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| ID | Type | Description | Link |
|---|---|---|---|
| 14-N-0033 | Other Identifier | NIH |
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Objective:
To perform a clinical trial assessing the safety, tolerability and efficacy of the GABA(B) receptor antagonist SGS-742 in patients with SSADH deficiency.
Study Population:
Twenty-two children and adults with SSADH deficiency.
Design:
Double-blind, cross-over, phase II clinical trial.
Outcome Measures:
The primary outcome measures for drug efficacy will be performance on neuropsychological testing and responses to parent questionnaire. The secondary outcome measure will be TMS parameters of cortical excitation and inhibition. The outcome measures for safety will include clinical examination and neuropsychological tests.
Objective:
To perform a clinical trial assessing the safety, tolerability and efficacy of the GABA(B) receptor antagonist SGS-742 in patients with SSADH deficiency.
Study Population:
Twenty-two children and adults with SSADH deficiency.
Design:
Double-blind, cross-over, phase II clinical trial. SGS-742 is a GABA (B) receptor antagonist that has shown to be safe and well-tolerated in clinical trials in adults with cognitive impairment. In addition, preliminary data in the SSADH knockout mouse model suggest efficacy in this specific syndrome. The primary outcome measure will be a change in the Auditory Comprehension subtest of the Neuropsychological Assessment Battery Language Module score; the secondary outcome measure will be a change in cortical excitation and inhibition measured by transcranial magnetic stimulation (TMS). Additional evaluations will include neurological and neuropsychological examinations, magnetic resonance spectroscopy and CSF collection to measure GABA levels. The trial will have a baseline phase in which each patient will undergo a neurological examination and a neuropsychological evaluation. During the subsequent treatment phase, patients will be randomized to SGS-742, supplied by IRIX Pharmaceuticals, and based on weight given a maximum tolerated dose not to exceed 600 mg t.i.d. orally, or placebo, each for 6 months. Patients will then have repeat TMS, neurological and neuropsychological evaluations, followed by cross-over to the alternate treatment arm, and re-evaluation after 6 months.
Outcome Measures:
The primary outcome measures for drug efficacy will be performance on neuropsychological testing and responses to parent questionnaire. The secondary outcome measure will be TMS parameters of cortical excitation and inhibition. The outcome measures for safety will include clinical examination and neuropsychological tests.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Experimental | Participants with SSADH Deficiency when on placebo for six months |
|
| Study Drug | Experimental | Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SGS-742 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline on the Adaptive Behavior Assessment System (ABAS) Test at the End of the Study Drug and Placebo Treatment Periods | The ABAS questionnaire was completed by the participant's parent or caregiver at the end of each six month treatment period.The ABAS provides a comprehensive picture of adaptive skills across the lifespan. The questionnaire addresses Conceptual, Social and Practical skills including communication, self-direction, use of leisure time, health, safety and self-care. The General Adaptive Composite score ranges from <40 to >160 with a lower score representing lower adaptive behavior. The difference between Placebo and Baseline and Study Drug and Baseline were obtained. These values were averaged across individuals to report a mean and a standard deviation of the baseline-to-treatment period change. The means for each treatment can be compared to have a baseline-adjusted treatment effect interpretation. A positive change represents an improvement in adaptive skills compared with baseline and a negative change represents a decline in adaptive skills compared with baseline. | baseline and six months |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline of TMS Measurement of Motor Threshold at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. The motor threshold is defined as the minimum percentage of the stimulator output that evoked a motor evoked potential of more than 50µV in at least 5 out of 10 trials. Motor threshold was measured at the end of the study drug period and the end of the Placebo period. The differences between Placebo and Baseline, and SGS and Baseline were obtained. A decrease from baseline value indicates increased cortical excitability and an increase from baseline value indicates reduced cortical excitability. These values were averaged across individuals to report a mean and standard deviation of this baseline-to-treatment period change. The mean for each treatment can be compared to have a baseline-adjusted treatment effect. |
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EXCLUSION CRITERIA
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| Name | Affiliation | Role |
|---|---|---|
| Sara K Inati, M.D. | National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10722966 | Background | Al-Essa MA, Bakheet SM, Patay ZJ, Powe JE, Ozand PT. Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography (FDG PET), MRI of the brain and biochemical observations in a patient with 4-hydroxybutyric aciduria; a progressive neurometabolic disease. Brain Dev. 2000 Mar;22(2):127-31. doi: 10.1016/s0387-7604(99)00121-7. | |
| 10897152 |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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Following a baseline visit, participants were randomized to receive either placebo or study drug for 6 months (Phase 1) followed by 6 months of the alternate treatment (Phase 2). Participants completed a 9-week washout period following each phase of the study.
Participants were recruited and enrolled in the protocol between March 2014 and October 2017, with assistance from referring physicians in the community and the SSADH foundation. A total of 19 participants were enrolled; 16 completed dosing in both placebo and active drug arms.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo First, Then SGS-742 | Participants were administered Placebo, followed by a washout period, and then administered SGS-742 |
| FG001 | SGS-742 First, Then Placebo | Participants were administered SGS-742, followed by a washout period, and then administered Placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (6 Months) |
|
| ||||||||||||||||||
| Washout Period (9 Weeks) |
| |||||||||||||||||||
| 2nd Intervention (6 Months) |
| |||||||||||||||||||
| Washout Period (9 Weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants with SSADH Deficiency who were randomized to receive either SGS-742 or Placebo |
| 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 | Change From Baseline on the Adaptive Behavior Assessment System (ABAS) Test at the End of the Study Drug and Placebo Treatment Periods | The ABAS questionnaire was completed by the participant's parent or caregiver at the end of each six month treatment period.The ABAS provides a comprehensive picture of adaptive skills across the lifespan. The questionnaire addresses Conceptual, Social and Practical skills including communication, self-direction, use of leisure time, health, safety and self-care. The General Adaptive Composite score ranges from <40 to >160 with a lower score representing lower adaptive behavior. The difference between Placebo and Baseline and Study Drug and Baseline were obtained. These values were averaged across individuals to report a mean and a standard deviation of the baseline-to-treatment period change. The means for each treatment can be compared to have a baseline-adjusted treatment effect interpretation. A positive change represents an improvement in adaptive skills compared with baseline and a negative change represents a decline in adaptive skills compared with baseline. | The ABAS was not able to be completed for all participants. | Posted | Mean | Standard Deviation | scores on a scale | baseline and six months |
Adverse events were collected over a 16-21 month time period which included a 6 month +/- 2 week Phase 1 period, a 9 week +/- 2 week Washout period, a 6 month +/- 2 week Phase 2 period, followed by a 9 week +/- Washout period.
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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 | Placebo | Participants with SSADH Deficiency while on placebo for six months Placebo |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. William Theodore | National Institutes of Health | 301-496-1505 | theodorw@ninds.nih.gov |
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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 | Aug 8, 2019 | Feb 13, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D012640 | Seizures |
| ID | Term |
|---|---|
| D009750 | Nutritional and Metabolic Diseases |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| C079148 | (3-aminopropyl)(n-butyl)phosphinic acid |
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|
| Baseline and Six months |
| Change From Baseline of TMS Measurement of Intracortical Facilitation at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. Intracortical facilitation (ICF) and inhibition (ICI) were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at an interstimulus interval (ISI) of 10 ms for ICF. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean. | Baseline and Six months |
| Change From Baseline of TMS Measurement of Short Interval Intracortical Inhibition (Short ICI) at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. Intracortical facilitation and inhibition were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at an interstimulus interval (ISI) of 2 ms for short ICI. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean. | Baseline and Six months |
| Change From Baseline of TMS Measurement of Long Interval Intracortical Inhibition (Long ICI) at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons.Intracortical facilitation and inhibition were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at 100 ms for long ICI. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean. | Baseline and Six months |
| Results of Physical Examination at the End of the Study Drug and Placebo Treatment Periods | A physical examination was administered by a physician to subjects at the end of each six month treatment period, i.e., following completion of a six month period on SGS-742 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0=No observation; 1=Stable baseline findings; 2=New asymptomatic finding; 3=Patient reports some worsening of a baseline daily function associated with new finding; 4=Patient unable to carry out a baseline daily function associated with new finding | Six months |
| Washington State University |
| Pullman |
| Washington |
| United States |
| Arnold S, Berthele A, Drzezga A, Tolle TR, Weis S, Werhahn KJ, Henkel A, Yousry TA, Winkler PA, Bartenstein P, Noachtar S. Reduction of benzodiazepine receptor binding is related to the seizure onset zone in extratemporal focal cortical dysplasia. Epilepsia. 2000 Jul;41(7):818-24. doi: 10.1111/j.1528-1157.2000.tb00248.x. |
| 16171286 | Background | Arnulf I, Konofal E, Gibson KM, Rabier D, Beauvais P, Derenne JP, Philippe A. Effect of genetically caused excess of brain gamma-hydroxybutyric acid and GABA on sleep. Sleep. 2005 Apr;28(4):418-24. doi: 10.1093/sleep/28.4.418. |
| 34015244 | Derived | Schreiber JM, Wiggs E, Cuento R, Norato G, Dustin IH, Rolinski R, Austermuehle A, Zhou X, Inati SK, Gibson KM, Pearl PL, Theodore WH. A Randomized Controlled Trial of SGS-742, a gamma-aminobutyric acid B (GABA-B) Receptor Antagonist, for Succinic Semialdehyde Dehydrogenase Deficiency. J Child Neurol. 2021 Nov;36(13-14):1189-1199. doi: 10.1177/08830738211012804. Epub 2021 May 20. |
| NOT COMPLETED |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo | Participants with SSADH Deficiency when on placebo for six months Placebo |
| OG001 | Study Drug | Participants with SSADH Deficiency receiving SGS-742 when on study drug for six months SGS-742 |
|
|
| Secondary | Change From Baseline of TMS Measurement of Motor Threshold at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. The motor threshold is defined as the minimum percentage of the stimulator output that evoked a motor evoked potential of more than 50µV in at least 5 out of 10 trials. Motor threshold was measured at the end of the study drug period and the end of the Placebo period. The differences between Placebo and Baseline, and SGS and Baseline were obtained. A decrease from baseline value indicates increased cortical excitability and an increase from baseline value indicates reduced cortical excitability. These values were averaged across individuals to report a mean and standard deviation of this baseline-to-treatment period change. The mean for each treatment can be compared to have a baseline-adjusted treatment effect. | We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported. | Posted | Mean | Standard Deviation | percentage of stimulator output | Baseline and Six months |
|
|
|
| Secondary | Change From Baseline of TMS Measurement of Intracortical Facilitation at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. Intracortical facilitation (ICF) and inhibition (ICI) were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at an interstimulus interval (ISI) of 10 ms for ICF. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean. | We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported. | Posted | Mean | Standard Deviation | ratio of MEP amplitude | Baseline and Six months |
|
|
|
| Secondary | Change From Baseline of TMS Measurement of Short Interval Intracortical Inhibition (Short ICI) at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons. Intracortical facilitation and inhibition were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at an interstimulus interval (ISI) of 2 ms for short ICI. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean. | We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported. | Posted | Mean | Standard Deviation | ratio of MEP amplitude | Baseline and Six months |
|
|
|
| Secondary | Change From Baseline of TMS Measurement of Long Interval Intracortical Inhibition (Long ICI) at the End of the Study Drug and Placebo Treatment Periods | Transcranial Magnetic Stimulation (TMS) is a non-invasive technique which applies magnetic pulses to the brain via a coil inducing an electrical current in the brain. Stimulation is typically applied at a sufficient intensity to trigger action potentials in nearby neurons.Intracortical facilitation and inhibition were studied using a paired stimulus paradigm. The motor threshold (MT) was first established. The conditioning stimulus (70% MT) followed by the test stimulus (120% MT) was delivered at 100 ms for long ICI. Each run consisted of 10 trials, and the amplitude ratio of the mean conditioned Motor Evoked Potential (MEP) to control MEP was determined. A larger amplitude ratio indicates greater cortical excitability. The differences between Placebo and Baseline, and SGS and Baseline were obtained. These values were averaged across individuals to report a mean. | We were unable to obtain Motor Thresholds for all participants at all three timepoints, resulting in different N for each time period. All available data is reported. | Posted | Mean | Standard Deviation | ratio of MEP amplitude | Baseline and Six months |
|
|
|
| Secondary | Results of Physical Examination at the End of the Study Drug and Placebo Treatment Periods | A physical examination was administered by a physician to subjects at the end of each six month treatment period, i.e., following completion of a six month period on SGS-742 or Placebo. Results of the examination ranged from 0-4 with scores defined as follows: 0=No observation; 1=Stable baseline findings; 2=New asymptomatic finding; 3=Patient reports some worsening of a baseline daily function associated with new finding; 4=Patient unable to carry out a baseline daily function associated with new finding | One subject withdrew prior to end of Phase 1 | Posted | Count of Participants | Participants | Six months |
|
|
|
| 0 |
| 18 |
| 0 |
| 18 |
| 16 |
| 18 |
| EG001 | Washout Period Following Placebo | Participants with SSADH Deficiency having received Placebo, during the 9 week washout period | 0 | 16 | 0 | 16 | 3 | 16 |
| EG002 | Study Drug | Participants with SSADH Deficiency receiving SGS-742 while on study drug for six months SGS-742 | 0 | 19 | 0 | 19 | 18 | 19 |
| EG003 | Washout Period Following Study Drug | Participants with SSADH Deficiency having received SGS-742, during the 9 week washout period | 0 | 18 | 0 | 18 | 6 | 18 |
| Abnormal Urinary Analysis results | Renal and urinary disorders | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Agitation | Psychiatric disorders | Non-systematic Assessment |
|
| Allergic Rhinitis | Ear and labyrinth disorders | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Blister | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Blister in the oral cavity | Gastrointestinal disorders | Non-systematic Assessment |
|
| Bloating | Gastrointestinal disorders | Non-systematic Assessment |
|
| Bruising | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| Concentration Impairment | Nervous system disorders | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | Non-systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | Non-systematic Assessment |
|
| Ear Pain | Ear and labyrinth disorders | Non-systematic Assessment |
|
| Fatigue | General disorders | Non-systematic Assessment |
|
| Fever | General disorders | Non-systematic Assessment |
|
| Flushing | Vascular disorders | Non-systematic Assessment |
|
| Head lice | Infections and infestations | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| Hyperactivity | Nervous system disorders | Non-systematic Assessment |
|
| Increased appetite | Gastrointestinal disorders | Non-systematic Assessment |
|
| Insomnia | Nervous system disorders | Non-systematic Assessment |
|
| Irritability | Psychiatric disorders | Non-systematic Assessment |
|
| Labile | Psychiatric disorders | Non-systematic Assessment |
|
| Labile | Infections and infestations | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | Non-systematic Assessment |
|
| Muscle weakness upper limb | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Nasal congestion | Ear and labyrinth disorders | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | Non-systematic Assessment |
|
| Priapism | Renal and urinary disorders | Non-systematic Assessment |
|
| Rash | Infections and infestations | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Red eyes | Eye disorders | Non-systematic Assessment |
|
| Seizures | Nervous system disorders | Non-systematic Assessment |
|
| Sleepiness | Nervous system disorders | Non-systematic Assessment |
|
| Strep throat | Infections and infestations | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | Non-systematic Assessment |
|
| Upper Respiratory Infection | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment |
|
| Vaginal infection | Infections and infestations | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Non-systematic Assessment |
|
| Weight gain | Investigations | Non-systematic Assessment |
|
Not provided
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| D013568 | Pathological Conditions, Signs and Symptoms |
| 2 |
|
| 3 |
|
| 4 |
|