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The study was a site-based retrospective non-interventional medical chart review of pediatric and adult male and female patients with PIK3CA-Related Overgrowth Spectrum (PROS) who initiated alpelisib at least 24 weeks before the cut-off date at a MAP site. The study cut-off date was 09-Mar-2020.
Patient-level data were abstracted from medical charts of all eligible patients at all participating sites. Study completion date refers to the last date data was extracted.
Information from patients treated with alpelisib was used to describe the efficacy and safety of alpelisib in PROS patients.
The index date (baseline) is defined as the date of alpelisib initiation. The study period is the period from the index date up to the most recent data available at the time of the cut-off date.
The maximum follow-up was 187 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| alpelisib | Patients treated with alpelisib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alpelisib | Other | Retrospective observational case-only study. There is no treatment allocation. Patients with severe or life-threatening PROS who have received alpelisib as part of a compassionate use program were invited to participate. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients Responders and Non-responders at Week 24 | Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. | Index date and week 24 or 6 months (± 4 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in the Sum of Measurable Target Lesion Volume | Percent change in the sum of measurable target lesion (1 to 3 lesions) volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date: (baseline) was defined as the date of alpelisib initiation End of study: patients were followed up to a maximum of 187 weeks. |
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Inclusion Criteria:
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Patients who participated in the compassionate use program and received alpelisib for the treatment of PIK3CA-related overgrowth spectrum (PROS).
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boston Childrens Hospital | Boston | Massachusetts | 02215 | United States | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38112724 | Derived | Fujino A, Kuniyeda K, Nozaki T, Ozeki M, Ohyama T, Sato I, Kamibeppu K, Tanaka A, Uemura N, Kanmuri K, Nakamura K, Kobayashi F, Suenobu S, Nomura T, Hayashi A, Nagao M, Kato A, Aramaki-Hattori N, Imagawa K, Ishikawa K, Ochi J, Horiuchi S, Nagabukuro H. The Prospective Natural History Study of Patients with Intractable Venous Malformation and Klippel-Trenaunay Syndrome to Guide Designing a Proof-of-Concept Clinical Trial for Novel Therapeutic Intervention. Lymphat Res Biol. 2024 Feb;22(1):27-36. doi: 10.1089/lrb.2023.0023. Epub 2023 Dec 19. | |
| 37634128 |
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Participants were from Australia (1), France (50), Ireland (1), Spain (3) and United States (2)
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| ID | Title | Description |
|---|---|---|
| FG000 | Pediatric Patients | Pediatric patients (< 18 years) treated with alpelisib |
| FG001 | Adult Patients | Adult patients (>= 18 years) treated with alpelisib |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pediatric Patients | Pediatric patients (< 18 years) treated with alpelisib |
| BG001 | Adult Patients | Adult patients (>= 18 years) treated with alpelisib |
| 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 | Percentage of Patients Responders and Non-responders at Week 24 | Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. | Efficacy population: It is a subset of the Full study population. It included patients with at least one target lesion and with an imaging scan performed on the index date (or up to 24 weeks prior to the index date) for at least one target lesion. | Posted | Number | 95% Confidence Interval | Percentage of participants | Index date and week 24 or 6 months (± 4 weeks) |
|
Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment or cut-off date whichever occurs first, up to maximum duration of 187 weeks
Any sign or symptom that occurs during the study treatment plus the 30 days post treatment or cut-off date whichever occurs first
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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 | Pediatric Patients | Pediatric patients (< 18 years) treated with alpelisib | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 4, 2020 | Feb 9, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 7, 2021 | Feb 9, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D009477 | Hereditary Sensory and Autonomic Neuropathies |
| ID | Term |
|---|---|
| D009421 | Nervous System Malformations |
| D009422 | Nervous System Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
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| ID | Term |
|---|---|
| C585539 | Alpelisib |
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| Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) |
| Percent Change in the Sum of All Measurable Lesion Volume | Percent change in the sum of all measurable (target and non-target) lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. End of study: patients were followed up to a maximum of 187 weeks As no measurable non-target lesions were identified, the results for changes in the sum of all measurable (target and non-target) lesion volume were identical to the results presented for measurable target lesion. | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) |
| Percent Change in the Sum of All Measurable Non-target Lesion Volume | Percent change in the sum of all measurable non-target lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) |
| Mean Duration of Response (DoR) | Duration of response is defined as the time from first documented response, to the date of the first documented disease progression or death due to any cause. Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. Disease progression is defined as an increase of any individual target lesions of ≥ 20% in volume from previous assessment, progression of non-target PIK3CA Related Overgrowth Spectrum (PROS) lesions or appearance of a new PROS lesion. | Up to 187 weeks |
| Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Number of participants with concomitant PIK3CA Related Overgrowth Spectrum (PROS)-related non-drug treatments and other medical interventions by reason for discontinuation. A patient may have multiple information, but was counted only once in type of other supportive non-drug treatment if more than one type in this category has been reported. | Up to 187 weeks |
| Participants With Concomitant PROS-related Medications Over Time | Number of participants with at least one concomitant utilization of PIK3CA Related Overgrowth Spectrum (PROS)-related medication. End of study: patients were followed up to a maximum of 187 weeks. Results are provided for the full study population as planned and documented in the protocol and SAP, and not by age group. | Index date, week 24 and end of study |
| Number of PROS-related Completed Surgeries During the Study Period | Number of surgeries by reason of surgery. A patient may have multiple anatomical sites of surgery and types of surgery on the same day. | Up to 187 weeks |
| Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Improvement in PIK3CA Related Overgrowth Spectrum (PROS) signs and symptoms was defined based on Common Toxicity Criteria (CTC) grade reduction or resolution of the event from index date. CTC is a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. The Common Terminology Criteria for Adverse Events (CTCAE) system is a product of the US National Cancer Institute (NCI). For this study, version 4.03 was used | Index date and week 24 or 6 months (± 4 weeks) |
| Change in Performance Status Score | Participants with a change in performance status score (ECOG, Karnofsky, Lansky) between the index date and week 24. Patients completed one questionnaire (ECOG, Karnofsky or Lansky) based on physicians choice. The Eastern Cooperative Oncology Group (ECOG) score runs from 0 to 5, with 0 denoting perfect health and 5 death. The Karnofsky Performance Score (KPS) and Lansky score run from 0 to 100, where 0 is death and 100 is perfect health. For the ECOG scale, "improvement" is defined as a decrease by at least 1 point and and "worsening" is defined as an increase by at least 1 point. For the Karnofsky and Lansky scale, "improvement" is defined as an increase by at least 20 points and worsening is defined as a decrease by at least 20 points. If neither of the criteria for improvement or worsening is met, then it is considered stable. | Index date and week 24 or 6 months (± 4 weeks) |
| Functional Status - Mobility Assessment | Change in functional status: Mobility severity assessment measured up to the judgment of the investigator. A patient may have multiple information | Up to 187 weeks |
| Change From Index Date in Functional Status - School Status During the Study Period | Change in functional status: School status during the study period (no attendance, part-time or full time). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" as well as , "Part-time" or "No attendance" to "Full-time"; Worsening is defined as a shift from reporting of "Part-time" to "No attendance", as well as from "Full-time" to "Part-time" or "No attendance". If neither of the criteria for improvement or worsening is met, then it is considered stable. | Index date, week 24 and end of study (up to 187 weeks) |
| Change From Index Date in Functional Status - Work Status | Change in functional status: Work status assessment during the study period (no attendance, part-time, full-time or unemployed). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" or "Full time", from "Part-time" to "Full-time", as well as from "Unemployed" to "Part-time" or "Full-time" work. Worsening is defined as a shift from reporting of "Part-time" to "No attendance", "Full-time" to "Part-time" or "No attendance" as well as "Part-time" or "Full-time" to "Unemployed" status. Change in score is only applicable if both index date and post-index date information are available. If a patient has more than 1 score reported within the same time window, the worst is considered. If neither of the criteria for improvement or worsening is met, then it is considered stable. | Index date, week 24 and end of study |
| Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient | Hospitalizations starting on or after the start of study treatment (index date) or starting prior to and continuing after the start of study treatment are summarized. | Up to 187 weeks |
| Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Worst post-index date hematology abnormalities based on Common Toxicity Criteria (CTC) grades during the study period. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized. | Up to 187 weeks |
| Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Worst post-index date biochemistry abnormalities based on Common Toxicity Criteria (CTC) grades. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized. | 187 weeks |
| Notable Vital Sign Values During the Study Period - Pediatric Patients | Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥95th percentile of the age and height group Low Systolic blood pressure: ≤5th percentile of the age and height group. High diastolic blood pressure: ≥95th percentile of the age and height group Low diastolic blood pressure: ≤5th percentile of the age and height group. High pulse rate (bpm): 2-3 years: >128; 3-4 years: >123; 4-6 years: >117; 6-8 years: >111; 8-12years: >103; 12-15 years: >96; ≥15 years: >92 Low pulse rate (bpm): 2-3 years: <92; 3-4 years: <86; 4-6 years: <81; 6-8 years: <74; 8-12 years: <67; 12-15 years: <62; ≥15 years: <58. High weight: increase from baseline of ≥2 Body mass index (BMI) for age percentile categories Low weight: decrease from baseline of ≥2 BMI-for-age percentile categories | End of study (up to week 187) |
| Notable Vital Sign Values During the Study Period - Adult Patients | Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥180 mmHg and increase ≥20 mmHg Low systolic blood pressure: ≤90 mmHg and decrease ≥20 mmHg. High diastolic blood pressure: ≥105 mmHg and increase ≥15 mmHg Low diastolic blood pressure: ≤50 mmHg and decrease ≥15 mmHg. High pulse rate: ≥120 bpm and increase ≥15 bpm Low pulse rate: ≤ 50 bpm and decrease ≥15 bpm. High weight: Increase ≥10% Low weight: Decrease ≥10% | End of study (up to week 187) |
| Number of Participants With Notable ECG Values. | Notable Electrocardiogram (ECG) values during the study period | Up to week 187 |
| Growth and Development in Pediatric Population | Assessed in patients who were aged <18 years at the time of alpelisib initiation. SDS (standard deviation scores) for height and BMI are obtained from the WHO Growth Charts, and SDS for height and weight velocity are obtained from Baumgartner et al. (1986). Height or weight velocity is a variable derived from the measurement of height or weight at different times and represents the increase in height or weight during a fixed period. SD- scores are used to describe how far a measurement is from the median (average). Weight-for-age reference data are not available beyond age 10. | Week 24 or 6 months (± 4 weeks) |
| Overview of Number of Patients With Adverse Events (AEs) | A patient with multiple severity grades for an AE is only counted under the maximum grade. All grades includes any AEs with missing grade. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. | Up to 187 weeks |
| Parkville |
| Victoria |
| 3052 |
| Australia |
| Novartis Investigative Site | Montpellier | Herault | 34059 | France |
| Novartis Investigative Site | Dijon | 21000 | France |
| Novartis Investigative Site | Paris | 75015 | France |
| Novartis Investigative Site | Dublin | 12 | Ireland |
| Novartis Investigative Site | Madrid | 28046 | Spain |
| Derived |
| Canaud G, Lopez Gutierrez JC, Irvine AD, Vabres P, Hansford JR, Ankrah N, Branle F, Papadimitriou A, Ridolfi A, O'Connell P, Turner S, Adams DM. Alpelisib for treatment of patients with PIK3CA-related overgrowth spectrum (PROS). Genet Med. 2023 Dec;25(12):100969. doi: 10.1016/j.gim.2023.100969. Epub 2023 Aug 24. |
| 37624421 | Derived | Singh S, Bradford D, Li X, Mishra-Kalyani PS, Shen YL, Wang L, Zhao H, Xiong Y, Liu J, Charlab R, Kraft J, Khasar S, Miller CP, Rivera DR, Kluetz PG, Pazdur R, Beaver JA, Singh H, Donoghue M. FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum. Clin Cancer Res. 2024 Jan 5;30(1):23-28. doi: 10.1158/1078-0432.CCR-23-1270. |
| No efficiency |
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| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 | Adult Patients | Adult patients (>= 18 years) treated with alpelisib |
|
|
| Secondary | Percent Change in the Sum of Measurable Target Lesion Volume | Percent change in the sum of measurable target lesion (1 to 3 lesions) volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date: (baseline) was defined as the date of alpelisib initiation End of study: patients were followed up to a maximum of 187 weeks. | Full study population: included all patients who satisfied the study inclusion criteria. At each time point, only patients with a value at both index date and that time point are included in the calculation of change | Posted | Mean | Standard Deviation | % change in the sum of lesion vol. | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) |
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|
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| Secondary | Percent Change in the Sum of All Measurable Lesion Volume | Percent change in the sum of all measurable (target and non-target) lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. End of study: patients were followed up to a maximum of 187 weeks As no measurable non-target lesions were identified, the results for changes in the sum of all measurable (target and non-target) lesion volume were identical to the results presented for measurable target lesion. | Full study population: included all patients who satisfied the study inclusion criteria. At each time point, only patients with a value at both index date and that time point are included in the calculation of change. | Posted | Mean | Standard Deviation | % change in the sum of lesion vol. | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) |
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| Secondary | Percent Change in the Sum of All Measurable Non-target Lesion Volume | Percent change in the sum of all measurable non-target lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. | Full study population: included all patients who satisfied the study inclusion criteria. Only patients with non-target lesion are included in the analysis. Zero patients were included in this measure since no measurable non-target lesions were identified by independent central radiology review (ICRR) at the index date. | Posted | Index date, week 4, 12 , 24, 52 and end of study (up to a maximum of week 187) |
|
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| Secondary | Mean Duration of Response (DoR) | Duration of response is defined as the time from first documented response, to the date of the first documented disease progression or death due to any cause. Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. Disease progression is defined as an increase of any individual target lesions of ≥ 20% in volume from previous assessment, progression of non-target PIK3CA Related Overgrowth Spectrum (PROS) lesions or appearance of a new PROS lesion. | Efficacy population: It is a subset of the Full study population. This analysis only applied to responders with documented disease progression or death due to any cause. | Posted | Up to 187 weeks |
|
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| Secondary | Reasons for Discontinuation of Concomitant PROS-related Non-drug Treatments | Number of participants with concomitant PIK3CA Related Overgrowth Spectrum (PROS)-related non-drug treatments and other medical interventions by reason for discontinuation. A patient may have multiple information, but was counted only once in type of other supportive non-drug treatment if more than one type in this category has been reported. | Full study population: included all patients who satisfied the study inclusion criteria. Only patients who were under concomitant PROS-related non-drug treatments were included in this analysis. | Posted | Count of Participants | Participants | Up to 187 weeks |
|
|
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| Secondary | Participants With Concomitant PROS-related Medications Over Time | Number of participants with at least one concomitant utilization of PIK3CA Related Overgrowth Spectrum (PROS)-related medication. End of study: patients were followed up to a maximum of 187 weeks. Results are provided for the full study population as planned and documented in the protocol and SAP, and not by age group. | Full study population: included all patients who satisfied the study inclusion criteria. | Posted | Count of Participants | Participants | Index date, week 24 and end of study |
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| Secondary | Number of PROS-related Completed Surgeries During the Study Period | Number of surgeries by reason of surgery. A patient may have multiple anatomical sites of surgery and types of surgery on the same day. | Full study population: included all patients who satisfied the study inclusion criteria. | Posted | Number | Surgeries | Up to 187 weeks |
|
|
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| Secondary | Number of Patients With Improvement in Most Frequent PROS-related Signs and Symptoms | Improvement in PIK3CA Related Overgrowth Spectrum (PROS) signs and symptoms was defined based on Common Toxicity Criteria (CTC) grade reduction or resolution of the event from index date. CTC is a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. The Common Terminology Criteria for Adverse Events (CTCAE) system is a product of the US National Cancer Institute (NCI). For this study, version 4.03 was used | Full study population: included all patients who satisfied the study inclusion criteria. For the assessment of improvement for the individual items, only patients with the symptom at the index date were included. | Posted | Count of Participants | Participants | Index date and week 24 or 6 months (± 4 weeks) |
|
|
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| Secondary | Change in Performance Status Score | Participants with a change in performance status score (ECOG, Karnofsky, Lansky) between the index date and week 24. Patients completed one questionnaire (ECOG, Karnofsky or Lansky) based on physicians choice. The Eastern Cooperative Oncology Group (ECOG) score runs from 0 to 5, with 0 denoting perfect health and 5 death. The Karnofsky Performance Score (KPS) and Lansky score run from 0 to 100, where 0 is death and 100 is perfect health. For the ECOG scale, "improvement" is defined as a decrease by at least 1 point and and "worsening" is defined as an increase by at least 1 point. For the Karnofsky and Lansky scale, "improvement" is defined as an increase by at least 20 points and worsening is defined as a decrease by at least 20 points. If neither of the criteria for improvement or worsening is met, then it is considered stable. | Full study population: included all patients who satisfied the study inclusion criteria. Only patients with performance status (ECOG, Karnofsky, Lansky) assessed at the index date were included in the calculation of change | Posted | Count of Participants | Participants | Index date and week 24 or 6 months (± 4 weeks) |
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| Secondary | Functional Status - Mobility Assessment | Change in functional status: Mobility severity assessment measured up to the judgment of the investigator. A patient may have multiple information | Full study population: included all patients who satisfied the study inclusion criteria. Only patients with at least one mobility assessment were included in the severity assessment. | Posted | Count of Units | Affected regions | Up to 187 weeks | Affected regions | Affected regions |
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| Secondary | Change From Index Date in Functional Status - School Status During the Study Period | Change in functional status: School status during the study period (no attendance, part-time or full time). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" as well as , "Part-time" or "No attendance" to "Full-time"; Worsening is defined as a shift from reporting of "Part-time" to "No attendance", as well as from "Full-time" to "Part-time" or "No attendance". If neither of the criteria for improvement or worsening is met, then it is considered stable. | Full study population: included all patients who satisfied the study inclusion criteria. Only patients reporting school status at index date were included in the calculation of change | Posted | Count of Participants | Participants | Index date, week 24 and end of study (up to 187 weeks) |
|
|
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| Secondary | Change From Index Date in Functional Status - Work Status | Change in functional status: Work status assessment during the study period (no attendance, part-time, full-time or unemployed). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" or "Full time", from "Part-time" to "Full-time", as well as from "Unemployed" to "Part-time" or "Full-time" work. Worsening is defined as a shift from reporting of "Part-time" to "No attendance", "Full-time" to "Part-time" or "No attendance" as well as "Part-time" or "Full-time" to "Unemployed" status. Change in score is only applicable if both index date and post-index date information are available. If a patient has more than 1 score reported within the same time window, the worst is considered. If neither of the criteria for improvement or worsening is met, then it is considered stable. | Full study population: included all patients who satisfied the study inclusion criteria. Only adult patients reporting work status at index date were included in the calculation of change. | Posted | Count of Participants | Participants | Index date, week 24 and end of study |
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| Secondary | Health Resource Utilization (HRU) - Number of Hospitalizations Per Patient | Hospitalizations starting on or after the start of study treatment (index date) or starting prior to and continuing after the start of study treatment are summarized. | Full study population: included all patients who satisfied the study inclusion criteria. | Posted | Mean | Standard Deviation | Number of hospitalizations | Up to 187 weeks |
|
|
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| Secondary | Number of Patients With Grade 3/4 on Laboratory Assessments: Hematology | Worst post-index date hematology abnormalities based on Common Toxicity Criteria (CTC) grades during the study period. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized. | Full study population: included all patients who satisfied the study inclusion criteria. | Posted | Count of Participants | Participants | Up to 187 weeks |
|
|
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| Secondary | Number of Patients With Grade 3/4 on Clinical Assessments - Clinical Chemistry | Worst post-index date biochemistry abnormalities based on Common Toxicity Criteria (CTC) grades. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized. | Full study population: included all patients who satisfied the study inclusion criteria. | Posted | Count of Participants | Participants | 187 weeks |
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|
|
| Secondary | Notable Vital Sign Values During the Study Period - Pediatric Patients | Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥95th percentile of the age and height group Low Systolic blood pressure: ≤5th percentile of the age and height group. High diastolic blood pressure: ≥95th percentile of the age and height group Low diastolic blood pressure: ≤5th percentile of the age and height group. High pulse rate (bpm): 2-3 years: >128; 3-4 years: >123; 4-6 years: >117; 6-8 years: >111; 8-12years: >103; 12-15 years: >96; ≥15 years: >92 Low pulse rate (bpm): 2-3 years: <92; 3-4 years: <86; 4-6 years: <81; 6-8 years: <74; 8-12 years: <67; 12-15 years: <62; ≥15 years: <58. High weight: increase from baseline of ≥2 Body mass index (BMI) for age percentile categories Low weight: decrease from baseline of ≥2 BMI-for-age percentile categories | Full study population: included all patients who satisfied the study inclusion criteria. Only pediatric patients were included in this analysis. | Posted | Count of Participants | Participants | End of study (up to week 187) |
|
|
|
| Secondary | Notable Vital Sign Values During the Study Period - Adult Patients | Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥180 mmHg and increase ≥20 mmHg Low systolic blood pressure: ≤90 mmHg and decrease ≥20 mmHg. High diastolic blood pressure: ≥105 mmHg and increase ≥15 mmHg Low diastolic blood pressure: ≤50 mmHg and decrease ≥15 mmHg. High pulse rate: ≥120 bpm and increase ≥15 bpm Low pulse rate: ≤ 50 bpm and decrease ≥15 bpm. High weight: Increase ≥10% Low weight: Decrease ≥10% | Full study population: included all patients who satisfied the study inclusion criteria. Only adult patients were included in this analysis | Posted | Count of Participants | Participants | End of study (up to week 187) |
|
|
|
| Secondary | Number of Participants With Notable ECG Values. | Notable Electrocardiogram (ECG) values during the study period | Full study population: included all patients who satisfied the study inclusion criteria. Only patients with ECG data are included in this analysis. | Posted | Count of Participants | Participants | Up to week 187 |
|
|
|
| Secondary | Growth and Development in Pediatric Population | Assessed in patients who were aged <18 years at the time of alpelisib initiation. SDS (standard deviation scores) for height and BMI are obtained from the WHO Growth Charts, and SDS for height and weight velocity are obtained from Baumgartner et al. (1986). Height or weight velocity is a variable derived from the measurement of height or weight at different times and represents the increase in height or weight during a fixed period. SD- scores are used to describe how far a measurement is from the median (average). Weight-for-age reference data are not available beyond age 10. | Full study population: included all pediatric patients who satisfied the study inclusion criteria. Only patients with SD-score available are included. | Posted | Mean | Standard Deviation | SD-score | Week 24 or 6 months (± 4 weeks) |
|
|
|
| Secondary | Overview of Number of Patients With Adverse Events (AEs) | A patient with multiple severity grades for an AE is only counted under the maximum grade. All grades includes any AEs with missing grade. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. | Full study population: included all patients who satisfied the study inclusion criteria | Posted | Count of Participants | Participants | Up to 187 weeks |
|
|
|
| 39 |
| 10 |
| 39 |
| 23 |
| 39 |
| EG001 | Adult Patients | Adult patients (>= 18 years) treated with alpelisib | 0 | 18 | 11 | 18 | 16 | 18 |
| Vascular malformation | Congenital, familial and genetic disorders | MedDRA (24.0) | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA (24.0) | Systematic Assessment |
|
| Volvulus | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Impaired healing | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Inflammation | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Otitis media acute | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Streptococcal sepsis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Multiple fractures | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Post procedural discomfort | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Pulmonary contusion | Injury, poisoning and procedural complications | MedDRA (24.0) | Systematic Assessment |
|
| Acidosis | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Haematoma muscle | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Lipoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (24.0) | Systematic Assessment |
|
| Hypotonia | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vaginal haemorrhage | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Venous thrombosis limb | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Coagulopathy | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vascular malformation | Congenital, familial and genetic disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hyperparathyroidism | Endocrine disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Inflammation | General disorders | MedDRA (24.0) | Systematic Assessment |
|
| Abscess soft tissue | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Prostatitis Escherichia coli | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Soft tissue infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (24.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (24.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Folate deficiency | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA (24.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Scoliosis | Musculoskeletal and connective tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA (24.0) | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA (24.0) | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Haematospermia | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Menstruation irregular | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Prostatitis | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vaginal ulceration | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Vulvovaginal pain | Reproductive system and breast disorders | MedDRA (24.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (24.0) | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (24.0) | Systematic Assessment |
|
| Haematoma | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Thrombophlebitis superficial | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
| Varicose vein | Vascular disorders | MedDRA (24.0) | Systematic Assessment |
|
Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| D011115 | Polyneuropathies |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| 12 weeks |
|
|
| 24 weeks |
|
|
| 52 weeks |
|
|
| End of study |
|
|
| 12 weeks |
|
|
| 24 weeks |
|
|
| 52 weeks |
|
|
| End of study |
|
|
| Unknown |
|
| Lack of efficacy |
|
| Other |
|
| Adverse event |
|
| Progressive disease |
|
| Subject decision |
|
|
| End of study |
|
|
| Disease progression (not radiologically confirmed) |
|
| Vascular malformation improved by week 24 |
|
|
| Disseminated intravascular coagulation improved by week 24 |
|
|
| Limb asymmetry improved by week 24 |
|
|
| Pain improved by week 24 |
|
|
| Worsened |
|
| Not reported |
|
| Moderate impairment |
|
| Severe impairment |
|
| Missing |
|
| missing |
|
| Worsening |
|
| End of study |
|
| Missing |
|
| Change end of study |
|
| Hemoglobin, decrease - Grade 3/4 |
|
| Leukocytes, increase - Grade 3/4 |
|
| Leukocytes, decrease - Grade 3/4 |
|
| Lymphocytes, increase - Grade 3/4 |
|
| Lymphocytes, decrease - Grade 3/4 |
|
| Neutrophils, decrease - Grade 3/4 |
|
| Platelets, decrease - Grade 3/4 |
|
| Alkaline Phosphatase Increase - Grade 3/4 |
|
| Aspartate Aminotransferase Increase - Grade 3/4 |
|
| Bilirubin Increase - Grade 3/4 |
|
| Calcium Corrected Increase - Grade 3/4 |
|
| Calcium Corrected Decrease - Grade 3/4 |
|
| Cholesterol Increase - Grade 3/4 |
|
| Creatine Kinase Increase - Grade 3/4 |
|
| Creatinine Increase - Grade 3/4 |
|
| Gamma Glutamyl Transferase Increase - Grade 3/4 |
|
| Glucose Increase - Grade 3/4 |
|
| Magnesium Increase - Grade 3/4 |
|
| Magnesium Decrease - Grade 3/4 |
|
| Phosphate Decrease - Grade 3/4 |
|
| Potassium Increase - Grade 3/4 |
|
| Potassium Decrease - Grade 3/4 |
|
| Sodium Increase - Grade 3/4 |
|
| Sodium Decrease - Grade 3/4 |
|
| Triglycerides Increase - Grade 3/4 |
|
| Urate Increase - Grade 3/4 |
|
|
| High Diastolic blood pressure |
|
|
| Low Diastolic blood pressure |
|
|
| High Pulse rate |
|
|
| Low Pulse rate |
|
|
| High Weight |
|
|
| Low Weight |
|
|
| Low Systolic blood pressure |
|
|
| High Diastolic blood pressure |
|
|
| Low Diastolic blood pressure |
|
|
| High Pulse rate |
|
|
| Low Pulse rate |
|
|
| High Weight |
|
|
| Low Weight |
|
|
| QT Increase >30 to <=60 ms |
|
|
| QT New >480 to <=500 ms |
|
|
|
| BMI SDS |
|
|
| Weight velocity SDS |
|
|
| SAEs - All grades |
|
| SAEs - Grade ≥ 3 |
|
| AEs leading to dose reduction - All grades |
|
| AEs leading to dose reduction - Grade ≥ 3 |
|
| AEs leading to dose interruption - All grades |
|
| AEs leading to dose interruption - Grade ≥ 3 |
|
| AEs leading to treatment discontinuation |
|
| SAEs treatment-related - All grades |
|
| SAEs treatment-related - Grade ≥ 3 |
|