Urea Cycle Disorder
Conditions
Keywords
UCD, BUPHENYL, RAVICTI, Urea, Urea cycle disorder, Glycerol phenylbutyrate, Benzoate, Sodium phenylbutyrate, Ornithine transcarbamylase (OTC), Argininosuccinate synthetase (ASS), Argininosuccinate lyase (ASL), Carbamyl phosphate synthetase (CPS), Arginine, Citrulline, Ammonia
Brief summary
THRIVE is an observational study that will collect information on patients with UCDs. THRIVE will follow enrolled participants for up to 10 years. As an observational study, enrolled patients will not be required to make any additional office visits or take any medicine outside of normal care.
Detailed description
UCDs disproportionately affect children and females: depending on the severity of the defect, a UCD can manifest shortly after birth or later in life. This study will track long-term outcomes in UCD patients and effects of ammonia-scavenging agents on neuropsychological functions of UCD patients. This is a non-interventional, multi-center registry to be conducted in patients with UCDs. Investigators will prescribe treatments based on usual clinical practice, and there will be no restrictions on the use of commercially available medications. As an observational study, this study will not change the patient/ healthcare provider relationship, nor influence the healthcare provider's drug prescription or the therapeutic management of the patient. Patients with UCDs will be recruited and invited to attend a Baseline visit. After eligible patients are enrolled, retrospective and baseline data will be collected. Patients will be followed for up to 10 years, during which time they will be assessed by their healthcare provider. Patients and healthcare provider will be asked to report episodes of hyperammonemic crisis, available ammonia values, and other information. Study acquired from Horizon in 2024.
Interventions
None listed
Sponsors
Amgen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Confirmed or suspected diagnosis of UCD * Signed informed consent/Health Insurance Portability and Accountability Act (HIPAA) Authorization and medical records release
Exclusion criteria
* Any other reason that, in the Investigator's opinion, makes the patient unsuitable to participate in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | 12 months prior to enrollment (retrospective), Baseline, Day 7 to 30, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, Month 48, Month 54, Month 60, Month 66, Month 72 | Retrospective is defined as the 12 months preceding enrollment. |
| Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | 12 months prior to enrollment (retrospective), Baseline, Day 7 to 30, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, Month 48, Month 54, Month 60, Month 66, Month 72 | Retrospective is defined as the 12 months preceding enrollment. |
| Percentage of Participants With Hyperammonemic Crisis (HAC) by Baseline Ammonia-Scavenging Medication, Retrospective Values | 12 months prior to enrollment (retrospective) | Percentage of participants experiencing HAC (reported for the 12 months preceding enrollment). |
| Percentage of Participants With Hyperammonemic Crisis (HAC), Post-Baseline by Last Known Ammonia-Scavenging Medication | From enrollment through the end of study (mean overall duration on study was 1187.7 days). | Percentage of participants experiencing HAC (post-Baseline). |
| Number of Participants With Serious Adverse Events (SAEs) | From enrollment through the end of study (mean overall duration on study was 1187.7 days). | An SAE is an adverse event that: is fatal or life-threatening; results in persistent or significant disability or incapacity. Disability is defined as a substantial disruption of a person's ability to conduct normal life functions; requires inpatient hospitalization or prolongation of an existing hospitalization; is a congenital anomaly/birth defect; any other important medical event that may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed above. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sodium Phenylbutyrate Participants with a confirmed or suspected diagnosis of UCD receiving sodium phenylbutyrate at Baseline. | 49 |
| Ravicti Participants with a confirmed or suspected diagnosis of UCD receiving Ravicti at Baseline. | 89 |
| Sodium Benzoate Participants with a confirmed or suspected diagnosis of UCD receiving sodium benzoate at Baseline. | 4 |
| Carglumic Acid Participants with a confirmed or suspected diagnosis of UCD receiving carglumic acid at Baseline. | 1 |
| Other Participants with a confirmed or suspected diagnosis of UCD receiving other (not specified) ammonia-scavenging medication at Baseline. | 60 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Investigator Request | 0 | 8 | 0 | 0 | 6 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 4 |
| Overall Study | Other, Not Specified | 1 | 9 | 0 | 0 | 2 |
| Overall Study | Serious Adverse Event | 3 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Sodium Phenylbutyrate | Ravicti | Sodium Benzoate | Carglumic Acid | Other | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 10.9 years STANDARD_DEVIATION 13.5 | 16.7 years STANDARD_DEVIATION 15.1 | 9.3 years STANDARD_DEVIATION 8.7 | 2.0 years | 14.7 years STANDARD_DEVIATION 16.9 | 14.5 years STANDARD_DEVIATION 15.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 16 Participants | 3 Participants | 0 Participants | 7 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 73 Participants | 1 Participants | 1 Participants | 53 Participants | 164 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race Asian | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants | 6 Participants |
| Race Black or African-American | 9 Participants | 9 Participants | 0 Participants | 0 Participants | 4 Participants | 22 Participants |
| Race Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race Other, Not Specified | 8 Participants | 15 Participants | 0 Participants | 0 Participants | 5 Participants | 28 Participants |
| Race White | 30 Participants | 63 Participants | 4 Participants | 1 Participants | 48 Participants | 146 Participants |
| Sex: Female, Male Female | 33 Participants | 54 Participants | 1 Participants | 0 Participants | 33 Participants | 121 Participants |
| Sex: Female, Male Male | 16 Participants | 35 Participants | 3 Participants | 1 Participants | 27 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 49 | 2 / 89 | 0 / 4 | 0 / 1 | 1 / 60 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 30 / 49 | 40 / 89 | 2 / 4 | 0 / 1 | 16 / 60 |
Outcome results
Primary
Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication
Retrospective is defined as the 12 months preceding enrollment.
Time frame: 12 months prior to enrollment (retrospective), Baseline, Day 7 to 30, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, Month 48, Month 54, Month 60, Month 66, Month 72
Population: Participants with a Baseline visit and an assessment at given time point. Participants are grouped by last-known ammonia-scavenging medication at given time point (participants may have been on more than 1 therapy during the study).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 36 | 36.2 µmol/L | Standard Deviation 18.9 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 30 | 42.0 µmol/L | Standard Deviation 18.18 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 6 | 48.7 µmol/L | Standard Deviation 53.77 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 24 | 53.9 µmol/L | Standard Deviation 38.49 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 18 | 54.5 µmol/L | Standard Deviation 53.89 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 12 | 42.4 µmol/L | Standard Deviation 20.87 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 66 | 62.0 µmol/L | — |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 60 | 57.3 µmol/L | Standard Deviation 22.37 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 54 | 55.6 µmol/L | Standard Deviation 8.59 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Baseline | 64.5 µmol/L | Standard Deviation 52.32 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 72 | 55.0 µmol/L | — |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 48 | 61.4 µmol/L | Standard Deviation 57.78 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 42 | 40.2 µmol/L | Standard Deviation 14.39 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Day 7 to 30 | 64.0 µmol/L | Standard Deviation 20.53 |
| Sodium Phenylbutyrate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Retrospective | 86.5 µmol/L | Standard Deviation 87.13 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 72 | 45.5 µmol/L | Standard Deviation 43.13 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 24 | 52.8 µmol/L | Standard Deviation 78.14 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Retrospective | 43.8 µmol/L | Standard Deviation 27.59 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Baseline | 49.1 µmol/L | Standard Deviation 43.58 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Day 7 to 30 | 79.6 µmol/L | Standard Deviation 72.23 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 6 | 45.0 µmol/L | Standard Deviation 30.26 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 12 | 39.4 µmol/L | Standard Deviation 24.43 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 18 | 45.9 µmol/L | Standard Deviation 28.26 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 30 | 47.5 µmol/L | Standard Deviation 33.27 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 36 | 45.9 µmol/L | Standard Deviation 34.95 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 42 | 43.3 µmol/L | Standard Deviation 27.3 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 48 | 54.2 µmol/L | Standard Deviation 42.95 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 54 | 45.0 µmol/L | Standard Deviation 29.44 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 60 | 45.2 µmol/L | Standard Deviation 32.78 |
| Ravicti | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 66 | 31.0 µmol/L | Standard Deviation 11.05 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 18 | 29.0 µmol/L | Standard Deviation 11.79 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 30 | 79.8 µmol/L | Standard Deviation 85.85 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Day 7 to 30 | 55.0 µmol/L | — |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 36 | 72.0 µmol/L | — |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 60 | 8.9 µmol/L | — |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 42 | 41.5 µmol/L | Standard Deviation 0.71 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Baseline | 48.0 µmol/L | Standard Deviation 29.73 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Retrospective | 23.0 µmol/L | — |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 48 | 36.0 µmol/L | — |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 54 | 66.0 µmol/L | Standard Deviation 0 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 12 | 51.0 µmol/L | Standard Deviation 16.97 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 6 | 190.3 µmol/L | Standard Deviation 257.8 |
| Sodium Benzoate | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 24 | 43.3 µmol/L | Standard Deviation 31.26 |
| Carglumic Acid | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 24 | 25.0 µmol/L | — |
| Carglumic Acid | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 18 | 13.0 µmol/L | — |
| Carglumic Acid | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 12 | 20.0 µmol/L | — |
| Carglumic Acid | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Baseline | 21.0 µmol/L | — |
| Carglumic Acid | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Retrospective | 13.0 µmol/L | — |
| Carglumic Acid | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 6 | 48.0 µmol/L | Standard Deviation 25.46 |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 18 | 106.0 µmol/L | Standard Deviation 110.31 |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 36 | 51.5 µmol/L | Standard Deviation 34.65 |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 6 | 129.4 µmol/L | Standard Deviation 110.54 |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 30 | 114.5 µmol/L | Standard Deviation 127.99 |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 54 | 292.0 µmol/L | — |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Day 7 to 30 | 143.5 µmol/L | Standard Deviation 98.29 |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 48 | 22.0 µmol/L | — |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Month 12 | 79.0 µmol/L | Standard Deviation 57.98 |
| Other | Mean Blood Ammonia Levels Over Time, by Last Known Ammonia-Scavenging Medication | Retrospective | 963.7 µmol/L | Standard Deviation 721.39 |
Primary
Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication
Retrospective is defined as the 12 months preceding enrollment.
Time frame: 12 months prior to enrollment (retrospective), Baseline, Day 7 to 30, Month 6, Month 12, Month 18, Month 24, Month 30, Month 36, Month 42, Month 48, Month 54, Month 60, Month 66, Month 72
Population: Participants with a Baseline visit and an assessment at given time point. Participants are grouped by last-known ammonia-scavenging medication at given time point (participants may have been on more than 1 therapy during the study).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 36 | 38.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 30 | 43.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 24 | 47.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 12 | 42.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Baseline | 50.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 18 | 36.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Retrospective | 46.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 60 | 62.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 54 | 57.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Day 7 to 30 | 60.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 72 | 55.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 48 | 39.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 42 | 40.5 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 6 | 33.0 µmol/L |
| Sodium Phenylbutyrate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 66 | 62.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 72 | 45.5 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Retrospective | 38.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Baseline | 37.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Day 7 to 30 | 61.5 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 6 | 34.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 12 | 34.5 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 18 | 45.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 24 | 34.5 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 30 | 35.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 36 | 34.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 42 | 38.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 48 | 40.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 54 | 35.8 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 60 | 29.0 µmol/L |
| Ravicti | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 66 | 27.5 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Day 7 to 30 | 55.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 30 | 52.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 48 | 36.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 18 | 26.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 6 | 44.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Retrospective | 23.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 12 | 51.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 36 | 72.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 24 | 48.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 54 | 66.0 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Baseline | 46.5 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 60 | 8.9 µmol/L |
| Sodium Benzoate | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 42 | 41.5 µmol/L |
| Carglumic Acid | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 6 | 48.0 µmol/L |
| Carglumic Acid | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 18 | 13.0 µmol/L |
| Carglumic Acid | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Retrospective | 13.0 µmol/L |
| Carglumic Acid | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 12 | 20.0 µmol/L |
| Carglumic Acid | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 24 | 25.0 µmol/L |
| Carglumic Acid | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Baseline | 21.0 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 54 | 292.0 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 30 | 114.5 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 36 | 51.5 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Day 7 to 30 | 143.5 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Retrospective | 1360.0 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 48 | 22.0 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 12 | 79.0 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 18 | 51.0 µmol/L |
| Other | Median Blood Ammonia Levels Over Time, by Last-Known Ammonia-Scavenging Medication | Month 6 | 96.0 µmol/L |
Primary
Number of Participants With Serious Adverse Events (SAEs)
An SAE is an adverse event that: is fatal or life-threatening; results in persistent or significant disability or incapacity. Disability is defined as a substantial disruption of a person's ability to conduct normal life functions; requires inpatient hospitalization or prolongation of an existing hospitalization; is a congenital anomaly/birth defect; any other important medical event that may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed above.
Time frame: From enrollment through the end of study (mean overall duration on study was 1187.7 days).
Population: All participants who attended a Baseline visit. Due to data collection complexities in this observational study (e.g., switching of medications, incomplete data on medications, and missing SAE dates) AEs could not be reliably summarized according to a participant's treatment at the time of SAE, and was therefore summarized by treatment at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sodium Phenylbutyrate | Number of Participants With Serious Adverse Events (SAEs) | 30 Participants |
| Ravicti | Number of Participants With Serious Adverse Events (SAEs) | 40 Participants |
| Sodium Benzoate | Number of Participants With Serious Adverse Events (SAEs) | 2 Participants |
| Carglumic Acid | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
| Other | Number of Participants With Serious Adverse Events (SAEs) | 16 Participants |
Primary
Percentage of Participants With Hyperammonemic Crisis (HAC) by Baseline Ammonia-Scavenging Medication, Retrospective Values
Percentage of participants experiencing HAC (reported for the 12 months preceding enrollment).
Time frame: 12 months prior to enrollment (retrospective)
Population: Participants with a baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sodium Phenylbutyrate | Percentage of Participants With Hyperammonemic Crisis (HAC) by Baseline Ammonia-Scavenging Medication, Retrospective Values | 44.9 percentage of participants |
| Ravicti | Percentage of Participants With Hyperammonemic Crisis (HAC) by Baseline Ammonia-Scavenging Medication, Retrospective Values | 15.7 percentage of participants |
| Sodium Benzoate | Percentage of Participants With Hyperammonemic Crisis (HAC) by Baseline Ammonia-Scavenging Medication, Retrospective Values | 25.0 percentage of participants |
| Carglumic Acid | Percentage of Participants With Hyperammonemic Crisis (HAC) by Baseline Ammonia-Scavenging Medication, Retrospective Values | 100.0 percentage of participants |
| Other | Percentage of Participants With Hyperammonemic Crisis (HAC) by Baseline Ammonia-Scavenging Medication, Retrospective Values | 8.3 percentage of participants |
Primary
Percentage of Participants With Hyperammonemic Crisis (HAC), Post-Baseline by Last Known Ammonia-Scavenging Medication
Percentage of participants experiencing HAC (post-Baseline).
Time frame: From enrollment through the end of study (mean overall duration on study was 1187.7 days).
Population: Participants with a baseline visit and at least 1 measurement of this assessment while on therapy. Participants are grouped by last-known ammonia-scavenging medication; participants may have been on more than 1 therapy during the study and the number of participants analyzed may be greater than the overall number of participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sodium Phenylbutyrate | Percentage of Participants With Hyperammonemic Crisis (HAC), Post-Baseline by Last Known Ammonia-Scavenging Medication | 42.6 percentage of participants |
| Ravicti | Percentage of Participants With Hyperammonemic Crisis (HAC), Post-Baseline by Last Known Ammonia-Scavenging Medication | 37.3 percentage of participants |
| Sodium Benzoate | Percentage of Participants With Hyperammonemic Crisis (HAC), Post-Baseline by Last Known Ammonia-Scavenging Medication | 40.0 percentage of participants |
| Carglumic Acid | Percentage of Participants With Hyperammonemic Crisis (HAC), Post-Baseline by Last Known Ammonia-Scavenging Medication | 0 percentage of participants |
| Other | Percentage of Participants With Hyperammonemic Crisis (HAC), Post-Baseline by Last Known Ammonia-Scavenging Medication | 72.7 percentage of participants |