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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
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | low dose 0.05mg digitoxin given once daily for 28 days |
|
| 2 | Active Comparator | higher dose 0.1mg digitoxin daily for 28 days |
|
| 3 | Placebo Comparator | placebo given daily for 28 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| digitoxin | Drug | 0.05mg tabs, once daily for 28 days |
| |
| digitoxin |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 42 days (Day 1 to Day 42) |
| 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. | 28 days (Day 28 minus Day 1) |
| 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). | 42 days (Day 1- Day 42) |
| 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). | 28 days (Day 28 minus Day 1) |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42 |
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Inclusion Criteria
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pamela L Zeitlin, MD, PhD | Johns Hopkins University, School of Medicine, Pediatric Pulmonary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Hospital | Baltimore | Maryland | 21287 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28006108 | Derived | Zeitlin PL, Diener-West M, Callahan KA, Lee S, Talbot CC Jr, Pollard B, Boyle MP, Lechtzin N. Digitoxin for Airway Inflammation in Cystic Fibrosis: Preliminary Assessment of Safety, Pharmacokinetics, and Dose Finding. Ann Am Thorac Soc. 2017 Feb;14(2):220-229. doi: 10.1513/AnnalsATS.201608-649OC. |
| Label | URL |
|---|---|
| Johns Hopkins Cystic Fibrosis website | View source |
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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.
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).
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | placebo given daily for 28 days placebo: pill taken once daily for 28 days |
| FG001 | Low Dose 0.05mg Digitoxin | low dose 0.05mg digitoxin given once daily for 28 days digitoxin: 0.05mg tabs, once daily for 28 days |
| FG002 | Higher Dose 0.1mg Digitoxin | higher dose 0.1mg digitoxin daily for 28 days digitoxin: 0.1mg pills, once daily for 28 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | placebo given daily for 28 days placebo: pill taken once daily for 28 days |
| BG001 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | 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. | Posted | Median | Inter-Quartile Range | log 10 (pg/mL) | 42 days (Day 1 to Day 42) |
|
Adverse events were collected from Screening through Day 42 or the Early Withdraw Visit.
Physical exams by study physician at each visit and documented in the subject case report forms. All Adverse Events were subsequently followed up until resolution.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | placebo given daily for 28 days placebo: pill taken once daily for 28 days |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| abdominal pain | Gastrointestinal disorders | CTCAE v3.0 | Non-systematic Assessment |
Steady states of digitoxin were not achieved in subjects until relatively late the in 28 day treatment period. This would suggest that it may require a much longer treatment course to meaningfully effect inflammation in the airways.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pamela L. Zeitlin, M.D., Ph.D., Professor and Director of SOM Pediatric Pulmonary | Johns Hopkins University | 443-287-8981 | pzeitlin@jhmi.edu |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D004074 | Digitoxin |
| ID | Term |
|---|---|
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
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| Drug |
0.1mg pills, once daily for 28 days. |
|
| placebo | Other | pill taken once daily for 28 days |
|
| 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. | Baseline and Day 28 |
| 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. | Baseline and Day 42 |
| 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. | Baseline and Day 28 |
| 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. | Baseline and Day 28 |
| 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). | Baseline and Day 28 |
| 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). | Day 0 and Day 28 |
| 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. | 28 days |
| 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. | 28 days |
| BG002 | Higher Dose 0.1mg Digitoxin | higher dose 0.1mg digitoxin daily for 28 days digitoxin: 0.1mg pills, once daily for 28 days. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
low dose 0.05mg digitoxin given once daily for 28 days digitoxin: 0.05mg tabs, once daily for 28 days |
| OG002 | Higher Dose 0.1mg Digitoxin | higher dose 0.1mg digitoxin daily for 28 days digitoxin: 0.1mg pills, once daily for 28 days. |
|
|
|
| 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). | 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. | Posted | Number | participants | Serum PK on Days 1 (pre-dose), 7, 14, 21 and 42 |
|
|
|
| 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. | Median changes in FEV1 in L by group for the 28 days of treatment. | Posted | Median | Inter-Quartile Range | liters | Baseline and Day 28 |
|
|
|
| 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. | Mean change in CFQ-R scores from Visit 1 to Visit 6, by domain. | Posted | Mean | Standard Deviation | mean change of scores on a scale | Baseline and Day 42 |
|
|
|
| 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. | Safety indices included changes in WBC during treatment for each group. | Posted | Median | Inter-Quartile Range | K/cu mm | Baseline and Day 28 |
|
|
|
| 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. | For change in Il-8 from Day 28 minus Day 1, a Kruskal-Wallis equality of populations rank was performed. | Posted | Median | Inter-Quartile Range | log10 (pg/mL) | 28 days (Day 28 minus Day 1) |
|
|
|
| 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). | 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. | Posted | Median | Inter-Quartile Range | log 10 (neutrophil cells/mL) | 42 days (Day 1- Day 42) |
|
|
|
|
| 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). | 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). | Posted | Median | Inter-Quartile Range | log 10 (neutrophil cell/mL) | 28 days (Day 28 minus Day 1) |
|
|
|
| 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. | 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). | Posted | Median | Inter-Quartile Range | mg/dL | Baseline and Day 28 |
|
|
|
| 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). | 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). | Posted | Median | Inter-Quartile Range | mm/hr | Baseline and Day 28 |
|
|
|
| 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). | 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. | Posted | Number | participants | Day 0 and Day 28 |
|
|
|
| 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. | Count of clinically significant alterations in the ECG in all subjects during the Treatment Phase of the study. | Posted | Number | participants | 28 days |
|
|
|
| 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. | There were no significant changes in the microbiology of sputum in any subjects over the course of treatment. | Posted | Number | participants | 28 days |
|
|
|
| 0 |
| 8 |
| 7 |
| 8 |
| EG001 | 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 | 0 | 8 | 5 | 8 |
| EG002 | Higher Dose 0.1mg Digitoxin | higher dose 0.1mg digitoxin daily for 28 days digitoxin: 0.1mg pills, once daily for 28 days. | 0 | 8 | 6 | 8 |
| anxiety | Nervous system disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| chills | Infections and infestations | CTCAE v3.0 | Non-systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| crackles | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| decrease breath sounds | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| decreased lung function | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| epistaxis | Injury, poisoning and procedural complications | CTCAE v3.0 | Systematic Assessment |
|
| erythema, nares | Injury, poisoning and procedural complications | CTCAE v3.0 | Systematic Assessment |
|
| fatigue | General disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| fever | Infections and infestations | CTCAE v3.0 | Non-systematic Assessment |
|
| GERD | Gastrointestinal disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| headache | General disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| hemoptysis | Injury, poisoning and procedural complications | CTCAE v3.0 | Non-systematic Assessment |
|
| increased sputum | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| increased urination | Renal and urinary disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| menstrual cramps | Reproductive system and breast disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| muscle pain | Musculoskeletal and connective tissue disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| pain, nares | Injury, poisoning and procedural complications | CTCAE v3.0 | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| night sweats | Infections and infestations | CTCAE v3.0 | Non-systematic Assessment |
|
| pulmonary exacerbation | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| rash | Skin and subcutaneous tissue disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| rhonchi | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| shortness of breath | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| sinusitis | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| sore throat | Infections and infestations | CTCAE v3.0 | Non-systematic Assessment |
|
| sprain | Musculoskeletal and connective tissue disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| syncope | Nervous system disorders | CTCAE v3.0 | Non-systematic Assessment |
|
| tonic clonic seizure | Nervous system disorders | CTCAE v3.0 | Systematic Assessment |
|
| upper respiratory infection | Reproductive system and breast disorders | CTCAE v3.0 | Systematic Assessment |
|
| urinary tract infection | Renal and urinary disorders | CTCAE v3.0 | Systematic Assessment |
|
| weight loss | General disorders | CTCAE v3.0 | Systematic Assessment |
|
| wheeze | Respiratory, thoracic and mediastinal disorders | CTCAE v3.0 | Systematic Assessment |
|
| vaginal yeast infection | Infections and infestations | CTCAE v3.0 | Non-systematic Assessment |
|
Not provided
Not provided
| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
|
| Day 7, digitoxin level 6.4 ng/mL |
|
| Day 7, digitoxin level 6.9 ng/mL |
|
| Day 7, digitoxin level 7.8 ng/mL |
|
| Day 7, digitoxin level none detected |
|
| Day 14, digitoxin level 10 ng/mL |
|
| Day 14, digitoxin level 11 ng/mL |
|
| Day 14, digitoxin level 13 ng/mL |
|
| Day 14, digitoxin level 6.8 ng/mL |
|
| Day 14, digitoxin level 6.9 ng/mL |
|
| Day 14, digitoxin level 7.3 ng/mL |
|
| Day 14, digitoxin level 7.5 ng/mL |
|
| Day 14, digitoxin level 8.1 ng/mL |
|
| Day 14, digitoxin level 9.3 ng/mL |
|
| Day 14, digitoxin level 9.4 ng/mL |
|
| Day 14, digitoxin level none detected |
|
| Day 21, digitoxin level 10 ng/mL |
|
| Day 21, digitoxin level 11 ng/mL |
|
| Day 21, digitoxin level 12 ng/mL |
|
| Day 21, digitoxin level 13 ng/mL |
|
| Day 21, digitoxin level 14 ng/mL |
|
| Day 21, digitoxin level 15 ng/mL |
|
| Day 21, digitoxin level 4 ng/mL |
|
| Day 21, digitoxin level 5 ng/mL |
|
| Day 21, digitoxin level 6 ng/mL |
|
| Day 21, digitoxin level 6.4 ng/mL |
|
| Day 21, digitoxin level 6.5 ng/mL |
|
| Day 21, digitoxin level 6.9 ng/mL |
|
| Day 21, digitoxin level 7.5 ng/mL |
|
| Day 21, digitoxin level none detected |
|
| Day 42, digitoxin level 5 ng/mL |
|
| Day 42, digitoxin level none detected |
|
|
| Vitality Domain |
|
| Emotional Domain |
|
| Social Domain |
|
| Body Domain |
|
| Eating Domain |
|
| Treatment Domain |
|
| Health Domain |
|
| Weight Domain |
|
| Respiratory Domain |
|
| Digestion Domain |
|
|
| Day 21 |
|
| Day 28 |
|
| Day 42 |
|