Urea Cycle Disorder
Conditions
Keywords
Urea Cycle Disorder, UCD, Buphenyl, Glycerol Phenylbutyrate, Ravicti, Hyperammonemia, Sodium Phenylbutyrate, GPB, HPN-100
Brief summary
This is an open-label study consisting of a transition period to RAVICTI, followed by a safety extension period for at least 6 months and up to 24 months of treatment with RAVICTI, depending on age at enrollment. It is designed to capture information important for evaluating safety, pharmacokinetics and efficacy in young children. Subjects who are followed by or referred to the Investigator for management of their UCD. Subjects eligible for this study will include patients ranging from newborn to \< 2 years of age with either a diagnosed or clinically suspected UCD.
Detailed description
Study acquired from Horizon in 2024.
Interventions
DRUGRAVICTI
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 2 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects up to 2 years of age * Signed informed consent by subject's parent/legal guardian * UCD diagnosis or suspected diagnosis of any subtype, except N-acetyl glutamate synthetase deficiency. If UCD has not been previously confirmed by genetic testing, consent must be obtained from parent/legal guardian prior to perform genetic testing. If genetic testing is inconsistent with or excludes a UCD diagnosis, the subject will be withdrawn from the study.
Exclusion criteria
* Use of any investigational drug within 30 days of Day 1 * Uncontrolled infection (viral or bacterial) or any other condition known to precipitate hyperammonemic crises. Once these precipitating factors are medically controlled, patients presenting in crisis are eligible. * Any clinical or laboratory abnormality of Grade 3 or greater severity according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03, except Grade 3 elevations in ammonia and liver enzymes, defined as levels 5-20 times the upper limit of normal in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma glutamyl transpeptidase (GGT) in a clinically stable subject * Any clinical or laboratory abnormality or medical condition that, at the discretion of the Investigator, may put the subject at increased risk by participating in this study * Known hypersensitivity to phenylacetate (PAA) or phenylbutyrate (PBA) * Liver transplantation, including hepatocellular transplant * Subjects on hemodialysis at time of initiating RAVICTI * Subjects on RAVICTI for UCD management * Currently treated with Carbaglu® (carglumic acid)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Successful Transition to RAVICTI With Controlled Ammonia (i.e. No Clinical Symptoms and Ammonia < 100 μmol/L): Cohort of 2 Months to <2 Years Participants | Up to Day 4 | The percentage of participants with successful transition is based on Investigator response to the question, Has transition to 100% RAVICTI been successful with controlled ammonia? For participants 2 months of age and older, after a minimum of 24 hours of ammonia monitoring following the first full dose of RAVICTI alone, the participant was effectively transitioned when following conditions were met: no signs and symptoms of hyperammonemia; ammonia level less than 100 μmol/L (without normalization of ammonia, ie, without conversion of values from local laboratories with varying normal ranges to standardized values); and eligible for discharge per Investigator judgment. |
| Percentage of Participants With Successful Transition to RAVICTI With Controlled Ammonia (i.e. No Clinical Symptoms and Ammonia < 100 μmol/L): Cohort of 0 Months to <2 Months Participants | Up to Day 4 | The percentage of participants with successful transition is based on Investigator response to the question, Has transition to 100% RAVICTI been successful with controlled ammonia? For participants \< 2 months of age, after a minimum of 24 hours of ammonia monitoring following the first full dose of RAVICTI alone, the participant was effectively transitioned when following conditions were met: no signs and symptoms of hyperammonemia; ammonia level less than 100 μmol/L (without normalization of ammonia, ie, without conversion of values from local laboratories with varying normal ranges to standardized values); and eligible for discharge per Investigator judgment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24 | — |
| Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BMI. The Z-scores are based on the World Health Organization's Child Growth Standards charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender. |
| Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BSA. The Z-scores are based on weight-for-length charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender. |
| Plasma Phenylbutyrate/Phenylbutyric Acid (PBA) Maximum Plasma Concentration (Cmax) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PBA Minimum Plasma Concentration (Cmin) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PBA Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PBA Time to Cmax (Tmax) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma Phenylacetate/Phenylacetic Acid (PAA) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma Phenylacetylglutamine (PAGN) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 0.5 and 1 hour, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, End of Trial (up to Month 18) | — |
| Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 and between 0.5 and 1.5 hours, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 15, Month 18, End of Trial (up to Month 18) | — |
| Rate of HACs: Cohort of 0 Months to <2 Months Participants | Day 8 through up to Month 6 | HAC is defined as having signs and symptoms consistent with hyperammonemia (such as but not limited to frequent vomiting, nausea, headache, lethargy, irritability, combativeness, and/or somnolence) associated with high blood ammonia and requiring medical intervention. Rate of HACs per 6 months during the safety extension was calculated as sum of (number of HAC) / sum of (days during first 6 months starting on Day 8 or number days on RAVICTI, whichever is less) across all participants in the corresponding group. |
| Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants | From the first dose of study treatment through 30 days after the final dose (mean [SD] duration of treatment was 10.67 [6.142] months). | An AE is any untoward medical occurrence, whether or not the event is considered related to the study drug. A serious AE is any AE that: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. TEAEs are defined as AEs with an onset date on or after the first dose of study medication until study discontinuation. The Investigator assessed the causal relationship of each TEAE to the study drug as not related, possibly related, or probably related. |
| Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | — |
| Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | — |
| Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BMI. The Z-scores are based on the World Health Organization's Child Growth Standards charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender. |
| Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24 | To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BSA. The Z-scores are based on weight-for-length charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender. |
| Plasma PBA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PBA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PBA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PBA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAGN Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Rate of Hyperammonemic Crises (HACs): Cohort of 2 Months to <2 Years Participants | Day 8 through up to Month 6 | HAC is defined having signs and symptoms consistent with hyperammonemia (such as but not limited to frequent vomiting, nausea, headache, lethargy, irritability, combativeness, and/or somnolence) associated with high blood ammonia and requiring medical intervention. Rate of HACs per 6 months during the safety extension is calculated as sum of (number of HAC) / sum of (days during first 6 months starting on Day 8 or number days on RAVICTI, whichever is less) across all participants in the corresponding group. |
| Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 0.5 and 1 hour, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, End of Trial (up to Month 15) | — |
| Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 0.5 and 1.5 hours, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 15, End of Trial (up to Month 15) | — |
| Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC | — |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants | From the first dose of study treatment through 30 days after the final dose (mean [SD] duration of treatment was 9.13 [6.838] months). | An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the study drug. A serious AE is any AE that: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. TEAEs are defined as AEs with an onset date on or after the first dose of study medication until study discontinuation. The Investigator assessed the causal relationship of each TEAE to the study drug as not related, possibly related, or probably related. |
Countries
Canada, United States
Participant flow
Pre-assignment details
A total of 27 participants were enrolled; 1 participant was not dosed and is not included in any analysis.
Participants by arm
| Arm | Count |
|---|---|
| RAVICTI: Age 2 Months to < 2 Years Participants age 2 months to \< 2 years received RAVICTI Oral Liquid administered just prior to breastfeeding or intake of formula or food. The recommended dosing regimen is 3-6 times per day depending on feeding schedule and at the discretion of the Investigator. | 10 |
| RAVICTI: Age 0 to <2 Months Participants age 0 to \< 2 months received RAVICTI Oral Liquid administered just prior to breastfeeding or intake of formula or food. The recommended dosing regimen is 3-6 times per day depending on feeding schedule and at the discretion of the Investigator. | 16 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Stopping Rule: Liver Transplant | 2 | 4 |
| Overall Study | Withdrawal by Parent/Guardian | 0 | 1 |
Baseline characteristics
| Characteristic | RAVICTI: Age 2 Months to < 2 Years | RAVICTI: Age 0 to <2 Months | Total |
|---|---|---|---|
| Age, Continuous | 9.87 months STANDARD_DEVIATION 5.529 | 0.83 months STANDARD_DEVIATION 0.697 | 4.31 months STANDARD_DEVIATION 5.606 |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 10 | 0 / 16 |
| other Total, other adverse events | 8 / 10 | 16 / 16 |
| serious Total, serious adverse events | 6 / 10 | 11 / 16 |
Outcome results
Primary
Percentage of Participants With Successful Transition to RAVICTI With Controlled Ammonia (i.e. No Clinical Symptoms and Ammonia < 100 μmol/L): Cohort of 0 Months to <2 Months Participants
The percentage of participants with successful transition is based on Investigator response to the question, Has transition to 100% RAVICTI been successful with controlled ammonia? For participants \< 2 months of age, after a minimum of 24 hours of ammonia monitoring following the first full dose of RAVICTI alone, the participant was effectively transitioned when following conditions were met: no signs and symptoms of hyperammonemia; ammonia level less than 100 μmol/L (without normalization of ammonia, ie, without conversion of values from local laboratories with varying normal ranges to standardized values); and eligible for discharge per Investigator judgment.
Time frame: Up to Day 4
Population: Safety Population: all enrolled participants who received any amount of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Percentage of Participants With Successful Transition to RAVICTI With Controlled Ammonia (i.e. No Clinical Symptoms and Ammonia < 100 μmol/L): Cohort of 0 Months to <2 Months Participants | 100 percentage of participants |
Primary
Percentage of Participants With Successful Transition to RAVICTI With Controlled Ammonia (i.e. No Clinical Symptoms and Ammonia < 100 μmol/L): Cohort of 2 Months to <2 Years Participants
The percentage of participants with successful transition is based on Investigator response to the question, Has transition to 100% RAVICTI been successful with controlled ammonia? For participants 2 months of age and older, after a minimum of 24 hours of ammonia monitoring following the first full dose of RAVICTI alone, the participant was effectively transitioned when following conditions were met: no signs and symptoms of hyperammonemia; ammonia level less than 100 μmol/L (without normalization of ammonia, ie, without conversion of values from local laboratories with varying normal ranges to standardized values); and eligible for discharge per Investigator judgment.
Time frame: Up to Day 4
Population: Safety Population: all enrolled participants who received any amount of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Percentage of Participants With Successful Transition to RAVICTI With Controlled Ammonia (i.e. No Clinical Symptoms and Ammonia < 100 μmol/L): Cohort of 2 Months to <2 Years Participants | 100 percentage of participants |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | 84.97 μmol/L | Standard Deviation 52.086 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Day 7 change from Baseline | 26.81 μmol/L | Standard Deviation 76.417 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | 25.16 μmol/L | Standard Deviation 64.474 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | 50.05 μmol/L | Standard Deviation 73.988 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | 18.77 μmol/L | Standard Deviation 67.561 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | 57.43 μmol/L | Standard Deviation 98.55 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | 43.65 μmol/L | Standard Deviation 140.985 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | 33.41 μmol/L | Standard Deviation 150.273 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | 8.75 μmol/L | Standard Deviation 97.329 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | 25.75 μmol/L | Standard Deviation 62.66 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | 2.50 μmol/L | Standard Deviation 21.92 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | 16.10 μmol/L | Standard Deviation 95.461 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 122.43 µmol/L | Standard Deviation 118.62 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Day 7 change from Baseline | -54.50 µmol/L | Standard Deviation 92.626 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | 7.80 µmol/L | Standard Deviation 25.646 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | -16.33 µmol/L | Standard Deviation 39.209 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | -13.00 µmol/L | Standard Deviation 39.59 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | 0.25 µmol/L | Standard Deviation 13.426 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | -2.20 µmol/L | Standard Deviation 34.463 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | 30.80 µmol/L | Standard Deviation 17.092 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | 22.20 µmol/L | Standard Deviation 23.506 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | 39.00 µmol/L | — |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | 48.00 µmol/L | Standard Deviation 53.74 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | 508.83 μmol/L | Standard Deviation 337.175 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Day 7 change from Baseline | 21.04 μmol/L | Standard Deviation 260.5 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | -27.62 μmol/L | Standard Deviation 379.796 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | -15.09 μmol/L | Standard Deviation 352.471 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | -113.98 μmol/L | Standard Deviation 230.855 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | -99.82 μmol/L | Standard Deviation 305.674 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | -138.16 μmol/L | Standard Deviation 349.269 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | -56.08 μmol/L | Standard Deviation 269.288 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | -181.50 μmol/L | Standard Deviation 118.604 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | -103.75 μmol/L | Standard Deviation 328.583 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | -184.00 μmol/L | Standard Deviation 80.61 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | -219.93 μmol/L | Standard Deviation 279.815 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 750.43 µmol/L | Standard Deviation 309 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Day 7 change from Baseline | -184.33 µmol/L | Standard Deviation 168.657 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | -174.60 µmol/L | Standard Deviation 318.249 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | -374.00 µmol/L | Standard Deviation 425.903 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | -252.75 µmol/L | Standard Deviation 323.852 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | -370.25 µmol/L | Standard Deviation 377.222 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | -113.20 µmol/L | Standard Deviation 519.71 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | -446.53 µmol/L | Standard Deviation 360.457 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | -450.50 µmol/L | Standard Deviation 386.699 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | -149.00 µmol/L | — |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | 195.00 µmol/L | Standard Deviation 554.372 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | 142.68 μmol/L | Standard Deviation 222.694 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Day 7 change from Baseline | -49.09 μmol/L | Standard Deviation 198.73 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | -1.62 μmol/L | Standard Deviation 233.754 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | -20.46 μmol/L | Standard Deviation 216.885 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | -67.32 μmol/L | Standard Deviation 173.564 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | -75.45 μmol/L | Standard Deviation 221.845 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | -35.94 μmol/L | Standard Deviation 78.367 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | -73.09 μmol/L | Standard Deviation 245.051 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | -178.50 μmol/L | Standard Deviation 335.538 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | -139.50 μmol/L | Standard Deviation 359.287 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | 1.00 μmol/L | Standard Deviation 45.255 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | -55.31 μmol/L | Standard Deviation 217.209 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 54.86 µmol/L | Standard Deviation 19.497 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Day 7 change from Baseline | 2.67 µmol/L | Standard Deviation 19.159 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | 4.20 µmol/L | Standard Deviation 45.861 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | -25.67 µmol/L | Standard Deviation 16.743 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | -20.25 µmol/L | Standard Deviation 20.353 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | -20.00 µmol/L | Standard Deviation 36.341 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | -16.40 µmol/L | Standard Deviation 12.137 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | -6.73 µmol/L | Standard Deviation 13.342 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | -13.33 µmol/L | Standard Deviation 15.885 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | -18.00 µmol/L | — |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | 1.50 µmol/L | Standard Deviation 10.607 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | 133.67 μmol/L | Standard Deviation 253.829 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Day 7 change from Baseline | -81.91 μmol/L | Standard Deviation 273.127 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | -60.80 μmol/L | Standard Deviation 278.083 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | -51.66 μmol/L | Standard Deviation 269.558 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | -82.82 μmol/L | Standard Deviation 224.269 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | -118.55 μmol/L | Standard Deviation 311.125 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | -11.85 μmol/L | Standard Deviation 40.693 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | -115.09 μmol/L | Standard Deviation 338.186 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | -249.50 μmol/L | Standard Deviation 483.776 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | -195.75 μmol/L | Standard Deviation 496.313 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | 6.00 μmol/L | Standard Deviation 62.225 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | -82.54 μmol/L | Standard Deviation 228.107 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | -31.25 µmol/L | Standard Deviation 24.771 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 90.86 µmol/L | Standard Deviation 29.249 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Day 7 change from Baseline | -0.83 µmol/L | Standard Deviation 32.762 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | 9.80 µmol/L | Standard Deviation 65.975 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | -33.00 µmol/L | Standard Deviation 25.239 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | -39.50 µmol/L | Standard Deviation 61.136 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | -25.40 µmol/L | Standard Deviation 13.594 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | -19.13 µmol/L | Standard Deviation 39.322 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | -34.37 µmol/L | Standard Deviation 23.283 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | -40.00 µmol/L | — |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | -1.50 µmol/L | Standard Deviation 31.82 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | 593.80 μmol/L | Standard Deviation 333.657 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Day 7 change from Baseline | 47.85 μmol/L | Standard Deviation 230.343 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | -2.46 μmol/L | Standard Deviation 402.919 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | 34.96 μmol/L | Standard Deviation 371.522 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | -95.21 μmol/L | Standard Deviation 238.136 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | -42.39 μmol/L | Standard Deviation 288.782 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | -94.51 μmol/L | Standard Deviation 297.378 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | -22.66 μmol/L | Standard Deviation 318.034 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | -172.75 μmol/L | Standard Deviation 210.202 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | -78.00 μmol/L | Standard Deviation 297.41 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | -181.50 μmol/L | Standard Deviation 102.53 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | -203.83 μmol/L | Standard Deviation 255.81 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 872.86 µmol/L | Standard Deviation 381.005 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Day 7 change from Baseline | -238.83 µmol/L | Standard Deviation 203.567 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | -166.80 µmol/L | Standard Deviation 332.421 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | -390.33 µmol/L | Standard Deviation 462.292 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | -265.75 µmol/L | Standard Deviation 339.015 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | -370.00 µmol/L | Standard Deviation 379.884 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | -115.40 µmol/L | Standard Deviation 546.796 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | -415.73 µmol/L | Standard Deviation 365.419 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | -428.30 µmol/L | Standard Deviation 404.351 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | -110.00 µmol/L | — |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Sum of Glutamine and Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | 243.00 µmol/L | Standard Deviation 608.112 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | 181.49 μmol/L | Standard Deviation 257.948 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Day 7 change from Baseline | -63.96 μmol/L | Standard Deviation 290.312 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | -39.04 μmol/L | Standard Deviation 297.634 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | -23.86 μmol/L | Standard Deviation 290.128 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | -74.41 μmol/L | Standard Deviation 233.538 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | -98.67 μmol/L | Standard Deviation 326.3 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | 2.64 μmol/L | Standard Deviation 77.843 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | -90.40 μmol/L | Standard Deviation 355.316 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | -238.25 μmol/L | Standard Deviation 506.435 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | -137.00 μmol/L | Standard Deviation 519.042 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | 38.00 μmol/L | Standard Deviation 67.882 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | -72.78 μmol/L | Standard Deviation 258.71 |
Secondary
Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants
Time frame: Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 171.43 µmol/L | Standard Deviation 42.887 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Day 7 change from Baseline | 4.00 µmol/L | Standard Deviation 24.133 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | 40.60 µmol/L | Standard Deviation 90.057 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | -27.33 µmol/L | Standard Deviation 37.018 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | -31.50 µmol/L | Standard Deviation 29.76 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | -56.00 µmol/L | Standard Deviation 75.939 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | -21.60 µmol/L | Standard Deviation 18.202 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | -11.90 µmol/L | Standard Deviation 71.753 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | -48.87 µmol/L | Standard Deviation 51.644 |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | -46.00 µmol/L | — |
| RAVICTI: Age 2 Months to < 2 Years | Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | 5.00 µmol/L | Standard Deviation 55.154 |
Secondary
Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants
To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BMI. The Z-scores are based on the World Health Organization's Child Growth Standards charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender.
Time frame: Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | -0.0544 z-score | Standard Deviation 1.26821 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 1 change from Baseline | -0.2158 z-score | Standard Deviation 1.3596 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | -0.2598 z-score | Standard Deviation 1.19544 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | -0.1617 z-score | Standard Deviation 1.02572 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | -0.0264 z-score | Standard Deviation 1.68215 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | 0.0828 z-score | Standard Deviation 1.14206 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | 0.0136 z-score | Standard Deviation 1.72106 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | 0.4614 z-score | Standard Deviation 1.25343 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | 0.6646 z-score | Standard Deviation 0.95334 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | 0.6830 z-score | Standard Deviation 0.55703 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | 0.3308 z-score | Standard Deviation 0.27572 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BMI Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | 0.7743 z-score | Standard Deviation 0.64962 |
Secondary
Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants
To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BMI. The Z-scores are based on the World Health Organization's Child Growth Standards charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender.
Time frame: Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 0.8107 z-score | Standard Deviation 2.17017 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 1 change from Baseline | -0.2385 z-score | Standard Deviation 0.7783 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | -0.0249 z-score | Standard Deviation 0.74861 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | 0.1815 z-score | Standard Deviation 0.86056 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | 0.4434 z-score | Standard Deviation 0.94854 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | 0.1484 z-score | Standard Deviation 0.76293 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | 0.2497 z-score | Standard Deviation 0.80923 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | 0.6407 z-score | Standard Deviation 0.98695 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | 0.4164 z-score | Standard Deviation 0.80674 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | -0.2997 z-score | Standard Deviation 0.16959 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 18 change from Baseline | -0.2038 z-score | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Mass Index (BMI) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | 0.5581 z-score | Standard Deviation 1.23993 |
Secondary
Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants
To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BSA. The Z-scores are based on weight-for-length charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender.
Time frame: Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Baseline | 0.7143 z-score | Standard Deviation 2.14922 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 1 change from Baseline | -0.2105 z-score | Standard Deviation 0.74135 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 2 change from Baseline | -0.0704 z-score | Standard Deviation 0.70393 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 3 change from Baseline | 0.1065 z-score | Standard Deviation 0.70165 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 4 change from Baseline | 0.3365 z-score | Standard Deviation 0.77672 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 5 change from Baseline | 0.1043 z-score | Standard Deviation 0.56747 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 6 change from Baseline | 0.1842 z-score | Standard Deviation 0.62205 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 9 change from Baseline | 0.4875 z-score | Standard Deviation 0.86137 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 12 change from Baseline | 0.2944 z-score | Standard Deviation 0.75133 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 15 change from Baseline | -0.3661 z-score | Standard Deviation 0.00932 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 18 change from Baseline | -0.2214 z-score | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in Body Surface Area (BSA) Z-Score Up to Month 24: Cohort of 2 Months to <2 Years Participants | Month 24 change from Baseline | 0.4310 z-score | Standard Deviation 1.1314 |
Secondary
Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants
To assess any effect of study drug treatment on growth, Z-scores were calculated to express the deviation from a reference population for BSA. The Z-scores are based on weight-for-length charts. Negative Z-scores indicate lower than typical for age and gender while positive scores indicate higher than typical for age and gender.
Time frame: Baseline, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, Month 24
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Baseline | -0.1980 z-score | Standard Deviation 2.11774 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 1 change from Baseline | 0.2336 z-score | Standard Deviation 1.95603 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 2 change from Baseline | 0.2006 z-score | Standard Deviation 1.72135 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 3 change from Baseline | 0.2684 z-score | Standard Deviation 1.37517 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 4 change from Baseline | 0.2372 z-score | Standard Deviation 2.30831 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 5 change from Baseline | 0.1810 z-score | Standard Deviation 1.70024 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 6 change from Baseline | 0.2902 z-score | Standard Deviation 2.05956 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 9 change from Baseline | 0.1679 z-score | Standard Deviation 1.32407 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 12 change from Baseline | 0.1308 z-score | Standard Deviation 0.50371 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 15 change from Baseline | 0.1595 z-score | Standard Deviation 0.75833 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 18 change from Baseline | 0.1050 z-score | Standard Deviation 0.73521 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Growth and Development: Baseline and Change From Baseline in BSA Z-Score Up to Month 24: Cohort of 0 Months to <2 Months Participants | Month 24 change from Baseline | 0.7341 z-score | Standard Deviation 1.35582 |
Secondary
Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 0.5 and 1.5 hours, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 | 11.1 μg/mL | Standard Deviation 10.4 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 0.5 to 1.5 hours | 46.2 μg/mL | Standard Deviation 58.6 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 1.5 to 2.5 hours | 62.5 μg/mL | Standard Deviation 42.8 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 4 to 6 hours | 34.6 μg/mL | Standard Deviation 56.2 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 7.5 to 8.5 hours | 22.8 μg/mL | Standard Deviation 25.3 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 12 to 24 hours | 35.2 μg/mL | Standard Deviation 51 |
Secondary
Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 0.5 and 1.5 hours, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 | 18.78 μg/mL | Standard Deviation 27.33 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 0.5 to 1.5 hours | 6.50 μg/mL | Standard Deviation 3.39 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 1.5 to 2.5 hours | 7.29 μg/mL | Standard Deviation 4.1 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 4 to 6 hours | 2.60 μg/mL | Standard Deviation 2.18 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 7.5 to 8.5 hours | 4.48 μg/mL | Standard Deviation 4.38 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 12 to 24 hours | 4.31 μg/mL | Standard Deviation 2.33 |
Secondary
Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants
Time frame: Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 15, End of Trial (up to Month 15)
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 12 | 6.0 μg/mL | Standard Deviation 3.8 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Day 7 | 23.7 μg/mL | Standard Deviation 31.2 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 1 | 14.6 μg/mL | Standard Deviation 17.2 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 2 | 12.3 μg/mL | Standard Deviation 13.3 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 3 | 14.4 μg/mL | Standard Deviation 10.7 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 4 | 6.4 μg/mL | Standard Deviation 7.1 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 5 | 13.2 μg/mL | Standard Deviation 14 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 6 | 5.5 μg/mL | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 9 | 11.8 μg/mL | Standard Deviation 8.5 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 15 | 4.9 μg/mL | Standard Deviation 0.3 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | End of trial | 11.6 μg/mL | Standard Deviation 9 |
Secondary
Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants
Time frame: Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 15, Month 18, End of Trial (up to Month 18)
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Day 7 | 5.82 μg/mL | Standard Deviation 2.21 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 1 | 4.44 μg/mL | Standard Deviation 4.61 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 2 | 3.69 μg/mL | Standard Deviation 1.82 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 3 | 4.65 μg/mL | Standard Deviation 0.49 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 4 | 7.14 μg/mL | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 5 | 3.27 μg/mL | Standard Deviation 1.96 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 6 | 1.59 μg/mL | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 9 | 4.10 μg/mL | Standard Deviation 1.65 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 15 | 2.04 μg/mL | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 18 | 1.64 μg/mL | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | End of trial | 7.0 μg/mL | Standard Deviation 5.16 |
Secondary
Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 0.5 and 1 hour, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | Hour 0 | 3530.43 μg/mL | Standard Deviation 3600.4 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 0.5 to 1.5 hours | 1828 μg/mL | Standard Deviation 2862 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 1.5 to 2.5 hours | 1746 μg/mL | Standard Deviation 1464 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 4 to 6 hours | 2260 μg/mL | Standard Deviation 1472 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 7.5 to 8.5 hours | 3530.43 μg/mL | Standard Deviation 3600.4 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 12 to 24 hours | 4404 μg/mL | Standard Deviation 3766 |
Secondary
Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 0.5 and 1 hour, 1.5 and 2.5 hours, 4 and 6 hours, 7.5 and 8.5 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | Hour 0 | 3273 μg/mL | Standard Deviation 1993 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 0.5 to 1.5 hours | 4140 μg/mL | Standard Deviation 4399 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 1.5 to 2.5 hours | 3145 μg/mL | Standard Deviation 5045 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 4 to 6 hours | 5202 μg/mL | Standard Deviation 4547 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 7.5 to 8.5 hours | 3950 μg/mL | Standard Deviation 3068 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 12 to 24 hours | 7561 μg/mL | Standard Deviation 6956 |
Secondary
Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants
Time frame: Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, End of Trial (up to Month 15)
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 15 | 3915 μg/mL | Standard Deviation 2584 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | End of trial | 6939 μg/mL | Standard Deviation 6581 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Day 7 | 4643 μg/mL | Standard Deviation 2506 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 1 | 4517 μg/mL | Standard Deviation 2485 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 2 | 4116 μg/mL | Standard Deviation 3137 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 3 | 7037 μg/mL | Standard Deviation 4493 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 4 | 2826 μg/mL | Standard Deviation 1543 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 5 | 6973 μg/mL | Standard Deviation 3682 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 6 | 5883 μg/mL | Standard Deviation 3128 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 9 | 7006 μg/mL | Standard Deviation 4289 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants | Month 12 | 5847 μg/mL | Standard Deviation 2992 |
Secondary
Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants
Time frame: Day 7, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 18, End of Trial (up to Month 18)
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Day 7 | 8859 μg/mL | Standard Deviation 10500 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 1 | 6274 μg/mL | Standard Deviation 4802 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 2 | 7386 μg/mL | Standard Deviation 6419 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 3 | 11456 μg/mL | Standard Deviation 14471 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 4 | 21416 μg/mL | Standard Deviation 33695 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 5 | 6129 μg/mL | Standard Deviation 8024 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 6 | 5347 μg/mL | Standard Deviation 3153 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 9 | 9357 μg/mL | Standard Deviation 7286 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 12 | 2580 μg/mL | Standard Deviation 286 |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 15 | 6400 μg/mL | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | Month 18 | 5250 μg/mL | — |
| RAVICTI: Age 2 Months to < 2 Years | Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants | End of trial | 25333 μg/mL | Standard Deviation 21324 |
Secondary
Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants
An AE is any untoward medical occurrence, whether or not the event is considered related to the study drug. A serious AE is any AE that: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. TEAEs are defined as AEs with an onset date on or after the first dose of study medication until study discontinuation. The Investigator assessed the causal relationship of each TEAE to the study drug as not related, possibly related, or probably related.
Time frame: From the first dose of study treatment through 30 days after the final dose (mean [SD] duration of treatment was 10.67 [6.142] months).
Population: Safety Population: all enrolled participants who received any amount of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants | ≥ 1 TEAE | 16 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants | ≥ 1 Related TEAE | 10 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants | ≥ 1 Serious TEAE | 11 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants | ≥ 1 Serious Related TEAE | 0 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants | Fatal Outcome TEAE | 0 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants | ≥ 1 TEAE Leading to Study Discontinuation | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants
An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the study drug. A serious AE is any AE that: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; is an important medical event. TEAEs are defined as AEs with an onset date on or after the first dose of study medication until study discontinuation. The Investigator assessed the causal relationship of each TEAE to the study drug as not related, possibly related, or probably related.
Time frame: From the first dose of study treatment through 30 days after the final dose (mean [SD] duration of treatment was 9.13 [6.838] months).
Population: Safety Population: all enrolled participants who received any amount of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants | ≥ 1 TEAE | 10 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants | ≥ 1 Related TEAE | 4 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants | ≥ 1 Serious TEAE | 6 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants | ≥ 1 Serious Related TEAE | 0 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants | Fatal Outcome TEAE | 1 Participants |
| RAVICTI: Age 2 Months to < 2 Years | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 2 Months to <2 Years Participants | ≥ 1 TEAE Leading to Study Discontinuation | 1 Participants |
Secondary
Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 1321.18 μg*hr/mL | Standard Deviation 1220.52 |
Secondary
Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 246.126 μg*hr/mL | Standard Deviation 238.547 |
Secondary
Plasma PAA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 115.3 μg/mL | Standard Deviation 102 |
Secondary
Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 98.98 μg/mL | Standard Deviation 122.07 |
Secondary
Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 4.197 μg/mL | Standard Deviation 6.434 |
Secondary
Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 9.85 hours | Standard Deviation 9.26 |
Secondary
Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 7.422 hours | Standard Deviation 7.351 |
Secondary
Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 1384.12 μg*hr/mL | Standard Deviation 1141.03 |
Secondary
Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 583.835 μg*hr/mL | Standard Deviation 285.241 |
Secondary
Plasma PAGN Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAGN Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 102.1 μg/mL | Standard Deviation 48.6 |
Secondary
Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 69.39 μg/mL | Standard Deviation 54.03 |
Secondary
Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 20.62 μg/mL | Standard Deviation 14.529 |
Secondary
Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 11.72 hours | Standard Deviation 8.24 |
Secondary
Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 6.573 hours | Standard Deviation 7.181 |
Secondary
Plasma PBA Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PBA Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 280.936 μg*hr/mL | Standard Deviation 293.553 |
Secondary
Plasma PBA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PBA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 374.53 μg*hr/mL | Standard Deviation 390.48 |
Secondary
Plasma PBA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PBA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 46.2 μg/mL | Standard Deviation 49.8 |
Secondary
Plasma PBA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PBA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 4.8 μg/mL | Standard Deviation 4.2 |
Secondary
Plasma PBA Minimum Plasma Concentration (Cmin) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PBA Minimum Plasma Concentration (Cmin) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 1.697 μg/mL | Standard Deviation 2.254 |
Secondary
Plasma PBA Time to Cmax (Tmax) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PBA Time to Cmax (Tmax) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 8.383 hours | Standard Deviation 4.564 |
Secondary
Plasma PBA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma PBA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants | 9.39 hours | Standard Deviation 7.41 |
Secondary
Plasma Phenylacetate/Phenylacetic Acid (PAA) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma Phenylacetate/Phenylacetic Acid (PAA) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 36.52 μg/mL | Standard Deviation 31.784 |
Secondary
Plasma Phenylacetylglutamine (PAGN) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma Phenylacetylglutamine (PAGN) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 62.45 μg/mL | Standard Deviation 27.281 |
Secondary
Plasma Phenylbutyrate/Phenylbutyric Acid (PBA) Maximum Plasma Concentration (Cmax) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
Time frame: Hour 0 and between 4 and 6 hours, 8 hours, and between 12 and 24 hours after the first dose of the day on Day 1 for stable participants and on Day 2 for participants in HAC
Population: Pharmacokinetic (PK) Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Plasma Phenylbutyrate/Phenylbutyric Acid (PBA) Maximum Plasma Concentration (Cmax) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants | 42.44 μg/mL | Standard Deviation 36.715 |
Secondary
Rate of HACs: Cohort of 0 Months to <2 Months Participants
HAC is defined as having signs and symptoms consistent with hyperammonemia (such as but not limited to frequent vomiting, nausea, headache, lethargy, irritability, combativeness, and/or somnolence) associated with high blood ammonia and requiring medical intervention. Rate of HACs per 6 months during the safety extension was calculated as sum of (number of HAC) / sum of (days during first 6 months starting on Day 8 or number days on RAVICTI, whichever is less) across all participants in the corresponding group.
Time frame: Day 8 through up to Month 6
Population: Safety Population: all enrolled participants who received any amount of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Rate of HACs: Cohort of 0 Months to <2 Months Participants | 0.003 HACs per half-year of patient exposure |
Secondary
Rate of Hyperammonemic Crises (HACs): Cohort of 2 Months to <2 Years Participants
HAC is defined having signs and symptoms consistent with hyperammonemia (such as but not limited to frequent vomiting, nausea, headache, lethargy, irritability, combativeness, and/or somnolence) associated with high blood ammonia and requiring medical intervention. Rate of HACs per 6 months during the safety extension is calculated as sum of (number of HAC) / sum of (days during first 6 months starting on Day 8 or number days on RAVICTI, whichever is less) across all participants in the corresponding group.
Time frame: Day 8 through up to Month 6
Population: Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAVICTI: Age 2 Months to < 2 Years | Rate of Hyperammonemic Crises (HACs): Cohort of 2 Months to <2 Years Participants | 0.005 HACs per half-year of patient exposure |