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An open-label, multi-part, first-in-human study of oral branaplam in infants with Type 1 spinal muscular atrophy. The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy after 13 weeks; and to estimate the Maximum Tolerated Dose (MTD) of orally administered branaplam; and to identify the dose that was safe for long term use as well as that can provide durable efficacy optimal dosing regimen in patients with Type 1 SMA.
This was an open-label, multi-part, first-in-human, proof of concept study in infants with Type 1 spinal muscular atrophy who have exactly 2 copies of SMN2, to evaluate safety, tolerability, PK, PD and efficacy of oral branaplam after 13 weeks treatment.
Parts 1,2 and 3 were intended to be non-confirmatory.
In Part 1 of the study, patients were dosed once weekly with branaplam. The branaplam dose was escalated in subsequent cohorts until MTD was determined or when sufficient PK results confirmed that the MTD could not be reached due to a potential pharmacokinetic plateau at higher doses. A decision to dose escalate the next cohort was made after safety data was collected for 14 days following the first dose (14-day DLT window). PK was used to confirm that there was no accumulation of the compound. After 13 weeks treatment, participants in part 1 could enter an extension treatment phase until they discontinued from the study or were transferred into part 3.
Part 2 of the study enrolled new patients into one 2 dose cohorts with once weekly dosing for 52 weeks. The branaplam dose was escalated in subsequent cohorts after 6 patients were enrolled and at least 3 patients from the previous cohort completed 13 weeks of treatment. After 52 weeks, patients may have continued treatment in part 3 if it was in the best interest of the patient.
Part 3, participants from part 1 and 2 who have completed at least 52 weeks of banaplam treatment were elegible to continue receiving treatment as long as in the best interest of the patient. In all cases continuation of the treatment was done at a dose selected as optimum, considering existing safety as well as efficacy data.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| branaplam | Experimental | branaplam Treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| branaplam | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLT) in Part 1 - Safety Analysis Set (SAS) | A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 14 days of treatment with LMI070 and meets any of the criteria for blood and lymphatic system disorders, gastrointestinal disorders, investigations and other toxicities considered clinically significant. | Baseline up to 2 weeks for Part 1 |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events and Deaths- SAS | TEAEs are defined as adverse events starting on or after the first dose of study treatment that were absent pre-treatment, or events present prior to the first dose but increased in severity after the first dose. Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment. | Baseline up to approximately 83 months |
| Measure | Description | Time Frame |
|---|---|---|
| Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUCinf) After a Single Dose - Part 1 - Pharmacokinetics Analysis Set (PAS) | The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume] | from 0 h to 168 h after first/single dose |
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Inclusion Criteria:
Common for both Parts 1 and 2:
Specific for Part 1
Specific for Part 2
Exclusion Criteria:
Common for both Parts 1 and 2:
Specific for Part 1
Specific for Part 2
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Ghent | 9000 | Belgium | |||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35241644 | Derived | Keller CG, Shin Y, Monteys AM, Renaud N, Beibel M, Teider N, Peters T, Faller T, St-Cyr S, Knehr J, Roma G, Reyes A, Hild M, Lukashev D, Theil D, Dales N, Cha JH, Borowsky B, Dolmetsch R, Davidson BL, Sivasankaran R. An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion. Nat Commun. 2022 Mar 3;13(1):1150. doi: 10.1038/s41467-022-28653-6. |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Cohorts in Part 1 were enrolled sequentially following a 14 day dose-limiting toxicity (DLT) window for each cohort before escalating to the next level. Forty participants were enrolled but only 38 received treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 LMI070 6mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| FG001 | Part 1 LMI070 12mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| FG002 | Part 1 LMI070 24mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| FG003 | Part 1 LMI070 48mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| FG004 | Part 1 LMI070 60mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| FG005 | Part 2 LMI070 0.625 mg/kg | LMI070 0.625 mg/kg by enteral route via feeding tube or oral |
| FG006 | Part 2 LMI070 2.5 mg/kg | LMI070 2.5 mg/kg by enteral route via feeding tube or oral |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
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| Part 2 |
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| Part 3 Extension |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 LMI070 6mg/m2 | Enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes for 13 weeks |
| BG001 | Part 1 LMI070 12mg/m2 | Single weekly dose for 13 weeks via e teral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| 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 | Number of Participants With Dose Limiting Toxicities (DLT) in Part 1 - Safety Analysis Set (SAS) | A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant therapies that occurs within the first 14 days of treatment with LMI070 and meets any of the criteria for blood and lymphatic system disorders, gastrointestinal disorders, investigations and other toxicities considered clinically significant. | Safety analysis set. No DLTs were observed, therefore maximum tolerated dose could not be determined. | Posted | Number | Participants | Baseline up to 2 weeks for Part 1 |
|
Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment up a maximum of 83 months.
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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 | Part 1 LMI070 6mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
In alignment with the study objectives, safety and tolerability of branaplam irrespective of the dose, and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. The fact that no dose limiting toxicity was observed in any of the doses and the lack of evidence for dose dependent safety findings further supports this strategy.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | + 1 862 778 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 | Jul 19, 2021 | Jun 28, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 13, 2023 | Jun 28, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009134 | Muscular Atrophy, Spinal |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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| Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUCinf) for All Observation Periods - Part 1 - PAS |
The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume] for all observations. AUC values used for comparison are combined from AUCinf values after single dose and AUC 0-168h values after repeated administration. |
| from 0 h to 168 h after first/single dose |
| Summary of Plasma Pharmacokinetic (PK) Parameter Cmax After a Single Dose - Part 1 - PAS | The observed maximum plasma concentration following drug administration [mass / volume).](streamdown:incomplete-link) | from 0 h to 168 h after first/single dose |
| Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for All Observation Periods - Part 1 - PAS | The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume](streamdown:incomplete-link) | from 0 h to 168 h after first/single dose |
| Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) After a Single Dose - Part 2 - PAS | The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume)](streamdown:incomplete-link) | from 0 h to 168 h after first/single dose |
| Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) for All Observation Periods - Part 2 - PAS | The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume). AUC values used for comparison are combined from AUCinf values after single dose and AUC0-168h values after repeated administration.](streamdown:incomplete-link) | from 0 h to 168 h after first/single dose |
| Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for a Single Dose - Part 2 - PAS | The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume)](streamdown:incomplete-link) | from 0 h to 168 h after first/single dose |
| Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for All Observation Periods - Part 2 - PAS | The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume)](streamdown:incomplete-link) | from 0 h to 168 h after first/single dose |
| Change From Baseline in Growth Parameters: Chest Circumference, Head Circumference and Body Length - Full Analysis Set (FAS) | The effect of branaplam on growth parameters: Length (measured from the top of the head to the sole of the foot), Head circumference and Chest circumference (measured across nipple line). Mean change from baseline in cm is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline, Week 52 and Month 6 of Part 3 |
| Change From Baseline in Growth Parameter: Body Weight - FAS | The effect of Branaplam on body weight in Kg was measured using a weight scale. Mean change from baseline in Kg is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline, Week 52 and Month 6 of Part 3 |
| Change From Baseline in Respiratory Function: Pulse Oximetry - FAS | The effect of branaplam on pulse oximetry in percentage of oxygen saturation was evaluated using a probe that measures oxygen in the blood. Mean change from baseline in percentage of oxygen saturation is reported. Negative numbers indicate a decrease from baseline In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline, Week 52 and Month 6 of Part 3 |
| Change From Baseline in Respiratory Function: Respiratory Rate - FAS | The effect of branaplam on respiratory rate was evaluated by counting the number of breaths for one minute. Mean change from baseline in breaths per minute is reported" In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline, Week 52 and Month 6 of Part 3 |
| Number of Participants With Presence of Paradoxical Breathing - FAS | A paradoxical breathing occurs when one compartment moves out of phase compared to another one. In SMA type I, paradoxical breathing is often a sign of breathing problems where the pulmonary ribcage moves inward during inspiration rather than outward while the abdomen expands. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline, Week 52 and Month 6 of Part 3 |
| Change From Baseline in Respiratory Function: Chest Circumference During Quiet Breathing - End of Inspiration and Expiration - FAS | The effect of branaplam on respiratory status was evaluated by measuring the circumference of the ribcage while taking a breathe in and out while quiet or sleeping. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline, Week 52 and Month 6 of Part 3 |
| Summary of CHOP INTEND Total Score - Parts 1 and 3 and Parts 2 and 3 - FAS | CHOP INTEND is a motor test measure for SMA Type 1 and similarly weak infants with neuromuscular disease. The CHOP INTEND provides a useful measure of motor skills and strength in this population. It is a 16 item, 64 point scale. Each item (motor skill) is given a score from zero to 4: zero indicates can't complete the movement, 1 to 3 indicates partial performance and a 4 indicates person can complete the movement on their own without assistance. These scores are added up to a possible total score of 64 and higher scores indicate better outcomes. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline, Week 52 and Month 6 of Part 3 |
| Number of Participants Fed Orally or by Feeding Tube for Parts 1 and 3 and Parts 2 and 3 - FAS | To evaluate the efficacy of branaplam on preservation of oral feeding In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline up Week 78 |
| Number of Participants and HINE Motor Subscale Milestones (Ability to Sit, Stand or Walk Without Support) - FAS | HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Week 52 and Month 6 of Part 3 |
| Summary of Hammersmith Infant Neurologic Examination Section 2 (HINE-2) - FAS | HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Week 52 and Month 6 of Part 3 |
| Ventilation Use for Parts 1 and 3 and Parts 2 and 3 - FAS | BiBAP (bilevel positive airway pressure) ventilation is a 2 level breathing support which has a tube that connects to a mask. It provides a different level of air pressure for inhalation vs. exhalation, whereas a CPAP (continuous positive airway pressure) only pumps one level of air pressure but is also non-invasiive. Invasive ventilation is delivered via an endotracheal or tracheostomy tube. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Baseline up to 82 months |
| Leuven |
| 3000 |
| Belgium |
| Novartis Investigative Site | Sofia | 1606 | Bulgaria |
| Novartis Investigative Site | Copenhagen | 2100 O | Denmark |
| Novartis Investigative Site | Essen | 45147 | Germany |
| Novartis Investigative Site | Milan | MI | 20133 | Italy |
| Novartis Investigative Site | Roma | RM | 00165 | Italy |
| Novartis Investigative Site | Warsaw | 04 730 | Poland |
| Novartis Investigative Site | Wroclaw | 50 420 | Poland |
| Novartis Investigative Site | Moscow | 119049 | Russia |
| Novartis Investigative Site | Moscow | 127412 | Russia |
| Novartis Investigative Site | Saint Petersburg | 197341 | Russia |
| Novartis Investigative Site | Volgograd | 400120 | Russia |
| Novartis Investigative Site | Yekaterinburg | 620134 | Russia |
| Subject/guardian decision |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG002 | Part 1 LMI070 24mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| BG003 | Part 1 LMI070 48mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| BG004 | Part 1 LMI070 60mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| BG005 | Part 2 LMI070 0.625 mg/kg | LMI070 0.625 mg/kg by enteral route via feeding tube or oral |
| BG006 | Part 2 LMI070 2.5 mg/kg | LMI070 2.5 mg/kg by enteral route via feeding tube or oral |
| BG007 | Total | Total of all reporting groups |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG001 |
| Part 1 LMI070 12mg/m2 |
Enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes for 13 weeks |
| OG002 | Part 1 LMI070 24mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| OG003 | Part 1 LMI070 48mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
| OG004 | Part 1 LMI070 60mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes |
|
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| Primary | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events and Deaths- SAS | TEAEs are defined as adverse events starting on or after the first dose of study treatment that were absent pre-treatment, or events present prior to the first dose but increased in severity after the first dose. Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post last treatment. | Safety analysis set, all enrolled participants who received at least one dose of study drug. | Posted | Count of Participants | Participants | Baseline up to approximately 83 months |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUCinf) After a Single Dose - Part 1 - Pharmacokinetics Analysis Set (PAS) | The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume] | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | h*ng/mL | from 0 h to 168 h after first/single dose |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUCinf) for All Observation Periods - Part 1 - PAS | The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume] for all observations. AUC values used for comparison are combined from AUCinf values after single dose and AUC 0-168h values after repeated administration. | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | h*ng/mL | from 0 h to 168 h after first/single dose | observations by subject and time point | observations by subject and time point |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Cmax After a Single Dose - Part 1 - PAS | The observed maximum plasma concentration following drug administration [mass / volume).](streamdown:incomplete-link) | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | ng/mL | from 0 h to 168 h after first/single dose |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for All Observation Periods - Part 1 - PAS | The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume](streamdown:incomplete-link) | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | ng/mL | from 0 h to 168 h after first/single dose | observations by subject and time point | observations by subject and time point |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) After a Single Dose - Part 2 - PAS | The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume)](streamdown:incomplete-link) | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | h*ng/mL | from 0 h to 168 h after first/single dose |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Area Under the Curve (AUC) for All Observation Periods - Part 2 - PAS | The area under the plasma (or serum or blood) concentration-time curve from time zero to infinity [mass x time / volume). AUC values used for comparison are combined from AUCinf values after single dose and AUC0-168h values after repeated administration.](streamdown:incomplete-link) | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | h*ng/mL | from 0 h to 168 h after first/single dose | observations by subject and time point | observations by subject and time point |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for a Single Dose - Part 2 - PAS | The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume)](streamdown:incomplete-link) | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | ng/mL | from 0 h to 168 h after first/single dose |
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| Secondary | Summary of Plasma Pharmacokinetic (PK) Parameter Cmax for All Observation Periods - Part 2 - PAS | The observed maximum plasma (or serum or blood) concentration following drug administration [mass / volume)](streamdown:incomplete-link) | Pharmacokinetic analysis set | Posted | Mean | Standard Deviation | ng/mL | from 0 h to 168 h after first/single dose | observations by subject and time point | observations by subject and time point |
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| Secondary | Change From Baseline in Growth Parameters: Chest Circumference, Head Circumference and Body Length - Full Analysis Set (FAS) | The effect of branaplam on growth parameters: Length (measured from the top of the head to the sole of the foot), Head circumference and Chest circumference (measured across nipple line). Mean change from baseline in cm is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Mean | Standard Deviation | cm | Baseline, Week 52 and Month 6 of Part 3 |
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| Secondary | Change From Baseline in Growth Parameter: Body Weight - FAS | The effect of Branaplam on body weight in Kg was measured using a weight scale. Mean change from baseline in Kg is presented In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Mean | Standard Deviation | kg | Baseline, Week 52 and Month 6 of Part 3 |
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| Secondary | Change From Baseline in Respiratory Function: Pulse Oximetry - FAS | The effect of branaplam on pulse oximetry in percentage of oxygen saturation was evaluated using a probe that measures oxygen in the blood. Mean change from baseline in percentage of oxygen saturation is reported. Negative numbers indicate a decrease from baseline In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Mean | Standard Deviation | percentage | Baseline, Week 52 and Month 6 of Part 3 |
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| Secondary | Change From Baseline in Respiratory Function: Respiratory Rate - FAS | The effect of branaplam on respiratory rate was evaluated by counting the number of breaths for one minute. Mean change from baseline in breaths per minute is reported" In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Mean | Standard Deviation | breaths per minute | Baseline, Week 52 and Month 6 of Part 3 |
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| Secondary | Number of Participants With Presence of Paradoxical Breathing - FAS | A paradoxical breathing occurs when one compartment moves out of phase compared to another one. In SMA type I, paradoxical breathing is often a sign of breathing problems where the pulmonary ribcage moves inward during inspiration rather than outward while the abdomen expands. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Count of Participants | Participants | Baseline, Week 52 and Month 6 of Part 3 |
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| Secondary | Change From Baseline in Respiratory Function: Chest Circumference During Quiet Breathing - End of Inspiration and Expiration - FAS | The effect of branaplam on respiratory status was evaluated by measuring the circumference of the ribcage while taking a breathe in and out while quiet or sleeping. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Mean | Standard Deviation | cm | Baseline, Week 52 and Month 6 of Part 3 |
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| Secondary | Summary of CHOP INTEND Total Score - Parts 1 and 3 and Parts 2 and 3 - FAS | CHOP INTEND is a motor test measure for SMA Type 1 and similarly weak infants with neuromuscular disease. The CHOP INTEND provides a useful measure of motor skills and strength in this population. It is a 16 item, 64 point scale. Each item (motor skill) is given a score from zero to 4: zero indicates can't complete the movement, 1 to 3 indicates partial performance and a 4 indicates person can complete the movement on their own without assistance. These scores are added up to a possible total score of 64 and higher scores indicate better outcomes. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Mean | Standard Deviation | scores on a scale | Baseline, Week 52 and Month 6 of Part 3 |
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|
|
| Secondary | Number of Participants Fed Orally or by Feeding Tube for Parts 1 and 3 and Parts 2 and 3 - FAS | To evaluate the efficacy of branaplam on preservation of oral feeding In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Number | participants | Baseline up Week 78 |
|
|
|
| Secondary | Number of Participants and HINE Motor Subscale Milestones (Ability to Sit, Stand or Walk Without Support) - FAS | HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Number | participants | Week 52 and Month 6 of Part 3 |
|
|
|
| Secondary | Summary of Hammersmith Infant Neurologic Examination Section 2 (HINE-2) - FAS | HINE Section 2 is a standardized evaluation of motor function. It evaluates 8 items; grasp, head control, kicking, rolling over, sitting up, crawling, standing and walking. Motor skills are assigned a score of 0 to 3 to 5 points and zero means the child lacks that motor skill. The maximum score is 26 which is dependent on age, level of development and severity of disease. A higher score is a better outcome. This assessment was added with amendment 6, therefore no baseline was available. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Mean | Standard Deviation | total scores | Week 52 and Month 6 of Part 3 |
|
|
|
| Secondary | Ventilation Use for Parts 1 and 3 and Parts 2 and 3 - FAS | BiBAP (bilevel positive airway pressure) ventilation is a 2 level breathing support which has a tube that connects to a mask. It provides a different level of air pressure for inhalation vs. exhalation, whereas a CPAP (continuous positive airway pressure) only pumps one level of air pressure but is also non-invasiive. Invasive ventilation is delivered via an endotracheal or tracheostomy tube. In alignment with the study objectives and protocol defined analyses, secondary efficacy endpoints were analyzed according to the treatment group that participants were assigned at baseline (Part 1&3 and Part 2&3) irrespective of study dose or route of administration. | Full analysis set - Number of patients who have an assessment available at Baseline and the relevant post-baseline visit. | Posted | Number | participants | Baseline up to 82 months |
|
|
|
| 1 |
| 2 |
| 2 |
| 2 |
| 2 |
| 2 |
| EG001 | Part 1 LMI070 12mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes | 2 | 2 | 2 | 2 | 2 | 2 |
| EG002 | Part 1 LMI070 24mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes | 2 | 2 | 2 | 2 | 2 | 2 |
| EG003 | Part 1 LMI070 48mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes | 3 | 4 | 4 | 4 | 4 | 4 |
| EG004 | Part 1 LMI070 60mg/m2 | Single weekly dose for 13 weeks via enteral dosing using nasogastric or nasojejunal or percutaneous endoscopic gastrostomy feeding tubes | 1 | 3 | 3 | 3 | 3 | 3 |
| EG005 | Part 2 LMI070 0.625 mg/kg | LMI070 0.625 mg/kg by enteral route via feeding tube or oral | 1 | 10 | 8 | 10 | 10 | 10 |
| EG006 | Part 2 LMI070 2.5 mg/kg | LMI070 2.5 mg/kg by enteral route via feeding tube or oral | 2 | 15 | 11 | 15 | 15 | 15 |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Cardiac arrest | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Left ventricular hypertrophy | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Gastric ulcer | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Intestinal ischaemia | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Peptic ulcer haemorrhage | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Multiple organ dysfunction syndrome | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Bronchiolitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Bronchitis bacterial | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| COVID-19 pneumonia | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Diarrhoea infectious | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Enterovirus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Gastroenteritis rotavirus | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Parainfluenzae virus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pneumococcal sepsis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pneumonia aspiration | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pneumonia bacterial | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pseudomonas infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pyelonephritis acute | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory syncytial virus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Rhinovirus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Staphylococcal sepsis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Foreign body in gastrointestinal tract | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Shunt malfunction | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Ejection fraction decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| N-terminal prohormone brain natriuretic peptide increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory syncytial virus test positive | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Rotavirus test positive | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Salmonella test positive | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Ultrasound kidney abnormal | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypophagia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Ischaemic cerebral infarction | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypercalciuria | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Renal tubular disorder | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Bronchostenosis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Laryngospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory arrest | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Circulatory collapse | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Monocytosis | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Polycythaemia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Reticulocytopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| White blood cell disorder | Blood and lymphatic system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Atrial tachycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Cardiac failure | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Myocarditis | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Right ventricular hypertrophy | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Sinus node dysfunction | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA (25.0) | Systematic Assessment |
|
| Cryptorchism | Congenital, familial and genetic disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dacryostenosis congenital | Congenital, familial and genetic disorders | MedDRA (25.0) | Systematic Assessment |
|
| Developmental hip dysplasia | Congenital, familial and genetic disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypertrophic cardiomyopathy | Congenital, familial and genetic disorders | MedDRA (25.0) | Systematic Assessment |
|
| Phimosis | Congenital, familial and genetic disorders | MedDRA (25.0) | Systematic Assessment |
|
| Plagiocephaly | Congenital, familial and genetic disorders | MedDRA (25.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | MedDRA (25.0) | Systematic Assessment |
|
| Tympanic membrane hyperaemia | Ear and labyrinth disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA (25.0) | Systematic Assessment |
|
| Astigmatism | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Chalazion | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Heterophoria | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypermetropia | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Myopia | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Ocular hyperaemia | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Optic atrophy | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Strabismus | Eye disorders | MedDRA (25.0) | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dental cyst | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Erosive oesophagitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Faecaloma | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Functional gastrointestinal disorder | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Gingival swelling | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hiatus hernia | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Malocclusion | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Oesophagitis haemorrhagic | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Regurgitation | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Salivary hypersecretion | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Teething | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Tongue disorder | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Catheter site haemorrhage | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Granuloma | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hyperpyrexia | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hyperthermia | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Medical device pain | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Medical device site granuloma | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pain | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Allergy to arthropod bite | Immune system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Immunisation reaction | Immune system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Multiple allergies | Immune system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Asymptomatic COVID-19 | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Bacterial disease carrier | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Bacterial rhinitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Bronchitis bacterial | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Candida infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Cytomegalovirus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Dermatitis infected | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Ear infection viral | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Fungal skin infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Gastroenteritis norovirus | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Infected bite | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Klebsiella infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Medical device site infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Oral fungal infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Otitis externa | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Otitis media acute | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pseudomonas infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Pyuria | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Rash pustular | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory syncytial virus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory tract infection viral | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Rhinovirus infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Roseola | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Skin bacterial infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Urethritis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Vulvitis | Infections and infestations | MedDRA (25.0) | Systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Exposure to SARS-CoV-2 | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Subdural haemorrhage | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Tibia fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Tracheostomy malfunction | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (25.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood alkaline phosphatase decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood creatinine decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood iron decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood parathyroid hormone decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Blood thyroid stimulating hormone increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Brain natriuretic peptide increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| C-reactive protein increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Crystal urine present | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Electrocardiogram P pulmonale | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Fungal test positive | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Haematocrit decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Heart rate decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| N-terminal prohormone brain natriuretic peptide increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Nerve conduction studies abnormal | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Red blood cell count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Reticulocyte count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Troponin T increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Troponin increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Ultrasound kidney abnormal | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Urine phosphorus increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Urine uric acid increased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Vitamin D decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| White blood cells urine positive | Investigations | MedDRA (25.0) | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Feeding disorder | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Feeding intolerance | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Fluid intake reduced | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypophagia | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA (25.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Deformity thorax | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Fracture pain | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Joint contracture | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Osteolysis | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Osteopenia | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Rib deformity | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Scoliosis | Musculoskeletal and connective tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (25.0) | Systematic Assessment |
|
| Brain injury | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Cerebral atrophy | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Complex regional pain syndrome | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Facial paresis | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Glossopharyngeal nerve disorder | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Motor dysfunction | Nervous system disorders | MedDRA (25.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
|
| Behaviour disorder | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA (25.0) | Systematic Assessment |
|
| Calculus urinary | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypercalciuria | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Ketonuria | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Nephrocalcinosis | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Nephroptosis | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pyelocaliectasis | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA (25.0) | Systematic Assessment |
|
| Genital rash | Reproductive system and breast disorders | MedDRA (25.0) | Systematic Assessment |
|
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA (25.0) | Systematic Assessment |
|
| Vulvovaginal rash | Reproductive system and breast disorders | MedDRA (25.0) | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Choking | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Increased bronchial secretion | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Increased upper airway secretion | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Nasal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Obstructive airways disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory depression | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Sputum discoloured | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Vasomotor rhinitis | Respiratory, thoracic and mediastinal disorders | MedDRA (25.0) | Systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dermatitis atopic | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Keratosis pilaris | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Perioral dermatitis | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (25.0) | Systematic Assessment |
|
| Therapy cessation | Surgical and medical procedures | MedDRA (25.0) | Systematic Assessment |
|
| Tracheostomy | Surgical and medical procedures | MedDRA (25.0) | Systematic Assessment |
|
| Cyanosis | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
| Diastolic hypertension | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA (25.0) | Systematic Assessment |
|
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 (i.e., data from all sites) in the clinical trial
| D019636 | Neurodegenerative Diseases |
| D009468 | Neuromuscular Diseases |
| Participants with serious adverse events |
|
| Deaths |
|
|
| 1.39 mg/kg - Actual |
|
|
| 2.49 mg/kg - Actual |
|
|
| 2.94 mg/kg - Actual |
|
|
| 0.644 mg/kg - Actual |
|
|
| 1.30 mg/kg - Actual |
|
|
| 2.52 mg/kg - Actual |
|
|
| 2.95 mg/kg - Actual |
|
|
|
| 1.39 mg/kg - Actual |
|
|
| 2.49 mg/kg - Actual |
|
|
| 2.94 mg/kg - Actual |
|
|
| 0.644 mg/kg - Actual |
|
|
| 1.30 mg/kg - Actual |
|
|
| 2.51 mg/kg - Actual |
|
|
| 2.95 mg/kg - Actual |
|
|
| Chest - P3 Month 6 |
|
|
| Head -Week 52 |
|
|
| Head -P3 Month 6 |
|
|
| Length - Week 52 |
|
|
| Length - P3 Month 6 |
|
|
| P3 Month 6 |
|
|
| P3 Month 6 |
|
|
| P3 Month 6 |
|
|
| P3 Month 6 |
|
|
| P3 Month 6 - end of inspiration |
|
|
| Week 52 - end of expiration |
|
|
| P3 Month 6 - end of expiration |
|
|
| Part 3, Month 6 |
|
|
| Started on orally fed, switched to tube fed |
|
| Started on tube fed, switched to orally fed |
|
| Other (mixture of both tube and oral feeding) |
|
| Week 52 Standing - Supports weight |
|
|
| Week 52: Walking - Makes any attempt (i.e., bounces) |
|
|
| Part 3, Month 6: Sitting - Stable independent sit or Pivots (rotates) |
|
|
| Part 3, Month 6: Standing - Supports weight |
|
|
| Part 3, Month 6: Walking - Makes any attempt (i.e., bounces) |
|
|
| Part 3 Month 6 |
|
|
| Invasive ventilation |
|