IMAGO: Safety and Efficacy Study of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Alagille Syndrome
Sponsor
Mirum Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01903460
Collaborator
(none)
20
3
2
19
6.7
0.4
Study Details
Study Description
Brief Summary
The study is a randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LUM001. Efficacy will be assessed by evaluating the effect of LUM001 versus placebo on the biochemical markers and pruritus associated with Alagille Syndrome.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
20 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Paediatric Patients With Alagille Syndrome
Study Start Date
:
Aug 1, 2013
Actual Primary Completion Date
:
Feb 1, 2015
Actual Study Completion Date
:
Mar 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LUM001 LUM001 administered orally once each day |
Drug: LUM001
|
| Placebo Comparator: Placebo Placebo administered orally once each day |
Drug: Placebo
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline to Week 13 (End of Treatment) in Fasting Serum Bile Acid Level [Baseline to 13 weeks or end of treatment]
Participants were required to fast for at least 4 hours; only water was permitted prior to collection. A negative change from baseline indicates that the level of bile acid decreased.
Secondary Outcome Measures
- Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes [Baseline to 13 weeks or end of treatment]
Analysis of liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A negative change from baseline indicates that the level of that enzyme decreased.
- Change From Baseline to Week 13 (End of Treatment) in Pruritus as Measured by The Patient And Observer Itch Reported Outcome (ItchRO) Average Daily Scores [Baseline to 13 weeks or end of treatment]
The ItchRO was administered as a twice daily electronic diary (eDiary). Children ≥9 years of age completed the patient ItchRO; those between the ages of 5 and 8 completed the patient ItchRO with the assistance of their caregiver. There was no patient report for subjects under the age of 5. ItchRO scores range from 0 to 4, with the higher score indicating increasing itch severity. ItchRO average daily scores were calculated as the sum of daily scores (ie, the maximum of morning and evening scores) divided by the number of days. The average daily score was calculated by using the 7 days pre-treatment for baseline, and the last 7 days of treatment for Week 13. A negative change from Baseline indicates that itch severity decreased.
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Months
to 18 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of Alagille Syndrome
-
Evidence of cholestasis
-
Moderate to severe pruritus
-
Ability to understand and willingness to sign informed consent/assent prior to initiation of any study procedures
Exclusion Criteria:
-
Surgical disruption of the enterohepatic circulation
-
Liver transplant
-
History or presence of other concomitant liver disease
-
Females who are pregnant or lactating
-
Known HIV infection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham Children's Hospital | Birmingham | West Midlands | United Kingdom | B4 6NH |
| 2 | Leeds Teaching Hospitals | Leeds | West Yorkshire | United Kingdom | LS9 7TF |
| 3 | Kings College Hospital | London | United Kingdom | SE5 9RS |
Sponsors and Collaborators
- Mirum Pharmaceuticals, Inc.
Investigators
- Study Director: Study Director, Mirum
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Mirum Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01903460
Other Study ID Numbers:
- LUM001-302
- 2012-005346-38
- SHP625-302
First Posted:
Jul 19, 2013
Last Update Posted:
Mar 28, 2019
Last Verified:
Mar 1, 2019
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | Placebo Cohort A | Placebo Cohort B |
|---|---|---|---|---|
| Arm/Group Description | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| Period Title: Overall Study | ||||
| STARTED | 6 | 8 | 3 | 3 |
| COMPLETED | 6 | 8 | 3 | 2 |
| NOT COMPLETED | 0 | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | Placebo Cohort A | Placebo Cohort B | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. | Total of all reporting groups |
| Overall Participants | 6 | 8 | 3 | 3 | 20 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
5.8
(4.49)
|
6.8
(6.73)
|
5.0
(2.00)
|
4.3
(3.21)
|
5.9
(4.93)
|
| Age, Customized (participants) [Number] | |||||
| < 2 years |
0
0%
|
3
37.5%
|
0
0%
|
0
0%
|
3
15%
|
| 2 to 4 years |
3
50%
|
1
12.5%
|
1
33.3%
|
2
66.7%
|
7
35%
|
| 5 to 8 years |
1
16.7%
|
1
12.5%
|
2
66.7%
|
1
33.3%
|
5
25%
|
| 9 to 12 years |
2
33.3%
|
0
0%
|
0
0%
|
0
0%
|
2
10%
|
| 13 to 18 years |
0
0%
|
3
37.5%
|
0
0%
|
0
0%
|
3
15%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
33.3%
|
3
37.5%
|
3
100%
|
2
66.7%
|
10
50%
|
| Male |
4
66.7%
|
5
62.5%
|
0
0%
|
1
33.3%
|
10
50%
|
| Region of Enrollment (participants) [Number] | |||||
| United Kingdom |
6
100%
|
8
100%
|
3
100%
|
3
100%
|
20
100%
|
Outcome Measures
| Title | Change From Baseline to Week 13 (End of Treatment) in Fasting Serum Bile Acid Level |
|---|---|
| Description | Participants were required to fast for at least 4 hours; only water was permitted prior to collection. A negative change from baseline indicates that the level of bile acid decreased. |
| Time Frame | Baseline to 13 weeks or end of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The modified Intent-to-Treat (mITT) population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug. |
| Arm/Group Title | LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | LUM001 Overall | Placebo Overall |
|---|---|---|---|---|
| Arm/Group Description | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received either dose of LUM001 for up to 10 or 13 weeks, then were followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| Measure Participants | 6 | 8 | 14 | 6 |
| Least Squares Mean (Standard Error) [umol/L] |
-82.864
(50.1513)
|
-49.388
(43.4732)
|
-66.126
(33.1208)
|
-42.157
(50.0903)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LUM001 140ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 140ug/kg/day | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5740 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -40.707 | |
| Confidence Interval |
(2-Sided) 95% -191.679 to 110.265 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LUM001 280ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 280ug/kg/day | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9147 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -7.231 | |
| Confidence Interval |
(2-Sided) 95% -148.726 to 134.264 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LUM001 Overall, Placebo Overall |
|---|---|---|
| Comments | Analysis of all doses of LUM001 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6954 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -23.969 | |
| Confidence Interval |
(2-Sided) 95% -151.969 to 104.031 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes |
|---|---|
| Description | Analysis of liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A negative change from baseline indicates that the level of that enzyme decreased. |
| Time Frame | Baseline to 13 weeks or end of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug. |
| Arm/Group Title | LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | LUM001 Overall | Placebo Overall |
|---|---|---|---|---|
| Arm/Group Description | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received either dose of LUM001 for up to 10 or 13 weeks, then were followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| Measure Participants | 6 | 8 | 14 | 6 |
| ALT |
59.3
(20.99)
|
10.5
(18.06)
|
34.9
(13.86)
|
2.7
(21.06)
|
| AST |
37.2
(13.64)
|
-2.7
(11.70)
|
17.3
(8.98)
|
13.2
(13.63)
|
| ALP |
71.4
(53.35)
|
31.6
(43.59)
|
51.5
(36.13)
|
19.7
(60.76)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LUM001 140ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 140ug/kg/day for ALT | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0783 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 56.7 | |
| Confidence Interval |
(2-Sided) 95% -7.2 to 120.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LUM001 280ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 280ug/kg/day for ALT | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7827 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 7.8 | |
| Confidence Interval |
(2-Sided) 95% -51.4 to 67.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LUM001 Overall, Placebo Overall |
|---|---|---|
| Comments | Analysis of all doses of LUM001 for ALT | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2235 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 32.2 | |
| Confidence Interval |
(2-Sided) 95% -21.9 to 86.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | LUM001 140ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 140ug/kg/day for AST | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2372 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 24.0 | |
| Confidence Interval |
(2-Sided) 95% -17.5 to 65.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | LUM001 280ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 280ug/kg/day for AST | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.3914 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -15.8 | |
| Confidence Interval |
(2-Sided) 95% -54.1 to 22.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | LUM001 Overall, Placebo Overall |
|---|---|---|
| Comments | Analysis of all doses of LUM001 for AST | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8081 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 4.1 | |
| Confidence Interval |
(2-Sided) 95% -31.0 to 39.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | LUM001 140ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 140ug/kg/day for ALP | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5748 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 51.7 | |
| Confidence Interval |
(2-Sided) 95% -140.3 to 243.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | LUM001 280ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 280ug/kg/day for ALP | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8835 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 11.9 | |
| Confidence Interval |
(2-Sided) 95% -158.4 to 182.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | LUM001 Overall, Placebo Overall |
|---|---|---|
| Comments | Analysis of all doses of LUM001 for ALP | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6917 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 31.8 | |
| Confidence Interval |
(2-Sided) 95% -135.8 to 199.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline to Week 13 (End of Treatment) in Pruritus as Measured by The Patient And Observer Itch Reported Outcome (ItchRO) Average Daily Scores |
|---|---|
| Description | The ItchRO was administered as a twice daily electronic diary (eDiary). Children ≥9 years of age completed the patient ItchRO; those between the ages of 5 and 8 completed the patient ItchRO with the assistance of their caregiver. There was no patient report for subjects under the age of 5. ItchRO scores range from 0 to 4, with the higher score indicating increasing itch severity. ItchRO average daily scores were calculated as the sum of daily scores (ie, the maximum of morning and evening scores) divided by the number of days. The average daily score was calculated by using the 7 days pre-treatment for baseline, and the last 7 days of treatment for Week 13. A negative change from Baseline indicates that itch severity decreased. |
| Time Frame | Baseline to 13 weeks or end of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The mITT population, defined as all participants in the Safety population who had at least 1 post-baseline efficacy assessment. The Safety population was defined as all participants who were randomly assigned to study treatment and who received any amount of study drug. |
| Arm/Group Title | LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | LUM001 Overall | Placebo Overall |
|---|---|---|---|---|
| Arm/Group Description | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received either dose of LUM001 for up to 10 or 13 weeks, then were followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. |
| Measure Participants | 6 | 8 | 14 | 6 |
| Patient ItchRO |
-1.159
(0.5396)
|
-0.608
(0.4399)
|
-0.883
(0.3484)
|
-0.811
(0.5684)
|
| Observer ItchRO |
-0.802
(0.2732)
|
-0.419
(0.2318)
|
-0.610
(0.1776)
|
-0.592
(0.2690)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | LUM001 140ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 140ug/kg/day for Patient ItchRO | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6907 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -0.348 | |
| Confidence Interval |
(2-Sided) 95% -2.468 to 1.772 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | LUM001 280ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 280ug/kg/day for Patient ItchRO | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7897 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 0.202 | |
| Confidence Interval |
(2-Sided) 95% -1.647 to 2.052 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | LUM001 Overall, Placebo Overall |
|---|---|---|
| Comments | Analysis of all doses of LUM001 for Patient ItchRO | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9203 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -0.073 | |
| Confidence Interval |
(2-Sided) 95% -1.850 to 1.705 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | LUM001 140ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 140ug/kg/day for Observer ItchRO | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.5966 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -0.210 | |
| Confidence Interval |
(2-Sided) 95% -1.038 to 0.618 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | LUM001 280ug/kg/Day, Placebo Overall |
|---|---|---|
| Comments | Analysis of LUM001 280ug/kg/day for Observer ItchRO | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6320 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | 0.173 | |
| Confidence Interval |
(2-Sided) 95% -0.580 to 0.926 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | LUM001 Overall, Placebo Overall |
|---|---|---|
| Comments | Analysis of all doses of LUM001 for Observer ItchRO | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9547 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference from placebo |
| Estimated Value | -0.019 | |
| Confidence Interval |
(2-Sided) 95% -0.710 to 0.673 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | Placebo Overall | |||
| Arm/Group Description | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 140ug/kg/day, then received 8 to 10 weeks of treatment at either 140ug/kg/day or the highest tolerated dose below 140ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received an escalating dose of LUM001 over 3 to 5 weeks, from 14ug/kg/day to 280ug/kg/day, then received 8 to 10 weeks of treatment at either 280ug/kg/day or the highest tolerated dose below 280ug/kg/day. Participants were then followed for 4 weeks after treatment. | Participants received LUM001-matching placebo for up to 13 weeks, then were followed for 4 weeks after treatment. | |||
All Cause Mortality |
||||||
| LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | Placebo Overall | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | Placebo Overall | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/8 (0%) | 0/6 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| LUM001 140ug/kg/Day | LUM001 280ug/kg/Day | Placebo Overall | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 7/8 (87.5%) | 4/6 (66.7%) | |||
| Cardiac disorders | ||||||
| Bradycardia | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| Deafness unilateral | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Ear pain | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Middle ear inflammation | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal discomfort | 0/6 (0%) | 0 | 1/8 (12.5%) | 3 | 0/6 (0%) | 0 |
| Abdominal pain | 1/6 (16.7%) | 1 | 5/8 (62.5%) | 8 | 1/6 (16.7%) | 5 |
| Abdominal pain lower | 1/6 (16.7%) | 2 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Abdominal pain upper | 1/6 (16.7%) | 4 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Diarrhoea | 4/6 (66.7%) | 5 | 5/8 (62.5%) | 9 | 2/6 (33.3%) | 3 |
| Frequent bowel movements | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Nausea | 1/6 (16.7%) | 2 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Proctalgia | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Toothache | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Vomiting | 0/6 (0%) | 0 | 2/8 (25%) | 2 | 1/6 (16.7%) | 1 |
| General disorders | ||||||
| Crying | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Feeling abnormal | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Malaise | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Pyrexia | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Infections and infestations | ||||||
| Ear infection | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Nasopharyngitis | 2/6 (33.3%) | 2 | 1/8 (12.5%) | 1 | 1/6 (16.7%) | 1 |
| Upper respiratory tract infection | 3/6 (50%) | 5 | 1/8 (12.5%) | 2 | 3/6 (50%) | 6 |
| Viral rash | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Anal injury | 0/6 (0%) | 0 | 2/8 (25%) | 3 | 0/6 (0%) | 0 |
| Contusion | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Excoriation | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Investigations | ||||||
| Body temperature increased | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Vitamin E deficiency | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Pain in extremity | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Nervous system disorders | ||||||
| Headache | 2/6 (33.3%) | 2 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Hypoaesthesia | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Somnolence | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Psychiatric disorders | ||||||
| Abnormal behaviour | 0/6 (0%) | 0 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Epistaxis | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Oropharyngeal pain | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Rhinorrhoea | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Wheezing | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Drug eruption | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
| Hyperhidrosis | 0/6 (0%) | 0 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Rash | 1/6 (16.7%) | 1 | 1/8 (12.5%) | 1 | 0/6 (0%) | 0 |
| Rash generalised | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 1/6 (16.7%) | 1 |
| Rash maculo-papular | 1/6 (16.7%) | 1 | 0/8 (0%) | 0 | 0/6 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Study Physician |
|---|---|
| Organization | Mirum |
| Phone | +1 650-667-4085 |
| medinfo@mirumpharma.com |
Responsible Party:
Mirum Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01903460
Other Study ID Numbers:
- LUM001-302
- 2012-005346-38
- SHP625-302
First Posted:
Jul 19, 2013
Last Update Posted:
Mar 28, 2019
Last Verified:
Mar 1, 2019