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Trial record 1 of 1 for:    ezutromid | Duchenne Muscular Dystrophy
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Proof of Concept Study to Assess Activity and Safety of SMT C1100 (Ezutromid) in Boys With Duchenne Muscular Dystrophy (DMD)

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ClinicalTrials.gov Identifier: NCT02858362
Recruitment Status : Terminated (The study was terminated due to lack of efficacy in Cohorts 1 and 2.)
First Posted : August 8, 2016
Results First Posted : January 2, 2020
Last Update Posted : January 2, 2020
Sponsor:
Information provided by (Responsible Party):
Summit Therapeutics

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Duchenne Muscular Dystrophy
Intervention Drug: Ezutromid
Enrollment 43
Recruitment Details Participants were enrolled in 16 sites across the United Kingdom (UK) and United States (US) between the dates of 16 June 2016 (First Patient In) and 11 September 2018 (Last Patient Out). Cohort 1 was conducted in the UK and US, Cohort 2 was conducted in the US only, and Cohort 3 was conducted in the UK only.
Pre-assignment Details  
Arm/Group Title Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1
Hide Arm/Group Description Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks. 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.
Period Title: Overall Study
Started 30 10 3
Did Not Enter Extension Phase [1] 1 2 0
Completed 28 9 0
Not Completed 2 1 3
Reason Not Completed
Protocol Violation             0             1             0
Withdrawal by Subject             1             0             0
Early Study Termination             0             0             3
Lost to Follow-up             1             0             0
[1]
Completed the study (Week 48 treatment visit) but did not enter the optional extension phase.
Arm/Group Title Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1 Total
Hide Arm/Group Description Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks. 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. Total of all reporting groups
Overall Number of Baseline Participants 30 10 3 43
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Children (2-11 years) Number Analyzed 30 participants 10 participants 3 participants 43 participants
30
 100.0%
10
 100.0%
1
  33.3%
41
  95.3%
Adolescents (12-17 years) Number Analyzed 30 participants 10 participants 3 participants 43 participants
0
   0.0%
0
   0.0%
2
  66.7%
2
   4.7%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 10 participants 3 participants 43 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
30
 100.0%
10
 100.0%
3
 100.0%
43
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 10 participants 3 participants 43 participants
Hispanic or Latino
1
   3.3%
2
  20.0%
0
   0.0%
3
   7.0%
Not Hispanic or Latino
29
  96.7%
8
  80.0%
3
 100.0%
40
  93.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 10 participants 3 participants 43 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   3.3%
1
  10.0%
0
   0.0%
2
   4.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
26
  86.7%
9
  90.0%
3
 100.0%
38
  88.4%
More than one race
2
   6.7%
0
   0.0%
0
   0.0%
2
   4.7%
Unknown or Not Reported
1
   3.3%
0
   0.0%
0
   0.0%
1
   2.3%
Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) Vastus Lateralis   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of fat in the muscle
Number Analyzed 29 participants 10 participants 0 participants 39 participants
13.78  (13.317) 18.36  (13.664) 14.95  (13.379)
[1]
Measure Analysis Population Description: 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.
Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) Soleus   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of fat in the muscle
Number Analyzed 30 participants 10 participants 0 participants 40 participants
8.57  (8.240) 10.79  (9.996) 9.12  (8.631)
[1]
Measure Analysis Population Description: Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) Vastus Lateralis   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliseconds
Number Analyzed 29 participants 10 participants 0 participants 39 participants
32.24  (1.980) 32.17  (2.146) 32.23  (1.995)
[1]
Measure Analysis Population Description: 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.
Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) Soleus   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliseconds
Number Analyzed 30 participants 10 participants 0 participants 40 participants
31.88  (1.936) 31.87  (1.988) 31.88  (1.923)
[1]
Measure Analysis Population Description: Efficacy measurements were planned and performed for Cohorts 1 and 2 only.
Development Heavy Chain Myosin (MHCd) Expression in Muscle Fibres   [1] 
Mean (Standard Deviation)
Unit of measure:  Percent of muscle fibres expressing MHCd
Number Analyzed 29 participants 10 participants 0 participants 39 participants
12.185  (3.8454) 11.587  (4.1344) 12.032  (3.8748)
[1]
Measure Analysis Population Description: 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.
Muscle Fibre Diameter   [1] 
Mean (Standard Deviation)
Unit of measure:  Micrometer
Number Analyzed 29 participants 10 participants 0 participants 39 participants
43.662  (5.3837) 42.086  (6.1878) 43.258  (5.5598)
[1]
Measure Analysis Population Description: 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.
Utrophin Intensity   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Arbitrary Units
Number Analyzed 30 participants 9 participants 0 participants 39 participants
0.368  (0.0480) 0.349  (0.0507) 0.364  (0.0486)
[1]
Measure Description: Utrophin intensity is measured in arbitrary units (0-1) with higher scores representing higher utrophin expression.
[2]
Measure Analysis Population Description: 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.
1.Primary Outcome
Title Change From Baseline in Magnetic Resonance Spectroscopy (MRS) Fat Fraction (FF) for Leg Muscles
Hide Description 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.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Cohorts 1 and 2: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 40
Mean (95% Confidence Interval)
Unit of Measure: Percentage of fat in the muscle
Vastus Lateralis: Week 12 Change from Baseline Number Analyzed 39 participants
1.779
(0.939 to 2.620)
Vastus Lateralis: Week 24 Change from Baseline Number Analyzed 36 participants
3.914
(2.695 to 5.132)
Vastus Lateralis: Week 36 Change from Baseline Number Analyzed 37 participants
5.238
(3.563 to 6.913)
Vastus Lateralis: Week 48 Change from Baseline Number Analyzed 36 participants
7.142
(4.866 to 9.417)
Soleus: Week 12 Change from Baseline Number Analyzed 40 participants
0.615
(0.068 to 1.162)
Soleus: Week 24 Change from Baseline Number Analyzed 38 participants
1.108
(0.350 to 1.865)
Soleus: Week 36 Change from Baseline Number Analyzed 38 participants
2.384
(1.287 to 3.481)
Soleus: Week 48 Change from Baseline Number Analyzed 37 participants
2.584
(1.258 to 3.909)
2.Primary Outcome
Title Change From Baseline for Magnetic Resonance Spectroscopy (MRS) Water Transverse Relaxation Time (WTRT) for Leg Muscles
Hide Description 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.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Cohorts 1 and 2: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 40
Mean (95% Confidence Interval)
Unit of Measure: Milliseconds
Vastus Lateralis: Week 12 Change from Baseline Number Analyzed 39 participants
-0.559
(-1.190 to 0.072)
Vastus Lateralis: Week 24 Change from Baseline Number Analyzed 36 participants
-0.486
(-1.193 to 0.221)
Vastus Lateralis: Week 36 Change from Baseline Number Analyzed 37 participants
-0.849
(-1.454 to -0.244)
Vastus Lateralis: Week 48 Change from Baseline Number Analyzed 36 participants
-0.822
(-1.673 to 0.028)
Soleus: Week 12 Change from Baseline Number Analyzed 40 participants
-0.655
(-1.209 to -0.101)
Soleus: Week 24 Change from Baseline Number Analyzed 38 participants
-0.861
(-1.440 to -0.281)
Soleus: Week 36 Change from Baseline Number Analyzed 38 participants
-0.447
(-1.085 to 0.190)
Soleus: Week 48 Change from Baseline Number Analyzed 37 participants
-0.119
(-0.747 to 0.509)
3.Primary Outcome
Title Observed Trough Plasma Concentration (Ctrough) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Hide Description 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.
Time Frame Pre-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2
Hide Arm/Group Description:
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
Overall Number of Participants Analyzed 30 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
SMT C1100
17
(140%)
80
(83.1%)
DHD 1
155
(61%)
365
(55%)
DHD 3
484
(67%)
1206
(68%)
4.Primary Outcome
Title Simulated Maximum Plasma Concentration (Cmax) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Hide Description Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Time Frame Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2
Hide Arm/Group Description:
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
Overall Number of Participants Analyzed 30 10
Geometric Mean (Full Range)
Unit of Measure: ng/mL
SMT C1100
135
(97 to 185)
415
(303 to 640)
DHD 1
1897
(1690 to 2158)
2829
(2597 to 3072)
DHD 3
3162
(2392 to 4053)
4652
(3802 to 6116)
5.Primary Outcome
Title Simulated Average Plasma Concentration (Cav) for SMT C1100, Dihydrodiol 1 (DHD1) and Dihydrodiol III (DHD 3)
Hide Description Pharmacokinetic analysis is presented by cohort due to the use of different formulations.
Time Frame Pre-dose and 3 to 10 hours post-dose at Weeks 1, 4, 8, 12, 24, 36 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2
Hide Arm/Group Description:
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
Overall Number of Participants Analyzed 30 10
Geometric Mean (Full Range)
Unit of Measure: ng/mL
SMT C1100
54
(37 to 82)
163
(114 to 272)
DHD 1
742
(685 to 836)
1109
(1028 to 1217)
DHD 3
1359
(972 to 1790)
2211
(1707 to 3066)
6.Primary Outcome
Title Number of Participants Reporting One or More Treatment-Emergent Adverse Events (TEAEs)
Hide Description 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.
Time Frame Day 1 to a maximum of Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study medication.
Arm/Group Title Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1
Hide Arm/Group Description:
Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks.
Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks.
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.
Overall Number of Participants Analyzed 30 10 3
Measure Type: Count of Participants
Unit of Measure: Participants
30
 100.0%
10
 100.0%
3
 100.0%
7.Secondary Outcome
Title Change From Baseline in Utrophin Intensity
Hide Description 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.
Time Frame Baseline, Week 24 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1 and 2: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 37
Mean (Standard Deviation)
Unit of Measure: Arbitrary units
Change from baseline at Week 24 Number Analyzed 22 participants
0.0232  (0.0601)
Change from baseline at Week 48 Number Analyzed 15 participants
0.0114  (0.0574)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1 and 2: SMT C1100
Comments Week 24 Change from Baseline
Type of Statistical Test Other
Comments Difference in least square means. All 23 participants in the population were included in the statistical analysis.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.023
Confidence Interval (2-Sided) 95%
-0.002 to 0.048
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1 and 2: SMT C1100
Comments Week 48 Change from Baseline
Type of Statistical Test Other
Comments Difference in least square means. All 16 participants in the population were included in the statistical analysis.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.006
Confidence Interval (2-Sided) 95%
-0.03 to 0.042
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Developmental Heavy Chain Myosin (MHCd) Expression
Hide Description 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.
Time Frame Baseline, Week 24 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1 and 2: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: Percent of muscle fibres expressing MHCd
Change from baseline at Week 24 Number Analyzed 22 participants
-2.3166  (3.9180)
Change from baseline at Week 48 Number Analyzed 16 participants
1.2248  (4.2596)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1 and 2: SMT C1100
Comments Week 24 Change from Baseline
Type of Statistical Test Other
Comments Difference in least square means. All 24 participants in the population were included in the statistical analysis.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.611
Confidence Interval (2-Sided) 95%
-4.324 to -0.898
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1 and 2: SMT C1100
Comments Week 48 Change from Baseline
Type of Statistical Test Other
Comments Difference in least square means. All 16 participants in the population were included in the statistical analysis.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.166
Confidence Interval (2-Sided) 95%
-1.103 to 3.435
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Muscle Fibre Diameter
Hide Description 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.
Time Frame Baseline, Week 24 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1 and 2: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: Micrometers (μm)
Change from baseline at Week 24 Number Analyzed 22 participants
-1.9205  (4.7250)
Change from baseline at Week 48 Number Analyzed 16 participants
2.0636  (4.1267)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohorts 1 and 2: SMT C1100
Comments Week 24 Change from Baseline
Type of Statistical Test Other
Comments Difference in least square means. All 24 participants in the population were included in the statistical analysis.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.837
Confidence Interval (2-Sided) 95%
-3.989 to 0.315
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohorts 1 and 2: SMT C1100
Comments Week 48 Change from Baseline
Type of Statistical Test Other
Comments Difference in least square means. All 16 participants in the population were included in the statistical analysis.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.21
Confidence Interval (2-Sided) 95%
0.096 to 4.324
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Hide Description Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: Percentage of FEV1
Week 12 Change from Baseline Number Analyzed 38 participants
-3.4  (20.86)
Week 24 Change from Baseline Number Analyzed 37 participants
-2.5  (24.88)
Week 36 Change from Baseline Number Analyzed 36 participants
-7.3  (24.26)
Week 48 Change from Baseline Number Analyzed 33 participants
2.0  (18.31)
11.Secondary Outcome
Title Change From Baseline in Forced Vital Capacity (FVC)
Hide Description Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: Percentage of FVC
Week 12 Change from Baseline Number Analyzed 39 participants
-4.0  (16.31)
Week 24 Change from Baseline Number Analyzed 38 participants
1.1  (16.75)
Week 36 Change from Baseline Number Analyzed 37 participants
-3.4  (18.39)
Week 48 Change from Baseline Number Analyzed 35 participants
1.1  (16.29)
12.Secondary Outcome
Title Change From Baseline in Maximum Inspiratory Pressure (MIP)
Hide Description Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 36
Mean (Standard Deviation)
Unit of Measure: cm H2O
Week 12 Change from Baseline Number Analyzed 36 participants
3.6  (32.68)
Week 24 Change from Baseline Number Analyzed 35 participants
3.0  (25.00)
Week 36 Change from Baseline Number Analyzed 31 participants
9.0  (18.40)
Week 48 Change from Baseline Number Analyzed 32 participants
8.7  (20.30)
13.Secondary Outcome
Title Change From Baseline in Maximum Expiratory Pressure (MEP)
Hide Description Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 35
Mean (Standard Deviation)
Unit of Measure: cm H2O
Week 12 Change from Baseline Number Analyzed 35 participants
1.8  (17.97)
Week 24 Change from Baseline Number Analyzed 34 participants
2.5  (22.95)
Week 36 Change from Baseline Number Analyzed 31 participants
-1.0  (23.53)
Week 48 Change from Baseline Number Analyzed 31 participants
6.5  (20.09)
14.Secondary Outcome
Title Change From Baseline in Peak Expiratory Flow (PEF)
Hide Description Results for Cohorts 1, 2 and 3 are pooled as specified in the protocol.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: Percentage of PEF
Week 12 Change from Baseline Number Analyzed 32 participants
0.5  (20.65)
Week 24 Change from Baseline Number Analyzed 34 participants
-0.1  (23.86)
Week 36 Change from Baseline Number Analyzed 32 participants
-0.4  (23.46)
Week 48 Change from Baseline Number Analyzed 32 participants
9.6  (30.09)
15.Secondary Outcome
Title Change From Baseline in Peak Cough Flow (PCF)
Hide Description Analysis of PCF was planned for Cohort 3 only.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
No evaluable data was collected from Cohort 3 participants due to early study termination.
Arm/Group Title Cohort 3: SMT C1100 Formulation 1
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Change From Baseline in Sniff Nasal Inspiratory Pressure (SNIP)
Hide Description Analysis of SNIP was planned for Cohort 3 only.
Time Frame Baseline, Week 12, Week 24, Week 36 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
No evaluable data was collected from Cohort 3 participants due to early study termination.
Arm/Group Title Cohort 3: SMT C1100 Formulation 1
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Number of Participants That Experienced a Clinically Significant Change in Vital Signs Measurements
Hide Description

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.

Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
SBP < 20% change
28
  70.0%
≥ 20% reduction and no < 20% increase
2
   5.0%
≥ 20% Increase and no < 20% reduction
10
  25.0%
≥ 20% reduction and ≥ 20% increase
0
   0.0%
DBP < 20% change
19
  47.5%
≥ 20% reduction and no < 20% increase
11
  27.5%
≥ 20% Increase and no < 20% reduction
10
  25.0%
≥ 20% reduction and ≥ 20% increase
0
   0.0%
Pulse < 20% change
21
  52.5%
≥ 20% reduction and no < 20% increase
6
  15.0%
≥ 20% Increase and no < 20% reduction
13
  32.5%
≥ 20% reduction and ≥ 20% increase
0
   0.0%
18.Secondary Outcome
Title Number of Participants That Experienced a Clinically Significant in Physical Examination Result
Hide Description 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.
Time Frame Day 1 to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study medication.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 43
Measure Type: Count of Participants
Unit of Measure: Participants
1
   2.3%
19.Secondary Outcome
Title Number of Participants That Experienced a Potentially Clinically Significant Electrocardiogram Measurements
Hide Description 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.
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
PRI: <170 ms
37
  92.5%
PRI: ≥170 ms
3
   7.5%
PRI: < 20% change
35
  87.5%
PRI: ≥ 20% reduction and no < 20% increase
2
   5.0%
PRI: ≥ 20% increase and no < 20% reduction
3
   7.5%
PRI: ≥ 20% reduction and ≥ 20% increase
0
   0.0%
HR: < 20% change
7
  17.5%
HR: ≥ 20% reduction and no < 20% increase
6
  15.0%
HR: ≥ 20% increase and no < 20% reduction
22
  55.0%
HR: ≥ 20% reduction and ≥ 20% increase
5
  12.5%
QTcF: < 450 ms
40
 100.0%
QTcF: ≥ 450 ms
0
   0.0%
IQTcF: < 30 ms
32
  80.0%
IQTcF: 30 - 59 ms
8
  20.0%
IQTcF: >= 60 ms
0
   0.0%
20.Secondary Outcome
Title Number of Participants That Experienced a Potentially Clinically Significant Echocardiogram Measurement
Hide Description 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.
Time Frame Baseline, Week 24 and Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 40
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 40 participants
Normal
38
  95.0%
Abnormal, Not Clinically Significant
2
   5.0%
Abnormal, Clinically Significant
0
   0.0%
Week 24 Number Analyzed 38 participants
Normal
33
  86.8%
Abnormal, Not Clinically Significant
5
  13.2%
Abnormal, Clinically Significant
0
   0.0%
Week 48 Number Analyzed 36 participants
Normal
33
  91.7%
Abnormal, Not Clinically Significant
2
   5.6%
Abnormal, Clinically Significant
1
   2.8%
21.Secondary Outcome
Title Number of Participants That Experienced a Clinically Significant Haematology Result (Investigator's Assessment)
Hide Description 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.
Time Frame Day 1 to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study medication.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 43
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
22.Secondary Outcome
Title Number of Participants Who Experienced a Clinically Significant Biochemistry Result (Investigator's Assessment)
Hide Description 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.
Time Frame Day 1 to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study medication.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 43
Measure Type: Count of Participants
Unit of Measure: Participants
3
   7.0%
23.Secondary Outcome
Title Number of Participants That Experienced a Potentially Clinically Significant Liver Function Result
Hide Description 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.
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study medication.
Arm/Group Title Cohorts 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 43
Measure Type: Count of Participants
Unit of Measure: Participants
ALT >= upper limit of normal (ULN)
43
 100.0%
ALT >= 2*ULN
43
 100.0%
ALT >= 3*ULN
42
  97.7%
AST >= ULN
43
 100.0%
AST >= 2*ULN
42
  97.7%
AST >= 3*ULN
42
  97.7%
TB >= ULN
0
   0.0%
TB >= 2*ULN
0
   0.0%
ALP >= 1.5*ULN
0
   0.0%
GLDH >= ULN excluding haemolysed samples
27
  62.8%
GLDH >= ULN including haemolysed samples
30
  69.8%
GLDH >= 2.5*ULN Excluding Haemolysed Samples
2
   4.7%
GLDH >= 2.5*ULN including haemolysed samples
2
   4.7%
Participants meeting Hy's law
0
   0.0%
24.Secondary Outcome
Title Number of Participants That Experienced a Clinically Significant Urinalysis Result (Investigator's Assessment)
Hide Description 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.
Time Frame Day 1 to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study medication.
Arm/Group Title Cohort 1, 2 and 3: SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 43
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
25.Secondary Outcome
Title Number of Participants That Experienced a Clinically Significant Coagulation Result (Investigator's Assessment)
Hide Description 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.
Time Frame Day 1 to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least one dose of study medication in Cohorts 2 and 3 only.
Arm/Group Title Cohorts 2 and 3 SMT C1100
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 13
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
Time Frame Day 1 to a maximum of 96 weeks
Adverse Event Reporting Description Treatment Emergent Adverse Events.
 
Arm/Group Title Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1
Hide Arm/Group Description Participants received 2.5 g SMT C1100 formulation 1 orally twice-daily for at least 48 weeks. Participants received 1 g SMT C1100 formulation 2 orally twice-daily for at least 48 weeks. 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.
All-Cause Mortality
Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)      0/10 (0.00%)      0/3 (0.00%)    
Hide Serious Adverse Events
Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/30 (13.33%)      0/10 (0.00%)      0/3 (0.00%)    
Gastrointestinal disorders       
Abdominal pain  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Vomiting  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
General disorders       
Peripheral swelling  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Non-cardiac chest pain  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Infections and infestations       
Viral infection  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Tonsillitis bacterial  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Gastritis viral  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Injury, poisoning and procedural complications       
Femur fracture  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Spinal compression fracture  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Rhabdomyolysis  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
Renal and urinary disorders       
Chromaturia  1  1/30 (3.33%)  1 0/10 (0.00%)  0 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: SMT C1100 Formulation 1 Cohort 2: SMT C1100 Formulation 2 Cohort 3: SMT C1100 Formulation 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/30 (100.00%)      10/10 (100.00%)      3/3 (100.00%)    
Congenital, familial and genetic disorders       
Cryptorchism  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Ear and labyrinth disorders       
Ear pain  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Eye disorders       
Vitreous floaters  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Gastrointestinal disorders       
Faeces pale  1  18/30 (60.00%)  3/10 (30.00%)  3/3 (100.00%) 
Vomiting  1  17/30 (56.67%)  6/10 (60.00%)  0/3 (0.00%) 
Diarrhoea  1  12/30 (40.00%)  4/10 (40.00%)  2/3 (66.67%) 
Abdominal pain upper  1  8/30 (26.67%)  3/10 (30.00%)  1/3 (33.33%) 
Abdominal pain  1  7/30 (23.33%)  0/10 (0.00%)  0/3 (0.00%) 
Nausea  1  5/30 (16.67%)  1/10 (10.00%)  1/3 (33.33%) 
Constipation  1  2/30 (6.67%)  1/10 (10.00%)  1/3 (33.33%) 
Abdominal discomfort  1  2/30 (6.67%)  1/10 (10.00%)  0/3 (0.00%) 
Toothache  1  3/30 (10.00%)  0/10 (0.00%)  0/3 (0.00%) 
Faeces discoloured  1  1/30 (3.33%)  1/10 (10.00%)  0/3 (0.00%) 
Gastritis  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Dyspepsia  1  3/30 (10.00%)  1/10 (10.00%)  0/3 (0.00%) 
Lip swelling  1  3/30 (10.00%)  0/10 (0.00%)  0/3 (0.00%) 
General disorders       
Pyrexia  1  7/30 (23.33%)  1/10 (10.00%)  0/3 (0.00%) 
Fatigue  1  4/30 (13.33%)  1/10 (10.00%)  0/3 (0.00%) 
Catheter site bruise  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Chest pain  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Infections and infestations       
Nasopharyngitis  1  6/30 (20.00%)  5/10 (50.00%)  0/3 (0.00%) 
Rhinitis  1  3/30 (10.00%)  1/10 (10.00%)  0/3 (0.00%) 
Upper respiratory tract infection  1  4/30 (13.33%)  0/10 (0.00%)  0/3 (0.00%) 
Ear infection  1  1/30 (3.33%)  2/10 (20.00%)  0/3 (0.00%) 
Gastroenteritis  1  2/30 (6.67%)  1/10 (10.00%)  0/3 (0.00%) 
Otitis media  1  3/30 (10.00%)  0/10 (0.00%)  0/3 (0.00%) 
Sinusitis  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Viral upper respiratory tract infection  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Campylobacter gastroenteritis  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Gastroenteritis viral  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Pharyngitis  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Injury, poisoning and procedural complications       
Fall  1  7/30 (23.33%)  1/10 (10.00%)  0/3 (0.00%) 
Procedural pain  1  7/30 (23.33%)  0/10 (0.00%)  0/3 (0.00%) 
Contusion  1  3/30 (10.00%)  0/10 (0.00%)  0/3 (0.00%) 
Head injury  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Joint injury  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Ligament sprain  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Skin abrasion  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Spinal fracture  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Foot fracture  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Investigations       
Glutamate dehydrogenase increased  1  3/30 (10.00%)  1/10 (10.00%)  0/3 (0.00%) 
Gamma-glutamyltransferase increased  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Metabolism and nutrition disorders       
Decreased appetite  1  3/30 (10.00%)  0/10 (0.00%)  0/3 (0.00%) 
Increased appetite  1  1/30 (3.33%)  1/10 (10.00%)  0/3 (0.00%) 
Vitamin D deficiency  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  10/30 (33.33%)  0/10 (0.00%)  0/3 (0.00%) 
Pain in extremity  1  7/30 (23.33%)  1/10 (10.00%)  0/3 (0.00%) 
Arthralgia  1  3/30 (10.00%)  1/10 (10.00%)  1/3 (33.33%) 
Neck pain  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Skin papilloma  1  3/30 (10.00%)  0/10 (0.00%)  0/3 (0.00%) 
Nervous system disorders       
Headache  1  9/30 (30.00%)  1/10 (10.00%)  1/3 (33.33%) 
Dizziness  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Psychiatric disorders       
Aggression  1  2/30 (6.67%)  1/10 (10.00%)  0/3 (0.00%) 
Abnormal behaviour  1  1/30 (3.33%)  1/10 (10.00%)  0/3 (0.00%) 
Anger  1  0/30 (0.00%)  1/10 (10.00%)  1/3 (33.33%) 
Belligerence  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Depressed mood  1  0/30 (0.00%)  0/10 (0.00%)  1/3 (33.33%) 
Enuresis  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Irritability  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Mood altered  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Renal and urinary disorders       
Pollakiuria  1  0/30 (0.00%)  0/10 (0.00%)  1/3 (33.33%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  8/30 (26.67%)  4/10 (40.00%)  0/3 (0.00%) 
Oropharyngeal pain  1  8/30 (26.67%)  2/10 (20.00%)  0/3 (0.00%) 
Rhinorrhoea  1  2/30 (6.67%)  1/10 (10.00%)  0/3 (0.00%) 
Sinus congestion  1  1/30 (3.33%)  1/10 (10.00%)  0/3 (0.00%) 
Wheezing  1  0/30 (0.00%)  1/10 (10.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders       
Rash  1  5/30 (16.67%)  0/10 (0.00%)  0/3 (0.00%) 
Swelling face  1  3/30 (10.00%)  0/10 (0.00%)  0/3 (0.00%) 
Dry skin  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Erythema  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Pruritus  1  2/30 (6.67%)  0/10 (0.00%)  0/3 (0.00%) 
Skin discolouration  1  1/30 (3.33%)  1/10 (10.00%)  0/3 (0.00%) 
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Analysis of the data collected from Cohort 3 was limited as the study was terminated prior to the first participant's Week 24 visit.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Clinical Disclosure
Organization: Summit Therapeutics
Phone: Please Email
EMail: clinicaltrials@summitplc.com
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Responsible Party: Summit Therapeutics
ClinicalTrials.gov Identifier: NCT02858362    
Other Study ID Numbers: SMT C11005
2015-004333-27 ( EudraCT Number )
First Submitted: July 27, 2016
First Posted: August 8, 2016
Results First Submitted: October 28, 2019
Results First Posted: January 2, 2020
Last Update Posted: January 2, 2020