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| ID | Type | Description | Link |
|---|---|---|---|
| 18-D-0086 |
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Study was stopped early due to a greater than expected incidence of ocular AEs and analysis of the data from the first 4 subjects indicating that the likelihood of permanent remission with this therapy was low.
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Background:
People with tumor-induced osteomalacia (TIO) have small tumors that may cause low blood phosphorus, weak muscles, bone pain, and broken bones. The tumors may be so small they are hard to find or impossible to remove. Researchers want to test a drug that may help treat TIO.
Objective:
To see how the drug BGJ398 affects people with tumor-induced osteomalacia.
Eligibility:
People ages 18-85 who are in NIH protocol 01-D-0184 and have TIO that cannot be found or easily removed
Design:
At every study visit, participants will have:
At the screening visit, participants will also have a heart and eye tests. They may have other tests to find their tumor.
The baseline visit will be a 1-week stay in the clinic. Participants will have the regular study tests, plus:
Participants will take the study drug for six 1-month cycles. In each cycle, participants will:
Participants will have 1 visit at the end of the last cycle and another 3 months later....
Background:
Objectives:
To induce complete metabolic response in subjects with tumor-induced osteomalacia (TIO) with BGJ-398 as demonstrated by normalization of FGF23 and phosphate homeostasis.
Eligibility:
Patients may be eligible if they:
Design:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Arm (TIO Subjects) | Experimental | Phase 2, open-label, non-randomized, single-arm, drug treatment trial. 10 subjects will be studied. Treatment duration of 6 months with 3 months off drug follow-up and optional extension phase. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BGJ398 | Drug | BGJ398, a pan-fibroblast growth factor receptor (FGFR) kinase inhibitor will be orally administered over six 4-week cycles (4 weeks on drug continuously). After the initial dose, escalation/de- escalation of BGJ398 will be based on FGF- 23 blood levels and adjusted according to protocol procedures. The six cycles of BGJ398 will be followed by 3 months off the drug and an optional extension phase. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Complete Metabolic Remission After Stopping BGJ398 | Participants were monitored for up to 12 weeks after stopping BGJ398. A participant was considered to have a complete metabolic remission by achieving both normal blood FGF23 and phosphorus levels in the blood for 12 weeks after stopping BGJ398. | Up to 12 weeks after stopping BGJ398 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Complete and Partial Metabolic Response Rate | Participants were monitored for metabolic response to BGJ398 every other week. A participant was considered to have a complete metabolic response by achieving both normal c-terminal FGF23 and phosphorus levels at each time point. A participant was considered to have a partial metabolic response by achieving both a decrease of at least 50% in c-terminal FGF23 levels and an increase of at least 50% in phosphorous at each time point |
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Patients eligible for inclusion in this study have to meet all of the following criteria:
EXCLUSION CRITERIA:
Patients eligible for this study must not meet any of the following criteria:
Have another genetic or secondary cause of hypophosphatemia.
History of any other malignancy that has not been cured/in remission for 5 years.
Patients who previously received treatment with an FGFR inhibitor other than BGJ398.
Current evidence of corneal or retinal disorder/keratopathy including, but not limited to: bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjuctivitis, confirmed by ophthalmologic examination
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BGJ398 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
Patients who are currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 are prohibited. This includes treatment with enzyme-inducing antiepileptic drugs including carbamazepine, phenytoin, phenobarbital, and primidone.
Consumption of grapefruit, grapefruit juice, pomegranates, star fruits, Seville oranges or products within 7 days prior to first dose
Use of amiodarone within 90 days prior to first dose
Current use of therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulants. Heparin and/or low molecular weight heparins are allowed.
Insufficient bone marrow function defined as all of the following:
Insufficient hepatic and renal function defined as one of the following:
Clinically significant cardiac disease including any of the following:
Recent (less than or equal to 3 months) transient ischemic attack or stroke
Patients under age 21 will have a bone age assessed as part of their clinically indicated skeletal survey under 01-D-0184 and will not be offered enrollment if their growth plates are open.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment. Highly effective contraception methods include:
Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject.
Combination of the following (a+b or a+c, or b+c):
Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
Placement of an intrauterine device (IUD) or intrauterine system (IUS)
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
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| Name | Affiliation | Role |
|---|---|---|
| Rachel I Gafni, M.D. | National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center | Bethesda | Maryland | 20892 | United States |
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| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | TIO Subjects Who Received BGJ398 (Single Arm) | TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Single Arm (TIO Subjects) | Phase 2, open-label, non-randomized, single-arm, drug treatment trial. 10 subjects will be studied. Treatment duration of 6 months with 3 months off drug follow-up and optional extension phase. BGJ398: BGJ398, a pan-fibroblast growth factor receptor (FGFR) kinase inhibitor will be orally administered over six 4-week cycles (3 weeks on drug, 1 week off drug). After the initial dose, escalation/de- escalation of BGJ398 will be based on FGF- 23 blood levels and adjusted according to protocol procedures. The six cycles of BGJ398 will be followed by 3 months off the drug and an optional extension phase. |
| 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 | Number of Participants With Complete Metabolic Remission After Stopping BGJ398 | Participants were monitored for up to 12 weeks after stopping BGJ398. A participant was considered to have a complete metabolic remission by achieving both normal blood FGF23 and phosphorus levels in the blood for 12 weeks after stopping BGJ398. | The population consisted of all participants enrolled in the study | Posted | Count of Participants | Participants | Up to 12 weeks after stopping BGJ398 |
|
|
Patients were monitored for adverse events during 24 weeks of treatment followed by 3 month follow-up period, with optional extension phase up to 37 weeks. If a patient was withdrawn from the study, adverse event data was no longer collected. Subjects who required permanent discontinuation of BGJ398 therapy due to an adverse event continued to be followed in the study until the toxicity had resolved or up to 30 days after study drug discontinuation.
Adverse Events information was collected through investigator assessment every 4 weeks and labs every 2 weeks while on treatment. During the extension phase, adverse event information was collected through investigator and lab assessment every 4 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 | TIO Subjects Who Received BGJ398 (Single Arm) | TIO subjects were treated with BGJ398 for 24 weeks with optional extension phase |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
This study was terminated early due to a lack of efficacy in the first 4 patients and an unexpectedly high rate of ocular adverse events. As a result, only 4 patients were enrolled in this study. Because of the small sample size, we were unable to perform the planned statistical analysis, and instead the results are primarily descriptive.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Rachel I. Gafni | National Institute of Dental and Craniofacial Research | 301-594-9924 | gafnir@mail.nih.gov |
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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 | May 21, 2019 | Jan 8, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| C537751 | Oncogenic osteomalacia |
| D017674 | Hypophosphatemia |
| ID | Term |
|---|---|
| D010760 | Phosphorus Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C568950 | infigratinib |
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|
| Every 2 weeks up to 24 weeks |
| Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events | Percentage of patients who incurred grade 3 or 4 adverse events (AEs) or serious adverse events (SAE) or AEs causing dose interruption/reduction | 24 week treatment phase followed by 3 month follow up or extension phase |
| Six-Minute Walk Test | The Six-Minute Walk Test (6MWT), is a self-paced practical test that measures the distance the patient can quickly cover on a flat, hard surface. Each subject was instructed to complete the maximum distance possible in six minutes. Feedback was given in two minute intervals and during the last 30 seconds. Patients were instructed to notify test administrator of leg cramping, pain, nausea, dizziness and shortness of breath. Test administrators counted each lap and upon test completion, the partial distance is measured and added to where the subject stopped. | Assessed at baseline and 24 weeks after starting BGJ398 |
| Hand Grip Strength Test | The person is seated, lower extremities flexed at 90 degrees. The individual uses the dominant hand for this activity. The individual sit with shoulder adducted and neutrally rotated elbow flexed at 90 degrees, forearm in neutral position, resting on the arm of a chair. The JAMAR Hand Dynamometer set to the third level position from the inside is used. The examiner lightly supports the readout dial to prevent it from dropping. The patient is asked to "Squeeze as hard as you can….squeeze…..squeeze….relax." Three successive trials is recorded in kilograms. A 10-15 second break occurs to prevent muscle fatigue. Scores are recorded and averaged for the final result. Scores within two standard deviations of the mean are considered within normal limits. | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Pinch Test | A lateral pinch is required of the patient, using the dominant hand. The individual is seated, lower extremities flexed at 90 degrees. The examiner stabilizes the patient's wrist as the patient holds the pinch gauge to perform the test. The examiner requests the person to pinch with maximum strength. The peak-hold needle will automatically record the highest force exerted. After the patient uses the Pinch gauge, the examiner records the reading and resets the peak-hold needle to zero before testing again. Three lateral pinch trials are recorded and averaged for the final result. | Assessed at baseline and every 4 weeks for the 24 treatment period, and every 4 weeks in the follow up phase, up to 37 weeks |
| Five Times Sit-to-Stand Test | The Five Times Sit to Stand Test measures an aspect of transfer skill. The test provides a method to quantify functional lower extremity strength and/or identify movement strategies a patient uses to complete transitional movements. The chair is free standing. Patient sits with arms folded across chest and with their back against the chair. A standard chair height 44 cm was used for each patient. Patient stands fully between repetitions of the test, careful to not touch the back of the chair during each repetition. Patient instructions: "I want you to stand up and sit down 5 times as quickly as you can when I say Go." Timing begins at "Go" and ends when the buttocks touches the chair after the 5th repetition. The results are recorded in seconds. | Assessed at baseline and every 4 weeks during the 24 week treatment period |
| The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) The minimum score value is 0, maximum is 100, where a higher school represents a worse outcome (significant symptoms/disability) | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| RAND SF-36 Survey Results | Evaluation using the RAND 36-Item Short Form Survey (SF-36). Results were separated into 8 domains - Physical Functioning, Role limitations due to physical health problems, Role limitations due to emotional problems, Emotional well-being, Energy/fatigue, Social functioning, Bodily Pain, and General health perceptions. The minimum value is 0, the maximum value is 100, which the higher the score, the better the outcome. | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| PROMIS Fatigue | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased feelings of fatigue. | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| PROMIS Pain Interference Score | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Pain Interference 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased pain interference | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| PROMIS Mobility Score | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Mobility bank. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents a better outcome (unencumbered mobility) | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Blood Intact FGF23 Levels | Measured Blood Intact FGF23 Levels. | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Blood C-terminal FGF23 Level | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Blood Phosphate Levels | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Blood 1,25-(OH)2-Vitamin D Level | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Blood Alkaline Phosphatase | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Tubular Reabsorption of Phosphate | Tubular Reabsorption of Phosphate was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples. | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples. | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
| Radiographic Evidence of Tumor-Induced Osteomalacia | In patients with radiographic evidence of TIO, 18FDG PET scans were performed | Baseline and at 24 weeks |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type of TIO Disease | Count of Participants | Participants |
|
| Blood Intact FGF23 on Initiation of Sutdy | Mean | Standard Deviation | pg/mL |
|
| Blood C-Terminal FGF23 on Initiation of Study | Mean | Standard Deviation | RU/mL |
|
| Blood Phosphate on Initiation of Study | Mean | Standard Deviation | mg/dL |
|
| Blood Alkaline Phosphatase on Initiation of Study | Mean | Standard Deviation | U/L |
|
| Counts |
|---|
| Participants |
|
|
| Secondary | Number of Participants With Complete and Partial Metabolic Response Rate | Participants were monitored for metabolic response to BGJ398 every other week. A participant was considered to have a complete metabolic response by achieving both normal c-terminal FGF23 and phosphorus levels at each time point. A participant was considered to have a partial metabolic response by achieving both a decrease of at least 50% in c-terminal FGF23 levels and an increase of at least 50% in phosphorous at each time point | Posted | Count of Participants | Participants | Every 2 weeks up to 24 weeks |
|
|
|
| Secondary | Number of Participants With Grade 3 or 4 Adverse Events or Serious Adverse Events | Percentage of patients who incurred grade 3 or 4 adverse events (AEs) or serious adverse events (SAE) or AEs causing dose interruption/reduction | Posted | Count of Participants | Participants | 24 week treatment phase followed by 3 month follow up or extension phase |
|
|
|
| Secondary | Six-Minute Walk Test | The Six-Minute Walk Test (6MWT), is a self-paced practical test that measures the distance the patient can quickly cover on a flat, hard surface. Each subject was instructed to complete the maximum distance possible in six minutes. Feedback was given in two minute intervals and during the last 30 seconds. Patients were instructed to notify test administrator of leg cramping, pain, nausea, dizziness and shortness of breath. Test administrators counted each lap and upon test completion, the partial distance is measured and added to where the subject stopped. | Posted | Mean | Standard Deviation | Meters | Assessed at baseline and 24 weeks after starting BGJ398 |
|
|
|
| Secondary | Hand Grip Strength Test | The person is seated, lower extremities flexed at 90 degrees. The individual uses the dominant hand for this activity. The individual sit with shoulder adducted and neutrally rotated elbow flexed at 90 degrees, forearm in neutral position, resting on the arm of a chair. The JAMAR Hand Dynamometer set to the third level position from the inside is used. The examiner lightly supports the readout dial to prevent it from dropping. The patient is asked to "Squeeze as hard as you can….squeeze…..squeeze….relax." Three successive trials is recorded in kilograms. A 10-15 second break occurs to prevent muscle fatigue. Scores are recorded and averaged for the final result. Scores within two standard deviations of the mean are considered within normal limits. | Only 2 patients performed strength testing at 28 weeks. | Posted | Mean | Standard Deviation | kg | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Pinch Test | A lateral pinch is required of the patient, using the dominant hand. The individual is seated, lower extremities flexed at 90 degrees. The examiner stabilizes the patient's wrist as the patient holds the pinch gauge to perform the test. The examiner requests the person to pinch with maximum strength. The peak-hold needle will automatically record the highest force exerted. After the patient uses the Pinch gauge, the examiner records the reading and resets the peak-hold needle to zero before testing again. Three lateral pinch trials are recorded and averaged for the final result. | Only 2 patients performed strength testing at 28 weeks. | Posted | Mean | Standard Deviation | kg | Assessed at baseline and every 4 weeks for the 24 treatment period, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Five Times Sit-to-Stand Test | The Five Times Sit to Stand Test measures an aspect of transfer skill. The test provides a method to quantify functional lower extremity strength and/or identify movement strategies a patient uses to complete transitional movements. The chair is free standing. Patient sits with arms folded across chest and with their back against the chair. A standard chair height 44 cm was used for each patient. Patient stands fully between repetitions of the test, careful to not touch the back of the chair during each repetition. Patient instructions: "I want you to stand up and sit down 5 times as quickly as you can when I say Go." Timing begins at "Go" and ends when the buttocks touches the chair after the 5th repetition. The results are recorded in seconds. | Only 2 patients performed strength testing at 28 weeks. | Posted | Mean | Standard Deviation | seconds | Assessed at baseline and every 4 weeks during the 24 week treatment period |
|
|
|
| Secondary | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) | The Disabilities of Arm Shoulder and Hand Outcome Measurement (DASH) The minimum score value is 0, maximum is 100, where a higher school represents a worse outcome (significant symptoms/disability) | 2 patients did not fill out their DASH at week 28 | Posted | Mean | Standard Deviation | DASH Disability/Symptom Score | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | RAND SF-36 Survey Results | Evaluation using the RAND 36-Item Short Form Survey (SF-36). Results were separated into 8 domains - Physical Functioning, Role limitations due to physical health problems, Role limitations due to emotional problems, Emotional well-being, Energy/fatigue, Social functioning, Bodily Pain, and General health perceptions. The minimum value is 0, the maximum value is 100, which the higher the score, the better the outcome. | Only 2 patients completed week 28 surveys | Posted | Mean | Standard Deviation | score on a scale | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | PROMIS Fatigue | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Fatigue 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased feelings of fatigue. | Posted | Mean | Standard Deviation | T score | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | PROMIS Pain Interference Score | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Pain Interference 8A short form. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents increased pain interference | Only 2 patients completed the week 28 surveys | Posted | Mean | Standard Deviation | T score | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | PROMIS Mobility Score | Assessed using the PROMIS (Patient-Reported Outcomes Measurement Information System) Mobility bank. Scores are given as T values when compared to a population where the mean is 50 and 1SD is 10. A higher score represents a better outcome (unencumbered mobility) | Only 2 patients completed the week 28 surveys | Posted | Mean | Standard Deviation | T score | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Blood Intact FGF23 Levels | Measured Blood Intact FGF23 Levels. | There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. | Posted | Mean | Standard Deviation | pg/mL | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Blood C-terminal FGF23 Level | There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22. | Posted | Mean | Standard Deviation | RU/mL | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Blood Phosphate Levels | There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22. | Posted | Mean | Standard Deviation | mg/dL | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Blood 1,25-(OH)2-Vitamin D Level | There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22. | Posted | Mean | Standard Deviation | pg/mL | Assessed at baseline and every 4 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Blood Alkaline Phosphatase | There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Only 3 patients provided follow up samples. There is missing data for 1 patient at week 10 and 22. | Posted | Mean | Standard Deviation | IU/L | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Tubular Reabsorption of Phosphate | Tubular Reabsorption of Phosphate was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples. | There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Missing urine samples resulted in several time points having fewer than 4 subjects. | Posted | Mean | Standard Deviation | % Filtered Phosphate | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) was calculated using blood phosphate and creatinine, as well as either 24 hour urine or spot urine samples. | There were dose interruptions throughout the 24 week treatment phase for 3 of the 4 subjects. Missing urine samples resulted in several time points having fewer than 4 subjects. | Posted | Mean | Standard Deviation | mg/dL | Assessed at baseline and every 2 weeks up to 24 weeks during the treatment phase, and every 4 weeks in the follow up phase, up to 37 weeks |
|
|
|
| Secondary | Radiographic Evidence of Tumor-Induced Osteomalacia | In patients with radiographic evidence of TIO, 18FDG PET scans were performed | Posted | Mean | Standard Deviation | Units | Baseline and at 24 weeks |
|
|
|
| 0 |
| 4 |
| 0 |
| 4 |
| 4 |
| 4 |
| Ear Pain | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hearing impairment | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry eye | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Corneal inflamation/keratitis | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nuclear Sclerosis | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glaucoma | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertrichosis of eyelashes | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash, pustular | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| C. difficile colitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Pelvic Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Parathyroid hormone increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypercalcemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hypercalciuria | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hyperphosphatemia | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (3.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dysgeusia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Gastroesophageal reflux | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Pain, musculoskeletal | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Headache | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Paresthesia | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Insomnia | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Dry lips | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Pain, nails | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Nail change/separation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
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Not provided
Not provided
| Week 2 |
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| Week 4 |
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| Week 6 |
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| Week 8 |
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| Week 10 |
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| Week 12 |
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| Week 14 |
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| Week 16 |
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| Week 18 |
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| Week 20 |
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| Week 22 |
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| Week 24 - prior to drug discontinuation |
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| Week 24 - after drug discontinuation |
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| Title |
|---|
| Measurements |
|---|
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| AE leading to dose interruption/reduction |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 20 |
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| Week 24 |
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| Week 28 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 20 |
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| Week 24 |
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| Week 28 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 20 |
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| Week 24 |
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| Week 28 |
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| Week 8 |
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| Week 12 |
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| Week 16 |
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| Week 20 |
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| Week 24 |
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| Week 28 |
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| Physical Functioning - 8 weeks |
|
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| Physical Functioning - 12 weeks |
|
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| Physical Functioning - 16 weeks |
|
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| Physical Functioning - 20 weeks |
|
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| Physical Functioning - 24 weeks |
|
|
| Physical Functioning - 28 weeks |
|
|
| Role limitations due to physical health problems - Baseline |
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| Role limitations due to physical health problems - 4 weeks |
|
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| Role limitations due to physical health problems - 8 weeks |
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| Role limitations due to physical health problems - 12 weeks |
|
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| Role limitations due to physical health problems - 16 weeks |
|
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| Role limitations due to physical health problems - 20 weeks |
|
|
| Role limitations due to physical health problems - 24 weeks |
|
|
| Role limitations due to physical health problems - 28 weeks |
|
|
| Role limitations due to emotional problems - Baseline |
|
|
| Role limitations due to emotional problems - 4 weeks |
|
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| Role limitations due to emotional problems - 8 weeks |
|
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| Role limitations due to emotional problems - 12 weeks |
|
|
| Role limitations due to emotional problems - 16 weeks |
|
|
| Role limitations due to emotional problems - 20 weeks |
|
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| Role limitations due to emotional problems - 24 weeks |
|
|
| Role limitations due to emotional problems - 28 weeks |
|
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| Emotional well-being - Baseline |
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|
| Emotional well-being - 4 weeks |
|
|
| Emotional well-being - 8 weeks |
|
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| Emotional well-being - 12 weeks |
|
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| Emotional well-being - 16 weeks |
|
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| Emotional well-being - 20 weeks |
|
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| Emotional well-being - 24 weeks |
|
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| Emotional well-being - 28 weeks |
|
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| Energy/fatigue - Baseline |
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| Energy/fatigue - Week 4 |
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| Energy/fatigue - week 8 |
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| Energy/fatigue - week 12 |
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| Energy/fatigue - week 16 |
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| Energy/fatigue - week 20 |
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| Energy/fatigue - week 24 |
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| Energy/fatigue - week 28 |
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| Social functioning - Baseline |
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|
| Social functioning - 4 weeks |
|
|
| Social functioning - 8 weeks |
|
|
| Social functioning - 12 weeks |
|
|
| Social functioning - 16 weeks |
|
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| Social functioning - 20 weeks |
|
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| Social functioning - 24 weeks |
|
|
| Social functioning - 28 weeks |
|
|
| Bodily Pain - Baseline |
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|
| Bodily Pain - week 4 |
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| Bodily Pain - week 8 |
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| Bodily Pain - week 12 |
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| Bodily Pain - week 16 |
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| Bodily Pain - week 20 |
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| Bodily Pain - week 24 |
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| Bodily Pain - week 28 |
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| General health perceptions - Baseline |
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| General health perceptions - week 4 |
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| General health perceptions - week 8 |
|
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| General health perceptions - week 12 |
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| General health perceptions - week 16 |
|
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| General health perceptions - week 20 |
|
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| General health perceptions - week 24 |
|
|
| General health perceptions - week 28 |
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|
| Title | Measurements |
|---|---|
|
| Week 12 |
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| Week 16 |
|
| Week 20 |
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| Week 24 |
|
| Week 28 |
|
|
| Week 8 |
|
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| Week 12 |
|
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| Week 16 |
|
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| Week 20 |
|
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| Week 24 |
|
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| Week 28 |
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|
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| Week 8 |
|
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| Week 12 |
|
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| Week 16 |
|
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| Week 20 |
|
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| Week 24 |
|
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| Week 28 |
|
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| 8 Weeks |
|
|
| 12 Weeks |
|
|
| 16 Weeks |
|
|
| 20 Weeks |
|
|
| 24 Weeks |
|
|
| Follow up |
|
|
|
| 4 Weeks |
|
|
| 6 Weeks |
|
|
| 8 Weeks |
|
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| 10 Weeks |
|
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| 12 Weeks |
|
|
| 14 Weeks |
|
|
| 16 Weeks |
|
|
| 18 Weeks |
|
|
| 20 Weeks |
|
|
| 22 Weeks |
|
|
| 24 Weeks |
|
|
| Follow up |
|
|
|
| Week 4 |
|
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| Week 6 |
|
|
| Week 8 |
|
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| Week 10 |
|
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| Week 12 |
|
|
| Week 14 |
|
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| Week 16 |
|
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| Week 18 |
|
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| Week 20 |
|
|
| Week 22 |
|
|
| Week 24 |
|
|
| Follow up |
|
|
|
| Week 4 |
|
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| Week 6 |
|
|
| Week 8 |
|
|
| Week 10 |
|
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| Week 12 |
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| Week 14 |
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| Week 16 |
|
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| Week 18 |
|
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| Week 20 |
|
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| Week 22 |
|
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| Week 24 |
|
|
| Follow up |
|
|
|
| Week 4 |
|
|
| Week 6 |
|
|
| Week 8 |
|
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| Week 10 |
|
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| Week 12 |
|
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| Week 14 |
|
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| Week 16 |
|
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| Week 18 |
|
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| Week 20 |
|
|
| Week 22 |
|
|
| Week 24 |
|
|
| Follow up |
|
|
|
| Week 4 |
|
|
| Week 6 |
|
|
| Week 8 |
|
|
| Week 10 |
|
|
| Week 12 |
|
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| Week 14 |
|
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| Week 16 |
|
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| Week 18 |
|
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| Week 20 |
|
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| Week 22 |
|
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| Week 24 |
|
|
|
| Week 4 |
|
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| Week 6 |
|
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| Week 8 |
|
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| Week 10 |
|
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| Week 12 |
|
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| Week 14 |
|
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| Week 16 |
|
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| Week 18 |
|
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| Week 20 |
|
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| Week 22 |
|
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| Week 24 |
|
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