A Study of UX007 (Triheptanoin) in Participants With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)

• Sponsor: Ultragenyx Pharmaceutical Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01886378
• Collaborator: (none)
• Enrollment: 29
• Locations: 10
• Arm: 1
• Actual Duration (Months): 30.6
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of the study was to evaluate the impact of UX007 on acute clinical pathophysiology associated with LC-FAOD following 24 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Long-chain Fatty Acid Oxidation Disorders (LC-FAOD); Carnitine Palmitoyltransferase (CPT II) Deficiency; Very Long Chain Acyl-CoA Dehydrogenase (VLCAD) Deficiency; Longchain 3-hydroxy-acyl-CoA Dehydrogenase (LCHAD) Deficiency; Trifunctional Protein (TFP) Deficiency	Drug: UX007	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Phase 2 Study to Assess Safety and Clinical Effects of UX007 in Subjects With Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
• Actual Study Start Date: Feb 6, 2014
• Actual Primary Completion Date: Aug 25, 2016
• Actual Study Completion Date: Aug 25, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: UX007 UX007 dosing titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants are followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.	Drug: UX007; Other Names: triheptanoin C7 oil

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Time Adjusted-Area Under the Curve (AUC/Time) for Workload During Cycle Ergometry at Week 24 [Baseline, Week 24]

   To evaluate the impact 24 weeks of treatment with UX007 has on exercise intolerance, the change from Baseline in time adjusted-AUC (AUC/time) for workload during 40-minute cycle ergometry tests at Week 24 were assessed using the generalized estimation equation (GEE) model. A cycle ergometer can measure the work performed by an individual over time during physical exercise, the work was measured every 10 minutes from 0 to 40 minutes at Baseline and Week 24. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. An increase in AUC is reflective of improved exercise tolerance; a negative change from Baseline indicates worsening.

2. Change From Baseline in Time-Adjusted-AUC for Respiratory Exchange Ratio (RER) During Cycle Ergometry at Week 24 [Baseline, Week 24]

   Change from baseline in time-adjusted-AUC for respiratory exchange ratio (RER) during cycle ergometry at Week 24, assessed using the GEE model, which included change from baseline as dependent variable, time as categorical variable, and adjusted for baseline measurement with compound symmetry covariance structure. RER during exercise is calculated as volume of carbon dioxide/volume of oxygen. RER measures whether carbohydrates or fats are being used as fuel. RER ≥1.0 indicates carbohydrates are the predominate fuel source. RER <1.0 and RER >0.70 indicates both fats and carbohydrates are the predominate fuel source. RER approximately =0.70 means fat is the predominant fuel source. RER would be expected to be lower, at similar exercise intensities, if a participant is able to utilize fat as an energy source. Therefore, an increase in RER (positive change from baseline) would suggest participants are still utilizing carbohydrates rather than fat, reflective a physiological response.

3. Change From Baseline in Actual Duration of Exercise During Cycle Ergometry at Week 24 [Baseline, Week 24]

   To evaluate the impact of 24 weeks of treatment with UX007 on exercise intolerance, the change from Baseline in actual duration of exercise during 40-minute cycle ergometry tests at Week 24 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Duration of exercise is expected to increase as exercise tolerance improves.

4. Change From Baseline in Distance Traveled During the 12-Minute Walk Test (12MWT) at Week 18 [Baseline (last assessment during the 4-week run-in period), Week 18]

   To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline in distance traveled during a 12MWT at Week 18 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Distance traveled during the 12MWT is expected to increase as muscle function increases.

5. Change From Baseline in Energy Expenditure Index (EEI) During the 12MWT at Week 18 [Baseline (last assessment during the 4-week run-in period), Week 18]

   To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline of EEI during the 12MWT at Week 18 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. EEI is quantified as the post-test heart rate minus the pre-test heart rate (in beats/min) divided by overall velocity, and is valued in beats/meter. A decrease in EEI when walking a similar distance or no change when walking longer distances, may indicate improved exercise tolerance.

6. Change From Baseline in Percentage of the Predicted 6-Minute Walk Test (6MWT) Distance Walked at Week 18 [Baseline (last assessment during the 4-week run-in period), Week 18]

   To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline in the percentage of the predicted distance traveled during the first 6 minutes (6MWT) of the 12MWT at Week 18 was assessed using the GEE model. A participant's mathematical formula to calculate their percent predicted (PP) distance walked in the 6MWT was based on their demographics at baseline. For participants < 20 years old, the formula used was referenced from (Gieger, et. al. 2007) which calculated PP distance walked based on age, gender, and height. For participants >= 20 years old, the formula used was referenced from (Gibbons, et. al. 2001) and calculated the PP distance walked based on age and gender. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Percent predicted values are expected to increase as muscle function increases.

7. Change From Baseline in Physical Summary Score (PHS-10) of the Short Form 10 (SF-10) at Week 24 [Baseline, Week 24]

   To evaluate the impact treatment with UX007 has on functional disability and health in participants between 5 and 17 years of age, change from Baseline in the T-scores of the PHS-10 were assessed at Week 24 and analyzed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. The SF-10 Health Survey for Children is a 10-item caregiver-completed assessment designed to measure children's health-related quality of life. The PHS-10 of the SF-10 is scored such that higher scores indicate more favorable functioning. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in a comprehensive sample of US population (scale scores are standardized to a mean of 50 and a standard deviation of 10).

8. Change From Baseline in Psychosocial Summary Score (PSS-10) of the SF10 at Week 24 [Baseline, Week 24]

   To evaluate the impact treatment with UX007 has on functional disability and health in participants between 5 and 17 years of age, changes from Baseline in the T-scores of the PSS-10 were assessed at Week 24 and analyzed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. The PSS-10 of the SF-10 is scored such that higher scores indicate more favorable functioning. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in a comprehensive sample of US population (scale scores are standardized to a mean of 50 and a standard deviation of 10). Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more favorable functioning/better health.

9. Change From Baseline in the Physical Component Summary Scale (PCS-12) at Week 24 [Baseline, Week 24]

   Changes from baseline in T-scores as assessed by the PCS-12 Short-Form Health Survey, version 2 (SF-12v2) at Week 24 were assessed using the GEE model, which included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. PCS-12 scores were calculated from the individual responses to those questions that contribute to physical health. Raw scores range from 0 to 100 with higher scores indicating better health. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in the US general population (scale scores are standardized to a mean of 50 and a standard deviation of 10). Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more favorable functioning/better health.

10. Change From Baseline in the Mental Component Summary Scale (MCS-12) at Week 24 [Baseline, Week 24]

    Changes from baseline of T-scores as assessed by the MCS-12 of the SF-12v2 at Week 24 were assessed using the GEE model, which included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. MCS-12 scores were calculated from the individual responses to those questions that contribute to mental health. Raw scores range from 0 to 100 with higher scores indicating better health. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in the US general population (scale scores are standardized to a mean of 50 and a standard deviation of 10). Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more favorable functioning/better health.

11. Annualized Event Rate of All Major Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Major clinical events are defined as adverse events (AEs) resulting in hospitalizations, emergency room (ER) visits, and emergency intervention.

12. Annualized Duration Rate of All Major Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Major clinical events are defined as AEs resulting in hospitalizations, ER visits, and emergency intervention.

13. Annualized Event Rate of Major Rhabdomyolysis Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly. Major rhabdomyolysis clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.

14. Annualized Duration Rate of Major Rhabdomyolysis Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly. Major rhabdomyolysis clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.

15. Annualized Event Rate of Major Hypoglycemia Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Major hypoglycemia clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.

16. Annualized Duration Rate of Major Hypoglycemia Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Major hypoglycemia clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.

17. Annualized Event Rate of Major Cardiac Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Major cardiac clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.

18. Annualized Duration Rate of Major Cardiac Clinical Events Pre- and Post-Treatment With UX007 [18 months before and after UX007 initiation]

    Major cardiac clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Confirmed diagnosis of CPT II, VLCAD, LCHAD, or TFP deficiency, based on results of acylcarnitine profiles, fatty acid oxidation probe studies in cultured fibroblasts, and/or mutation analysis obtained from medical records.

• Male or female, at least 6 months of age

• Willing and able to complete all aspects of the study through the end of the study. If a minor, have a caregiver(s) willing and able to assist in all applicable study requirements.

• Provide written informed consent (subjects aged ≥ 18 years), or provide written assent (where appropriate) and have a legally authorized representative willing and able to provide written informed consent

• Willing and able to provide access to medical records charting the last 18-24 months of care prior to the study initiation, or from birth for those subjects less than 18 months of age

• No history of serious adverse reactions or known hypersensitivity to triheptanoin

• Currently managed on a stable treatment regimen (including diet), which may include low-fat/high-carbohydrate diet, avoidance of fasting, carnitine and/or medium-chain triglyceride (MCT) oil. The treatment regimen (including diet) should be stable for the last 60 days to assure that changes in the subject's condition are not confounded by recent changes in the treatment regimen that could affect the 4 week run-in evaluation period. Once study drug treatment has started, must be willing to maintain all aspects of the subject's treatment regimen and diet unchanged, other than discontinuation of MCT oil, in order to avoid potential variability of response due to variations in dietary intake.

• Have severe LC-FAOD, as evidenced by ANY ONE of the following significant clinical manifestations despite therapy:

• Chronic Elevated Creatine Kinase (CK) with Major Clinical Events: Elevated mean CK levels over the last 6 months -1 year (defined as ≥ 2X upper limit of age/gender-matched normal, or ≥ 500 units/L if age-matched reference not established) not associated with an acute rhabdomyolysis event, AND at least two major clinical events (as defined in the protocol) in the last year, or at least four major clinical events over the last two years,

• Episodic Elevated CK with Reported Muscle Dysfunction: Episodes of elevated CK levels over the last 6 months -1 year (defined as ≥ 2X upper limit of age/gender-matched normal, or ≥ 500 units/L if age-matched reference is not established) not associated with an acute rhabdomyolysis event, AND patient report of frequent muscle fatigue, exercise intolerance, or limitation of exercise,

• Highly Elevated CK but Asymptomatic: More seriously elevated mean CK levels (defined as ≥ 4X upper limit of age/gender-matched normal, or ≥ 1000 units/L if age-matched reference is not established) consistent with substantial chronic muscle rupture over the last 6 months-1 year, regardless of frequency of hospitalizations or ER events,

• Frequent Severe Major Medical Episodes (at least 3 within the past year, or 5 within 2 years) of hypoglycemia, rhabdomyolysis, or exacerbation of cardiomyopathy [CM], requiring emergency room [ER]/acute care visits or hospitalizations,

• Severe Susceptibility to Hypoglycemia (serum glucose <60 mg/dL) after short periods of fasting (less than 4-12 hours, depending on age), with at least 2 events in the last year that require ongoing prophylactic management, OR recurrent symptomatic hypoglycemia (blood glucose levels or clinical symptoms of hypoglycemia) at home requiring intervention ≥ 2 times per week,

• Evidence of Functional Cardiomyopathy (with echocardiogram (ECHO) within past 90 days documenting poor ejection fraction [EF]) requiring ongoing medical management

• Females who have reached menarche must have a negative pregnancy test at Screening. If sexually active, subject must be willing to use acceptable method of contraception and have additional pregnancy tests during the study.

Exclusion Criteria:

• Diagnosis of carnitine-acylcarnitine translocase (CACT) or CPT I

• Diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, short- or medium-chain FAOD, ketone body metabolism defect, propionic acidemia or methylmalonic acidemia

• Enrolled in a clinical study involving concurrent use of an investigational drug product within the last 30 days, or unwilling to discontinue use of a prohibited medication or other substance that may confound study objectives

• Unwilling to sign informed consent or release of medical records

• Have any co-morbid conditions, including unstable major organ-system disease(s) that in the opinion of the Investigator, places the subject at increased risk of complications, interferes with study participation or compliance, or confounds study objectives

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center	Washington	District of Columbia	United States	20010
2	University of Southern Florida	Tampa	Florida	United States	33606
3	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	Boston Children's Hospital	Boston	Massachusetts	United States	02115
5	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
6	Vanderbilt Medical Center	Nashville	Tennessee	United States	37232
7	University of Utah	Salt Lake City	Utah	United States	84132
8	Birmingham Children's Hospital	Birmingham		United Kingdom	B4 6NH
9	National Hospital for Neurology and Neurosurgery	London		United Kingdom	WC1N 3BP
10	Great Ormond Street Hospital	London		United Kingdom	WC1N 3JH

Sponsors and Collaborators

• Ultragenyx Pharmaceutical Inc

Investigators

• Study Director: Medical Director, Ultragenyx Pharmaceutical

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ultragenyx Pharmaceutical Inc
• ClinicalTrials.gov Identifier: NCT01886378
• Other Study ID Numbers: UX007-CL201; 2013-004830-14
• First Posted: Jun 25, 2013
• Last Update Posted: Feb 11, 2021
• Last Verified: Jan 1, 2021

• Keywords provided by Ultragenyx Pharmaceutical Inc: FAOD; VLCAD; CPT II; CPT2; CPT 2; LCHAD; UX007; Triheptanoin; TFP; C7
• Additional relevant MeSH terms: Disease

Study Results

Participant Flow

Pre-assignment Detail	Following the signing of informed consent at the Screening visit, each participant continued on current long-chain fatty acid oxidation disorder (LC-FAOD) management for a 4-week Run-in Period to establish a clinical baseline. Following completion of the 4-week Run-in Period, participants discontinued any use of medium chain triglycerides (MCT) and began treatment with UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Period Title: Overall Study
STARTED	29
Completed 24 Weeks of UX007 Treatment	25
COMPLETED	24
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Overall Participants	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.06 (5.26)
Age, Customized (Count of Participants)
0 - 1 years	2 6.9%
> 1 - 6 years	13 44.8%
> 6 -18 years	8 27.6%
> 18 years	6 20.7%
Sex: Female, Male (Count of Participants)
Female	12 41.4%
Male	17 58.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Time Adjusted-Area Under the Curve (AUC/Time) for Workload During Cycle Ergometry at Week 24
Description	To evaluate the impact 24 weeks of treatment with UX007 has on exercise intolerance, the change from Baseline in time adjusted-AUC (AUC/time) for workload during 40-minute cycle ergometry tests at Week 24 were assessed using the generalized estimation equation (GEE) model. A cycle ergometer can measure the work performed by an individual over time during physical exercise, the work was measured every 10 minutes from 0 to 40 minutes at Baseline and Week 24. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. An increase in AUC is reflective of improved exercise tolerance; a negative change from Baseline indicates worsening.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - Cycle Ergometry: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one cycle ergometry test performed with any duration.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	7
Least Squares Mean (Standard Error) [watts]	423.594 (295.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1518
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	Least squares (LS) mean
	Estimated Value	423.594
	Confidence Interval	(2-Sided) 95%; -155.66 to 1002.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean, 95% confidence interval (CI), and p-values are based on the GEE model.

2. Primary Outcome

Title	Change From Baseline in Time-Adjusted-AUC for Respiratory Exchange Ratio (RER) During Cycle Ergometry at Week 24
Description	Change from baseline in time-adjusted-AUC for respiratory exchange ratio (RER) during cycle ergometry at Week 24, assessed using the GEE model, which included change from baseline as dependent variable, time as categorical variable, and adjusted for baseline measurement with compound symmetry covariance structure. RER during exercise is calculated as volume of carbon dioxide/volume of oxygen. RER measures whether carbohydrates or fats are being used as fuel. RER ≥1.0 indicates carbohydrates are the predominate fuel source. RER <1.0 and RER >0.70 indicates both fats and carbohydrates are the predominate fuel source. RER approximately =0.70 means fat is the predominant fuel source. RER would be expected to be lower, at similar exercise intensities, if a participant is able to utilize fat as an energy source. Therefore, an increase in RER (positive change from baseline) would suggest participants are still utilizing carbohydrates rather than fat, reflective a physiological response.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - Cycle Ergometry: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one cycle ergometry test performed with any duration.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	7
Least Squares Mean (Standard Error) [respiratory exchange ratio]	-0.011 (0.0132)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3964
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	-0.011
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean, 95% CI, and p-values are based on the GEE model.

3. Primary Outcome

Title	Change From Baseline in Actual Duration of Exercise During Cycle Ergometry at Week 24
Description	To evaluate the impact of 24 weeks of treatment with UX007 on exercise intolerance, the change from Baseline in actual duration of exercise during 40-minute cycle ergometry tests at Week 24 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Duration of exercise is expected to increase as exercise tolerance improves.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - Cycle Ergometry: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one cycle ergometry test performed with any duration.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	7
Least Squares Mean (Standard Error) [minutes]	4.671 (2.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0777
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	4.671
	Confidence Interval	(2-Sided) 95%; -0.52 to 9.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean, 95% CI, and p-values are based on the GEE model.

4. Primary Outcome

Title	Change From Baseline in Distance Traveled During the 12-Minute Walk Test (12MWT) at Week 18
Description	To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline in distance traveled during a 12MWT at Week 18 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Distance traveled during the 12MWT is expected to increase as muscle function increases.
Time Frame	Baseline (last assessment during the 4-week run-in period), Week 18

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - 12MWT: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one 12MWT performed with any distance walked.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	8
Least Squares Mean (Standard Error) [meters]	181.37 (104.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0830
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	181.37
	Confidence Interval	(2-Sided) 95%; -23.70 to 386.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean, 95% CI, and p-values are based on the GEE model.

5. Primary Outcome

Title	Change From Baseline in Energy Expenditure Index (EEI) During the 12MWT at Week 18
Description	To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline of EEI during the 12MWT at Week 18 was assessed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. EEI is quantified as the post-test heart rate minus the pre-test heart rate (in beats/min) divided by overall velocity, and is valued in beats/meter. A decrease in EEI when walking a similar distance or no change when walking longer distances, may indicate improved exercise tolerance.
Time Frame	Baseline (last assessment during the 4-week run-in period), Week 18

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - 12MWT: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one 12MWT performed with any distance walked.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	8
Least Squares Mean (Standard Error) [beats/meter]	-0.185 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0320
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	-0.185
	Confidence Interval	(2-Sided) 95%; -0.35 to -0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean, 95% CI, and p-values are based on the GEE model.

6. Primary Outcome

Title	Change From Baseline in Percentage of the Predicted 6-Minute Walk Test (6MWT) Distance Walked at Week 18
Description	To evaluate the impact 18 weeks of treatment with UX007 has on muscle function, the change from Baseline in the percentage of the predicted distance traveled during the first 6 minutes (6MWT) of the 12MWT at Week 18 was assessed using the GEE model. A participant's mathematical formula to calculate their percent predicted (PP) distance walked in the 6MWT was based on their demographics at baseline. For participants < 20 years old, the formula used was referenced from (Gieger, et. al. 2007) which calculated PP distance walked based on age, gender, and height. For participants >= 20 years old, the formula used was referenced from (Gibbons, et. al. 2001) and calculated the PP distance walked based on age and gender. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. Percent predicted values are expected to increase as muscle function increases.
Time Frame	Baseline (last assessment during the 4-week run-in period), Week 18

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - 12MWT: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one 12MWT performed with any distance walked.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	8
Least Squares Mean (Standard Error) [% of predicted distance (in meters)]	12.44 (7.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0850
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	12.44
	Confidence Interval	(2-Sided) 95%; -1.72 to 26.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean, 95% CI, and p-values are based on the GEE model.

7. Primary Outcome

Title	Change From Baseline in Physical Summary Score (PHS-10) of the Short Form 10 (SF-10) at Week 24
Description	To evaluate the impact treatment with UX007 has on functional disability and health in participants between 5 and 17 years of age, change from Baseline in the T-scores of the PHS-10 were assessed at Week 24 and analyzed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. The SF-10 Health Survey for Children is a 10-item caregiver-completed assessment designed to measure children's health-related quality of life. The PHS-10 of the SF-10 is scored such that higher scores indicate more favorable functioning. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in a comprehensive sample of US population (scale scores are standardized to a mean of 50 and a standard deviation of 10).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - SF-10: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one SF-10 test performed.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	5
Least Squares Mean (Standard Error) [T-score]	2.16 (2.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3754
	Comments	The LS Mean, standard error (SE), 95% CI, and 2-sided p-value are from the GEE model.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	2.16
	Confidence Interval	(2-Sided) 95%; -2.62 to 6.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Primary Outcome

Title	Change From Baseline in Psychosocial Summary Score (PSS-10) of the SF10 at Week 24
Description	To evaluate the impact treatment with UX007 has on functional disability and health in participants between 5 and 17 years of age, changes from Baseline in the T-scores of the PSS-10 were assessed at Week 24 and analyzed using the GEE model. The GEE model included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. The PSS-10 of the SF-10 is scored such that higher scores indicate more favorable functioning. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in a comprehensive sample of US population (scale scores are standardized to a mean of 50 and a standard deviation of 10). Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more favorable functioning/better health.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - SF-10: the subset of participants in the primary analysis set (all enrolled participants who completed the 4 week Run-in Period and received at least one dose of UX007) who had at least one SF-10 test performed.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	5
Least Squares Mean (Standard Error) [T-score]	0.816 (2.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7564
	Comments	The LS Mean, SE, 95% CI, and 2-sided p-value are from the GEE model.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	0.816
	Confidence Interval	(2-Sided) 95%; -4.34 to 5.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Primary Outcome

Title	Change From Baseline in the Physical Component Summary Scale (PCS-12) at Week 24
Description	Changes from baseline in T-scores as assessed by the PCS-12 Short-Form Health Survey, version 2 (SF-12v2) at Week 24 were assessed using the GEE model, which included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. PCS-12 scores were calculated from the individual responses to those questions that contribute to physical health. Raw scores range from 0 to 100 with higher scores indicating better health. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in the US general population (scale scores are standardized to a mean of 50 and a standard deviation of 10). Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more favorable functioning/better health.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - SF-12: the subset of participants in the primary analysis set (those who completed the 4-week run-in period and received at least one dose of UX007) who had at least one SF-12 test performed.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	5
Least Squares Mean (Standard Deviation) [T-score]	8.88 (1.63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	8.88
	Confidence Interval	(2-Sided) 95%; 5.67 to 12.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Primary Outcome

Title	Change From Baseline in the Mental Component Summary Scale (MCS-12) at Week 24
Description	Changes from baseline of T-scores as assessed by the MCS-12 of the SF-12v2 at Week 24 were assessed using the GEE model, which included the change from Baseline as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure. MCS-12 scores were calculated from the individual responses to those questions that contribute to mental health. Raw scores range from 0 to 100 with higher scores indicating better health. The T-score based scoring signifies that scale scores are centered so that a score of 50 corresponds to the average score in the US general population (scale scores are standardized to a mean of 50 and a standard deviation of 10). Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of more favorable functioning/better health.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Primary Analysis Set - SF-12: the subset of participants in the primary analysis set (those who completed the 4-week run-in period and received at least one dose of UX007) who had at least one SF-12 test performed.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	5
Least Squares Mean (Standard Error) [T-score]	9.7 (4.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	UX007
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0152
	Comments	The GEE model included the change from Baseline for each parameter as the dependent variable, time as the categorical variable, and adjusted for Baseline measurement with compound symmetry covariance structure.
	Method	GEE model
	Comments
Method of Estimation	Estimation Parameter	LS mean
	Estimated Value	9.70
	Confidence Interval	(2-Sided) 95%; 1.87 to 17.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean, 95% CI, and p-values are based on the GEE model.

11. Primary Outcome

Title	Annualized Event Rate of All Major Clinical Events Pre- and Post-Treatment With UX007
Description	Major clinical events are defined as adverse events (AEs) resulting in hospitalizations, emergency room (ER) visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	1.69 (1.6081)
Post-UX007	0.877 (1.142)

12. Primary Outcome

Title	Annualized Duration Rate of All Major Clinical Events Pre- and Post-Treatment With UX007
Description	Major clinical events are defined as AEs resulting in hospitalizations, ER visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	5.961 (6.0783)
Post-UX007	2.964 (3.9733)

13. Primary Outcome

Title	Annualized Event Rate of Major Rhabdomyolysis Clinical Events Pre- and Post-Treatment With UX007
Description	Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly. Major rhabdomyolysis clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	1.303 (1.5007)
Post-UX007	0.833 (1.1513)

14. Primary Outcome

Title	Annualized Duration Rate of Major Rhabdomyolysis Clinical Events Pre- and Post-Treatment With UX007
Description	Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly. Major rhabdomyolysis clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	3.949 (4.3687)
Post-UX007	2.792 (3.8452)

15. Primary Outcome

Title	Annualized Event Rate of Major Hypoglycemia Clinical Events Pre- and Post-Treatment With UX007
Description	Major hypoglycemia clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	0.318 (0.9053)
Post-UX007	0.023 (0.1224)

16. Primary Outcome

Title	Annualized Duration Rate of Major Hypoglycemia Clinical Events Pre- and Post-Treatment With UX007
Description	Major hypoglycemia clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	1.414 (4.3025)
Post-UX007	0.023 (0.1224)

17. Primary Outcome

Title	Annualized Event Rate of Major Cardiac Clinical Events Pre- and Post-Treatment With UX007
Description	Major cardiac clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	0.069 (0.2728)
Post-UX007	0.021 (0.115)

18. Primary Outcome

Title	Annualized Duration Rate of Major Cardiac Clinical Events Pre- and Post-Treatment With UX007
Description	Major cardiac clinical events are defined as those AEs resulting in hospitalizations, ER visits, and emergency intervention.
Time Frame	18 months before and after UX007 initiation

Outcome Measure Data

Analysis Population Description

Primary Analysis Set: participants who completed the 4-week run-in period and received at least one dose of UX007.

Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
Measure Participants	29
Pre-UX007	0.598 (2.4054)
Post-UX007	0.149 (0.8047)

Adverse Events

Time Frame	From the first dose of UX007 through the Follow-up visit (Week 82) or 30 days following the last UX007 administration.
Adverse Event Reporting Description	Events presented are treatment-emergent. An event was considered as treatment-emergent if it occurred on or after the date of the first treatment of UX007.
Arm/Group Title	UX007
Arm/Group Description	UX007 dosing was titrated to a target dose of 25-35% of total caloric intake or maximum tolerated dose. Participants were followed to evaluate the effects of UX007 over 24 weeks (Treatment Period), then continued treatment in the Extension Period for an additional 54 weeks for a total of 78 weeks of treatment.
All Cause Mortality
	UX007
	Affected / at Risk (%)	# Events
Total	0/29 (0%)
Serious Adverse Events
	UX007
	Affected / at Risk (%)	# Events
Total	19/29 (65.5%)
Cardiac disorders
Cardiomyopathy Acute	1/29 (3.4%)
Congenital, familial and genetic disorders
Talipes	1/29 (3.4%)
Gastrointestinal disorders
Gastrointestinal Disorder	1/29 (3.4%)
Gastrointestinal Haemorrhage	1/29 (3.4%)
Vomiting	1/29 (3.4%)
Infections and infestations
Gastroenteritis	6/29 (20.7%)
Gastroenteritis Viral	6/29 (20.7%)
Gastrointestinal Viral Infection	2/29 (6.9%)
Upper Respiratory Tract Infection	2/29 (6.9%)
Adenoviral Upper Respiratory Infection	1/29 (3.4%)
Adenovirus Infection	1/29 (3.4%)
Conjunctivitis	1/29 (3.4%)
Coxsackie Viral Infection	1/29 (3.4%)
Croup Infectious	1/29 (3.4%)
Otitis Media	1/29 (3.4%)
Otitis Media Acute	1/29 (3.4%)
Pneumonia Mycoplasmal	1/29 (3.4%)
Respiratory Tract Infection Viral	1/29 (3.4%)
Roseola	1/29 (3.4%)
Urinary Tract Infection	1/29 (3.4%)
Viral Upper Respiratory Tract Infection	1/29 (3.4%)
Metabolism and nutrition disorders
Metabolic Disorder	1/29 (3.4%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	11/29 (37.9%)
Reproductive system and breast disorders
Menorrhagia	1/29 (3.4%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/29 (3.4%)
Surgical and medical procedures
Infection Prophylaxis	1/29 (3.4%)
Other (Not Including Serious) Adverse Events
	UX007
	Affected / at Risk (%)	# Events
Total	29/29 (100%)
Blood and lymphatic system disorders
Lymphadenopathy	2/29 (6.9%)
Cardiac disorders
Tachycardia	2/29 (6.9%)
Eye disorders
Eye Swelling	2/29 (6.9%)
Gastrointestinal disorders
Diarrhoea	16/29 (55.2%)
Vomiting	13/29 (44.8%)
Abdominal Pain	8/29 (27.6%)
Abdominal Pain Upper	4/29 (13.8%)
Gastrointestinal Pain	3/29 (10.3%)
Gastrooesophageal Reflux Disease	3/29 (10.3%)
Abdominal Distension	2/29 (6.9%)
Constipation	2/29 (6.9%)
Flatulence	2/29 (6.9%)
Nausea	2/29 (6.9%)
Teething	2/29 (6.9%)
General disorders
Pyrexia	9/29 (31%)
Pain	3/29 (10.3%)
Infections and infestations
Upper Respiratory Tract Infection	11/29 (37.9%)
Ear Infection	5/29 (17.2%)
Nasopharyngitis	5/29 (17.2%)
Bronchitis	4/29 (13.8%)
Gastroenteritis Viral	4/29 (13.8%)
Gastrointestinal Viral Infection	4/29 (13.8%)
Rhinitis	4/29 (13.8%)
Viral Upper Respiratory Tract Infection	4/29 (13.8%)
Conjunctivitis	3/29 (10.3%)
Gastroenteritis	3/29 (10.3%)
Sinusitis	3/29 (10.3%)
Urinary Tract Infection	3/29 (10.3%)
Otitis Media	2/29 (6.9%)
Respiratory Tract Infection Viral	2/29 (6.9%)
Injury, poisoning and procedural complications
Arthropod Bite	3/29 (10.3%)
Fall	3/29 (10.3%)
Laceration	2/29 (6.9%)
Procedural Pain	2/29 (6.9%)
Stoma Site Pain	2/29 (6.9%)
Investigations
Blood Creatine Phosphokinase Increased	3/29 (10.3%)
Carnitine Decreased	2/29 (6.9%)
Metabolism and nutrition disorders
Decreased Appetite	4/29 (13.8%)
Dehydration	2/29 (6.9%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	8/29 (27.6%)
Myalgia	5/29 (17.2%)
Arthralgia	2/29 (6.9%)
Muscle Spasms	2/29 (6.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic Naevus	2/29 (6.9%)
Nervous system disorders
Headache	9/29 (31%)
Psychiatric disorders
Anxiety	2/29 (6.9%)
Irritability	2/29 (6.9%)
Panic Attack	2/29 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	4/29 (13.8%)
Nasal Congestion	3/29 (10.3%)
Oropharyngeal Pain	3/29 (10.3%)
Rhinorrhoea	2/29 (6.9%)
Sinus Congestion	2/29 (6.9%)
Skin and subcutaneous tissue disorders
Acne	3/29 (10.3%)
Dermatitis Allergic	2/29 (6.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.