Trial Outcomes & Findings for A Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS) (NCT NCT02000440)
NCT ID: NCT02000440
Last Updated: 2017-06-12
Results Overview
Proteinuria is defined as the presence of an excess of serum proteins in the urine. Participant was considered as a responder on achieving \>=50 percent reduction in proteinuria from Baseline (measured as 24 hour total protein) and also having a stable renal function of \>=70 percent of Baseline estimated glomerular filtration rate (eGFR) at end of treatment (\>=16 Weeks). Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
17 participants
Primary outcome timeframe
Week 2, Week 4, Week 8, Week 16 and Week 24
Results posted on
2017-06-12
Participant Flow
This single-arm, multicenter, fixed sequence open-label study consisted of 2 screening visits, run-in phase before the first dose of study treatment, followed by treatment phase in which participants received losmapimod 7.5 milligrams (mg) twice daily (BID) for 2 weeks and 15 mg BID for an additional 22 weeks, and a follow-up visit (12 weeks).
A total of 29 participants were screened and entered into the run-in phase, of which 17 participants received at least one dose of losmapimod.
Participant milestones
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Overall Study
STARTED
|
17
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Other-Protocol-defined Stopping Criteria
|
1
|
Baseline Characteristics
A Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS)
Baseline characteristics by cohort
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Age, Continuous
|
40.4 Years
STANDARD_DEVIATION 13.68 • n=99 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian - Central/South Asian Heritage
|
2 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
1 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Asian - South East Asian Heritage
|
2 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
11 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Week 2, Week 4, Week 8, Week 16 and Week 24Population: Completed Treatment Population: comprised of participants who had completed \>=16 weeks of losmapimod treatment or who withdrew from the treatment. Participants who withdrew prior to Week 16 were considered as non-responders.
Proteinuria is defined as the presence of an excess of serum proteins in the urine. Participant was considered as a responder on achieving \>=50 percent reduction in proteinuria from Baseline (measured as 24 hour total protein) and also having a stable renal function of \>=70 percent of Baseline estimated glomerular filtration rate (eGFR) at end of treatment (\>=16 Weeks). Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points
Week 2, n= 17
|
0 Participants
|
|
Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points
Week 4, n=15
|
1 Participants
|
|
Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points
Week 8, n=15
|
0 Participants
|
|
Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points
Week 16, n=13
|
0 Participants
|
|
Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points
Week 24, n=13
|
0 Participants
|
SECONDARY outcome
Timeframe: Any time during the treatment phase (Week 2 to Week 24)Population: Completed Treatment Population
Proteinuria is defined as the presence of an excess of serum proteins in the urine. Participant was considered as responder on achieving \>=50 percent reduction in proteinuria from Baseline (measured as 24 hour total protein) and also having a stable renal function of \>=70 percent of Baseline eGFR at any time during the treatment phase of the study. Reduction in proteinuria assessment at any time during the treatment phase of the study was done by utilizing a responder analysis.
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at Any Time During the Treatment Phase (Week 2 to Week 24)
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, Week 30 and Week 36Population: All Subject Population: all eligible participants who received at least one dose of investigational drug.
Reduction in proteinuria was measured by the Up/c ratio (spot and 24 hr) at Baseline, Week 2, 4, 8, 16, 24, end of study and at Follow-up (FU) visits Week 30 and 36. Spot urine sample was provided by the participants on site. The 24 hour urine collection started with the second morning void and ended with the first morning void on the following day; generally, 24 hour urine collection was initiated the day prior to the study visit. Baseline was defined as the value obtained at Week 0. Percent change from Baseline was calculated as change from Baseline value divided by Baseline value multiplied by 100. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio 24 hr, Week 8, n= 15
|
24.32547 Percent change
Standard Deviation 39.925052
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio 24 hr, End of study, n= 4
|
10.79660 Percent change
Standard Deviation 54.170928
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio 24 hr, Week 2, n= 17
|
-0.45807 Percent change
Standard Deviation 25.696890
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio 24 hr, Week 4, n= 15
|
-0.07037 Percent change
Standard Deviation 28.954312
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio 24 hr, Week 16, n= 13
|
-10.57111 Percent change
Standard Deviation 37.211084
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio 24 hr, Week 24, n= 13
|
-0.59030 Percent change
Standard Deviation 29.616932
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio 24 hr, Follow-up Week 36, n= 16
|
-6.56589 Percent change
Standard Deviation 43.863442
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, Week 2, n= 17
|
8.45052 Percent change
Standard Deviation 27.531444
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, Week 4, n= 16
|
11.44257 Percent change
Standard Deviation 24.783744
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, Week 8, n= 15
|
41.43955 Percent change
Standard Deviation 50.144228
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, Week 16, n= 13
|
-0.99691 Percent change
Standard Deviation 34.890578
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, Week 24, n= 12
|
4.05899 Percent change
Standard Deviation 40.301958
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, End of study, n= 4
|
13.88998 Percent change
Standard Deviation 57.089949
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, Follow-up Week 30, n= 15
|
3.66036 Percent change
Standard Deviation 35.011255
|
|
Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Up/c ratio spot, Follow-up Week 36, n= 17
|
-2.91757 Percent change
Standard Deviation 44.251282
|
SECONDARY outcome
Timeframe: Week 2, Week 4, Week 8, Week 16 and Week 24Population: Completed Treatment Population
Incidence of complete remissions at any time point was defined as 24 hour total protein \<0.3 gram (g) per Day and maintenance of \>=70 percent of Baseline eGFR throughout the treatment period. Only those participants available at the specified time points (represented by n=X in the category titles) were analyzed.
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Number of Participants With Complete Proteinuria Remissions at the Indicated Time Points
Week 2, n= 17
|
0 Participants
|
|
Number of Participants With Complete Proteinuria Remissions at the Indicated Time Points
Week 4, n= 15
|
0 Participants
|
|
Number of Participants With Complete Proteinuria Remissions at the Indicated Time Points
Week 8, n= 15
|
0 Participants
|
|
Number of Participants With Complete Proteinuria Remissions at the Indicated Time Points
Week 16, n= 13
|
0 Participants
|
|
Number of Participants With Complete Proteinuria Remissions at the Indicated Time Points
Week 24, n= 13
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of the study treatment (Week 0) until the Follow-up phase (Week 36)Population: All Subject Population
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia were categorized as SAE. Participants having any AE or SAE were included in the analysis.
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs)
Non-serious AEs
|
16 Participants
|
|
Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
SECONDARY outcome
Timeframe: From start of the study treatment (Week 0) until the Follow-up phase (Week 36)Population: All Subject Population
Participants were monitored from start of the study treatment (Week 0) up to Week 36 for development of toxicity. Participants who developed toxicity during the period were to be withdrawn from the study.
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Number of Participants Withdrawn Due to Toxicities
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population
Blood pressure was measured in a sitting position after 5 minutes rest with comfortably seated, legs uncrossed and the back and arm supported, such that the middle of the cuff on the upper arm is at the level of the right atrium and asked to remove all clothing that covered the location of cuff placement. It was recorded at Screening, Baseline, Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36). Vital sign measurements were repeated if the values were \< 80 mmHg or \> 140 mmHg SBP and \<40 mmHg or \>90 mmHg for DBP. Baseline was defined as the value obtained on Week 0. Change from Baseline was calculated as visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Week 2, n= 17
|
3.5 Millimeter of mercury (mmHg)
Standard Deviation 9.87
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Week 4, n= 16
|
0.9 Millimeter of mercury (mmHg)
Standard Deviation 12.15
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Week 8, n= 15
|
2.0 Millimeter of mercury (mmHg)
Standard Deviation 13.50
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Week 16, n= 13
|
-1.8 Millimeter of mercury (mmHg)
Standard Deviation 13.16
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Week 24, n= 13
|
-1.4 Millimeter of mercury (mmHg)
Standard Deviation 16.44
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, End of study, n=4
|
11.3 Millimeter of mercury (mmHg)
Standard Deviation 9.00
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Follow-up Week 30, n=15
|
0.5 Millimeter of mercury (mmHg)
Standard Deviation 15.94
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Follow-up Week 36, n=17
|
3.8 Millimeter of mercury (mmHg)
Standard Deviation 15.64
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Week 2, n= 17
|
1.5 Millimeter of mercury (mmHg)
Standard Deviation 6.21
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Week 4, n= 16
|
-1.2 Millimeter of mercury (mmHg)
Standard Deviation 7.81
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Week 8, n= 15
|
1.7 Millimeter of mercury (mmHg)
Standard Deviation 7.11
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Week 16, n= 13
|
-3.0 Millimeter of mercury (mmHg)
Standard Deviation 9.87
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Week 24, n= 13
|
0.2 Millimeter of mercury (mmHg)
Standard Deviation 10.14
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, End of study, n=4
|
6.0 Millimeter of mercury (mmHg)
Standard Deviation 7.16
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Follow-up Week 30, n=15
|
1.3 Millimeter of mercury (mmHg)
Standard Deviation 9.85
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Follow-up Week 36, n=17
|
3.8 Millimeter of mercury (mmHg)
Standard Deviation 11.84
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population
Heart rate was measured at screening, Baseline and throughout the treatment phase (Week 24) and Follow-up phase (Week 36). Heart rate measurement was repeated if the values are calculated \<50 beats per minute. (bpm) or \>110 bpm after the start of dosing. Baseline was defined as the value obtained at Week 0. Change from Baseline was calculated as visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, End of study, n=4
|
1.3 bpm
Standard Deviation 10.31
|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, Week 2, n= 17
|
2.6 bpm
Standard Deviation 7.05
|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, Week 4, n= 16
|
4.4 bpm
Standard Deviation 8.61
|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, Week 8, n= 15
|
2.3 bpm
Standard Deviation 7.45
|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, Week 16, n= 13
|
3.8 bpm
Standard Deviation 12.08
|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, Week 24, n= 13
|
1.5 bpm
Standard Deviation 8.41
|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, Follow-up Week 30, n=15
|
5.3 bpm
Standard Deviation 10.66
|
|
Change From Baseline in Heart Rate at Indicated Time Points
Heart rate, Follow-up Week 36, n=17
|
3.6 bpm
Standard Deviation 11.57
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population
Blood samples were collected at Screening (Week -4 and -2), Baseline (Week 0) and at Weeks 2, 4, 8, 16, 24 and Follow-up (Week 30 and 36) to evaluate ALT, AST, AP and GGT. Baseline was defined as the value obtained at Week 0. Change from Baseline was calculated as visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, End of study, n=4
|
1.8 International Units/liter (IU/L)
Standard Deviation 3.95
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, Week 24, n= 13
|
-0.3 International Units/liter (IU/L)
Standard Deviation 3.20
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, Follow-up Week 30, n=15
|
-0.5 International Units/liter (IU/L)
Standard Deviation 7.75
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, Follow-up Week 30, n=15
|
-0.5 International Units/liter (IU/L)
Standard Deviation 5.10
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, Follow-up Week 36, n=17
|
2.0 International Units/liter (IU/L)
Standard Deviation 6.89
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, Week 2, n= 17
|
-1.3 International Units/liter (IU/L)
Standard Deviation 5.87
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, Week 4, n= 16
|
-2.0 International Units/liter (IU/L)
Standard Deviation 9.42
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, Week 8, n= 15
|
-0.7 International Units/liter (IU/L)
Standard Deviation 13.45
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, Week 16, n= 13
|
-1.6 International Units/liter (IU/L)
Standard Deviation 8.65
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, Week 24, n= 13
|
-2.0 International Units/liter (IU/L)
Standard Deviation 7.68
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, End of study, n=4
|
-10.0 International Units/liter (IU/L)
Standard Deviation 25.10
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
GGT, Follow-up Week 36, n=17
|
-0.6 International Units/liter (IU/L)
Standard Deviation 13.18
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, Week 2, n= 17
|
1.8 International Units/liter (IU/L)
Standard Deviation 4.01
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, Week 4, n= 16
|
6.7 International Units/liter (IU/L)
Standard Deviation 9.44
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, Week 8, n= 15
|
7.1 International Units/liter (IU/L)
Standard Deviation 14.54
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, Week 16, n= 13
|
2.6 International Units/liter (IU/L)
Standard Deviation 6.02
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, Week 24, n= 13
|
1.2 International Units/liter (IU/L)
Standard Deviation 5.01
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, Follow-up Week 30, n=15
|
0.5 International Units/liter (IU/L)
Standard Deviation 5.74
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
ALT, Follow-up Week 36, n=17
|
4.3 International Units/liter (IU/L)
Standard Deviation 9.47
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, Week 2, n= 17
|
0.6 International Units/liter (IU/L)
Standard Deviation 10.22
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, Week 4, n= 16
|
-0.8 International Units/liter (IU/L)
Standard Deviation 8.92
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, Week 8, n= 15
|
3.1 International Units/liter (IU/L)
Standard Deviation 8.15
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, Week 16, n= 13
|
0.2 International Units/liter (IU/L)
Standard Deviation 9.04
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, Week 24, n= 13
|
-0.8 International Units/liter (IU/L)
Standard Deviation 7.31
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, End of study, n=4
|
-8.5 International Units/liter (IU/L)
Standard Deviation 21.39
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, Follow-up Week 30, n=15
|
2.5 International Units/liter (IU/L)
Standard Deviation 14.38
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AP, Follow-up Week 36, n=17
|
2.9 International Units/liter (IU/L)
Standard Deviation 20.23
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, Week 2, n= 17
|
1.2 International Units/liter (IU/L)
Standard Deviation 3.34
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, Week 4, n= 16
|
6.4 International Units/liter (IU/L)
Standard Deviation 16.17
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, Week 8, n= 15
|
5.8 International Units/liter (IU/L)
Standard Deviation 13.99
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, Week 16, n= 13
|
2.2 International Units/liter (IU/L)
Standard Deviation 5.65
|
|
Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
AST, End of study, n=4
|
-3.8 International Units/liter (IU/L)
Standard Deviation 8.18
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population
Clinical chemistry parameters: direct bilirubin and total bilirubin were assessed at Baseline (Week 0) and at Weeks 2, 4, 8, 16 24, End of studyand Follow-up (Week 30 and 36) phase. Baseline was defined as the value obtained at Week 0. Change from Baseline was calculated as visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, Week 2, n= 17
|
-0.503 Micromoles per liter (umol/L)
Standard Deviation 1.0053
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, Week 8, n= 15
|
0.114 Micromoles per liter (umol/L)
Standard Deviation 1.5112
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, Week 4, n= 16
|
-0.107 Micromoles per liter (umol/L)
Standard Deviation 0.9811
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, Week 8, n= 15
|
-0.684 Micromoles per liter (umol/L)
Standard Deviation 0.8671
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, Week 16, n= 13
|
-0.263 Micromoles per liter (umol/L)
Standard Deviation 0.9485
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, Week 24, n= 13
|
0.000 Micromoles per liter (umol/L)
Standard Deviation 0.0000
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, End of study, n=4
|
0.000 Micromoles per liter (umol/L)
Standard Deviation 1.3962
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, Follow-up Week 30, n=15
|
-0.228 Micromoles per liter (umol/L)
Standard Deviation 0.8830
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Direct bilirubin, Follow-up Week 36, n=17
|
0.101 Micromoles per liter (umol/L)
Standard Deviation 1.2783
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, Week 2, n= 17
|
0.503 Micromoles per liter (umol/L)
Standard Deviation 2.4754
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, Week 4, n= 16
|
0.855 Micromoles per liter (umol/L)
Standard Deviation 1.5295
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, Week 16, n= 13
|
0.789 Micromoles per liter (umol/L)
Standard Deviation 2.2745
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, Week 24, n= 13
|
0.921 Micromoles per liter (umol/L)
Standard Deviation 2.9300
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, End of study, n=4
|
0.855 Micromoles per liter (umol/L)
Standard Deviation 2.2076
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, Follow-up Week 30, n=15
|
0.684 Micromoles per liter (umol/L)
Standard Deviation 2.1240
|
|
Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Total bilirubin, Follow-up Week 36, n=17
|
1.006 Micromoles per liter (umol/L)
Standard Deviation 2.1848
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population
Clinical chemistry parameters: albumin and total protein were assessed at Baseline (Week 0), at Weeks 2, 4, 8, 16, 24 and Follow up (Week 30 and 36) phase. Baseline was defined as the value obtained at Week 0. Change from Baseline was calculated as visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, Week 16, n= 13
|
2.4 Grams per liter (g/L)
Standard Deviation 5.09
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, Week 24, n= 13
|
2.8 Grams per liter (g/L)
Standard Deviation 4.69
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, End of study, n=4
|
-1.0 Grams per liter (g/L)
Standard Deviation 13.14
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, Follow-up Week 30, n=15
|
2.2 Grams per liter (g/L)
Standard Deviation 4.04
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, Follow-up Week 36, n=17
|
2.7 Grams per liter (g/L)
Standard Deviation 5.58
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, Week 2, n= 17
|
0.0 Grams per liter (g/L)
Standard Deviation 2.87
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, Week 16, n= 13
|
1.8 Grams per liter (g/L)
Standard Deviation 3.39
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, Week 24, n= 13
|
1.8 Grams per liter (g/L)
Standard Deviation 3.44
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, End of study, n=4
|
-1.8 Grams per liter (g/L)
Standard Deviation 9.64
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, Follow-up-U Week 30, n=15
|
1.9 Grams per liter (g/L)
Standard Deviation 4.22
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, Follow-up Week 36, n=17
|
1.8 Grams per liter (g/L)
Standard Deviation 4.73
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, Week 4, n= 16
|
-0.6 Grams per liter (g/L)
Standard Deviation 3.63
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Total protein, Week 8, n= 15
|
0.8 Grams per liter (g/L)
Standard Deviation 6.38
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, Week 2, n= 17
|
0.4 Grams per liter (g/L)
Standard Deviation 2.29
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, Week 4, n= 15
|
0.2 Grams per liter (g/L)
Standard Deviation 3.03
|
|
Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Albumin, Week 8, n= 15
|
0.4 Grams per liter (g/L)
Standard Deviation 4.34
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population
Serum creatinine were assessed at Baseline (Week 0), at Weeks 2, 4, 8, 16, 24 and Follow-up (Week 30 and 36) phase. Baseline was defined as the value obtained at Week 0. Change from Baseline was calculated as visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, Week 4, n= 16
|
0.04187 Milligram per deciliter (mg/dl)
Standard Deviation 0.189076
|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, Week 8, n= 15
|
0.11933 Milligram per deciliter (mg/dl)
Standard Deviation 0.407387
|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, Week 16, n= 13
|
-0.02692 Milligram per deciliter (mg/dl)
Standard Deviation 0.167252
|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, Week 2, n= 17
|
0.01294 Milligram per deciliter (mg/dl)
Standard Deviation 0.150738
|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, Week 24, n= 13
|
-0.04538 Milligram per deciliter (mg/dl)
Standard Deviation 0.267071
|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, End of study, n=4
|
0.51000 Milligram per deciliter (mg/dl)
Standard Deviation 0.703468
|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, Follow-up Week 30, n=15
|
-0.10000 Milligram per deciliter (mg/dl)
Standard Deviation 0.271662
|
|
Change From Baseline in Serum Creatinine at Indicated Time Points
Serum creatinine, Follow-up Week 36, n=17
|
0.00588 Milligram per deciliter (mg/dl)
Standard Deviation 0.503079
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population.
eGFR was calculated by using the 4-variable Modification of Diet in Renal Disease (MDRD) at Baseline (Week 0), at Weeks 2, 4, 8, 16, 24 and Follow-up (Week 30 and 36) phase. Baseline was defined as the value obtained at Week 0. Change from Baseline was calculated as visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, End of study, n=4
|
-7.00 milliliter/minute/1.73 square meters
Standard Deviation 14.095
|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, Week 2, n= 17
|
-0.29 milliliter/minute/1.73 square meters
Standard Deviation 8.844
|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, Week 4, n= 16
|
-1.87 milliliter/minute/1.73 square meters
Standard Deviation 12.148
|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, Week 8, n= 15
|
-5.00 milliliter/minute/1.73 square meters
Standard Deviation 10.522
|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, Week 16, n= 13
|
-3.00 milliliter/minute/1.73 square meters
Standard Deviation 15.422
|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, Week 24, n= 13
|
-0.38 milliliter/minute/1.73 square meters
Standard Deviation 17.524
|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, Follow-up Week 30, n=15
|
4.87 milliliter/minute/1.73 square meters
Standard Deviation 19.108
|
|
Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
GFR, Follow-up Week 36, n=17
|
4.24 milliliter/minute/1.73 square meters
Standard Deviation 20.398
|
SECONDARY outcome
Timeframe: Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, and until the follow-up visit (Week 30 and Week 36)Population: All Subject Population
Cystatin C was assessed at Baseline (Week 0), at Weeks 2, 4, 8, 16, 24 and Follow-up (Week 30 and 36) phase. Baseline was defined as the value obtained at Week 0. Change from Baseline was calculated as visit value minus value at Baseline.
Outcome measures
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 Participants
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Percent Change From Baseline in Cystatin C at Indicated Time Points
Cystatin C, Week 2, n= 17
|
-6.15 Percent change
Standard Deviation 13.548
|
|
Percent Change From Baseline in Cystatin C at Indicated Time Points
Cystatin C, Week 4, N= 16
|
-4.44 Percent change
Standard Deviation 18.610
|
|
Percent Change From Baseline in Cystatin C at Indicated Time Points
Cystatin C, Week 24, n= 13
|
-3.42 Percent change
Standard Deviation 19.061
|
|
Percent Change From Baseline in Cystatin C at Indicated Time Points
Cystatin C, Week 8, n= 15
|
2.93 Percent change
Standard Deviation 17.083
|
|
Percent Change From Baseline in Cystatin C at Indicated Time Points
Cystatin C, Week 16, n= 13
|
-1.10 Percent change
Standard Deviation 17.267
|
|
Percent Change From Baseline in Cystatin C at Indicated Time Points
Cystatin C, End of study, n=4
|
24.70 Percent change
Standard Deviation 47.357
|
|
Percent Change From Baseline in Cystatin C at Indicated Time Points
Cystatin C, Follow-up Week 36, n=17
|
0.03 Percent change
Standard Deviation 28.071
|
SECONDARY outcome
Timeframe: Week 0 (Pre-dose and 1, 2, 4, 6 hrs post-dose)Population: PK Population: All participants from whom a PK sample obtained and analyzed, included in the PK population.
Pharmacokinetics (PK) of losmapimod 7.5 mg was evaluated in participants with focal segmental glomerulosclerosis (FSGS) using AUC over the dosing interval of losmapimod 7.5 mg. PK samples were collected at Week 0 (pre-dose and 1, 2, 4, 6 hrs post-dose). Plasma concentration-time data were collected only up to 6 hours post the first 7.5 mg dose and only up to 2 hours post the first 15 mg dose and were not adequate to conduct a noncompartmental analysis to compare with historical data.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 2 (Pre-dose, 2 hrs post-dose) and Week 4, 8, 16, 24 (at one of the following post-dose times: 0-2 hrs, 2-4 hrs, 4-6 hrs, and 6-8 hrs post-dose)Population: PK Population.
PK of losmapimod 15 mg was evaluated in participants with FSGS using AUC over the dosing interval of losmapimod 15 mg. PK samples were collected at Week 2 (Pre-dose, 2 hrs post-dose) and Week 4, 8, 16, 24 (one of the following post-dose times: 0-2 hrs, 2-4 hrs, 4-6 hrs, and 6-8 hrs post-dose). Plasma concentration-time data were collected only up to 6 hours post the first 7.5 mg dose and only up to 2 hours post the first 15 mg dose and were not adequate to conduct a noncompartmental analysis to compare with historical data.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Week 0 (Pre-dose and 1, 2, 4, 6 hrs post-dose)Population: PK Population.
PK of losmapimod 7.5 mg was evaluated in participants with FSGS using Cmax PK samples were collected at Week 0 (pre-dose and 1, 2, 4, 6 hrs post-dose). Plasma concentration-time data were collected only up to 6 hours post the first 7.5 mg dose and only up to 2 hours post the first 15 mg dose and were not adequate to conduct a noncompartmental analysis to compare with historical data.
Outcome measures
Outcome data not reported
Adverse Events
Losmapimod 7.5 mg BID / 15 mg BID
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Losmapimod 7.5 mg BID / 15 mg BID
n=17 participants at risk
Participants received losmapimod 7.5 mg BID (morning and evening), orally after 30 minutes (min.) of their starting meal for approximately 2 weeks. After all the pre-dose assessments at the Week 2 visit, participants received losmapimod 15 mg BID (2 tablets of 7.5 mg each, morning and evening), orally after 30 min. of their starting meal for approximately 22 weeks. Study treatment doses were separated by at least 6 hours.
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
17.6%
3/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Gastrointestinal disorders
Vomiting
|
17.6%
3/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Gastrointestinal disorders
Abdominal pain
|
11.8%
2/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Gastrointestinal disorders
Dyspepsia
|
11.8%
2/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Gastrointestinal disorders
Flatulence
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Nervous system disorders
Headache
|
29.4%
5/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Nervous system disorders
Dizziness
|
17.6%
3/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Nervous system disorders
Dizziness postural
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Nervous system disorders
Presyncope
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
General disorders
Fatigue
|
23.5%
4/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
General disorders
Oedema peripheral
|
11.8%
2/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
General disorders
Chest discomfort
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
General disorders
Localised oedema
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
General disorders
Pyrexia
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
General disorders
Swelling
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Upper respiratory tract infection
|
11.8%
2/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Bronchitis
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Ear infection
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Gastroenteritis viral
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Nasopharyngitis
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Pneumonia
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Respiratory tract infection viral
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Sinusitis
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Infections and infestations
Urinary tract infection
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
17.6%
3/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Investigations
Blood creatinine increased
|
17.6%
3/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Investigations
Blood pressure increased
|
11.8%
2/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Investigations
Blood albumin increased
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Investigations
Blood urea increased
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Investigations
Cystatin C increased
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Investigations
Eosinophils urine
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Investigations
Vitamin D decreased
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
17.6%
3/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Skin and subcutaneous tissue disorders
Rash
|
17.6%
3/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Metabolism and nutrition disorders
Gout
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Injury, poisoning and procedural complications
Animal bite
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Injury, poisoning and procedural complications
Contusion
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Psychiatric disorders
Anxiety
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Psychiatric disorders
Confusional state
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Renal and urinary disorders
Dysuria
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Renal and urinary disorders
Proteinuria
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Blood and lymphatic system disorders
Anaemia
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Cardiac disorders
Palpitations
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Ear and labyrinth disorders
Ear pain
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Immune system disorders
Multiple allergies
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
|
Reproductive system and breast disorders
Breast pain
|
5.9%
1/17 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from start of the study treatment (Week 0) until the Follow-up phase (Week 36).
All Subject Population
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER