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A randomised, open-label study evaluating the pharmacokinetics, safety, and tolerability of a new once daily dose of 900mg of TETA 4HCL by comparing it against the current marketed Cuprior® formulation (450mg trientine base, twice daily) in healthy male and female participants.
This is a single centre, phase I, randomized, controlled trial with a crossover design to evaluate the pharmacokinetics (PK), safety, and tolerability of a new once daily TETA 4HCL formulation (300mg) (3x300mg trientine base tablets, OD) compared to the current marketed Cuprior® formulation (150mg) (3x150mg trientine base tablets, BD) in adult healthy male and female participants.
Participants: 26 healthy participants will be enrolled to ensure 24 participants complete the study, with a balanced gender split.
Treatment: Participants will be randomized to receive either the new or the current formulation of the drug, and then switch to the other formulation after a period of time (see study flow chart below).
To remain in line with current EU SmPC and US PIL, being:
Patients will be randomised in a 1:1 ratio to either one of the following sequences:
Treatment Sequence Period 1 Period 2 Sequence 1 Treatment A Treatment B Sequence 2 Treatment B Treatment A
Assessments: Participants will be assessed for eligibility criteria and will be monitored closely throughout the study. Assessments will be performed during the study and at the end of the study follow-up visit.
Duration: The duration of the study will be up to approximately 7 weeks, from screening to follow-up:
At least 5 days and a maximum of 10 days between treatment period study drug administration
Objective: To evaluate the PK, safety, and tolerability of the new once daily TETA 4HCL formulation compared to the current marketed Cuprior® formulation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Once Daily Dose Formulation (Treatment A) | Experimental | 1 x 900mg TETA 4HCl, new once daily formulation (3x300mg trientine base tablets as a single AM dose) |
|
| Cuprior® comparator (Treatment B) | Active Comparator | 2 x 450mg TETA 4HCl, Marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 900mg TETA 4HCl Once Daily Formulation | Drug | 3x300mg trientine base tablets as a single AM dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Up to 48 hours post first dose initiation. |
| Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Up to 48 hours post first dose initiation. |
| Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Up to 48 hours post first dose initiation. |
| Pharmacokinetic Parameters (AUC) of TETA in Plasma | PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. |
| Measure | Description | Time Frame |
|---|---|---|
| To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | The incidence, severity, and relationship of Treatment-Emergent Adverse Events (TEAEs). | Adverse events were collected from the patient signing the ICF until the end of study/follow-up (EOS/FU) visit. The Mean (Min, Max) number of days between signing ICF and the EOS/FU visit in the study was 20.2 (16, 25). All patients completed the study. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas Ashdown, MBBCh Ssc | Richmond Pharmacology Limited | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Richmond Pharmacology Ltd | London | SE1 1YR | United Kingdom |
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1: Once Daily TETA 4HCl Formulation, Followed by Twice Daily Cuprior® Formulation | Participants first received 1 x 900mg TETA 4HCl, once daily formulation (3x300mg trientine base tablets as a single AM dose), for 3 days. After a washout period of a minimum of 5 days and up to 10 days, they then received 2 x 450mg TETA 4HCl, marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart) for 3 days. |
| FG001 | Sequence 2: Twice Daily Cuprior® Formulation, Followed by Once Daily TETA 4HCl Formulation | Participants first received 2 x 450mg TETA 4HCl, marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart), for 3 days. After a washout period of a minimum of 5 days and up to 10 days, they then received 1 x 900mg TETA 4HCl, once daily formulation (3x300mg trientine base tablets as a single AM dose) for 3 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Cross over design of two treatment sequences where 26 study participants are studied in both sequences.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sequence 1: Once Daily TETA 4HCl Formulation, Followed by Twice Daily Cuprior® Formulation | Participants first received 1 x 900mg TETA 4HCl, once daily formulation (3x300mg trientine base tablets as a single AM dose), for 3 days. After a washout period of a minimum of 5 days and up to 10 days, they then received 2 x 450mg TETA 4HCl, marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart) for 3 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Plasma Concentrations (AUC) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Posted | Geometric Mean | 90% Confidence Interval | h*ng/mL | Up to 48 hours post first dose initiation. |
|
Adverse events were collected from the patient signing the ICF until the end of study/follow-up (EOS/FU) visit. The Mean (Min, Max) number of days between signing ICF and the EOS/FU visit in the study was 20.2 (16, 25). All patients completed the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Once Daily Dose Formulation (Treatment A) | 1 x 900mg TETA 4HCl, new once daily formulation (3x300mg trientine base tablets as a single AM dose) 900mg TETA 4HCl Once Daily Formulation: 3x300mg trientine base tablets as a single AM dose |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Presyncope | Cardiac disorders | MedDRA 26.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Carla Bennett | Orphalan SA | 07918380893 | carla.bennett@orphalan.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Study Protocol | Jan 9, 2024 | May 12, 2025 | Prot_SAP_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan: Statistical Analysis Plan | Jan 31, 2024 | May 29, 2025 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 17, 2024 | May 12, 2025 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D006527 | Hepatolenticular Degeneration |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
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| 900mg TETA 4HCl Cuprior® | Drug | 6 x150mg trientine base tablets in two equally divided doses |
|
| Up to 48 hours post first dose initiation. |
| Plasma Concentrations (Cmax) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: Cmax. | Up to 48 hours post first dose initiation. |
| Pharmacokinetic Parameters (Time) of TETA in Plasma | PK parameters derived by non-compartmental methods including: Thalf and Tmax. | Up to 48 hours post first dose initiation. |
| Pharmacokinetic Parameters (Concentration) of TETA in Plasma | PK parameters derived by non-compartmental methods including: Clast and Cmax. | Up to 48 hours post first dose initiation. |
| Pharmacokinetic Parameters (AUC) of MAT in Plasma | PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Up to 48 hours post first dose initiation |
| Plasma Concentrations (Cmax) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: Cmax. | Up to 48 hours post first dose initiation. |
| Pharmacokinetic Parameters (Time) of MAT in Plasma | PK parameters derived by non-compartmental methods including: Thalf and Tmax.. | Up to 48 hours post first dose initiation |
| Pharmacokinetic Parameters (Concentration) of MAT in Plasma | PK parameters derived by non-compartmental methods including: Clast and Cmax.. | Up to 48 hours post first dose initiation |
| Pharmacokinetic Parameters (AUC) of DAT in Plasma | PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Up to 48 hours post first dose initiation. |
| Plasma Concentrations (Cmax) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: Cmax. | Up to 48 hours post first dose initiation. |
| Pharmacokinetic Parameters (Time) of DAT in Plasma | PK parameters derived by non-compartmental methods including: Thalf and Tmax. | Up to 48 hours post first dose initiation. |
| Pharmacokinetic Parameters (Concentration) of DAT in Plasma | PK parameters derived by non-compartmental methods including: Clast and Cmax. | Up to 48 hours post first dose initiation. |
| BG001 | Sequence 2: Twice Daily Cuprior® Formulation, Followed by Once Daily TETA 4HCl Formulation | Participants first received 2 x 450mg TETA 4HCl, marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart), for 3 days. After a washout period of a minimum of 5 days and up to 10 days, they then received 1 x 900mg TETA 4HCl, once daily formulation (3x300mg trientine base tablets as a single AM dose) for 3 days. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
900mg TETA 4HCl Cuprior®: 6 x150mg trientine base tablets in two equally divided doses |
|
|
| Primary | Plasma Concentrations (AUC) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Posted | Geometric Mean | 90% Confidence Interval | h*ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Plasma Concentrations (AUC) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: AUC 24 and AUCinf. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Posted | Geometric Mean | 90% Confidence Interval | h*ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Pharmacokinetic Parameters (AUC) of TETA in Plasma | PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Plasma Concentrations (Cmax) of TETA 4HCL Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: Cmax. | Posted | Geometric Mean | 90% Confidence Interval | ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Pharmacokinetic Parameters (Time) of TETA in Plasma | PK parameters derived by non-compartmental methods including: Thalf and Tmax. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Pharmacokinetic Parameters (Concentration) of TETA in Plasma | PK parameters derived by non-compartmental methods including: Clast and Cmax. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Pharmacokinetic Parameters (AUC) of MAT in Plasma | PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Up to 48 hours post first dose initiation |
|
|
|
| Primary | Plasma Concentrations (Cmax) of N1-acetyltriethylenetetramine (MAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: Cmax. | Posted | Geometric Mean | 90% Confidence Interval | ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Pharmacokinetic Parameters (Time) of MAT in Plasma | PK parameters derived by non-compartmental methods including: Thalf and Tmax.. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Up to 48 hours post first dose initiation |
|
|
|
| Primary | Pharmacokinetic Parameters (Concentration) of MAT in Plasma | PK parameters derived by non-compartmental methods including: Clast and Cmax.. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Up to 48 hours post first dose initiation |
|
|
|
| Primary | Pharmacokinetic Parameters (AUC) of DAT in Plasma | PK parameters derived by non-compartmental methods including: AUCinf and AUC 24. PK sampling was done pre-first dose and then post-first dose for Treatment A (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48. Post-first dose for Treatment B (hours): 0.5, 1, 1.25, 1.5, 2, 3, 4, 5, 6, 8 (before 2nd dose), 8.5, 9, 9.25, 9.5, 10, 11, 12, 13, 14, 16, 20, 24, 36, 48. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Up to 48 hours post first dose initiation. |
|
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|
| Primary | Plasma Concentrations (Cmax) of N1, N10-diacetyltriethylenetetramine (DAT) Following Administration of Two TETA 4HCL Tablet Formulations. | PK parameters derived by non-compartmental methods including: Cmax. | Posted | Geometric Mean | 90% Confidence Interval | ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Pharmacokinetic Parameters (Time) of DAT in Plasma | PK parameters derived by non-compartmental methods including: Thalf and Tmax. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | Up to 48 hours post first dose initiation. |
|
|
|
| Primary | Pharmacokinetic Parameters (Concentration) of DAT in Plasma | PK parameters derived by non-compartmental methods including: Clast and Cmax. | Crossover design, participants exposed to both treatments. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Up to 48 hours post first dose initiation. |
|
|
|
| Secondary | To Compare the Safety and Tolerability of the Two TETA 4HCL Tablet Formulations. | The incidence, severity, and relationship of Treatment-Emergent Adverse Events (TEAEs). | Posted | Count of Participants | Participants | Adverse events were collected from the patient signing the ICF until the end of study/follow-up (EOS/FU) visit. The Mean (Min, Max) number of days between signing ICF and the EOS/FU visit in the study was 20.2 (16, 25). All patients completed the study. |
|
|
|
| 0 |
| 26 |
| 0 |
| 26 |
| 3 |
| 26 |
| EG001 | Cuprior® Comparator (Treatment B) | 2 x 450mg TETA 4HCl, Marketed Cuprior® formulation (6 x150mg trientine base tablets in two equally divided doses (450mg doses 8 hours apart) 900mg TETA 4HCl Cuprior®: 6 x150mg trientine base tablets in two equally divided doses | 0 | 26 | 0 | 26 | 3 | 26 |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
|
| Aphthous ulcer | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
|
| Epigastric discomfort | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 26.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 26.1 | Non-systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 26.1 | Non-systematic Assessment |
|
Full study agreement in place with Richmond Pharmacology.
| D002493 |
| Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D009069 | Movement Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D008664 | Metal Metabolism, Inborn Errors |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| Participants with morphological and/or rhythm abnormalities on electrocardiogram (ECG) |
|
| Participants with clinically significant changes in vital signs |
|