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| Name | Class |
|---|---|
| Cardero Therapeutics, Inc. | INDUSTRY |
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This single center open-label pilot study will enroll 15 non-ambulatory children with Duchenne muscular dystrophy at least 8 years of age and who demonstrate pre-clinical cardiomyopathy (defined as a cardiac ejection fraction >55% with abnormal LV strain by cardiac MRI). They will receive (+)-epicatechin at one of three doses during an 8-week dose-ranging study with assessments at baseline, 2 Weeks, 4weeks, and 8 weeks. The study will determine optimal dosing for future cardiac efficacy studies based on serum / plasma biomarker response using follistatin: myostatin ratio, nitrite/nitrate ratio, cardiac troponins and cardiac BNP. Secondary endpoints will include additional biomarker assessments by SOMAscanTM, cardiac functional evaluations by cardiac MRI (LV strain), and echocardiogram (LV strain by speckle tracking) and measures of strength, range of motion and mobility, and clinical safety assessments. Results of secondary endpoint analysis will be used to refine design of subsequent clinical trials powered to detect changes in clinical outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 8-weeks open-label (+)- Epicatechin at 25mg/day twice per day, |
|
| Cohort 2 | Experimental | 8-weeks open-label (+)- Epicatechin at 25mg/day three times per day |
|
| Cohort 3 | Experimental | 8-weeks open-label (+)- Epicatechin at 75mg/day at two times per day |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| (+)- Epicatechin | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) | Pharmacokinetic evaluation for dose-response evaluation. | Pre-dose and 2 hours post-dose at baseline |
| Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) | Pharmacokinetic evaluation for dose-response evaluation. | Week 4 |
| Laboratory Outcome: Absolute Plasma Follistatin:Myostatin Ratio at Baseline, Week 4 and Week 8 | Evaluation of follistatin:myostatin ratio from plasma samples. | Baseline, Week 4 and Week 8 |
| Clinical Outcome: Mean Percent of Baseline Cardiac Ejection Fraction by MRI | Evaluation of change in cardiac volume and performance, as measured by the mean percent of baseline ejection fraction using Cardiac MRI, measured at 8 weeks. | Week 8 |
| Safety: Number of Participants Who Experienced Treatment-Related Laboratory Abnormalities | Treatment-related laboratory abnormalities, defined as values outside of the typical range for Duchenne Muscular Dystrophy. Safety laboratory tests included blood chemistry panel, complete blood count w/ differential panel, & urinalysis assessments for clinical safety monitoring. | Study duration (8 weeks) |
| Laboratory Outcome: Absolute Values of Nitric Oxide (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Outcome: Percent of Normalized Upper Extremity Reachable Surface Area at Week 4 and Week 8 | Quantitative upper extremity reachable workspace will be assessed using the XBox Kinect system. The KINECT Upper Extremity Reachable Workspace test measures surface area of a reachable workspace "bubble", normalized to the size of the individual, noted as the RSA or Reachable Surface Area. The Total RSA measure is the sum of four quadrants dividing superior and inferior medial and lateral spaces. A total score of 1 indicates a typical reachable workspace, while lower scores indicate restrictions in one or more of the four quadrants. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Outcome: Mean Strain Index (Ecc%) of Cardiac Mid-Ventricular Strain by MRI | Cardiac MRI using tagged imaging detects changes in heart muscle contractility in people with DMD. It measures how the heart deforms throughout the cardiac cycle, and is used to calculate strain on the heart muscle. Peak strain is a measure of distortion in the heart muscle during contraction versus when it is at rest. Mid-ventricular peak circumferential strain is a sensitive marker of cardiac function and can detect effects of therapeutic interventions. Strain is expressed in the negative, so more negative measurements indicate a healthy state while less negative measurements (closer to zero) indicate an unhealthy state. |
Inclusion Criteria:
Male
Age 8 years to 17 years
Non-Ambulatory (unable to complete 10m run/walk under 10s)
Weight </=100Kg
Diagnosis of DMD confirmed by at least one the following:
Cardiac ejection fraction >55% on echocardiogram
Use of nutritional, herbal and antioxidant supplements taken with the intent of maintaining or improving skeletal muscle strength or functional mobility has been discontinued at least 4 weeks prior to screening (daily multivitamin use is acceptable).
Glucocorticoid therapy, if used, must have a stable weight-based dose for at least 3 months prior to enrollment
Cardiac therapy, if used, includes prophylactic ACE inhibitors, aldosterone receptor antagonists (e.g.
spironolactone, eplerenone, etc.), and/or beta-blocker therapy, and must be stable for 3 months prior to enrollment.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC Davis Medical Center | Sacramento | California | 95817 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | (+)- Epicatechin at 25mg/day twice per day |
| FG001 | Cohort 2 | (+)- Epicatechin at 25mg/day three times per day |
| FG002 | Cohort 3 | (+)- Epicatechin at 75mg/day at two times per day. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | (+)- Epicatechin at 25mg/day twice per day |
| BG001 | Cohort 2 | (+)- Epicatechin at 25mg/day three times per day |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) | Pharmacokinetic evaluation for dose-response evaluation. | One Cohort 3 participant post-dose sample was missed. | Posted | Mean | Standard Deviation | nM | Pre-dose and 2 hours post-dose at baseline |
|
8 weeks
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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 | Cohort 1 | 8-weeks open-label (+)- Epicatechin at 25mg/day twice per day | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Craig McDonald, Professor and Chair | UC Davis Health | (916) 734-4293 | cmmcdonald@ucdavis.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 14, 2017 | Oct 12, 2021 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 9, 2017 | Apr 2, 2021 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| D009135 | Muscular Diseases |
| D009202 | Cardiomyopathies |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
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| ID | Term |
|---|---|
| D002392 | Catechin |
| ID | Term |
|---|---|
| D002839 | Chromans |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
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| Baseline, Week 4, Week 8 |
| Laboratory Outcome: Absolute Values of Carbonylation (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). | Baseline, Week 4, Week 8 |
| Laboratory Outcome: Absolute Values of Follistatin (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). | Baseline, Week 4, Week 8 |
| Laboratory Outcome: Absolute Values of Myostatin (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). | Baseline, Week 4, Week 8 |
| Baseline, Week 4, Week 8 |
| Clinical Outcome: Total Score Using Performance of the Upper Limb Assessment | The standardized Performance of Upper Limb (PUL) measure will be assessed at baseline and after 4 & 8 weeks. The Performance of the Upper Limb module is an observer-administered performance battery of upper extremity mobility tasks for the shoulder (upper, 6 items, 12 points), elbow (middle, 9 items, 17 points) and wrist/hand (distal, 7 items, 13 points). Higher scores indicate higher level of function. Total score ranges from 0-42 points and is the sum of the scores for the three subscales (10 upper, 10 mid, and 14 distal). | Baseline, Week 4, Week 8 |
| Clinical Outcome: Mean Maximal Attained Revolutions Per 6-minute Cycle Test | The Assisted Six-Minute Cycle Test is an ergometer-based assessment of upper limb function. Test results indicate the maximum number of ergometer revolutions achieved in six-minutes, with higher numbers indicating a greater degree of functional capacity. | Baseline, Week 4, Week 8 |
| Person-Reported Outcome: Upper Extremity Standardized Mean Score Using Pediatric Outcomes Data Collection Instrument (PODCI) Quality of Life Instrument | The PODCI instrument was developed by Daltroy and colleagues with support by the Pediatric Orthopaedic Society of North America (POSNA). The PODCI is a 108-item questionnaire that evaluates global functioning in the pediatric orthopedic population utilizing four components: upper extremity functioning, transfers and basic mobility, sports and physical functioning and a comfort/pain score. Global functioning is assessed by the average of the four previous scores. All scales are scored from zero to 100, with 100 representing the highest level of functioning and least pain. The PODCI asks questions such as "During the last week, was it easy or hard for you to … lift heavy books". | Baseline to Week 4 and Week 8 |
| Person-Reported Outcome: Mean Person-Reported Outcome Measure Upper Limb (PROM-UL) Functional Capacity Score | The Performance of Upper Limb module (PUL) for DMD was designed according to a specific contextual framework of upper limb function in both ambulant and non-ambulant individuals with DMD. The UL-PROM closely linked to this motor performance based clinician-reported outcome measure, was developed to evaluate manual ability related to activities of daily living (ADL) that cannot be observed in a clinical setting. Items were selected in relation to the different domains of the PUL from proximal to distal performance in order to cover the full range of upper limb functions. The questionnaire consists of 33 items covering four domains (3 points each for Food/Nutrition 7 items, Self Care 8 items, Household/Environment 6 items, Leisure/Communication 12 items). Higher scores indicate greater function, with total score being a sum of the subscale scores (Ranging from 0 to 99). | Change from Baseline to Week 4 and Week 8 |
| Baseline, Week 8 |
| BG002 | Cohort 3 | (+)- Epicatechin at 75mg/day at two times per day. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Cohort 3 |
8-weeks open-label (+)- Epicatechin at 75mg/day at two times per day |
|
|
|
| Primary | Pharmacokinetics Outcome: Absolute Values of (+)-Epicatechin Serum Concentration, Pre-dose (Trough) and 2 Hours Post-dose (Peak) | Pharmacokinetic evaluation for dose-response evaluation. | Posted | Mean | Standard Deviation | nM | Week 4 |
|
|
|
|
| Primary | Laboratory Outcome: Absolute Plasma Follistatin:Myostatin Ratio at Baseline, Week 4 and Week 8 | Evaluation of follistatin:myostatin ratio from plasma samples. | Posted | Mean | Standard Deviation | Ratio of follistatin to myostatin (AU) | Baseline, Week 4 and Week 8 |
|
|
|
|
| Primary | Clinical Outcome: Mean Percent of Baseline Cardiac Ejection Fraction by MRI | Evaluation of change in cardiac volume and performance, as measured by the mean percent of baseline ejection fraction using Cardiac MRI, measured at 8 weeks. | Missing data due to poor image quality. | Posted | Mean | Standard Deviation | percentage | Week 8 |
|
|
|
| Primary | Safety: Number of Participants Who Experienced Treatment-Related Laboratory Abnormalities | Treatment-related laboratory abnormalities, defined as values outside of the typical range for Duchenne Muscular Dystrophy. Safety laboratory tests included blood chemistry panel, complete blood count w/ differential panel, & urinalysis assessments for clinical safety monitoring. | Posted | Count of Participants | Participants | Study duration (8 weeks) |
|
|
|
| Primary | Laboratory Outcome: Absolute Values of Nitric Oxide (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). | Posted | Mean | Standard Deviation | AU | Baseline, Week 4, Week 8 |
|
|
|
|
| Primary | Laboratory Outcome: Absolute Values of Carbonylation (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). | Posted | Mean | Standard Deviation | AU | Baseline, Week 4, Week 8 |
|
|
|
|
| Primary | Laboratory Outcome: Absolute Values of Follistatin (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). | Posted | Mean | Standard Deviation | AU | Baseline, Week 4, Week 8 |
|
|
|
|
| Primary | Laboratory Outcome: Absolute Values of Myostatin (AU) Measured by ELISA | Proteomics evaluation of plasma biomarkers to confirm intervention-responsive pathophysiological pathways, using enzyme-linked immunosorbent assay (ELISA). | Posted | Mean | Standard Deviation | AU | Baseline, Week 4, Week 8 |
|
|
|
|
| Secondary | Clinical Outcome: Percent of Normalized Upper Extremity Reachable Surface Area at Week 4 and Week 8 | Quantitative upper extremity reachable workspace will be assessed using the XBox Kinect system. The KINECT Upper Extremity Reachable Workspace test measures surface area of a reachable workspace "bubble", normalized to the size of the individual, noted as the RSA or Reachable Surface Area. The Total RSA measure is the sum of four quadrants dividing superior and inferior medial and lateral spaces. A total score of 1 indicates a typical reachable workspace, while lower scores indicate restrictions in one or more of the four quadrants. | Missing data due to equipment malfunction | Posted | Mean | Standard Deviation | % normalized reachable surface area | Baseline, Week 4, Week 8 |
|
|
|
| Secondary | Clinical Outcome: Total Score Using Performance of the Upper Limb Assessment | The standardized Performance of Upper Limb (PUL) measure will be assessed at baseline and after 4 & 8 weeks. The Performance of the Upper Limb module is an observer-administered performance battery of upper extremity mobility tasks for the shoulder (upper, 6 items, 12 points), elbow (middle, 9 items, 17 points) and wrist/hand (distal, 7 items, 13 points). Higher scores indicate higher level of function. Total score ranges from 0-42 points and is the sum of the scores for the three subscales (10 upper, 10 mid, and 14 distal). | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 4, Week 8 |
|
|
|
|
| Secondary | Clinical Outcome: Mean Maximal Attained Revolutions Per 6-minute Cycle Test | The Assisted Six-Minute Cycle Test is an ergometer-based assessment of upper limb function. Test results indicate the maximum number of ergometer revolutions achieved in six-minutes, with higher numbers indicating a greater degree of functional capacity. | Posted | Mean | Standard Deviation | revolutions | Baseline, Week 4, Week 8 |
|
|
|
|
| Secondary | Person-Reported Outcome: Upper Extremity Standardized Mean Score Using Pediatric Outcomes Data Collection Instrument (PODCI) Quality of Life Instrument | The PODCI instrument was developed by Daltroy and colleagues with support by the Pediatric Orthopaedic Society of North America (POSNA). The PODCI is a 108-item questionnaire that evaluates global functioning in the pediatric orthopedic population utilizing four components: upper extremity functioning, transfers and basic mobility, sports and physical functioning and a comfort/pain score. Global functioning is assessed by the average of the four previous scores. All scales are scored from zero to 100, with 100 representing the highest level of functioning and least pain. The PODCI asks questions such as "During the last week, was it easy or hard for you to … lift heavy books". | Posted | Mean | Standard Deviation | score on a scale | Baseline to Week 4 and Week 8 |
|
|
|
|
| Secondary | Person-Reported Outcome: Mean Person-Reported Outcome Measure Upper Limb (PROM-UL) Functional Capacity Score | The Performance of Upper Limb module (PUL) for DMD was designed according to a specific contextual framework of upper limb function in both ambulant and non-ambulant individuals with DMD. The UL-PROM closely linked to this motor performance based clinician-reported outcome measure, was developed to evaluate manual ability related to activities of daily living (ADL) that cannot be observed in a clinical setting. Items were selected in relation to the different domains of the PUL from proximal to distal performance in order to cover the full range of upper limb functions. The questionnaire consists of 33 items covering four domains (3 points each for Food/Nutrition 7 items, Self Care 8 items, Household/Environment 6 items, Leisure/Communication 12 items). Higher scores indicate greater function, with total score being a sum of the subscale scores (Ranging from 0 to 99). | Posted | Mean | Standard Deviation | score on a scale | Change from Baseline to Week 4 and Week 8 |
|
|
|
|
| Other Pre-specified | Clinical Outcome: Mean Strain Index (Ecc%) of Cardiac Mid-Ventricular Strain by MRI | Cardiac MRI using tagged imaging detects changes in heart muscle contractility in people with DMD. It measures how the heart deforms throughout the cardiac cycle, and is used to calculate strain on the heart muscle. Peak strain is a measure of distortion in the heart muscle during contraction versus when it is at rest. Mid-ventricular peak circumferential strain is a sensitive marker of cardiac function and can detect effects of therapeutic interventions. Strain is expressed in the negative, so more negative measurements indicate a healthy state while less negative measurements (closer to zero) indicate an unhealthy state. | 3 of the participants were unable to undergo the procedure and thus were not included in the analysis. | Posted | Mean | Standard Deviation | Ecc% | Baseline, Week 8 |
|
|
|
| 5 |
| 0 |
| 5 |
| 4 |
| 5 |
| EG001 | Cohort 2 | 8-weeks open-label (+)- Epicatechin at 25mg/day three times per day | 0 | 5 | 0 | 5 | 2 | 5 |
| EG002 | Cohort 3 | 8-weeks open-label (+)- Epicatechin at 75mg/day at two times per day | 0 | 5 | 0 | 5 | 4 | 5 |
| Stomach upset | General disorders | Systematic Assessment |
|
| Troponin elevation | Cardiac disorders | Systematic Assessment |
|
| Seasonal cold | General disorders | Systematic Assessment |
|
| Sinus congestion | General disorders | Systematic Assessment |
|
| Skin rash (diaper rash) | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Nausea/vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| Strep throat | Infections and infestations | Systematic Assessment |
|
| Flu-like symptoms | General disorders | Systematic Assessment |
|
| Cough, lower respiratory congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Body aches | General disorders | Systematic Assessment |
|
| Vision, diagnosed as needing glasses | Eye disorders | Systematic Assessment |
|
| Elevated triglycerides | Blood and lymphatic system disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D006571 |
| Heterocyclic Compounds |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Male |
|
|
| Equivalence |
Difference in trough vs. peak values was evaluated using a paired t-test analysis. |
| t-test, 2 sided | 0.0007 | Equivalence | Difference in trough vs. peak values was evaluated using a paired t-test analysis. |
|
| Week 8 |
|
| <0.0001 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 4 (Cohort 3) | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 (Cohort 1) | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 (Cohort 2) | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 (Cohort 3) | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
|
| Week 8 |
|
| <0.001 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 4 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
|
| Week 8 |
|
| <0.0001 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 4 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
|
| Week 8 |
|
| <0.0001 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 4 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
|
| Week 8 |
|
| <0.0001 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 4 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | 0.01 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.0001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Week 4 |
|
|
| Week 8 |
|
|
|
| Week 8 |
|
| 0.019 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | <0.001 | Other | Mixed Model Repeated Measures (MMRM) regression |
| Baseline vs. Week 8 | Regression, Linear | 0.05 | Other | Mixed Model Repeated Measures (MMRM) regression |
|
| Week 8 |
|
| Regression, Linear |
| 0.009 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
|
| Week 8 |
|
| 0.026 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
|
| Week 8 |
|
| 0.002 |
| Other |
Mixed Model Repeated Measures (MMRM) regression |
|