Proof of Concept Study to Assess Activity and Safety of S... | NCT02858362

ID	Type	Description	Link
2015-004333-27	EudraCT Number

Label	Type	Description	Intervention Names
Cohort 1: SMT C1100 Formulation 1	Experimental	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.	Drug: Ezutromid
Cohort 2: SMT C1100 Formulation 2	Experimental	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.	Drug: Ezutromid
Cohort 3: SMT C1100 Formulation 1	Experimental	Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.	Drug: Ezutromid

Name	Type	Description	Arm Group Labels	Other Names
Ezutromid	Drug	Administered orally.	Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles	MRS FF was analysed for vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.	Baseline, Week 12, Week 24, Week 36 and Week 48
Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles	MRS WTRT was analysed for the vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.	Baseline, Week 12, Week 24, Week 36 and Week 48
Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)	Pharmacokinetic analysis is presented by cohort due to the use of different formulations. The median pre-dose concentration was derived for each participant and then summarized across participants.	Pre-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)	Pharmacokinetic analysis is presented by cohort due to the use of different formulations.	Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)	Pharmacokinetic analysis is presented by cohort due to the use of different formulations.	Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Utrophin Intensity	A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. Utrophin intensity was analyzed using a semiautomated quantitative assay on the biopsy samples. A positive change from baseline represents an increase in utrophin expression, no change from baseline represents maintenance of utrophin expression and a negative change from baseline represents a reduction in utrophin expression. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Be able to provide written informed consent/assent as per local requirements.
Be male.
Have phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (e.g., proximal muscle weakness, waddling gait, and Gowers' manoeuvre), an elevated serum creatinine kinase level, and ongoing difficulty with walking.
Have prior confirmation of the duchenne muscular dystrophy (DMD) diagnosis through:

Documentation of the presence of a mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists, the Clinical Laboratory Improvement Act/Amendment or an equivalent organisation or documentation of the absence of dystrophin in the muscle (via biopsy).

Be able to undergo MRI examination.
Participants must have used stable systemic corticosteroids (prednisone, prednisolone or deflazacort) for a minimum of 6 months immediately prior to the start of the Treatment Phase, with no significant change in dosage or dosing regimen (not related to body weight change) and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
Confirmed screening laboratory values within the central laboratory ranges (haematology, renal and serum electrolyte parameters and serum chemistry parameters) or considered not clinically significant in the opinion of the Investigator. Variations in specific parameters expected in a DMD population classed by the Investigator as not clinically significant will not exclude the participant.
Be willing and able to comply with scheduled visits, drug administration plan, study procedures, laboratory tests and study restrictions.

Cohort 1 and 2 Specific Inclusion Criteria:

Be aged ≥5 years to <10 years of age (from 5th birthday to 10th birthday).
Be willing and able to comply with 2 muscle biopsy procedures.
Have the ability to walk at least 300 meters unassisted during the screening 6 minute walk distance (6MWD) and be below the protocol-specified threshold for 80%-predicted 6MWD.
Have results of 2 6MWD by Baseline determined as valid. The results of the second 6MWD (baseline) must be within 20% of the first 6MWD (screening).
Have cardiac echocardiogram (ECHO) measurements showing an ejection fraction of ≥55% and fractional shortening of ≥28%.

Cohort 3 Specific Inclusion Criteria:

Have taken part in a prior SMT C1100 study.

Exclusion Criteria:

Have physical exam findings that in the Investigator's opinion should be exclusionary e.g., lower limb injury that may affect 6MWD performance.
Have any change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation or reinitiation) in prophylaxis/treatment for congestive heart failure (CHF) within 3 months prior to the start of study treatment.
Have uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D).
Have abnormal glutamate dehydrogenase (GLDH) at baseline (>1.5 x upper limit of normal [ULN]).
Have abnormal coagulation times at baseline (>1.5 x ULN).
Have an abnormal electrocardiograms (ECG).
Use herbal supplements and be unwilling to stop these for the duration of the study.
Have been exposed to another investigational drug or DMD interventional agent within 3 months prior to start of the Treatment Phase. Prior exposure to SMT C1100 or participation in an approved deflazacort access program within this period would not exclude the participant (provided they have been on stable treatment for 6 months).
Have a history of major surgical procedure within 12 weeks prior to the start of the Treatment Phase (Week 1).
Be undertaking ongoing immunosuppressive therapy (other than corticosteroids).
Require daytime ventilator assistance.
Have a prior or ongoing medical condition, medical history, ECG findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
Be dairy or lactose intolerant or have any other dietary restrictions that might interfere with the conduct of the study.
Be a smoker, use other tobacco or nicotine products or be exposed to daily passive smoking (including parent/legal guardian, siblings) so as to minimise environmental factors causing CYP1A induction.
Be using an approved DMD medication or anticipates using one during the duration of the study. Participants who are taking part in the FOR-DMD and ACCESS DMD studies will be allowed to take part.
Be using an inducer of CYP1A1 or CYP1A2.
Be using a substrate of CYP2B6.
All prescription, over the counter, and herbal products that are known CYP2B6 sensitive substrates will be excluded 14 days prior to study conduct (beginning at screening) through 14 days after study conduct completion. Please note, this is not an exhaustive list of CYP2B6 substrates and a discussion with the Medical Monitor may be warranted.
Be using drugs that have serotonergic, norepinephrinergic or dopaminergic activity, or treatments used in attention deficit hyperactivity disorder.
Use of substrates of BRCP.

Cohort 1 and 2 Specific Exclusion Criteria:

Use beta blockers (however, if during the course of the study they are clinically indicated they can be initiated).

Cohort 1 and 3 Specific Exclusion Criteria:

Have a known hypersensitivity to any of the ingredients or excipients of the investigational medicinal product: Poloxamer 188, Methylparaben, Propylparaben, Hydroxypropylmethyl cellulose, Glycerol, Non-crystallising sorbitol [70%], Xanthan gum, Strawberry cream flavour [PHS-132963].

Cohort 2 Specific Exclusion Criteria:

Have a known hypersensitivity to any of the ingredients or excipients of the investigational medicinal product: hypromellose acetate succinate.

Name	Affiliation	Role
Medical Monitor	Summit (Oxford) Limited	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
UCLA-David Geffen School of Medicine		Los Angeles	California		United States
Children's Hosptial of Colorado

ID	Title	Description
FG000	Cohort 1: SMT C1100 Formulation 1	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
FG001	Cohort 2: SMT C1100 Formulation 2	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 24, 2017	Oct 24, 2019

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Customized

Count of Participants

Participants

Title	Denominators	Categories
Children (2-11 years)	ParticipantsBG00030 ParticipantsBG00110 ParticipantsBG0023 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00030 ParticipantsBG00110 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00030 ParticipantsBG00110 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG00030 ParticipantsBG00110 ParticipantsBG002

Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) Vastus Lateralis

Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS FF vastus lateralis at the baseline visit.

Mean

Standard Deviation

Percentage of fat in the muscle

Title	Denominators	Categories
	ParticipantsBG00029 ParticipantsBG00110 ParticipantsBG002

Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) Soleus

Efficacy measurements were planned and performed for Cohorts 1 and 2 only.

Mean

Standard Deviation

Percentage of fat in the muscle

Title	Denominators	Categories
	ParticipantsBG00030 ParticipantsBG00110 ParticipantsBG002

Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) Vastus Lateralis

Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MRS WTRT vastus lateralis at the baseline visit.

Mean

Standard Deviation

Milliseconds

Title	Denominators	Categories
	ParticipantsBG00029 ParticipantsBG00110 ParticipantsBG002

Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) Soleus

Efficacy measurements were planned and performed for Cohorts 1 and 2 only.

Mean

Standard Deviation

Milliseconds

Title	Denominators	Categories
	ParticipantsBG00030 ParticipantsBG00110 ParticipantsBG002

Development Heavy Chain Myosin (MHCd) Expression in Muscle Fibres

Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for MHCd expression at the baseline visit.

Mean

Standard Deviation

Percent of muscle fibres expressing MHCd

Title	Denominators	Categories
	ParticipantsBG00029 ParticipantsBG00110 ParticipantsBG002

Muscle Fibre Diameter

Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 1 did not have analyzable results for muscle fibre diameter at the baseline visit.

Mean

Standard Deviation

Micrometer

Title	Denominators	Categories
	ParticipantsBG00029 ParticipantsBG00110 ParticipantsBG002

Utrophin Intensity

Utrophin intensity is measured in arbitrary units (0-1) with higher scores representing higher utrophin expression.

Efficacy measurements were planned and performed for Cohorts 1 and 2 only. One participant in Cohort 2 did not have analyzable results for utrophin expression at the baseline visit.

Mean

Standard Deviation

Arbitrary Units

Title	Denominators	Categories
	ParticipantsBG00030 ParticipantsBG0019 ParticipantsBG002

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 in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles

MRS FF was analysed for vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.

All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment).

Posted

Mean

95% Confidence Interval

Percentage of fat in the muscle

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohorts 1 and 2: SMT C1100	Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG00040

Title

Denominators

Categories

Vastus Lateralis: Week 12 Change from Baseline

- ParticipantsOG00039

Title	Measurements
	OG0001.779(0.939 to 2.620)

Vastus Lateralis: Week 24 Change from Baseline

- ParticipantsOG000

Primary

Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles

MRS WTRT was analysed for the vastus lateralis and soleus leg muscles. The endpoints were measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.

All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment).

Posted

Mean

95% Confidence Interval

Milliseconds

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohorts 1 and 2: SMT C1100	Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Primary

Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)

Pharmacokinetic analysis is presented by cohort due to the use of different formulations. The median pre-dose concentration was derived for each participant and then summarized across participants.

All participants in Cohorts 1 or 2 who received at least one dose of study medication and had at least one concentration measurement (which could be below the limit of quantification). No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose at Weeks 1, 4, 8, 12, 24, 36 and 48

ID	Title	Description
OG000	Cohort 1: SMT C1100 Formulation 1	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
OG001	Cohort 2: SMT C1100 Formulation 2	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants

Primary

Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)

Pharmacokinetic analysis is presented by cohort due to the use of different formulations.

Posted

Geometric Mean

Full Range

ng/mL

Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48

ID	Title	Description
OG000	Cohort 1: SMT C1100 Formulation 1	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
OG001	Cohort 2: SMT C1100 Formulation 2	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Primary

Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)

Pharmacokinetic analysis is presented by cohort due to the use of different formulations.

Posted

Geometric Mean

Full Range

ng/mL

Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48

ID	Title	Description
OG000	Cohort 1: SMT C1100 Formulation 1	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
OG001	Cohort 2: SMT C1100 Formulation 2	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Primary

Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)

An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A TEAE is defined as any event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

All participants who received at least one dose of study medication.

Posted

Count of Participants

Participants

Day 1 to a maximum of Week 96

ID	Title	Description
OG000	Cohort 1: SMT C1100 Formulation 1	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
OG001	Cohort 2: SMT C1100 Formulation 2	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
OG002	Cohort 3: SMT C1100 Formulation 1	Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.

Secondary

Change From Baseline in Utrophin Intensity

A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. Utrophin intensity was analyzed using a semiautomated quantitative assay on the biopsy samples. A positive change from baseline represents an increase in utrophin expression, no change from baseline represents maintenance of utrophin expression and a negative change from baseline represents a reduction in utrophin expression. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.

All participants who received at least one dose of study medication and had at least one assessment of the endpoint (which could be their baseline assessment). For the summaries of changes from baseline only those participants in this population who had measurements at both baseline and the relevant post-baseline visit were included.

Posted

Mean

Standard Deviation

Arbitrary units

Baseline, Week 24 and Week 48

ID	Title	Description
OG000	Cohorts 1 and 2: SMT C1100	Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Developmental Heavy Chain Myosin (MHCd) Expression

A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. MHCd expression was analyzed using a semiautomated quantitative assay on the biopsy samples. A positive change from baseline represents an increase in MHCd expression, no change from baseline represents maintenance of MHCd expression and a negative change from baseline represents a reduction in MHCd expression. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.

Posted

Mean

Standard Deviation

Percent of muscle fibres expressing MHCd

Baseline, Week 24 and Week 48

ID	Title	Description
OG000	Cohorts 1 and 2: SMT C1100	Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in Muscle Fibre Diameter

A maximum of two muscle biopsies were taken, one at baseline and the other at Week 24 or Week 48. Muscle fibre diameter was analyzed using a semiautomated quantitative assay on the biopsy samples. The endpoint was measured for Cohorts 1 and 2 only. Results for Cohorts 1 and 2 are pooled as specified in the protocol.

Posted

Mean

Standard Deviation

Micrometers (μm)

Baseline, Week 24 and Week 48

ID	Title	Description
OG000	Cohorts 1 and 2: SMT C1100	Cohort 1 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)

Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Mean

Standard Deviation

Percentage of FEV1

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Forced Vital Capacity (FVC)

Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Mean

Standard Deviation

Percentage of FVC

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Maximum Inspiratory Pressure (MIP)

Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Mean

Standard Deviation

cm H2O

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Maximum Expiratory Pressure (MEP)

Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Mean

Standard Deviation

cm H2O

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Peak Expiratory Flow (PEF)

Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Mean

Standard Deviation

Percentage of PEF

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Peak Cough Flow (PCF)

Analysis of PCF was planned for Cohort 3 only.

No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohort 3: SMT C1100 Formulation 1	Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG0000

Secondary

Change From Baseline in Sniff Nasal Inspiratory Pressure (SNIP)

Analysis of SNIP was planned for Cohort 3 only.

No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Baseline, Week 12, Week 24, Week 36 and Week 48

ID	Title	Description
OG000	Cohort 3: SMT C1100 Formulation 1	Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG0000

Secondary

Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements

Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse will be disclosed with the following categories:

All values within 20% of change from baseline (< 20% change).
At least one value ≥ 20% reduction from baseline, but no increases ≥ 20% from baseline (≥ 20% reduction and no < 20% increase).
At least one value ≥ 20% increase from baseline, but no reductions ≥ 20% from baseline (≥ 20% Increase and no < 20% reduction).
At least one value ≥ 20% reduction from baseline and at least one value ≥ 20% increase from baseline (≥ 20% reduction and ≥ 20% increase).

Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Count of Participants

Participants

Baseline to Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants

Secondary

Number of Participants That Experienced a Clinically Significant in Physical Examination Result

Examinations included: ear, nose and throat, cardiovascular system, pulmonary system, skin, abdomen, neurological system, height and weight. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication.

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements

PR interval (PRI), heart rate (HR), QTcF and increase from baseline in QTcF (IQTcF) were summarized categorically. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Count of Participants

Participants

Baseline to Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement

Participants were at rest in a supine position for 10 minutes before the measurements were performed. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication. No evaluable data was collected from Cohort 3 participants due to early study termination.

Posted

Count of Participants

Participants

Baseline, Week 24 and Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Participants That Experienced a Clinically Significant Haematology Result (Investigator's Assessment)

Parameters included: haemoglobin, haematocrit, mean corpuscular volume, white blood cells, red blood cells, neutrophils (percentage and absolute), lymphocytes (percentage and absolute), monocytes (percentage and absolute), eosinophils (percentage and absolute), basophils (percentage and absolute) and platelets. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication.

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Participants Who Experienced a Clinically Significant Biochemistry Result (Investigator's Assessment)

Parameters included: calcium, potassium, sodium, albumin, urea nitrogen, uric acid, creatinine, creatine kinase, fasting glucose, cystatin C, lactate dehydrogenase, amylase, lipase, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol, cholesterol, non-HDL cholesterol, total HDL cholesterol ratio, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and glutamate dehydrogenase. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication.

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result

Laboratory measurements for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), and glutamate dehydrogenase (GLDH). Hy's Law is defined as an increase in ALT, AST and TB, indicating hepatocyte necrosis and functional deficit. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication.

Posted

Count of Participants

Participants

Baseline to Week 48

ID	Title	Description
OG000	Cohorts 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Participants That Experienced a Clinically Significant Urinalysis Result (Investigator's Assessment)

Parameters included: glucose, bilirubin, ketones, specific gravity, blood, pH, protein, urobilinogen, nitrites and leucocytes. Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication.

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	Cohort 1, 2 and 3: SMT C1100	Cohorts 1 and 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Secondary

Number of Participants That Experienced a Clinically Significant Coagulation Result (Investigator's Assessment)

Parameters included: activated partial thromboplastin time, prothrombin time and international normalised ratio. Coagulation was only assessed for Cohorts 2 and 3. Results for Cohorts 2 and 3 are pooled as specified in the protocol.

All participants who received at least one dose of study medication in Cohorts 2 and 3 only.

Posted

Count of Participants

Participants

Day 1 to Week 48

ID	Title	Description
OG000	Cohorts 2 and 3 SMT C1100	Cohort 2 participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks. Cohort 3 participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Femur fracture	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Peripheral swelling	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Chromaturia	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Non-cardiac chest pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Viral infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Tonsillitis bacterial	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Gastritis viral	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0001 events1 affected30 at risk EG0010 events0 affected10 at risk EG0020 events0 affected3 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Faeces pale	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG00018 affected30 at risk EG0013 affected10 at risk EG0023 affected3 at risk
Vomiting	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG00017 affected30 at risk EG0016 affected10 at risk EG0020 affected3 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG00012 affected30 at risk EG0014 affected10 at risk EG0022 affected3 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0008 affected30 at risk EG0013 affected10 at risk EG0021 affected3 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0007 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Nausea	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0005 affected30 at risk EG0011 affected10 at risk EG0021 affected3 at risk
Constipation	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0011 affected10 at risk EG0021 affected3 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Toothache	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Gastritis	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Nasopharyngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0006 affected30 at risk EG0015 affected10 at risk EG0020 affected3 at risk
Rhinitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0004 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Ear infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0001 affected30 at risk EG0012 affected10 at risk EG0020 affected3 at risk
Gastroenteritis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Otitis media	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Sinusitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Campylobacter gastroenteritis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Pharyngitis	Infections and infestations	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Fall	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0007 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0007 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Joint injury	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Skin abrasion	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Spinal fracture	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Pyrexia	General disorders	MedDRA (19.0)	Systematic Assessment	EG0007 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Fatigue	General disorders	MedDRA (19.0)	Systematic Assessment	EG0004 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Catheter site bruise	General disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Chest pain	General disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0008 affected30 at risk EG0014 affected10 at risk EG0020 affected3 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0008 affected30 at risk EG0012 affected10 at risk EG0020 affected3 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG00010 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0007 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0011 affected10 at risk EG0021 affected3 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Headache	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0009 affected30 at risk EG0011 affected10 at risk EG0021 affected3 at risk
Dizziness	Nervous system disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0005 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Swelling face	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Skin discolouration	Skin and subcutaneous tissue disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Aggression	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Abnormal behaviour	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Anger	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0021 affected3 at risk
Belligerence	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Depressed mood	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0010 affected10 at risk EG0021 affected3 at risk
Enuresis	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Irritability	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Mood altered	Psychiatric disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Glutamate dehydrogenase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Increased appetite	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0001 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Vitreous floaters	Eye disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Ear pain	Ear and labyrinth disorders	MedDRA (19.0)	Systematic Assessment	EG0002 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk
Cryptorchism	Congenital, familial and genetic disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Pollakiuria	Renal and urinary disorders	MedDRA (19.0)	Systematic Assessment	EG0000 affected30 at risk EG0010 affected10 at risk EG0021 affected3 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0011 affected10 at risk EG0020 affected3 at risk
Lip swelling	Gastrointestinal disorders	MedDRA (19.0)	Systematic Assessment	EG0003 affected30 at risk EG0010 affected10 at risk EG0020 affected3 at risk

ID	Term
D020388	Muscular Dystrophy, Duchenne
D009136	Muscular Dystrophies

ID	Term
D020966	Muscular Disorders, Atrophic
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases
D040181	Genetic Diseases, X-Linked
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Title	Description
BG000	Cohort 1: SMT C1100 Formulation 1	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
BG001	Cohort 2: SMT C1100 Formulation 2	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
BG002	Cohort 3: SMT C1100 Formulation 1	Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1: SMT C1100 Formulation 1	Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.	30	4	30	30	30
EG001	Cohort 2: SMT C1100 Formulation 2	Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.	10	0	10	10	10
EG002	Cohort 3: SMT C1100 Formulation 1	Participants in this cohort had previously received SMT C1100, but were not eligible for Cohorts 1 or 2. Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.	3	0	3	3	3

Title	Denominators	Categories
Week 12 Change from Baseline
Week 24 Change from Baseline
Week 36 Change from Baseline
Week 48 Change from Baseline