on Gene Expression. | Day 0 and Day 28 | Rhinoprobe was used to collect nasal epithelial cells. The cells were collected pre and post-treatment and placed in Trizol for RNA isolation then used to measure the effect of digitoxin on gene expression. The full set of microarray data has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). The accession number for that data is GSE76347 (data available Dec 2018). |
| Safety Indices Including Change in FEV1 in Stable CF Patients. | Baseline and Day 28 | Safety indices included changes in FEV1 (forced expiratory volume in 1 second), changes in WBC (white blood cell count), alterations in ECG and sputum microbiology. The median changes in FEV1 are reported. |
| Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Baseline and Day 42 | CFQ-R is a disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms. Developed specifically for use in patients with a diagnosis of cystic fibrosis. There are 9 Quality of life domains: physical, role/school, vitality, emotion, social, body image, eating, treatment burden, health perceptions and 3 symptom scales: weight, respiratory, and digestion. Scaling of items is done via 5 distinct 4-point Likert scales. Scores for each domain; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health. Based on clinician judgment of global clinical change, a moderate change was a standardized effect size of 0.50 units and an important change was a standardized effect size of 0.80 units evaluating pre- and post-treatment for CF exacerbation. Mean changes in CFQ-R Scores by Group were evaluated between Visit 6 and Visit 1, by Domain. |
| Change in WBC (White Blood Cell) Count by Group During Treatment Period | Baseline and Day 28 | Safety indices included changes in FEV1 (lung function), changes in WBC, alterations in ECG and sputum microbiology. There were no significant alterations in the ECG in any subjects over the course of the study. There were no subjects who acquired multiple resistant changes in microbiology of sputum and no acquisition of B. cepacia in any subjects. Therefore, these data were not analyzed. The median changes in FEV1 and median changes in WBC, ESR and CRP are reported. |
Countries
United States
Participant flow
Recruitment details
All participants were recruited from the Johns Hopkins University in Baltimore, Maryland. The first participant was enrolled on October 13, 2010 and the last participant was enrolled on May 6, 2014. All study visits were completed as of June 2014. There was a DSMB safety review prior to enrolling any subjects into the higher dose group (0.1 mg).
Pre-assignment details
Participants were all consented on a Johns Hopkins IRB approved consent form and screened 2 or 4 weeks prior to enrollment. Enrollment was contingent on meeting all inclusion/exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo given daily for 28 days
placebo: pill taken once daily for 28 days | 8 |
| Low Dose 0.05 mg Digitoxin low dose 0.05mg digitoxin given once daily for 28 days
digitoxin: 0.05mg tabs, once daily for 28 days | 8 |
| Higher Dose 0.1mg Digitoxin higher dose 0.1mg digitoxin daily for 28 days
digitoxin: 0.1mg pills, once daily for 28 days. | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Placebo | Low Dose 0.05 mg Digitoxin | Higher Dose 0.1mg Digitoxin | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Age, Continuous | 24.8 years | 23.5 years | 30.3 years | 26.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 24 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 8 | 5 / 8 | 6 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period).
Change in Il-8 values are expressed as a change in log 10 Il-8 pg/mL from Day 28 minus Day 1.
Time frame: 28 days (Day 28 minus Day 1)
Population: For change in Il-8 from Day 28 minus Day 1, a Kruskal-Wallis equality of populations rank was performed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period). | 0.13 log10 (pg/mL) |
| Low Dose 0.05 mg Digitoxin | Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period). | -0.13 log10 (pg/mL) |
| Higher Dose 0.1mg Digitoxin | Change in Il-8 (Interleukin 8) Levels From Day 28 Minus Day 1 (Treatment Period). | 0.04 log10 (pg/mL) |
Primary
Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period).
The change in log 10 neutrophil cell count from Day 28 minus Day 1 (during the treatment period) expressed as log (10\^4 neutrophil/mL).
Time frame: 28 days (Day 28 minus Day 1)
Population: The change in neutrophil cell count from Day 1 to Day 28 was performed using a Kruskal-Wallis equality of populations rank test. The cells counts are expressed as log 10 (neutrophil cell/mL).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period). | 0.19 log 10 (neutrophil cell/mL) |
| Low Dose 0.05 mg Digitoxin | Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period). | -0.26 log 10 (neutrophil cell/mL) |
| Higher Dose 0.1mg Digitoxin | Change in Neutrophil Cell Count Day 28 Minus Day 1 (Treatment Period). | -0.02 log 10 (neutrophil cell/mL) |
Primary
Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
The Il-8 measurements of sputum digitoxin levels for each group is shown for 5 days (Days 1, 14, 21, 28 and 42).
Time frame: 42 days (Day 1 to Day 42)
Population: Sputum was collected for Il-8 biomarkers on Days 1,14, 21, 28 during the treatment phase and at Day 42. Measures were compared between Baseline, Treatment and Recovery periods to determine if changes from baseline differed between placebo and the two doses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 28 | 4.66 log 10 (pg/mL) |
| Placebo | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 42 | 4.59 log 10 (pg/mL) |
| Placebo | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 21 | 5.08 log 10 (pg/mL) |
| Placebo | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 14 | 4.94 log 10 (pg/mL) |
| Placebo | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 1 | 4.59 log 10 (pg/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 28 | 4.79 log 10 (pg/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 1 | 4.96 log 10 (pg/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 14 | 4.89 log 10 (pg/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 42 | 4.74 log 10 (pg/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 21 | 4.77 log 10 (pg/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 42 | 4.97 log 10 (pg/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 1 | 5.04 log 10 (pg/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 21 | 5.17 log 10 (pg/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 28 | 5.20 log 10 (pg/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on IL-8 (Interleukin 8) in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | IL-8 Day 14 | 5.01 log 10 (pg/mL) |
Comparison: Measures were compared between Baseline, Treatment \& Recovery periods to determine if changes from baseline differed between placebo and the two digitoxin dose levels. Kruskal-Wallis equity of population rank test was performed on the changes Day 28 minus Day 1. To compare the change from baseline to treatment period between the two arms, a Wilcoxon rank sum test was performed. To determine whether induced sputum Il-8 returned to baseline at the final visit, a one sample sign test was performed.p-value: >0.05Wilcoxon (Mann-Whitney)
Primary
Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients.
The neutrophil counts were measured in the induced sputum of participants in each group on study 5 days (Days 1, 14, 21, 28 and 42).
Time frame: 42 days (Day 1- Day 42)
Population: Neutrophil cell counts were compared between Baseline, Treatment and Recovery periods to determine if changes from baseline differed between the placebo and the two digitoxin dose levels.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 28 | 2.71 log 10 (neutrophil cells/mL) |
| Placebo | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 21 | 2.86 log 10 (neutrophil cells/mL) |
| Placebo | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 1 | 2.58 log 10 (neutrophil cells/mL) |
| Placebo | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 14 | 2.89 log 10 (neutrophil cells/mL) |
| Placebo | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 42 | 2.55 log 10 (neutrophil cells/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 21 | 2.23 log 10 (neutrophil cells/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 1 | 2.82 log 10 (neutrophil cells/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 14 | 2.26 log 10 (neutrophil cells/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 28 | 2.16 log 10 (neutrophil cells/mL) |
| Low Dose 0.05 mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 42 | 2.06 log 10 (neutrophil cells/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 42 | 2.82 log 10 (neutrophil cells/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 28 | 2.77 log 10 (neutrophil cells/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 1 | 2.93 log 10 (neutrophil cells/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 21 | 2.88 log 10 (neutrophil cells/mL) |
| Higher Dose 0.1mg Digitoxin | Effect of Digitoxin on Neutrophil Counts in Induced Sputum in Stable Cystic Fibrosis (CF) Patients. | Day 14 | 2.71 log 10 (neutrophil cells/mL) |
Comparison: Baseline,Treatment and Recovery periods were compared to determine if changes from baseline differed between placebo and the two digitoxin doses.p-value: >0.05Wilcoxon (Mann-Whitney)
Secondary
Change in WBC (White Blood Cell) Count by Group During Treatment Period
Safety indices included changes in FEV1 (lung function), changes in WBC, alterations in ECG and sputum microbiology. There were no significant alterations in the ECG in any subjects over the course of the study. There were no subjects who acquired multiple resistant changes in microbiology of sputum and no acquisition of B. cepacia in any subjects. Therefore, these data were not analyzed. The median changes in FEV1 and median changes in WBC, ESR and CRP are reported.
Time frame: Baseline and Day 28
Population: Safety indices included changes in WBC during treatment for each group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Change in WBC (White Blood Cell) Count by Group During Treatment Period | -510.28 K/cu mm |
| Low Dose 0.05 mg Digitoxin | Change in WBC (White Blood Cell) Count by Group During Treatment Period | -0.98 K/cu mm |
| Higher Dose 0.1mg Digitoxin | Change in WBC (White Blood Cell) Count by Group During Treatment Period | -0.13 K/cu mm |
Secondary
Changes in C Reactive Protein (CRP) During Treatment.
Median changes in CRP and IQR were assessed from serum samples collected at Visits 1,3, 4 and 5.
Time frame: Baseline and Day 28
Population: All subjects had blood labs for CRP drawn on Visits 1,3,4 and 5. The changes in median CRP were calculated during the Treatment Period (28 days).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Changes in C Reactive Protein (CRP) During Treatment. | -0.20 mg/dL |
| Low Dose 0.05 mg Digitoxin | Changes in C Reactive Protein (CRP) During Treatment. | 0.05 mg/dL |
| Higher Dose 0.1mg Digitoxin | Changes in C Reactive Protein (CRP) During Treatment. | -0.05 mg/dL |
Secondary
Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period.
Median change in serum ESR (mm/hr) and IQR was calculated from Treatment Period (28 days).
Time frame: Baseline and Day 28
Population: All subjects had blood labs for ESR drawn on Visits 1,3,4 and 5. The changes in median ESR were calculated during the Treatment Period (28 days).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period. | -1.00 mm/hr |
| Low Dose 0.05 mg Digitoxin | Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period. | 3.50 mm/hr |
| Higher Dose 0.1mg Digitoxin | Changes in Erythrocyte Sedimentation Rate (ESR) During Treatment Period. | 0.00 mm/hr |
Secondary
Clinically Significant Alterations in ECG Readings
Safety indices included an assessment for the number of clinically significant alterations in the subjects ECG readings from Day 1 to Day 28.
Time frame: 28 days
Population: Count of clinically significant alterations in the ECG in all subjects during the Treatment Phase of the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Clinically Significant Alterations in ECG Readings | 0 participants |
| Low Dose 0.05 mg Digitoxin | Clinically Significant Alterations in ECG Readings | 0 participants |
| Higher Dose 0.1mg Digitoxin | Clinically Significant Alterations in ECG Readings | 0 participants |
Secondary
Clinically Significant Changes in the Microbiology of Sputum in Subjects
Count of clinically significant changes in sputum microbiology during the Treatment phase (Day 1 to Day 28) to include any new acquisition of B. cepacia or new acquisition of any multiple resistant organism.
Time frame: 28 days
Population: There were no significant changes in the microbiology of sputum in any subjects over the course of treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Clinically Significant Changes in the Microbiology of Sputum in Subjects | 0 participants |
| Low Dose 0.05 mg Digitoxin | Clinically Significant Changes in the Microbiology of Sputum in Subjects | 0 participants |
| Higher Dose 0.1mg Digitoxin | Clinically Significant Changes in the Microbiology of Sputum in Subjects | 0 participants |
Secondary
Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R).
CFQ-R is a disease-specific instrument designed to measure impact on overall health, daily life, perceived well-being and symptoms. Developed specifically for use in patients with a diagnosis of cystic fibrosis. There are 9 Quality of life domains: physical, role/school, vitality, emotion, social, body image, eating, treatment burden, health perceptions and 3 symptom scales: weight, respiratory, and digestion. Scaling of items is done via 5 distinct 4-point Likert scales. Scores for each domain; after recoding, each item is summed to generate a domain score and standardized. Scores range from 0 to 100, with higher scores indicating better health. Based on clinician judgment of global clinical change, a moderate change was a standardized effect size of 0.50 units and an important change was a standardized effect size of 0.80 units evaluating pre- and post-treatment for CF exacerbation. Mean changes in CFQ-R Scores by Group were evaluated between Visit 6 and Visit 1, by Domain.
Time frame: Baseline and Day 42
Population: Mean change in CFQ-R scores from Visit 1 to Visit 6, by domain.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Physical Domain | -5.21 mean change of scores on a scale | Standard Deviation 8.55 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Role Domain | 0.00 mean change of scores on a scale | Standard Deviation 7.72 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Vitality Domain | -2.08 mean change of scores on a scale | Standard Deviation 5.89 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Emotional Domain | -5.83 mean change of scores on a scale | Standard Deviation 12.57 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Social Domain | -2.08 mean change of scores on a scale | Standard Deviation 9.36 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Body Domain | 6.94 mean change of scores on a scale | Standard Deviation 14.47 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Eating Domain | -1.39 mean change of scores on a scale | Standard Deviation 11.01 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Treatment Domain | 1.39 mean change of scores on a scale | Standard Deviation 9.27 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Health Domain | 1.39 mean change of scores on a scale | Standard Deviation 9.27 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Weight Domain | 0.00 mean change of scores on a scale | Standard Deviation 0 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Respiratory Domain | -2.78 mean change of scores on a scale | Standard Deviation 13.61 |
| Placebo | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Digestion Domain | -9.72 mean change of scores on a scale | Standard Deviation 12.51 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Digestion Domain | 4.17 mean change of scores on a scale | Standard Deviation 10.18 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Physical Domain | -14.58 mean change of scores on a scale | Standard Deviation 17.11 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Eating Domain | -1.39 mean change of scores on a scale | Standard Deviation 3.93 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Health Domain | 4.17 mean change of scores on a scale | Standard Deviation 5.75 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Role Domain | -1.04 mean change of scores on a scale | Standard Deviation 5.34 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Body Domain | -4.17 mean change of scores on a scale | Standard Deviation 22.17 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Respiratory Domain | 2.78 mean change of scores on a scale | Standard Deviation 13.28 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Vitality Domain | 4.17 mean change of scores on a scale | Standard Deviation 6.3 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Treatment Domain | 6.94 mean change of scores on a scale | Standard Deviation 11.79 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Social Domain | -5.56 mean change of scores on a scale | Standard Deviation 6.64 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Emotional Domain | -5.00 mean change of scores on a scale | Standard Deviation 17.73 |
| Low Dose 0.05 mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Weight Domain | 12.50 mean change of scores on a scale | Standard Deviation 17.25 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Emotional Domain | 4.17 mean change of scores on a scale | Standard Deviation 13.3 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Social Domain | -4.17 mean change of scores on a scale | Standard Deviation 15.92 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Weight Domain | -0.00 mean change of scores on a scale | Standard Deviation 17.82 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Body Domain | 8.33 mean change of scores on a scale | Standard Deviation 11.5 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Eating Domain | -1.39 mean change of scores on a scale | Standard Deviation 3.93 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Treatment Domain | 5.56 mean change of scores on a scale | Standard Deviation 8.4 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Respiratory Domain | -6.94 mean change of scores on a scale | Standard Deviation 22.17 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Physical Domain | -2.60 mean change of scores on a scale | Standard Deviation 11.34 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Role Domain | 1.04 mean change of scores on a scale | Standard Deviation 8.26 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Health Domain | -4.17 mean change of scores on a scale | Standard Deviation 11.79 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Vitality Domain | 1.04 mean change of scores on a scale | Standard Deviation 20.62 |
| Higher Dose 0.1mg Digitoxin | Mean Change in Quality of Life Scores, for Each Domain, From Day 1 to Day 42 Using the Cystic Fibrosis Questionnaire Revised (CFQ-R). | Digestion Domain | -5.56 mean change of scores on a scale | Standard Deviation 16.8 |
Secondary
Number of CF Subjects With Microarray Results From Nasal Epithelial Cells to Measure the Effect of Digitoxin on Gene Expression.
Rhinoprobe was used to collect nasal epithelial cells. The cells were collected pre and post-treatment and placed in Trizol for RNA isolation then used to measure the effect of digitoxin on gene expression. The full set of microarray data has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). The accession number for that data is GSE76347 (data available Dec 2018).
Time frame: Day 0 and Day 28
Population: The full set of microarray data has been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). Results can be found under the accession number GSE76347. One subject's pair of specimens in the placebo group was not collected.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of CF Subjects With Microarray Results From Nasal Epithelial Cells to Measure the Effect of Digitoxin on Gene Expression. | 23 participants |
Secondary
Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients.
Digitoxin serum levels were drawn on Days 1 (pre-dose), 7, 14, 21 and 42. The range of digitoxin levels for each visit is listed and the number of subjects who had that level are marked by group (placebo, low dose and high dose).
Time frame: Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42
Population: Subjects had serum digitoxin levels drawn at Day 1 (pre-dose) with no levels observed, as expected. Digitoxin was drawn on Day 7, 14, 21 and 42 to determine the number of subjects with a detectable level of digitoxin (ng/mL) in serum by group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 11 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 13 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 5.6 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6.4 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6.9 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 7.8 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level none detected | 8 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 10 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 6.8 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 6.9 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 7.3 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 7.5 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 8.1 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 9.3 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 9.4 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level none detected | 8 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 10 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 11 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 12 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 13 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 14 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 15 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 4 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 5 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.4 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.5 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.9 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 7.5 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level none detected | 8 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 42, digitoxin level 5 ng/mL | 0 participants |
| Placebo | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 42, digitoxin level none detected | 8 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 8.1 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 42, digitoxin level 5 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level none detected | 5 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 15 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 7.3 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.5 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 5.6 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 10 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 7.5 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6.4 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.4 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 4 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6.9 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 9.3 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 11 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 7.8 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 7.5 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 42, digitoxin level none detected | 7 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level none detected | 7 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 12 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 5 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 10 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.9 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 11 ng/mL | 1 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 13 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 13 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 9.4 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 6.8 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level none detected | 3 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 14 ng/mL | 0 participants |
| Low Dose 0.05 mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 6.9 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 7.3 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 7.5 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 8.1 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 9.3 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.4 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 9.4 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level none detected | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level none detected | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 10 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.5 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 11 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 12 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 13 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 6.9 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 14 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 11 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 42, digitoxin level none detected | 8 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 15 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 6.9 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6.4 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 6.9 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 4 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 7.8 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 7.5 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level none detected | 3 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 10 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 7, digitoxin level 5.6 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 13 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 21, digitoxin level 5 ng/mL | 0 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 14, digitoxin level 6.8 ng/mL | 1 participants |
| Higher Dose 0.1mg Digitoxin | Pharmacokinetics (PK) of Digitoxin in Serum in Stable CF Patients. | Day 42, digitoxin level 5 ng/mL | 0 participants |
Secondary
Safety Indices Including Change in FEV1 in Stable CF Patients.
Safety indices included changes in FEV1 (forced expiratory volume in 1 second), changes in WBC (white blood cell count), alterations in ECG and sputum microbiology. The median changes in FEV1 are reported.
Time frame: Baseline and Day 28
Population: Median changes in FEV1 in L by group for the 28 days of treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Safety Indices Including Change in FEV1 in Stable CF Patients. | -0.00 liters |
| Low Dose 0.05 mg Digitoxin | Safety Indices Including Change in FEV1 in Stable CF Patients. | 0.10 liters |
| Higher Dose 0.1mg Digitoxin | Safety Indices Including Change in FEV1 in Stable CF Patients. | -0.02 liters |