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A Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS)

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ClinicalTrials.gov Identifier: NCT02000440
Recruitment Status : Completed
First Posted : December 4, 2013
Results First Posted : June 12, 2017
Last Update Posted : June 12, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glomerulosclerosis, Focal Segmental
Intervention Drug: Losmapimod
Enrollment 17
Recruitment Details 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).
Pre-assignment Details 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.
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 17
Completed 13
Not Completed 4
Reason Not Completed
Adverse Event             3
Other-Protocol-defined Stopping Criteria             1
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description 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 Number of Baseline Participants 17
Hide Baseline Analysis Population Description
Losmapimod 7.5 mg BID / 15 mg BID
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants
40.4  (13.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants
Female
8
  47.1%
Male
9
  52.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants
African American/African Heritage 1
Asian - Central/South Asian Heritage 2
Asian - East Asian Heritage 1
Asian - South East Asian Heritage 2
White - White/Caucasian/European Heritage 11
1.Primary Outcome
Title Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at the Indicated Time Points
Hide Description 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.
Time Frame Week 2, Week 4, Week 8, Week 16 and Week 24
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Hide Analysis Population Description
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.
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Participants
Week 2, n= 17 0
Week 4, n=15 1
Week 8, n=15 0
Week 16, n=13 0
Week 24, n=13 0
2.Secondary Outcome
Title Number of Participants Meeting the Definition of Responder for Reduction in Proteinuria at Any Time During the Treatment Phase (Week 2 to Week 24)
Hide Description 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.
Time Frame Any time during the treatment phase (Week 2 to Week 24)
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Hide Analysis Population Description
Completed Treatment Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Participants
1
3.Secondary Outcome
Title Percent Change From Baseline in Urinary Protein/Creatinine (Up/c) Ratio (Spot and 24 Hours [hr])
Hide Description 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.
Time Frame Baseline (Week 0), Week 2, Week 4, Week 8, Week 16, Week 24, End of study, Week 30 and Week 36
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Hide Analysis Population Description
All Subject Population: all eligible participants who received at least one dose of investigational drug.
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: Percent change
Up/c ratio 24 hr, Week 2, n= 17 -0.45807  (25.696890)
Up/c ratio 24 hr, Week 4, n= 15 -0.07037  (28.954312)
Up/c ratio 24 hr, Week 8, n= 15 24.32547  (39.925052)
Up/c ratio 24 hr, Week 16, n= 13 -10.57111  (37.211084)
Up/c ratio 24 hr, Week 24, n= 13 -0.59030  (29.616932)
Up/c ratio 24 hr, End of study, n= 4 10.79660  (54.170928)
Up/c ratio 24 hr, Follow-up Week 36, n= 16 -6.56589  (43.863442)
Up/c ratio spot, Week 2, n= 17 8.45052  (27.531444)
Up/c ratio spot, Week 4, n= 16 11.44257  (24.783744)
Up/c ratio spot, Week 8, n= 15 41.43955  (50.144228)
Up/c ratio spot, Week 16, n= 13 -0.99691  (34.890578)
Up/c ratio spot, Week 24, n= 12 4.05899  (40.301958)
Up/c ratio spot, End of study, n= 4 13.88998  (57.089949)
Up/c ratio spot, Follow-up Week 30, n= 15 3.66036  (35.011255)
Up/c ratio spot, Follow-up Week 36, n= 17 -2.91757  (44.251282)
4.Secondary Outcome
Title Number of Participants With Complete Proteinuria Remissions at the Indicated Time Points
Hide Description 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.
Time Frame Week 2, Week 4, Week 8, Week 16 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Completed Treatment Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Participants
Week 2, n= 17 0
Week 4, n= 15 0
Week 8, n= 15 0
Week 16, n= 13 0
Week 24, n= 13 0
5.Secondary Outcome
Title Number of Participants Having Any Adverse Events (AEs), Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame From start of the study treatment (Week 0) until the Follow-up phase (Week 36)
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Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Participants
Non-serious AEs 16
SAEs 0
6.Secondary Outcome
Title Number of Participants Withdrawn Due to Toxicities
Hide Description 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.
Time Frame From start of the study treatment (Week 0) until the Follow-up phase (Week 36)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Measure Type: Number
Unit of Measure: Participants
0
7.Secondary Outcome
Title Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: Millimeter of mercury (mmHg)
SBP, Week 2, n= 17 3.5  (9.87)
SBP, Week 4, n= 16 0.9  (12.15)
SBP, Week 8, n= 15 2.0  (13.50)
SBP, Week 16, n= 13 -1.8  (13.16)
SBP, Week 24, n= 13 -1.4  (16.44)
SBP, End of study, n=4 11.3  (9.00)
SBP, Follow-up Week 30, n=15 0.5  (15.94)
SBP, Follow-up Week 36, n=17 3.8  (15.64)
DBP, Week 2, n= 17 1.5  (6.21)
DBP, Week 4, n= 16 -1.2  (7.81)
DBP, Week 8, n= 15 1.7  (7.11)
DBP, Week 16, n= 13 -3.0  (9.87)
DBP, Week 24, n= 13 0.2  (10.14)
DBP, End of study, n=4 6.0  (7.16)
DBP, Follow-up Week 30, n=15 1.3  (9.85)
DBP, Follow-up Week 36, n=17 3.8  (11.84)
8.Secondary Outcome
Title Change From Baseline in Heart Rate at Indicated Time Points
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: bpm
Heart rate, Week 2, n= 17 2.6  (7.05)
Heart rate, Week 4, n= 16 4.4  (8.61)
Heart rate, Week 8, n= 15 2.3  (7.45)
Heart rate, Week 16, n= 13 3.8  (12.08)
Heart rate, Week 24, n= 13 1.5  (8.41)
Heart rate, End of study, n=4 1.3  (10.31)
Heart rate, Follow-up Week 30, n=15 5.3  (10.66)
Heart rate, Follow-up Week 36, n=17 3.6  (11.57)
9.Secondary Outcome
Title Change From Baseline in Liver Function Parameters: Alkaline Phosphatase (AP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) at Indicated Time Points
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: International Units/liter (IU/L)
ALT, Week 2, n= 17 1.8  (4.01)
ALT, Week 4, n= 16 6.7  (9.44)
ALT, Week 8, n= 15 7.1  (14.54)
ALT, Week 16, n= 13 2.6  (6.02)
ALT, Week 24, n= 13 1.2  (5.01)
ALT, End of study, n=4 1.8  (3.95)
ALT, Follow-up Week 30, n=15 0.5  (5.74)
ALT, Follow-up Week 36, n=17 4.3  (9.47)
AP, Week 2, n= 17 0.6  (10.22)
AP, Week 4, n= 16 -0.8  (8.92)
AP, Week 8, n= 15 3.1  (8.15)
AP, Week 16, n= 13 0.2  (9.04)
AP, Week 24, n= 13 -0.8  (7.31)
AP, End of study, n=4 -8.5  (21.39)
AP, Follow-up Week 30, n=15 2.5  (14.38)
AP, Follow-up Week 36, n=17 2.9  (20.23)
AST, Week 2, n= 17 1.2  (3.34)
AST, Week 4, n= 16 6.4  (16.17)
AST, Week 8, n= 15 5.8  (13.99)
AST, Week 16, n= 13 2.2  (5.65)
AST, Week 24, n= 13 -0.3  (3.20)
AST, End of study, n=4 -3.8  (8.18)
AST, Follow-up Week 30, n=15 -0.5  (5.10)
AST, Follow-up Week 36, n=17 2.0  (6.89)
GGT, Week 2, n= 17 -1.3  (5.87)
GGT, Week 4, n= 16 -2.0  (9.42)
GGT, Week 8, n= 15 -0.7  (13.45)
GGT, Week 16, n= 13 -1.6  (8.65)
GGT, Week 24, n= 13 -2.0  (7.68)
GGT, End of study, n=4 -10.0  (25.10)
GGT, Follow-up Week 30, n=15 -0.5  (7.75)
GGT, Follow-up Week 36, n=17 -0.6  (13.18)
10.Secondary Outcome
Title Change From Baseline in Liver Function Parameters: Direct Bilirubin and Total Bilirubin at Indicated Time Points
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter (umol/L)
Direct bilirubin, Week 2, n= 17 -0.503  (1.0053)
Direct bilirubin, Week 4, n= 16 -0.107  (0.9811)
Direct bilirubin, Week 8, n= 15 -0.684  (0.8671)
Direct bilirubin, Week 16, n= 13 -0.263  (0.9485)
Direct bilirubin, Week 24, n= 13 0.000  (0.0000)
Direct bilirubin, End of study, n=4 0.000  (1.3962)
Direct bilirubin, Follow-up Week 30, n=15 -0.228  (0.8830)
Direct bilirubin, Follow-up Week 36, n=17 0.101  (1.2783)
Total bilirubin, Week 2, n= 17 0.503  (2.4754)
Total bilirubin, Week 4, n= 16 0.855  (1.5295)
Total bilirubin, Week 8, n= 15 0.114  (1.5112)
Total bilirubin, Week 16, n= 13 0.789  (2.2745)
Total bilirubin, Week 24, n= 13 0.921  (2.9300)
Total bilirubin, End of study, n=4 0.855  (2.2076)
Total bilirubin, Follow-up Week 30, n=15 0.684  (2.1240)
Total bilirubin, Follow-up Week 36, n=17 1.006  (2.1848)
11.Secondary Outcome
Title Change From Baseline in Liver Function Parameters: Albumin and Total Protein at Indicated Time Points
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: Grams per liter (g/L)
Albumin, Week 2, n= 17 0.4  (2.29)
Albumin, Week 4, n= 15 0.2  (3.03)
Albumin, Week 8, n= 15 0.4  (4.34)
Albumin, Week 16, n= 13 1.8  (3.39)
Albumin, Week 24, n= 13 1.8  (3.44)
Albumin, End of study, n=4 -1.8  (9.64)
Albumin, Follow-up-U Week 30, n=15 1.9  (4.22)
Albumin, Follow-up Week 36, n=17 1.8  (4.73)
Total protein, Week 2, n= 17 0.0  (2.87)
Total protein, Week 4, n= 16 -0.6  (3.63)
Total protein, Week 8, n= 15 0.8  (6.38)
Total protein, Week 16, n= 13 2.4  (5.09)
Total protein, Week 24, n= 13 2.8  (4.69)
Total protein, End of study, n=4 -1.0  (13.14)
Total protein, Follow-up Week 30, n=15 2.2  (4.04)
Total protein, Follow-up Week 36, n=17 2.7  (5.58)
12.Secondary Outcome
Title Change From Baseline in Serum Creatinine at Indicated Time Points
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: Milligram per deciliter (mg/dl)
Serum creatinine, Week 2, n= 17 0.01294  (0.150738)
Serum creatinine, Week 4, n= 16 0.04187  (0.189076)
Serum creatinine, Week 8, n= 15 0.11933  (0.407387)
Serum creatinine, Week 16, n= 13 -0.02692  (0.167252)
Serum creatinine, Week 24, n= 13 -0.04538  (0.267071)
Serum creatinine, End of study, n=4 0.51000  (0.703468)
Serum creatinine, Follow-up Week 30, n=15 -0.10000  (0.271662)
Serum creatinine, Follow-up Week 36, n=17 0.00588  (0.503079)
13.Secondary Outcome
Title Change From Baseline in Glomerular Filtration Rate (GFR) at Indicated Time Points
Hide Description 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).
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All Subject Population.
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: milliliter/minute/1.73 square meters
GFR, Week 2, n= 17 -0.29  (8.844)
GFR, Week 4, n= 16 -1.87  (12.148)
GFR, Week 8, n= 15 -5.00  (10.522)
GFR, Week 16, n= 13 -3.00  (15.422)
GFR, Week 24, n= 13 -0.38  (17.524)
GFR, End of study, n=4 -7.00  (14.095)
GFR, Follow-up Week 30, n=15 4.87  (19.108)
GFR, Follow-up Week 36, n=17 4.24  (20.398)
14.Secondary Outcome
Title Percent Change From Baseline in Cystatin C at Indicated Time Points
Hide Description 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.
Time Frame 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)
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All Subject Population
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
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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 Number of Participants Analyzed 17
Mean (Standard Deviation)
Unit of Measure: Percent change
Cystatin C, Week 2, n= 17 -6.15  (13.548)
Cystatin C, Week 4, N= 16 -4.44  (18.610)
Cystatin C, Week 8, n= 15 2.93  (17.083)
Cystatin C, Week 16, n= 13 -1.10  (17.267)
Cystatin C, Week 24, n= 13 -3.42  (19.061)
Cystatin C, End of study, n=4 24.70  (47.357)
Cystatin C, Follow-up Week 36, n=17 0.03  (28.071)
15.Secondary Outcome
Title Area Under Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) and AUC From Time Zero to the End of Dosing Period (AUC[0-tau]) of Losmapimod 7.5 mg in Plasma
Hide Description 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.
Time Frame Week 0 (Pre-dose and 1, 2, 4, 6 hrs post-dose)
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PK Population: All participants from whom a PK sample obtained and analyzed, included in the PK population.
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
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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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title (AUC[0-tau]) of Losmapimod 15 mg in Plasma
Hide Description 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.
Time Frame 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)
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Hide Analysis Population Description
PK Population.
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
17.Secondary Outcome
Title Plasma Losmapimod 7.5 mg Maximum Observed Concentration (Cmax)
Hide Description 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.
Time Frame Week 0 (Pre-dose and 1, 2, 4, 6 hrs post-dose)
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Hide Analysis Population Description
PK Population.
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description:
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 Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame 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).
Adverse Event Reporting Description All Subject Population
 
Arm/Group Title Losmapimod 7.5 mg BID / 15 mg BID
Hide Arm/Group Description 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.
All-Cause Mortality
Losmapimod 7.5 mg BID / 15 mg BID
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Losmapimod 7.5 mg BID / 15 mg BID
Affected / at Risk (%)
Total   0/17 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Losmapimod 7.5 mg BID / 15 mg BID
Affected / at Risk (%)
Total   16/17 (94.12%) 
Blood and lymphatic system disorders   
Anaemia  1  1/17 (5.88%) 
Cardiac disorders   
Palpitations  1  1/17 (5.88%) 
Ear and labyrinth disorders   
Ear pain  1  1/17 (5.88%) 
Gastrointestinal disorders   
Nausea  1  3/17 (17.65%) 
Vomiting  1  3/17 (17.65%) 
Abdominal pain  1  2/17 (11.76%) 
Dyspepsia  1  2/17 (11.76%) 
Abdominal pain upper  1  1/17 (5.88%) 
Diarrhoea  1  1/17 (5.88%) 
Flatulence  1  1/17 (5.88%) 
General disorders   
Fatigue  1  4/17 (23.53%) 
Oedema peripheral  1  2/17 (11.76%) 
Chest discomfort  1  1/17 (5.88%) 
Localised oedema  1  1/17 (5.88%) 
Pyrexia  1  1/17 (5.88%) 
Swelling  1  1/17 (5.88%) 
Immune system disorders   
Multiple allergies  1  1/17 (5.88%) 
Infections and infestations   
Upper respiratory tract infection  1  2/17 (11.76%) 
Bronchitis  1  1/17 (5.88%) 
Ear infection  1  1/17 (5.88%) 
Gastroenteritis viral  1  1/17 (5.88%) 
Nasopharyngitis  1  1/17 (5.88%) 
Pneumonia  1  1/17 (5.88%) 
Respiratory tract infection viral  1  1/17 (5.88%) 
Sinusitis  1  1/17 (5.88%) 
Urinary tract infection  1  1/17 (5.88%) 
Injury, poisoning and procedural complications   
Animal bite  1  1/17 (5.88%) 
Contusion  1  1/17 (5.88%) 
Investigations   
Blood creatinine increased  1  3/17 (17.65%) 
Blood pressure increased  1  2/17 (11.76%) 
Blood albumin increased  1  1/17 (5.88%) 
Blood urea increased  1  1/17 (5.88%) 
Cystatin C increased  1  1/17 (5.88%) 
Eosinophils urine  1  1/17 (5.88%) 
Vitamin D decreased  1  1/17 (5.88%) 
Metabolism and nutrition disorders   
Decreased appetite  1  1/17 (5.88%) 
Gout  1  1/17 (5.88%) 
Hyperglycaemia  1  1/17 (5.88%) 
Musculoskeletal and connective tissue disorders   
Muscle spasms  1  3/17 (17.65%) 
Back pain  1  1/17 (5.88%) 
Joint stiffness  1  1/17 (5.88%) 
Musculoskeletal stiffness  1  1/17 (5.88%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Skin papilloma  1  1/17 (5.88%) 
Nervous system disorders   
Headache  1  5/17 (29.41%) 
Dizziness  1  3/17 (17.65%) 
Dizziness postural  1  1/17 (5.88%) 
Presyncope  1  1/17 (5.88%) 
Psychiatric disorders   
Anxiety  1  1/17 (5.88%) 
Confusional state  1  1/17 (5.88%) 
Renal and urinary disorders   
Dysuria  1  1/17 (5.88%) 
Proteinuria  1  1/17 (5.88%) 
Reproductive system and breast disorders   
Breast pain  1  1/17 (5.88%) 
Respiratory, thoracic and mediastinal disorders   
Oropharyngeal pain  1  3/17 (17.65%) 
Asthma  1  1/17 (5.88%) 
Cough  1  1/17 (5.88%) 
Epistaxis  1  1/17 (5.88%) 
Nasal congestion  1  1/17 (5.88%) 
Skin and subcutaneous tissue disorders   
Rash  1  3/17 (17.65%) 
Hyperhidrosis  1  1/17 (5.88%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
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.
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.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02000440    
Other Study ID Numbers: 117283
First Submitted: November 27, 2013
First Posted: December 4, 2013
Results First Submitted: March 1, 2017
Results First Posted: June 12, 2017
Last Update Posted: June 12, 2017