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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-004014-17 | EudraCT Number |
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The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of lumasiran in infants and young children with confirmed primary hyperoxaluria type 1 (PH1).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lumasiran | Experimental | Lumasiran will be administered by subcutaneous (SC) injection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lumasiran | Drug | Lumasiran will be administered by subcutaneous (SC) injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 | Percent change in spot urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. | Baseline to Month 6 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Spot Urinary Oxalate: Creatinine Ratio in the Extension Period (Month 6 to End of Study [Month 60]) | A negative change from baseline indicates a favorable outcome. | From Month 6 to Month 60 |
| Percentage of Time That Spot Urinary Oxalate: Creatinine Ratio is at or Below the Near-normalization Threshold (≤1.5 × Upper Limit of Normal (ULN) for Age) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Alnylam Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Trial Site | Rochester | Minnesota | 55905 | United States | ||
| Clinical Trial Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39355649 | Derived | Frishberg Y, Hayes W, Shasha-Lavsky H, Sas DJ, Michael M, Sellier-Leclerc AL, Hogan J, Willey R, Gansner JM, Magen D. Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 30-month analysis of the phase 3 ILLUMINATE-B trial. Front Pediatr. 2024 Sep 16;12:1392644. doi: 10.3389/fped.2024.1392644. eCollection 2024. | |
| 38332115 |
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Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the United States (US) and/or the European Union (EU).
Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.
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A total of 18 participants with Primary hyperoxaluria type 1 (PH1) were enrolled and treated in this study.
Participants took part in the study at investigative sites in France, Germany, Israel, the United Kingdom, and the United States from 22 April 2019 to 26 July 2024.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lumasiran | Participants weighing <10 kg received loading doses of lumasiran subcutaneous (SC) injection 6.0 mg/kg monthly (QM) for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month primary analysis period (PAP) & QM during the 54-month extension period (EP). Participants who transitioned from <10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to <20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 & 6 in the 6-month PAP & Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg at Months 3 & 6 in the 6-month PAP & Q3M during the 54-month EP. Participants with weight increases to a new dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary Analysis Period |
| |||||||||||||
| Long-term Extension Period |
|
Safety analysis set included all participants who had received at least one dose of Lumasiran during study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Lumasiran | Participants weighing <10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP & QM during the 54-month EP. Participants who transitioned from <10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to <20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 & 6 in the 6-month PAP & Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 & 6 in the 6-month PAP & Q3M during the 54-month EP. Participants with weight increases to a new dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased. |
| 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 Change in Spot Urinary Oxalate:Creatinine Ratio From Baseline to Month 6 | Percent change in spot urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. | Efficacy Analysis Set: All participants who received any amount of lumasiran and had at least 1 valid spot urinary oxalate:creatinine ratio value at baseline and at least 1 valid spot urinary oxalate:creatinine ratio value from assessment(s) at Month 3 through Month 6. | Posted | Least Squares Mean | Standard Error | percent change | Baseline to Month 6 |
|
Up to 60 months
Safety analysis set included all subjects who had received at least one dose of Lumasiran.
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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 | Lumasiran | Participants weighing <10 kg received loading doses of lumasiran SC injection 6.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg QM during the 6-month PAP & QM during the 54-month EP. Participants who transitioned from <10 kg to ≥10 kg continued monthly doses at 3.0 mg/kg until the next visit that coincided with a dose for participants weighing ≥10 kg. Thereafter, participants followed Q3M dosing until the end of the study. Participants weighing ≥10 to <20 kg received lumasiran 6.0 mg/kg QM for 3 months, then maintenance doses of 6.0 mg/kg at Months 3 & 6 in the 6-month PAP & Q3M during the 54-month EP. Participants ≥20 kg received lumasiran 3.0 mg/kg QM for 3 months, followed by maintenance doses of 3.0 mg/kg Months 3 & 6 in the 6-month PAP & Q3M during the 54-month EP. Participants with weight increases to a new dosing category (<10 kg to ≥10 kg or <20 kg to ≥20 kg) followed the new regimen for the rest of the study or until the next dosing category threshold was reached; participants did not switch back to lower-weight dosing schedules if their body weight subsequently decreased. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Viral infection | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Eosinophilia | Blood and lymphatic system disorders | MedDRA25.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Alnylam Pharmaceuticals Inc. | 866-330-0326 | clinicaltrials@alnylam.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 | Jun 29, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 3, 2020 | Jan 24, 2025 | SAP_002.pdf |
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| ID | Term |
|---|---|
| D006960 | Hyperoxaluria, Primary |
| C536414 | Primary hyperoxaluria type 1 |
| D006959 | Hyperoxaluria |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C000716350 | lumasiran |
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Percentage of time that spot urinary oxalate: creatinine (UOx:Cr) ratio level is at or below ≤ 1.5xULN is calculated as (cumulative months at or below near normalization threshold divided by cumulative months of assessments)*100. Cumulative months in near-normalization is defined as the summation across all intervals that met the near-normal threshold and cumulative months of valid assessments is defined as the summation across all valid post-baseline collections. ULN levels of spot urinary oxalate to creatinine ratio where urine oxalate levels were analyzed using enzymatic assay. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073. |
| Up to 60 months |
| Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline | The absolute change is represented as ratio of millimoles of urinary oxalate to millimoles of urinary creatinine. | From Baseline to Month 6 and Month 60 |
| Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ the ULN for Age | The percentage of participants meeting the criteria (UOx:Cr ratio ≤ the ULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073. | Up to 60 months |
| Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ 1.5xULN for Age | The percentage of participants meeting the criteria (UOx:Cr ratio ≤ 1.5xULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073. | Up to 60 months |
| Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60) | The lower limit of quantification (LLOQ) was 5.55 micromoles per liter (μmol/L). A negative change from baseline indicates a favorable outcome. | From Baseline to Month 6 and Month 60 |
| Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60) | The LLOQ was 5.55 μmol/L. A negative change from Baseline indicates a favorable outcome. | From Baseline to Month 6 and Month 60 |
| Maximum Observed Plasma Concentration (Cmax) of Lumasiran | Cmax was the maximum plasma concentration post-dose within the pharmacokinetic (PK) sampling time frame. Higher Cmax generally indicates higher drug exposure. | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran | Tmax was estimated by calculating the time required to reach the maximum plasma concentration (Cmax) after the drug administration. Lower Tmax generally indicates faster drug absorption from the administration site. | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Elimination Half-life (t1/2beta) of Lumasiran | Elimination half-life was estimated from the terminal phase of the plasma concentration-time profile post-dose. Shorter half-life generally indicates rapid drug elimination from the body. | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran | AUC0-24 was the total drug exposure calculated as the area under the plasma concentration-time curve from the time of dosing (t = 0) to 24 hours. | 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran | AUC0-last was the total drug exposure calculated as the area under the plasma concentration-time curve from time 0 to the time of the last measurable (quantifiable) concentration (C_last). | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran | AUC0-infinity was the total drug exposure estimated as the area under the plasma concentration-time curve from time 0 extrapolated to infinity. | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Apparent Clearance (CL/F) of Lumasiran | Apparent clearance was calculated by dividing the area under the plasma concentration-time curve from zero infinity by the dose administered. A higher clearance generally indicates faster elimination from the body. | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Apparent Volume of Distribution (V/F) of Lumasiran | Apparent Volume of Distribution generally indicates the extent of drug distribution in the body. | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
| Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | eGFR [in milliliters per minute per 1.73 meters square (mL/min/1.73m^2)] was calculated from serum creatinine (SCr) based on the Schwartz Bedside Formula for participants ≥12 months of age at the time of assessment. | From Baseline to Month 6 and Month 60 |
| Number of Participants With Adverse Events (AEs) | An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Up to 60 months |
| Houston |
| Texas |
| 77030 |
| United States |
| Clinical Trial Site | Lyon | France |
| Clinical Trial Site | Paris | France |
| Clinical Trial Site | Bonn | Germany |
| Clinical Trial Site | Haifa | Israel |
| Clinical Trial Site | Jerusalem | Israel |
| Clinical Trial Site | Nahariya | Israel |
| Clinical Trial Site | London | United Kingdom |
| Sankar A, Y S RK, Singh A, Roy R, Shukla R, Verma B. Next-generation therapeutics for rare genetic disorders. Mutagenesis. 2024 Apr 24;39(3):157-171. doi: 10.1093/mutage/geae002. |
| 35913563 | Derived | Hayes W, Sas DJ, Magen D, Shasha-Lavsky H, Michael M, Sellier-Leclerc AL, Hogan J, Ngo T, Sweetser MT, Gansner JM, McGregor TL, Frishberg Y. Efficacy and safety of lumasiran for infants and young children with primary hyperoxaluria type 1: 12-month analysis of the phase 3 ILLUMINATE-B trial. Pediatr Nephrol. 2023 Apr;38(4):1075-1086. doi: 10.1007/s00467-022-05684-1. Epub 2022 Aug 1. |
| 34906487 | Derived | Sas DJ, Magen D, Hayes W, Shasha-Lavsky H, Michael M, Schulte I, Sellier-Leclerc AL, Lu J, Seddighzadeh A, Habtemariam B, McGregor TL, Fujita KP, Frishberg Y; ILLUMINATE-B Workgroup. Phase 3 trial of lumasiran for primary hyperoxaluria type 1: A new RNAi therapeutic in infants and young children. Genet Med. 2022 Mar;24(3):654-662. doi: 10.1016/j.gim.2021.10.024. Epub 2021 Dec 8. |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Spot Urinary Oxalate:Creatinine Ratio | Mean | Standard Deviation | mmol/mmol |
|
|
|
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| Secondary | Percentage Change in Spot Urinary Oxalate: Creatinine Ratio in the Extension Period (Month 6 to End of Study [Month 60]) | A negative change from baseline indicates a favorable outcome. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) at Month 6 through Month 60. | Posted | Mean | Standard Error | percent change | From Month 6 to Month 60 |
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| Secondary | Percentage of Time That Spot Urinary Oxalate: Creatinine Ratio is at or Below the Near-normalization Threshold (≤1.5 × Upper Limit of Normal (ULN) for Age) | Percentage of time that spot urinary oxalate: creatinine (UOx:Cr) ratio level is at or below ≤ 1.5xULN is calculated as (cumulative months at or below near normalization threshold divided by cumulative months of assessments)*100. Cumulative months in near-normalization is defined as the summation across all intervals that met the near-normal threshold and cumulative months of valid assessments is defined as the summation across all valid post-baseline collections. ULN levels of spot urinary oxalate to creatinine ratio where urine oxalate levels were analyzed using enzymatic assay. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) throughout the study duration. | Posted | Median | Full Range | percentage of time | Up to 60 months |
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| Secondary | Absolute Change in Spot Urinary Oxalate: Creatinine Ratio From Baseline | The absolute change is represented as ratio of millimoles of urinary oxalate to millimoles of urinary creatinine. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) throughout the study duration. | Posted | Mean | Standard Error | mmol/mmol | From Baseline to Month 6 and Month 60 |
|
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| Secondary | Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ the ULN for Age | The percentage of participants meeting the criteria (UOx:Cr ratio ≤ the ULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) throughout the study duration. | Posted | Number | percentage of participants | Up to 60 months |
|
|
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| Secondary | Percentage of Participants With Spot Urinary Oxalate: Creatinine Ratio Levels ≤ 1.5xULN for Age | The percentage of participants meeting the criteria (UOx:Cr ratio ≤ 1.5xULN for age) at least at one post-baseline visit were reported for this outcome measure. The age-dependent reference ULN levels of spot urinary oxalate to creatinine ratio are as follows: 1-1.5 years=0.158; 1.5-2 years=0.138; 2-2.5 years=0.124; 2.5-3 years=0.116; 3-3.5 years=0.102; 3.5-4 years=0.094; 4-4.5 years=0.088; 4.5-5 years=0.082; 5-5.5 years=0.077; 5.5-6 years=0.073. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) throughout the study duration. | Posted | Number | percentage of participants | Up to 60 months |
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| Secondary | Percentage Change in Plasma Oxalate From Baseline to End of Study (Month 60) | The lower limit of quantification (LLOQ) was 5.55 micromoles per liter (μmol/L). A negative change from baseline indicates a favorable outcome. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) throughout the study duration. | Posted | Mean | Standard Error | percent change | From Baseline to Month 6 and Month 60 |
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| Secondary | Absolute Change in Plasma Oxalate From Baseline to End of Study (Month 60) | The LLOQ was 5.55 μmol/L. A negative change from Baseline indicates a favorable outcome. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) throughout the study duration. | Posted | Mean | Standard Error | µmol/L | From Baseline to Month 6 and Month 60 |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) of Lumasiran | Cmax was the maximum plasma concentration post-dose within the pharmacokinetic (PK) sampling time frame. Higher Cmax generally indicates higher drug exposure. | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Time to Maximum Observed Plasma Concentration (Tmax) of Lumasiran | Tmax was estimated by calculating the time required to reach the maximum plasma concentration (Cmax) after the drug administration. Lower Tmax generally indicates faster drug absorption from the administration site. | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Median | Full Range | hours (h) | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Elimination Half-life (t1/2beta) of Lumasiran | Elimination half-life was estimated from the terminal phase of the plasma concentration-time profile post-dose. Shorter half-life generally indicates rapid drug elimination from the body. | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Median | Full Range | hours (h) | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Area Under the Concentration-time Curve From 0 to 24 Hours (AUC0-24) of Lumasiran | AUC0-24 was the total drug exposure calculated as the area under the plasma concentration-time curve from the time of dosing (t = 0) to 24 hours. | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | hours*nanograms per milliliter (h*ng/mL) | 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Area Under the Concentration-time Curve From 0 to Last Quantifiable Concentration (AUC0-last) of Lumasiran | AUC0-last was the total drug exposure calculated as the area under the plasma concentration-time curve from time 0 to the time of the last measurable (quantifiable) concentration (C_last). | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Area Under the Concentration-time Curve From 0 to Infinity (AUC0-infinity) of Lumasiran | AUC0-infinity was the total drug exposure estimated as the area under the plasma concentration-time curve from time 0 extrapolated to infinity. | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Apparent Clearance (CL/F) of Lumasiran | Apparent clearance was calculated by dividing the area under the plasma concentration-time curve from zero infinity by the dose administered. A higher clearance generally indicates faster elimination from the body. | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | liters per hour (L/h) | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Apparent Volume of Distribution (V/F) of Lumasiran | Apparent Volume of Distribution generally indicates the extent of drug distribution in the body. | PK analysis set included all participants who had received at least one full dose of Lumasiran and had at least one post-dose blood sample for PK parameters and had evaluable PK data. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at specified timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters (L) | 2 hours, 4 hours, 8 hours, 12 hours, and 24 hours post-dose on Day 1, Month 6, Month 12, Month 18 and Month 24 |
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| Secondary | Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) | eGFR [in milliliters per minute per 1.73 meters square (mL/min/1.73m^2)] was calculated from serum creatinine (SCr) based on the Schwartz Bedside Formula for participants ≥12 months of age at the time of assessment. | Efficacy analysis set included all participants who were treated with Lumasiran and had at least one spot urinary oxalate:creatinine ratio value at baseline and at least one spot urinary oxalate:creatinine ratio value from assessment(s) throughout the study duration. Overall number analyzed is the number of participants with data available for analysis. | Posted | Mean | Standard Error | mL/min/1.73m^2 | From Baseline to Month 6 and Month 60 |
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| Secondary | Number of Participants With Adverse Events (AEs) | An Adverse Event (AE) is any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. | Safety analysis set included all participants who had received at least one dose of Lumasiran. | Posted | Count of Participants | Participants | Up to 60 months |
|
|
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| 0 |
| 18 |
| 2 |
| 18 |
| 18 |
| 18 |
| Ear haemorrhage | Ear and labyrinth disorders | MedDRA 25.0 | Systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA25.0 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA25.0 | Systematic Assessment |
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| Microcytosis | Blood and lymphatic system disorders | MedDRA25.0 | Systematic Assessment |
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| Factor XII deficiency | Congenital, familial and genetic disorders | MedDRA25.0 | Systematic Assessment |
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| Ear pain | Ear and labyrinth disorders | MedDRA25.0 | Systematic Assessment |
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| Conjunctivitis allergic | Eye disorders | MedDRA25.0 | Systematic Assessment |
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| Myopia | Eye disorders | MedDRA25.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Anal pruritus | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Aphthous ulcer | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Mouth ulceration | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Teething | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA25.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA25.0 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA25.0 | Systematic Assessment |
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| Injection site haematoma | General disorders | MedDRA25.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA25.0 | Systematic Assessment |
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| Injection site urticaria | General disorders | MedDRA25.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA25.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA25.0 | Systematic Assessment |
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| Asymptomatic bacteriuria | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Conjunctivitis bacterial | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Croup infectious | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Ear infection | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Eye infection | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Gastroenteritis viral | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Otitis media | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Pharyngitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Pharyngitis streptococcal | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Pneumonia bacterial | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Streptococcal infection | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Tooth infection | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Varicella | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Viral infection | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Viral pharyngitis | Infections and infestations | MedDRA25.0 | Systematic Assessment |
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| Arthropod bite | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
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| Arthropod sting | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
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| Hand fracture | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
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| Skin abrasion | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
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| Ulna fracture | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA25.0 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA25.0 | Systematic Assessment |
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| Blood bicarbonate decreased | Investigations | MedDRA25.0 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA25.0 | Systematic Assessment |
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| SARS-CoV-2 antibody test positive | Investigations | MedDRA25.0 | Systematic Assessment |
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| Transaminases increased | Investigations | MedDRA25.0 | Systematic Assessment |
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| Urine analysis abnormal | Investigations | MedDRA25.0 | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA25.0 | Systematic Assessment |
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| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA25.0 | Systematic Assessment |
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| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA25.0 | Systematic Assessment |
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| Iron deficiency | Metabolism and nutrition disorders | MedDRA25.0 | Systematic Assessment |
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| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA25.0 | Systematic Assessment |
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| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA25.0 | Systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA25.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA25.0 | Systematic Assessment |
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| Behaviour disorder | Psychiatric disorders | MedDRA25.0 | Systematic Assessment |
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| Bruxism | Psychiatric disorders | MedDRA25.0 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA25.0 | Systematic Assessment |
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| Stress | Psychiatric disorders | MedDRA25.0 | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA25.0 | Systematic Assessment |
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| Proteinuria | Renal and urinary disorders | MedDRA25.0 | Systematic Assessment |
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| Renal impairment | Renal and urinary disorders | MedDRA25.0 | Systematic Assessment |
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| Gynaecomastia | Reproductive system and breast disorders | MedDRA25.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA25.0 | Systematic Assessment |
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| Laryngeal obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA25.0 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA25.0 | Systematic Assessment |
|
| Nasal septum deviation | Respiratory, thoracic and mediastinal disorders | MedDRA25.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA25.0 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA25.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA25.0 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA25.0 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA25.0 | Systematic Assessment |
|
| Excessive granulation tissue | Skin and subcutaneous tissue disorders | MedDRA25.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA25.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA25.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA25.0 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA25.0 | Systematic Assessment |
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It is intended that after completion of the study, the data are to be submitted for publication in a scientific journal and/or for reporting at a scientific meeting. A separate publication by Institution or PI may not be submitted for publication until after this primary manuscript is published or following 12 months after completion of the study. A copy of any proposed publication based on this study, must be provided and confirmed received at the Sponsor at least 30 days before its submission.
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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