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Trial record 21 of 34 for:    Biliary Cirrhosis, Primary, 4

Phase 2 Study to Evaluate LUM001 in Combination With Ursodeoxycholic Acid in Patients With Primary Biliary Cirrhosis (CLARITY)

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ClinicalTrials.gov Identifier: NCT01904058
Recruitment Status : Completed
First Posted : July 22, 2013
Results First Posted : July 6, 2016
Last Update Posted : March 27, 2019
Sponsor:
Information provided by (Responsible Party):
Mirum Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions PBC
Primary Biliary Cirrhosis
Interventions Drug: LUM001
Drug: Placebo
Drug: Ursodeoxycholic Acid
Enrollment 66
Recruitment Details The study was conducted in 24 centers in the United Kingdom, Canada, and the United States between 19 August 2013 and 09 April 2015.
Pre-assignment Details A total of 87 participants were screened out of which 66 participants were randomized into the study and the remaining 21 were screen failures.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B)
Hide Arm/Group Description In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks. In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks. In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks. In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Period Title: Overall Study
Started 21 21 11 13
Completed 18 21 10 12
Not Completed 3 0 1 1
Reason Not Completed
Adverse Event             2             0             0             0
Withdrawal by Subject             1             0             1             0
Pregnancy             0             0             0             1
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B) Total
Hide Arm/Group Description In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks. In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks. In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks. In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks. Total of all reporting groups
Overall Number of Baseline Participants 21 21 11 13 66
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 21 participants 11 participants 13 participants 66 participants
54.7  (12.74) 53.5  (10.53) 47.5  (8.14) 55.8  (8.73) 53.3  (10.77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 21 participants 11 participants 13 participants 66 participants
Female
20
  95.2%
17
  81.0%
11
 100.0%
12
  92.3%
60
  90.9%
Male
1
   4.8%
4
  19.0%
0
   0.0%
1
   7.7%
6
   9.1%
1.Primary Outcome
Title Change From Baseline in Pruritus Using Adult Itch Reported Outcome (ItchRO) Weekly Sum Score at Week 13/ Early Termination (ET)
Hide Description Pruritus was assessed using ItchRO measure, administered as an electronic diary (eDiary) which was completed by the participants twice daily (morning and evening). (ItchRO) scores ranged from 0 to 10, with 0 representing no itch and 10 representing very severe itching. The highest score between the morning and evening ItchRO reports represented the daily score: a measure of the worst itching over the previous 24-hour period. The weekly sum score was calculated as the sum of the daily scores for the 7 days prior to the time point being reported: 7 days prior to randomization or 7 days prior to Week 13/ET visit.
Time Frame Baseline and Week 13/ET
Hide Outcome Measure Data
Hide Analysis Population Description
The mITT population included all participants who were randomized, received at least 1 dose of treatment, and had at least 1 post-baseline ItchRO assessment.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B)
Hide Arm/Group Description:
In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Overall Number of Participants Analyzed 21 21 11 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 48.11  (13.363) 52.10  (13.780) 54.64  (9.157) 49.46  (14.110)
Change at Week 13/ET -24.59  (15.240) -27.67  (19.888) -26.18  (18.313) -22.77  (17.123)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LUM001 10 mg + UDCA (Cohort A, Placebo + UDCA (Cohort A), Placebo + UDCA (Cohort B)
Comments The difference between treatment groups in change from Baseline to Week 13/ET in ItchRO weekly sum score evaluated by analysis of covariance (ANCOVA) using generalized linear model (GLM). The model included terms for treatment group, alkaline phosphatase (ALP) level (strata), treatment group by ALP level interaction and Baseline ItchRO weekly sum score as a covariate. Least squares mean change from Baseline to Week 13/ET, along with 95 percentage (%) confidence interval for mean were presented.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6603
Comments p-value (LUM001 LS Mean = Placebo LS Mean).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -2.28
Confidence Interval (2-Sided) 95%
-12.59 to 8.03
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LUM001 20 mg + UDCA (Cohort B), Placebo + UDCA (Cohort A), Placebo + UDCA (Cohort B)
Comments The difference between treatment groups in change from Baseline to Week 13/ET in ItchRO weekly sum score was evaluated by ANCOVA using a GLM. The model included terms for treatment group, ALP level (strata), treatment group by ALP level interaction, and Baseline ItchRO weekly sum score as a covariate. Least squares mean change from Baseline to Week 13/ET, along with 95% confidence interval for the mean, were presented.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4380
Comments p-value (LUM001 LS Mean = Placebo LS Mean).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -3.99
Confidence Interval (2-Sided) 95%
-14.20 to 6.23
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Pruritus Using Adult ItchRO Weekly Sum Scores at Weeks 4, 8 and 13
Hide Description ItchRO scores had a range from 0 to 10, with 0 representing no itch and 10 representing very severe itching. The highest score between the morning and evening ItchRO reports represented the daily score: a measure of the worst itching over the previous 24-hour period. The weekly sum score was calculated as the sum of the daily scores for the 7 days prior to the time point being reported: 7 days prior to randomization or 7 days prior to Week 13/ET visit.
Time Frame Baseline, Weeks 4, 8 and 13
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Here, “n” signifies the number of participants evaluable for the respective time points.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B)
Hide Arm/Group Description:
In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Overall Number of Participants Analyzed 21 21 11 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=21, 21, 11, 13) 48.11  (13.363) 52.10  (13.780) 54.64  (9.157) 49.46  (14.110)
Change at Week 4 (n=20, 21, 11, 13) -15.62  (13.708) -22.19  (18.101) -10.55  (11.103) -16.23  (12.749)
Change at Week 8 (n=20, 21, 10, 13) -21.92  (13.089) -23.97  (20.398) -23.50  (18.585) -19.15  (15.302)
Change at Week 13 (n=18, 21, 10, 12) -27.41  (14.346) -27.67  (19.888) -28.50  (17.520) -22.92  (17.876)
3.Secondary Outcome
Title Change From Baseline in Pruritus Using Adult ItchRO Average Daily Scores at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET)
Hide Description ItchRO scores had a range from 0 to 10, with 0 representing no itch and 10 representing very severe itching. The highest score between the morning and evening ItchRO reports represented the daily score: a measure of the worst itching over the previous 24-hour period. Adult ItchRO average daily score was the sum of daily scores divided by the number of days adult ItchRO was completed, using the 7 days prior to the reported visit date.
Time Frame Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Here, “n” signifies the number of participants evaluable for the respective time points.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B)
Hide Arm/Group Description:
In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Overall Number of Participants Analyzed 21 21 11 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=21, 21, 11, 13) 6.873  (1.9091) 7.442  (1.9686) 7.805  (1.3082) 7.066  (2.0158)
Change at Week 4 (n=20, 21, 11, 13 -2.231  (1.9587) -3.170  (2.5859) -1.506  (1.5861) -2.319  (1.8212)
Change at Week 8 (n=20, 21, 10, 13) -3.131  (1.8703) -3.424  (2.9139) -3.357  (2.6549) -2.736  (2.1860)
Change at Week 13 (n=18, 21, 10, 12) -3.915  (2.0496) -3.952  (2.8411) -4.071  (2.5028) -3.274  (2.5537)
Change at Week 13/ET (n=21, 21, 11, 13) -3.512  (2.1774) -3.952  (2.8411) -3.740  (2.6161) -3.253  (2.4461)
4.Secondary Outcome
Title Change From Baseline in Alkaline Phosphatase (ALP) at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET)
Hide Description Laboratory serum ALP enzyme levels were evaluated using blood samples collected.
Time Frame Baseline, Weeks 4, 8, 13 and Last Post-baseline (Week 13/ET)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Here, “n” signifies the number of participants evaluable for the respective time points.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B)
Hide Arm/Group Description:
In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Overall Number of Participants Analyzed 21 21 11 13
Mean (Standard Deviation)
Unit of Measure: units per liter (U/L)
Baseline (n=21, 21, 11, 13) 288.2  (193.91) 257.6  (190.38) 253.9  (96.83) 274.2  (190.85)
Change at Week 4 (n=20, 21, 10, 13) -22.1  (54.94) 13.2  (47.76) 20.3  (49.68) -0.7  (39.69)
Change at Week 8 (n=20, 21, 10, 12 2.6  (53.95) 1.1  (41.98) 8.8  (38.72) -4.8  (55.70)
Change at Week 13 (n=17, 20, 10, 12) -15.2  (97.19) 18.5  (56.21) 24.3  (76.48) -7.2  (83.70)
Change at Week 13/ET (n=21, 21, 11, 13) -8.0  (93.02) 16.4  (55.60) 22.9  (72.70) -7.9  (80.19)
5.Secondary Outcome
Title Change From Baseline in 5-D Itch Score at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET)
Hide Description The 5-D itch (validated instrument to measure pruritus) scale was developed for the multidimensional quantification of pruritus that is sensitive to change over time. The 5-D itch scale included 5 domains (duration, degree, direction, disability, and distribution of pruritus). The total 5-D score was obtained by scoring each of the domains separately and then summing them together. 5-D total scores ranged between 5 (no pruritus) and 25 (most severe pruritus).
Time Frame Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Here, “n” signifies the number of participants evaluable for the respective time points.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B
Hide Arm/Group Description:
In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Overall Number of Participants Analyzed 21 21 11 13
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=21, 21, 11, 13) 18.7  (3.47) 19.4  (3.49) 19.6  (2.94) 19.2  (3.32)
Change at Week 4 (n=20, 21, 10, 13) -4.8  (3.91) -6.3  (4.96) -3.4  (3.89) -4.2  (3.81)
Change at Week 8 (n=20, 21, 10, 12) -6.8  (3.16) -5.9  (5.62) -6.4  (6.20) -4.4  (4.27)
Change at Week 13 (n=18, 21, 10, 12) -7.4  (3.68) -7.0  (5.89) -7.8  (5.94) -6.1  (4.68)
Change at Week 13/ET (n=21, 21, 10, 13) -6.5  (4.11) -7.0  (5.89) -7.8  (5.94) -5.6  (4.79)
6.Secondary Outcome
Title Change From Baseline in Fasting Serum Bile Acid Level at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET)
Hide Description Laboratory serum bile acid level levels were evaluated using blood samples collected.
Time Frame Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Here, “n” signifies the number of participants evaluable for the respective time points.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B)
Hide Arm/Group Description:
In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Overall Number of Participants Analyzed 21 21 11 13
Mean (Standard Deviation)
Unit of Measure: micromoles per liter
Baseline (n=21, 21, 11, 13) 33.110  (30.5943) 52.460  (94.3892) 52.615  (64.6162) 58.434  (73.9895)
Change at Week 4 (n=20, 21, 10, 13) -11.204  (31.6132) -14.465  (58.5891) -10.221  (50.0398) 14.317  (75.1092)
Change at Week 8 (n=20, 21, 10, 12) -3.968  (45.7388) -21.983  (78.6134) -3.585  (52.4398) 34.893  (67.7189)
Change at Week 13 (n=18, 21, 10, 12) -8.122  (48.1290) -19.098  (81.8452) 11.481  (44.0465) 4.123  (46.2170)
Change at Week 13/ET (n=21, 21, 10, 13) -4.504  (45.7595) -19.098  (81.8452) 11.481  (44.0465) 3.690  (44.2770)
7.Secondary Outcome
Title Change From Baseline in Bile Acid Synthesis as Measured by Serum 7 Alpha-Hydroxy-4-Cholesten-3-One C4 Level [7 Alpha C4]) at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET)
Hide Description C4 7 alpha-hydroxy-4-cholesten-3-one is an intermediate in the biochemical synthesis of bile acids from cholesterol and its concentrations reflect the activity of the bile acid synthetic pathway. Elevated levels of C4 indicate bile acid malabsorption. Laboratory C4 levels were evaluated using blood samples collected.
Time Frame Baseline, Weeks 4, 8, 13 and Last Post-baseline Visit (Week 13/ET)
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Here, “n” signifies the number of participants evaluable for the respective time points.
Arm/Group Title LUM001 10 mg + UDCA (Cohort A) LUM001 20 mg + UDCA (Cohort B) Placebo + UDCA (Cohort A) Placebo + UDCA (Cohort B)
Hide Arm/Group Description:
In Cohort A, participants received LUM001 tablet in combination with ursodeoxycholic acid (UDCA) orally once daily at a dosage of 2.5 up to a maximum of 10 milligram (mg) during the dose-escalation period over a 3 week period. Thereafter, participants received LUM001 10 mg tablet along with one placebo matched to LUM001 orally once daily for another 10 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received LUM001 tablets in combination with UDCA orally once daily at a dosage of 2.5 mg up to a maximum of 20 mg during the dose-escalation period over a 4 week period. Thereafter, participants received LUM001 20 mg (2x10 mg) tablet orally once daily for another 9 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort A, participants received placebo (matched to LUM001) once daily for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
In Cohort B, participants received placebo (matched to LUM001) for a period of 13 weeks, in combination with UDCA. Participants continued UDCA alone for an additional period of 4 weeks.
Overall Number of Participants Analyzed 21 21 11 13
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
Baseline (n=21, 21, 10, 13) 18.74  (16.180) 13.17  (11.851) 22.31  (20.769) 16.98  (33.093)
Change at Week 4 (n=20, 21, 9, 13) 8.66  (23.422) 17.03  (18.380) -6.80  (6.783) -0.19  (8.856)
Change at Week 8 (n=20, 21, 9, 12) 13.04  (17.895) 15.03  (31.120) -12.57  (14.630) 3.43  (16.666)
Change at Week 13 (n=18, 21, 9, 12) 24.38  (38.105) 6.62  (10.116) -12.72  (10.374) 4.56  (13.610)
Change at Week 13/ET (n=21, 21, 9, 13) 20.56  (37.312) 6.62  (10.116) -12.72  (10.374) 4.74  (13.047)
8.Other Pre-specified Outcome
Title Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Hide Description An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. A serious adverse event (SAE) was defined as an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly or birth defect; an important medical event that did not meet any of the above criteria but jeopardized the participant or required medical or surgical intervention to prevent one of the outcomes listed above. A TEAE was defined as any AE that occurred during the study, from the start of investigational product dosing through the end of the study (13 weeks of treatment period (or ET) + 14 days ]), or that worsened since the start of dosing.
Time Frame From the first dose of study drug until the 13 weeks of treatment period (or ET) + 14 days (approximately 15 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Population included all participants who were randomized and received at least 1 dose of the study drug. One participant was randomized to LUM001 10 mg, but was down-titrated to 5 mg dose due to tolerability issues. The safety data has been summarized based on the study dose actually received by the participant.
Arm/Group Title LUM001 5 mg + UDCA LUM001 10 mg + UDCA LUM001 20 mg + UDCA Placebo + UDCA
Hide Arm/Group Description:
Participants received LUM001 5 milligram (mg) tablet orally once daily for a period of 13 weeks in combination with UDCA.
Participants received LUM001 10 mg tablet orally once daily for a period of 13 weeks in combination with UDCA.
Participants received LUM001 20 mg (2x 10 mg) tablet for 20 mg daily dose in combination with UDCA orally once daily for a period of 13 weeks.
Participants received placebo matched to LUM001 tablet orally once daily for a period of 13 weeks in combination with UDCA.
Overall Number of Participants Analyzed 1 20 21 24
Measure Type: Number
Unit of Measure: participants
TEAEs 1 19 21 17
TESAEs 0 2 1 0
Time Frame From the first dose of study drug until the 13 weeks of treatment period (or ET) + 14 days (approximately 15 weeks)
Adverse Event Reporting Description One subject was randomized to LUM001 10 mg, but was down-titrated to 5mg dose due to tolerability issues. One participant was randomized to LUM001 10 mg, but was down-titrated to 5 mg dose due to tolerability issues. The safety data has been summarized based on the study dose actually received by the participant.
 
Arm/Group Title LUM001 5 mg + UDCA LUM001 10 mg + UDCA LUM001 20 mg + UDCA Placebo + UDCA
Hide Arm/Group Description Participants received LUM001 5 mg tablet orally once daily for a period of 13 weeks in combination with UDCA. Participants received LUM001 10 mg tablet orally once daily for a period of 13 weeks in combination with UDCA. Participants received LUM001 20 mg (2x 10 mg) tablet for 20 mg daily dose in combination with UDCA orally once daily for a period of 13 weeks. Participants received placebo matched to LUM001 tablet orally once daily for a period of 13 weeks in combination with UDCA.
All-Cause Mortality
LUM001 5 mg + UDCA LUM001 10 mg + UDCA LUM001 20 mg + UDCA Placebo + UDCA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LUM001 5 mg + UDCA LUM001 10 mg + UDCA LUM001 20 mg + UDCA Placebo + UDCA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/1 (0.00%)      2/20 (10.00%)      1/21 (4.76%)      0/24 (0.00%)    
Cardiac disorders         
Myocardial Infarction * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders         
Abdominal Pain * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal Haemorrhage * 1  0/1 (0.00%)  0 0/20 (0.00%)  0 1/21 (4.76%)  1 0/24 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
LUM001 5 mg + UDCA LUM001 10 mg + UDCA LUM001 20 mg + UDCA Placebo + UDCA
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/1 (100.00%)      18/20 (90.00%)      20/21 (95.24%)      16/24 (66.67%)    
Blood and lymphatic system disorders         
Pancytopenia * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Eye disorders         
Dry Eye * 1  0/1 (0.00%)  0 2/20 (10.00%)  2 0/21 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders         
Abdominal Distension * 1  0/1 (0.00%)  0 3/20 (15.00%)  3 0/21 (0.00%)  0 3/24 (12.50%)  4
Abdominal Pain * 1  1/1 (100.00%)  3 4/20 (20.00%)  4 5/21 (23.81%)  6 1/24 (4.17%)  1
Abdominal Pain Upper * 1  0/1 (0.00%)  0 4/20 (20.00%)  6 6/21 (28.57%)  9 2/24 (8.33%)  2
Constipation * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 1/21 (4.76%)  1 1/24 (4.17%)  1
Diarrhoea * 1  1/1 (100.00%)  3 14/20 (70.00%)  16 11/21 (52.38%)  19 6/24 (25.00%)  7
Dry Mouth * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 1/21 (4.76%)  1 0/24 (0.00%)  0
Dyspepsia * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 1/21 (4.76%)  1 2/24 (8.33%)  2
Faeces Discoloured * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 1/24 (4.17%)  2
Flatulence * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 1/24 (4.17%)  1
Gastrooesophageal Reflux Disease * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 2/21 (9.52%)  2 0/24 (0.00%)  0
Gingival Pain * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Mouth Ulceration * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 1/24 (4.17%)  1
Nausea * 1  1/1 (100.00%)  2 5/20 (25.00%)  6 4/21 (19.05%)  5 4/24 (16.67%)  4
Toothache * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Vomiting * 1  1/1 (100.00%)  1 0/20 (0.00%)  0 1/21 (4.76%)  1 2/24 (8.33%)  2
General disorders         
Asthenia * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Chills * 1  0/1 (0.00%)  0 2/20 (10.00%)  2 0/21 (0.00%)  0 0/24 (0.00%)  0
Fatigue * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 2/21 (9.52%)  2 1/24 (4.17%)  1
Influenza Like Illness * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Pain * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Pyrexia * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 1/21 (4.76%)  1 0/24 (0.00%)  0
Infections and infestations         
Bronchitis * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Sinusitis * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Upper Respiratory Tract Infection * 1  0/1 (0.00%)  0 0/20 (0.00%)  0 2/21 (9.52%)  2 1/24 (4.17%)  1
Urinary Tract Infection * 1  0/1 (0.00%)  0 0/20 (0.00%)  0 2/21 (9.52%)  2 1/24 (4.17%)  1
Injury, poisoning and procedural complications         
Anal Injury * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Excoriation * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Back Pain * 1  0/1 (0.00%)  0 2/20 (10.00%)  2 0/21 (0.00%)  0 0/24 (0.00%)  0
Muscle Spasms * 1  0/1 (0.00%)  0 2/20 (10.00%)  2 0/21 (0.00%)  0 0/24 (0.00%)  0
Muscular Weakness * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Musculoskeletal Chest Pain * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Myalgia * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 1/24 (4.17%)  1
Pain In Extremity * 1  0/1 (0.00%)  0 0/20 (0.00%)  0 3/21 (14.29%)  3 0/24 (0.00%)  0
Nervous system disorders         
Dizziness * 1  1/1 (100.00%)  1 0/20 (0.00%)  0 1/21 (4.76%)  1 1/24 (4.17%)  1
Headache * 1  0/1 (0.00%)  0 3/20 (15.00%)  3 2/21 (9.52%)  2 8/24 (33.33%)  10
Paraesthesia * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Reproductive system and breast disorders         
Vaginal Discharge * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Cough * 1  0/1 (0.00%)  0 4/20 (20.00%)  4 1/21 (4.76%)  1 0/24 (0.00%)  0
Laryngeal Inflammation * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Nasal Congestion * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Oropharyngeal Pain * 1  0/1 (0.00%)  0 1/20 (5.00%)  2 0/21 (0.00%)  0 0/24 (0.00%)  0
Pharyngeal Erythema * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
Skin and subcutaneous tissue disorders         
Pruritus * 1  0/1 (0.00%)  0 0/20 (0.00%)  0 1/21 (4.76%)  1 3/24 (12.50%)  3
Rash * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 1/24 (4.17%)  2
Surgical and medical procedures         
Sinus Operation * 1  0/1 (0.00%)  0 1/20 (5.00%)  1 0/21 (0.00%)  0 0/24 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (16.0)
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.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Physician
Organization: Mirum
Phone: 1-650-667-4085
EMail: medinfo@mirumpharma.com
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Responsible Party: Mirum Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01904058     History of Changes
Other Study ID Numbers: LUM001-201
2013-000482-36 ( EudraCT Number )
First Submitted: July 17, 2013
First Posted: July 22, 2013
Results First Submitted: April 1, 2016
Results First Posted: July 6, 2016
Last Update Posted: March 27, 2019