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A Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate in Pediatric Subjects Under 2 Years of Age With Urea Cycle Disorders

Sponsor
Horizon Therapeutics, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT02246218
Collaborator
(none)
27
Enrollment
17
Locations
1
Arm
30.5
Actual Duration (Months)
1.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
27 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Study of the Safety, Efficacy and Pharmacokinetics of Glycerol Phenylbutyrate (GPB; RAVICTI®) in Pediatric Subjects Under Two Years of Age With Urea Cycle Disorders (UCDs)
Actual Study Start Date :
Dec 31, 2014
Actual Primary Completion Date :
Oct 17, 2016
Actual Study Completion Date :
Jul 17, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: RAVICTI

RAVICTI Oral Liquid should be 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.

Drug: RAVICTI
Other Names:
  • HPN-100
  • Glycerol Phenylbutyrate
  • GPB

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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 Outcome Measures

    1. 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.

    2. 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.

    3. 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]

    4. 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]

    5. 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]

    6. 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]

    7. 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]

    8. 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]

    9. 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.

    10. 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.

    11. 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]

    12. 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]

    13. 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]

    14. 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]

    15. 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]

    16. 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]

    17. 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]

    18. 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]

    19. 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]

    20. 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]

    21. 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]

    22. 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]

    23. 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]

    24. 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)]

    25. 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]

    26. 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)]

    27. 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.

    28. 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.

    29. 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]

    30. 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]

    31. 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]

    32. 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]

    33. 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]

    34. 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]

    35. 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.

    36. 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.

    37. 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]

    38. 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]

    39. 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]

    40. 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]

    41. 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]

    42. 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]

    43. 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]

    44. 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]

    45. 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]

    46. 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]

    47. 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]

    48. 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]

    49. 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]

    50. 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)]

    51. 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]

    52. 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)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    1 Day to 2 Years
    Sexes Eligible for Study:
    All
    Accepts 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kaiser Permanente Regional Metabolic Center Los Angeles California United States 90027
    2 Stanford Center for Clinical & Translational Research & Education Palo Alto California United States 94034
    3 Children's National Medical Center Washington District of Columbia United States 20010
    4 Shands at University of Florida Gainesville Florida United States 32610
    5 Emory University Decatur Georgia United States 30033
    6 Indiana University Indianapolis Indiana United States 46202
    7 Maine Medical Center Portland Maine United States 04102
    8 Children's Hospital of Michigan Detroit Michigan United States 48201
    9 University of Minnesota Minneapolis Minnesota United States 55455
    10 Mount Sinai School of Medicine New York New York United States 10029
    11 University Hospitals Case Medical Center Cleveland Ohio United States 44106
    12 Oregon Health & Science University Portland Oregon United States 97239
    13 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
    14 Children's Hospital of Pittsburgh Pittsburgh Pennsylvania United States 15224
    15 University of Utah Salt Lake City Utah United States 84132
    16 Seattle Children's Hospital Seattle Washington United States 98105
    17 The Hospital for Sick Children Toronto Canada M5G 1Hs

    Sponsors and Collaborators

    • Horizon Therapeutics, LLC

    Investigators

    • Study Director: Colleen Canavan, BS, Horizon Therapeutics, LLC

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Horizon Therapeutics, LLC
    ClinicalTrials.gov Identifier:
    NCT02246218
    Other Study ID Numbers:
    • HPN-100-009
    • 2016-003460-38
    First Posted:
    Sep 22, 2014
    Last Update Posted:
    Mar 5, 2019
    Last Verified:
    Feb 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Horizon Therapeutics, LLC
    Urea Cycle Disorder
    UCD
    Buphenyl
    Glycerol Phenylbutyrate
    Ravicti
    Hyperammonemia
    Sodium Phenylbutyrate
    GPB
    HPN-100
    Additional relevant MeSH terms:
    Urea Cycle Disorders, Inborn
    Disease
    Glycerol

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 27 participants were enrolled; 1 participant was not dosed and is not included in any analysis.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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. 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.
    Period Title: Overall Study
    STARTED 10 16
    COMPLETED 6 10
    NOT COMPLETED 4 6

    Baseline Characteristics

    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years RAVICTI: Age 0 to <2 Months Total
    Arm/Group Description 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. 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. Total of all reporting groups
    Overall Participants 10 16 26
    Age (months) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [months]
    9.87
    (5.529)
    0.83
    (0.697)
    4.31
    (5.606)
    Sex: Female, Male (Count of Participants)
    Female
    5
    50%
    7
    43.8%
    12
    46.2%
    Male
    5
    50%
    9
    56.3%
    14
    53.8%

    Outcome Measures

    1. Primary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Number [percentage of participants]
    100
    1000%
    2. Primary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Number [percentage of participants]
    100
    1000%
    3. Secondary Outcome
    Title Rate of Hyperammonemic Crises (HACs): Cohort of 2 Months to <2 Years Participants
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 9
    Number [HACs per half-year of patient exposure]
    0.005
    4. Secondary Outcome
    Title 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
    Description 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).

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    ≥ 1 TEAE
    10
    100%
    ≥ 1 Related TEAE
    4
    40%
    ≥ 1 Serious TEAE
    6
    60%
    ≥ 1 Serious Related TEAE
    0
    0%
    Fatal Outcome TEAE
    1
    10%
    ≥ 1 TEAE Leading to Study Discontinuation
    1
    10%
    5. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 2 Months to <2 Years Participants
    Description
    Time Frame Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    122.43
    (118.620)
    Day 7 change from Baseline
    -54.50
    (92.626)
    Month 2 change from Baseline
    7.80
    (25.646)
    Month 3 change from Baseline
    -16.33
    (39.209)
    Month 4 change from Baseline
    -13.00
    (39.590)
    Month 5 change from Baseline
    0.25
    (13.426)
    Month 6 change from Baseline
    -2.20
    (34.463)
    Month 9 change from Baseline
    30.80
    (17.092)
    Month 12 change from Baseline
    22.20
    (23.506)
    Month 15 change from Baseline
    39.00
    (NA)
    Month 24 change from Baseline
    48.00
    (53.740)
    6. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 2 Months to <2 Years Participants
    Description
    Time Frame Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    750.43
    (309.000)
    Day 7 change from Baseline
    -184.33
    (168.657)
    Month 2 change from Baseline
    -174.60
    (318.249)
    Month 3 change from Baseline
    -374.00
    (425.903)
    Month 4 change from Baseline
    -252.75
    (323.852)
    Month 5 change from Baseline
    -370.25
    (377.222)
    Month 6 change from Baseline
    -113.20
    (519.710)
    Month 9 change from Baseline
    -446.53
    (360.457)
    Month 12 change from Baseline
    -450.50
    (386.699)
    Month 15 change from Baseline
    -149.00
    (NA)
    Month 24 change from Baseline
    195.00
    (554.372)
    7. Secondary Outcome
    Title 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
    Description
    Time Frame Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    872.86
    (381.005)
    Day 7 change from Baseline
    -238.83
    (203.567)
    Month 2 change from Baseline
    -166.80
    (332.421)
    Month 3 change from Baseline
    -390.33
    (462.292)
    Month 4 change from Baseline
    -265.75
    (339.015)
    Month 5 change from Baseline
    -370.00
    (379.884)
    Month 6 change from Baseline
    -115.40
    (546.796)
    Month 9 change from Baseline
    -415.73
    (365.419)
    Month 12 change from Baseline
    -428.30
    (404.351)
    Month 15 change from Baseline
    -110.00
    (NA)
    Month 24 change from Baseline
    243.00
    (608.112)
    8. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 2 Months to <2 Years Participants
    Description
    Time Frame Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    54.86
    (19.497)
    Day 7 change from Baseline
    2.67
    (19.159)
    Month 2 change from Baseline
    4.20
    (45.861)
    Month 3 change from Baseline
    -25.67
    (16.743)
    Month 4 change from Baseline
    -20.25
    (20.353)
    Month 5 change from Baseline
    -20.00
    (36.341)
    Month 6 change from Baseline
    -16.40
    (12.137)
    Month 9 change from Baseline
    -6.73
    (13.342)
    Month 12 change from Baseline
    -13.33
    (15.885)
    Month 15 change from Baseline
    -18.00
    (NA)
    Month 24 change from Baseline
    1.50
    (10.607)
    9. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 2 Months to <2 Years Participants
    Description
    Time Frame Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    90.86
    (29.249)
    Day 7 change from Baseline
    -0.83
    (32.762)
    Month 2 change from Baseline
    9.80
    (65.975)
    Month 3 change from Baseline
    -33.00
    (25.239)
    Month 4 change from Baseline
    -31.25
    (24.771)
    Month 5 change from Baseline
    -39.50
    (61.136)
    Month 6 change from Baseline
    -25.40
    (13.594)
    Month 9 change from Baseline
    -19.13
    (39.322)
    Month 12 change from Baseline
    -34.37
    (23.283)
    Month 15 change from Baseline
    -40.00
    (NA)
    Month 24 change from Baseline
    -1.50
    (31.820)
    10. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 2 Months to <2 Years Participants
    Description
    Time Frame Baseline, Day 7, Month 2, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15, Month 24

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment at given time point.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    171.43
    (42.887)
    Day 7 change from Baseline
    4.00
    (24.133)
    Month 2 change from Baseline
    40.60
    (90.057)
    Month 3 change from Baseline
    -27.33
    (37.018)
    Month 4 change from Baseline
    -31.50
    (29.760)
    Month 5 change from Baseline
    -56.00
    (75.939)
    Month 6 change from Baseline
    -21.60
    (18.202)
    Month 9 change from Baseline
    -11.90
    (71.753)
    Month 12 change from Baseline
    -48.87
    (51.644)
    Month 15 change from Baseline
    -46.00
    (NA)
    Month 24 change from Baseline
    5.00
    (55.154)
    11. Secondary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    0.8107
    (2.17017)
    Month 1 change from Baseline
    -0.2385
    (0.77830)
    Month 2 change from Baseline
    -0.0249
    (0.74861)
    Month 3 change from Baseline
    0.1815
    (0.86056)
    Month 4 change from Baseline
    0.4434
    (0.94854)
    Month 5 change from Baseline
    0.1484
    (0.76293)
    Month 6 change from Baseline
    0.2497
    (0.80923)
    Month 9 change from Baseline
    0.6407
    (0.98695)
    Month 12 change from Baseline
    0.4164
    (0.80674)
    Month 15 change from Baseline
    -0.2997
    (0.16959)
    Month 18 change from Baseline
    -0.2038
    (NA)
    Month 24 change from Baseline
    0.5581
    (1.23993)
    12. Secondary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Baseline
    0.7143
    (2.14922)
    Month 1 change from Baseline
    -0.2105
    (0.74135)
    Month 2 change from Baseline
    -0.0704
    (0.70393)
    Month 3 change from Baseline
    0.1065
    (0.70165)
    Month 4 change from Baseline
    0.3365
    (0.77672)
    Month 5 change from Baseline
    0.1043
    (0.56747)
    Month 6 change from Baseline
    0.1842
    (0.62205)
    Month 9 change from Baseline
    0.4875
    (0.86137)
    Month 12 change from Baseline
    0.2944
    (0.75133)
    Month 15 change from Baseline
    -0.3661
    (0.00932)
    Month 18 change from Baseline
    -0.2214
    (NA)
    Month 24 change from Baseline
    0.4310
    (1.13140)
    13. Secondary Outcome
    Title 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
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    Pharmacokinetic (PK) Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg/mL]
    42.44
    (36.715)
    14. Secondary Outcome
    Title Plasma PBA Minimum Plasma Concentration (Cmin) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg/mL]
    1.697
    (2.254)
    15. Secondary Outcome
    Title 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
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg*hr/mL]
    280.936
    (293.553)
    16. Secondary Outcome
    Title Plasma PBA Time to Cmax (Tmax) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [hours]
    8.383
    (4.564)
    17. Secondary Outcome
    Title Plasma Phenylacetate/Phenylacetic Acid (PAA) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg/mL]
    36.52
    (31.784)
    18. Secondary Outcome
    Title Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg/mL]
    4.197
    (6.434)
    19. Secondary Outcome
    Title Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg*hr/mL]
    246.126
    (238.547)
    20. Secondary Outcome
    Title Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [hours]
    7.422
    (7.351)
    21. Secondary Outcome
    Title Plasma Phenylacetylglutamine (PAGN) Cmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg/mL]
    62.45
    (27.281)
    22. Secondary Outcome
    Title Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg/mL]
    20.62
    (14.529)
    23. Secondary Outcome
    Title Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg*hr/mL]
    583.835
    (285.241)
    24. Secondary Outcome
    Title Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [hours]
    6.573
    (7.181)
    25. Secondary Outcome
    Title Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Hour 0
    3273
    (1993)
    0.5 to 1.5 hours
    4140
    (4399)
    1.5 to 2.5 hours
    3145
    (5045)
    4 to 6 hours
    5202
    (4547)
    7.5 to 8.5 hours
    3950
    (3068)
    12 to 24 hours
    7561
    (6956)
    26. Secondary Outcome
    Title Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Day 7
    8859
    (10500)
    Month 1
    6274
    (4802)
    Month 2
    7386
    (6419)
    Month 3
    11456
    (14471)
    Month 4
    21416
    (33695)
    Month 5
    6129
    (8024)
    Month 6
    5347
    (3153)
    Month 9
    9357
    (7286)
    Month 12
    2580
    (286)
    Month 15
    6400
    (NA)
    Month 18
    5250
    (NA)
    End of trial
    25333
    (21324)
    27. Secondary Outcome
    Title Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 2 Months to <2 Years Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Hour 0
    18.78
    (27.33)
    0.5 to 1.5 hours
    6.50
    (3.39)
    1.5 to 2.5 hours
    7.29
    (4.10)
    4 to 6 hours
    2.60
    (2.18)
    7.5 to 8.5 hours
    4.48
    (4.38)
    12 to 24 hours
    4.31
    (2.33)
    28. Secondary Outcome
    Title Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 2 Months to <2 Years Participants
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years
    Arm/Group Description 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.
    Measure Participants 10
    Day 7
    5.82
    (2.21)
    Month 1
    4.44
    (4.61)
    Month 2
    3.69
    (1.82)
    Month 3
    4.65
    (0.49)
    Month 4
    7.14
    (NA)
    Month 5
    3.27
    (1.96)
    Month 6
    1.59
    (NA)
    Month 9
    4.10
    (1.65)
    Month 15
    2.04
    (NA)
    Month 18
    1.64
    (NA)
    End of trial
    7.0
    (5.16)
    29. Secondary Outcome
    Title Rate of HACs: Cohort of 0 Months to <2 Months Participants
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Number [HACs per half-year of patient exposure]
    0.003
    30. Secondary Outcome
    Title Number of Participants With TEAEs, Serious TEAEs, Deaths, and Discontinuations Due to TEAEs: Cohort of 0 Months to <2 Months Participants
    Description 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).

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    ≥ 1 TEAE
    16
    160%
    ≥ 1 Related TEAE
    10
    100%
    ≥ 1 Serious TEAE
    11
    110%
    ≥ 1 Serious Related TEAE
    0
    0%
    Fatal Outcome TEAE
    0
    0%
    ≥ 1 TEAE Leading to Study Discontinuation
    1
    10%
    31. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Glutamate Up to Month 24: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    84.97
    (52.086)
    Day 7 change from Baseline
    26.81
    (76.417)
    Month 2 change from Baseline
    25.16
    (64.474)
    Month 3 change from Baseline
    50.05
    (73.988)
    Month 4 change from Baseline
    18.77
    (67.561)
    Month 5 change from Baseline
    57.43
    (98.550)
    Month 6 change from Baseline
    43.65
    (140.985)
    Month 9 change from Baseline
    33.41
    (150.273)
    Month 12 change from Baseline
    8.75
    (97.329)
    Month 15 change from Baseline
    25.75
    (62.660)
    Month 18 change from Baseline
    2.50
    (21.920)
    Month 24 change from Baseline
    16.10
    (95.461)
    32. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Glutamine Up to Month 24: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    508.83
    (337.175)
    Day 7 change from Baseline
    21.04
    (260.500)
    Month 2 change from Baseline
    -27.62
    (379.796)
    Month 3 change from Baseline
    -15.09
    (352.471)
    Month 4 change from Baseline
    -113.98
    (230.855)
    Month 5 change from Baseline
    -99.82
    (305.674)
    Month 6 change from Baseline
    -138.16
    (349.269)
    Month 9 change from Baseline
    -56.08
    (269.288)
    Month 12 change from Baseline
    -181.50
    (118.604)
    Month 15 change from Baseline
    -103.75
    (328.583)
    Month 18 change from Baseline
    -184.00
    (80.610)
    Month 24 change from Baseline
    -219.93
    (279.815)
    33. Secondary Outcome
    Title 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
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    593.80
    (333.657)
    Day 7 change from Baseline
    47.85
    (230.343)
    Month 2 change from Baseline
    -2.46
    (402.919)
    Month 3 change from Baseline
    34.96
    (371.522)
    Month 4 change from Baseline
    -95.21
    (238.136)
    Month 5 change from Baseline
    -42.39
    (288.782)
    Month 6 change from Baseline
    -94.51
    (297.378)
    Month 9 change from Baseline
    -22.66
    (318.034)
    Month 12 change from Baseline
    -172.75
    (210.202)
    Month 15 change from Baseline
    -78.00
    (297.410)
    Month 18 change from Baseline
    -181.50
    (102.530)
    Month 24 change from Baseline
    -203.83
    (255.810)
    34. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Isoleucine Up to Month 24: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    142.68
    (222.694)
    Day 7 change from Baseline
    -49.09
    (198.730)
    Month 2 change from Baseline
    -1.62
    (233.754)
    Month 3 change from Baseline
    -20.46
    (216.885)
    Month 4 change from Baseline
    -67.32
    (173.564)
    Month 5 change from Baseline
    -75.45
    (221.845)
    Month 6 change from Baseline
    -35.94
    (78.367)
    Month 9 change from Baseline
    -73.09
    (245.051)
    Month 12 change from Baseline
    -178.50
    (335.538)
    Month 15 change from Baseline
    -139.50
    (359.287)
    Month 18 change from Baseline
    1.00
    (45.255)
    Month 24 change from Baseline
    -55.31
    (217.209)
    35. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Leucine Up to Month 24: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    133.67
    (253.829)
    Day 7 change from Baseline
    -81.91
    (273.127)
    Month 2 change from Baseline
    -60.80
    (278.083)
    Month 3 change from Baseline
    -51.66
    (269.558)
    Month 4 change from Baseline
    -82.82
    (224.269)
    Month 5 change from Baseline
    -118.55
    (311.125)
    Month 6 change from Baseline
    -11.85
    (40.693)
    Month 9 change from Baseline
    -115.09
    (338.186)
    Month 12 change from Baseline
    -249.50
    (483.776)
    Month 15 change from Baseline
    -195.75
    (496.313)
    Month 18 change from Baseline
    6.00
    (62.225)
    Month 24 change from Baseline
    -82.54
    (228.107)
    36. Secondary Outcome
    Title Amino Acid Assessment: Baseline and Change From Baseline in Valine Up to Month 24: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    181.49
    (257.948)
    Day 7 change from Baseline
    -63.96
    (290.312)
    Month 2 change from Baseline
    -39.04
    (297.634)
    Month 3 change from Baseline
    -23.86
    (290.128)
    Month 4 change from Baseline
    -74.41
    (233.538)
    Month 5 change from Baseline
    -98.67
    (326.300)
    Month 6 change from Baseline
    2.64
    (77.843)
    Month 9 change from Baseline
    -90.40
    (355.316)
    Month 12 change from Baseline
    -238.25
    (506.435)
    Month 15 change from Baseline
    -137.00
    (519.042)
    Month 18 change from Baseline
    38.00
    (67.882)
    Month 24 change from Baseline
    -72.78
    (258.710)
    37. Secondary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    -0.0544
    (1.26821)
    Month 1 change from Baseline
    -0.2158
    (1.35960)
    Month 2 change from Baseline
    -0.2598
    (1.19544)
    Month 3 change from Baseline
    -0.1617
    (1.02572)
    Month 4 change from Baseline
    -0.0264
    (1.68215)
    Month 5 change from Baseline
    0.0828
    (1.14206)
    Month 6 change from Baseline
    0.0136
    (1.72106)
    Month 9 change from Baseline
    0.4614
    (1.25343)
    Month 12 change from Baseline
    0.6646
    (0.95334)
    Month 15 change from Baseline
    0.6830
    (0.55703)
    Month 18 change from Baseline
    0.3308
    (0.27572)
    Month 24 change from Baseline
    0.7743
    (0.64962)
    38. Secondary Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety Population: all enrolled participants who received any amount of study medication and had an assessment.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Baseline
    -0.1980
    (2.11774)
    Month 1 change from Baseline
    0.2336
    (1.95603)
    Month 2 change from Baseline
    0.2006
    (1.72135)
    Month 3 change from Baseline
    0.2684
    (1.37517)
    Month 4 change from Baseline
    0.2372
    (2.30831)
    Month 5 change from Baseline
    0.1810
    (1.70024)
    Month 6 change from Baseline
    0.2902
    (2.05956)
    Month 9 change from Baseline
    0.1679
    (1.32407)
    Month 12 change from Baseline
    0.1308
    (0.50371)
    Month 15 change from Baseline
    0.1595
    (0.75833)
    Month 18 change from Baseline
    0.1050
    (0.73521)
    Month 24 change from Baseline
    0.7341
    (1.35582)
    39. Secondary Outcome
    Title Plasma PBA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [μg/mL]
    46.2
    (49.8)
    40. Secondary Outcome
    Title Plasma PBA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 7
    Mean (Standard Deviation) [μg/mL]
    4.8
    (4.2)
    41. Secondary Outcome
    Title Plasma PBA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [μg*hr/mL]
    374.53
    (390.48)
    42. Secondary Outcome
    Title Plasma PBA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [hours]
    9.39
    (7.41)
    43. Secondary Outcome
    Title Plasma PAA Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [μg/mL]
    115.3
    (102.0)
    44. Secondary Outcome
    Title Plasma PAA Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 10
    Mean (Standard Deviation) [μg/mL]
    98.98
    (122.07)
    45. Secondary Outcome
    Title Plasma PAA AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [μg*hr/mL]
    1321.18
    (1220.52)
    46. Secondary Outcome
    Title Plasma PAA Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [hours]
    9.85
    (9.26)
    47. Secondary Outcome
    Title Plasma PAGN Cmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [μg/mL]
    102.1
    (48.6)
    48. Secondary Outcome
    Title Plasma PAGN Cmin on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 13
    Mean (Standard Deviation) [μg/mL]
    69.39
    (54.03)
    49. Secondary Outcome
    Title Plasma PAGN AUC(0-last) on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [μg*hr/mL]
    1384.12
    (1141.03)
    50. Secondary Outcome
    Title Plasma PAGN Tmax on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Mean (Standard Deviation) [hours]
    11.72
    (8.24)
    51. Secondary Outcome
    Title Assessment of Urinary PAGN Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Hour 0
    3530.43
    (3600.4)
    0.5 to 1.5 hours
    1828
    (2862)
    1.5 to 2.5 hours
    1746
    (1464)
    4 to 6 hours
    2260
    (1472)
    7.5 to 8.5 hours
    3530.43
    (3600.4)
    12 to 24 hours
    4404
    (3766)
    52. Secondary Outcome
    Title Assessment of Urinary PAGN Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Day 7
    4643
    (2506)
    Month 1
    4517
    (2485)
    Month 2
    4116
    (3137)
    Month 3
    7037
    (4493)
    Month 4
    2826
    (1543)
    Month 5
    6973
    (3682)
    Month 6
    5883
    (3128)
    Month 9
    7006
    (4289)
    Month 12
    5847
    (2992)
    Month 15
    3915
    (2584)
    End of trial
    6939
    (6581)
    53. Secondary Outcome
    Title Assessment of Urinary PAA Concentrations on the First Full Day of RAVICTI Dosing: Cohort of 0 Months to <2 Months Participants
    Description
    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

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Hour 0
    11.1
    (10.4)
    0.5 to 1.5 hours
    46.2
    (58.6)
    1.5 to 2.5 hours
    62.5
    (42.8)
    4 to 6 hours
    34.6
    (56.2)
    7.5 to 8.5 hours
    22.8
    (25.3)
    12 to 24 hours
    35.2
    (51.0)
    54. Secondary Outcome
    Title Assessment of Urinary PAA Concentrations Up to End of Trial: Cohort of 0 Months to <2 Months Participants
    Description
    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)

    Outcome Measure Data

    Analysis Population Description
    PK Evaluable Population: all participants from the safety population with individual concentration-time profiles that allow computation of meaningful PK parameter values.
    Arm/Group Title RAVICTI: Age 0 to < 2 Months
    Arm/Group Description 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.
    Measure Participants 16
    Day 7
    23.7
    (31.2)
    Month 1
    14.6
    (17.2)
    Month 2
    12.3
    (13.3)
    Month 3
    14.4
    (10.7)
    Month 4
    6.4
    (7.1)
    Month 5
    13.2
    (14.0)
    Month 6
    5.5
    (NA)
    Month 9
    11.8
    (8.5)
    Month 12
    6.0
    (3.8)
    Month 15
    4.9
    (0.3)
    End of trial
    11.6
    (9.0)

    Adverse Events

    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 for Cohort of 2 Months to <2 Years Participants and 10.67 [6.142] months for Cohort of 0 Months to <2 Months Participants).
    Adverse Event Reporting Description TEAEs (defined as AEs with an onset date on or after the first dose of study medication until study discontinuation) are presented.
    Arm/Group Title RAVICTI: Age 2 Months to < 2 Years RAVICTI: Age 0 to <2 Months
    Arm/Group Description 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. 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.
    All Cause Mortality
    RAVICTI: Age 2 Months to < 2 Years RAVICTI: Age 0 to <2 Months
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/10 (10%) 0/16 (0%)
    Serious Adverse Events
    RAVICTI: Age 2 Months to < 2 Years RAVICTI: Age 0 to <2 Months
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/10 (60%) 11/16 (68.8%)
    Blood and lymphatic system disorders
    Neutropenia 0/10 (0%) 1/16 (6.3%)
    Cardiac disorders
    Cyanosis 1/10 (10%) 0/16 (0%)
    Gastrointestinal disorders
    Pneumatosis intestinalis 1/10 (10%) 0/16 (0%)
    Vomiting 0/10 (0%) 2/16 (12.5%)
    General disorders
    Pyrexia 1/10 (10%) 0/16 (0%)
    Infections and infestations
    Croup infectious 1/10 (10%) 1/16 (6.3%)
    Gastroenteritis 1/10 (10%) 0/16 (0%)
    Urinary tract infection 1/10 (10%) 1/16 (6.3%)
    Viral infection 2/10 (20%) 1/16 (6.3%)
    Influenza 1/10 (10%) 0/16 (0%)
    Peritonitis 1/10 (10%) 0/16 (0%)
    Rhinovirus infection 1/10 (10%) 0/16 (0%)
    Viral upper respiratory tract infection 1/10 (10%) 0/16 (0%)
    Bacteraemia 0/10 (0%) 1/16 (6.3%)
    Cellulitis 0/10 (0%) 1/16 (6.3%)
    Device related infection 0/10 (0%) 1/16 (6.3%)
    Medical device site infection 0/10 (0%) 1/16 (6.3%)
    Meningitis bacterial 0/10 (0%) 1/16 (6.3%)
    Respiratory syncytial virus infection 0/10 (0%) 1/16 (6.3%)
    Tracheitis 0/10 (0%) 1/16 (6.3%)
    Upper respiratory tract infection 0/10 (0%) 1/16 (6.3%)
    Investigations
    Ammonia increased 1/10 (10%) 0/16 (0%)
    Metabolism and nutrition disorders
    Hyperammonaemia 3/10 (30%) 5/16 (31.3%)
    Dehydration 0/10 (0%) 1/16 (6.3%)
    Feeding disorder 0/10 (0%) 1/16 (6.3%)
    Nervous system disorders
    Lethargy 0/10 (0%) 1/16 (6.3%)
    Respiratory, thoracic and mediastinal disorders
    Apnoeic attack 1/10 (10%) 0/16 (0%)
    Asthma 1/10 (10%) 0/16 (0%)
    Status asthmaticus 1/10 (10%) 0/16 (0%)
    Atelectasis 0/10 (0%) 1/16 (6.3%)
    Other (Not Including Serious) Adverse Events
    RAVICTI: Age 2 Months to < 2 Years RAVICTI: Age 0 to <2 Months
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/10 (80%) 16/16 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/10 (10%) 3/16 (18.8%)
    Neutropenia 0/10 (0%) 1/16 (6.3%)
    Thrombocytopenia 0/10 (0%) 2/16 (12.5%)
    Thrombocytosis 0/10 (0%) 2/16 (12.5%)
    Leukocytosis 0/10 (0%) 1/16 (6.3%)
    Lymphocytosis 0/10 (0%) 1/16 (6.3%)
    Microcytic anaemia 0/10 (0%) 1/16 (6.3%)
    Cardiac disorders
    Tachycardia 0/10 (0%) 1/16 (6.3%)
    Congenital, familial and genetic disorders
    Dacryostenosis congenital 1/10 (10%) 0/16 (0%)
    Plagiocephaly 0/10 (0%) 2/16 (12.5%)
    Ear and labyrinth disorders
    Excessive cerumen production 1/10 (10%) 0/16 (0%)
    Eye disorders
    Eye discharge 0/10 (0%) 1/16 (6.3%)
    Ocular hyperaemia 0/10 (0%) 1/16 (6.3%)
    Gastrointestinal disorders
    Diarrhoea 1/10 (10%) 5/16 (31.3%)
    Vomiting 4/10 (40%) 5/16 (31.3%)
    Teething 1/10 (10%) 3/16 (18.8%)
    Constipation 2/10 (20%) 2/16 (12.5%)
    Gastrooesophageal reflux disease 0/10 (0%) 6/16 (37.5%)
    Flatulence 0/10 (0%) 3/16 (18.8%)
    Dysphagia 0/10 (0%) 1/16 (6.3%)
    Post-tussive vomiting 0/10 (0%) 1/16 (6.3%)
    General disorders
    Pyrexia 2/10 (20%) 2/16 (12.5%)
    Catheter site rash 0/10 (0%) 1/16 (6.3%)
    Device occlusion 0/10 (0%) 1/16 (6.3%)
    Drug withdrawal syndrome 0/10 (0%) 1/16 (6.3%)
    Medical device site haemorrhage 0/10 (0%) 1/16 (6.3%)
    Hepatobiliary disorders
    Hepatic calcification 0/10 (0%) 1/16 (6.3%)
    Immune system disorders
    Seasonal allergy 1/10 (10%) 0/16 (0%)
    Infections and infestations
    Gastroenteritis 1/10 (10%) 1/16 (6.3%)
    Upper respiratory tract infection 4/10 (40%) 5/16 (31.3%)
    Urinary tract infection 1/10 (10%) 2/16 (12.5%)
    Viral infection 1/10 (10%) 1/16 (6.3%)
    Nasopharyngitis 2/10 (20%) 4/16 (25%)
    Croup infectious 1/10 (10%) 1/16 (6.3%)
    Otitis media 2/10 (20%) 1/16 (6.3%)
    Conjunctivitis 1/10 (10%) 0/16 (0%)
    Pharyngitis 1/10 (10%) 0/16 (0%)
    Pneumonia 1/10 (10%) 0/16 (0%)
    Sinusitis 1/10 (10%) 1/16 (6.3%)
    Ear infection 0/10 (0%) 3/16 (18.8%)
    Oral candidiasis 0/10 (0%) 2/16 (12.5%)
    Respiratory syncytial virus infection 0/10 (0%) 1/16 (6.3%)
    Angular cheilitis 0/10 (0%) 1/16 (6.3%)
    Candida infection 0/10 (0%) 1/16 (6.3%)
    Gastrointestinal viral infection 0/10 (0%) 1/16 (6.3%)
    Lower respiratory tract infection 0/10 (0%) 1/16 (6.3%)
    Otitis media acute 0/10 (0%) 1/16 (6.3%)
    Rhinovirus infection 0/10 (0%) 1/16 (6.3%)
    Injury, poisoning and procedural complications
    Stoma site reaction 1/10 (10%) 1/16 (6.3%)
    Tibia fracture 1/10 (10%) 0/16 (0%)
    Arthropod bite 0/10 (0%) 1/16 (6.3%)
    Investigations
    Amino acid level decreased 1/10 (10%) 1/16 (6.3%)
    Ammonia increased 1/10 (10%) 1/16 (6.3%)
    Carbon dioxide decreased 1/10 (10%) 1/16 (6.3%)
    Hepatic enzyme increased 0/10 (0%) 2/16 (12.5%)
    Alanine aminotransferase increased 0/10 (0%) 1/16 (6.3%)
    Amino acid level increased 0/10 (0%) 1/16 (6.3%)
    Anion gap increased 0/10 (0%) 1/16 (6.3%)
    Aspartate aminotransferase increased 0/10 (0%) 1/16 (6.3%)
    Blood bicarbonate decreased 0/10 (0%) 1/16 (6.3%)
    Blood urea decreased 0/10 (0%) 1/16 (6.3%)
    Body height below normal 0/10 (0%) 1/16 (6.3%)
    Gamma-glutamyltransferase increased 0/10 (0%) 1/16 (6.3%)
    Platelet count increased 0/10 (0%) 1/16 (6.3%)
    Transaminases increased 0/10 (0%) 1/16 (6.3%)
    Weight decreased 0/10 (0%) 1/16 (6.3%)
    Metabolism and nutrition disorders
    Metabolic acidosis 2/10 (20%) 2/16 (12.5%)
    Hypophagia 2/10 (20%) 1/16 (6.3%)
    Hyperammonaemia 0/10 (0%) 2/16 (12.5%)
    Dehydration 0/10 (0%) 2/16 (12.5%)
    Decreased appetite 0/10 (0%) 1/16 (6.3%)
    Feeding disorder of infancy or early childhood 0/10 (0%) 1/16 (6.3%)
    Protein deficiency 0/10 (0%) 1/16 (6.3%)
    Musculoskeletal and connective tissue disorders
    Torticollis 0/10 (0%) 1/16 (6.3%)
    Nervous system disorders
    Gross motor delay 1/10 (10%) 0/16 (0%)
    Lethargy 0/10 (0%) 1/16 (6.3%)
    Tremor 0/10 (0%) 1/16 (6.3%)
    Psychiatric disorders
    Agitation 0/10 (0%) 1/16 (6.3%)
    Irritability 0/10 (0%) 1/16 (6.3%)
    Renal and urinary disorders
    Vesicoureteric reflux 1/10 (10%) 0/16 (0%)
    Nephrolithiasis 0/10 (0%) 1/16 (6.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/10 (20%) 4/16 (25%)
    Rhinorrhoea 1/10 (10%) 0/16 (0%)
    Apnoea 1/10 (10%) 0/16 (0%)
    Nasal congestion 1/10 (10%) 2/16 (12.5%)
    Respiratory disorder 1/10 (10%) 0/16 (0%)
    Oropharyngeal pain 0/10 (0%) 2/16 (12.5%)
    Pneumothorax 0/10 (0%) 1/16 (6.3%)
    Tachypnoea 0/10 (0%) 1/16 (6.3%)
    Use of accessory respiratory muscles 0/10 (0%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Nail ridging 1/10 (10%) 0/16 (0%)
    Rash 2/10 (20%) 5/16 (31.3%)
    Dermatitis diaper 1/10 (10%) 6/16 (37.5%)
    Eczema 1/10 (10%) 1/16 (6.3%)
    Red man syndrome 0/10 (0%) 1/16 (6.3%)
    Seborrhoeic dermatitis 0/10 (0%) 1/16 (6.3%)
    Vascular disorders
    Venous thrombosis limb 1/10 (10%) 0/16 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.

    Results Point of Contact

    Name/Title Colleen Canavan, Director
    Organization Horizon Therapeutics, LLC
    Phone 866-479-6742
    Email clinicaltrials@horizonpharma.com
    Responsible Party:
    Horizon Therapeutics, LLC
    ClinicalTrials.gov Identifier:
    NCT02246218
    Other Study ID Numbers:
    • HPN-100-009
    • 2016-003460-38
    First Posted:
    Sep 22, 2014
    Last Update Posted:
    Mar 5, 2019
    Last Verified:
    Feb 1, 2019