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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01904058
First received: July 17, 2013
Last updated: May 24, 2016
Last verified: May 2016
  Purpose
The study is a randomized, double-blind, placebo-controlled, multicenter study. It is a 13-week Phase 2 study in adults with primary biliary cirrhosis designed to compare the effect of daily dosing with UDCA in combination with LUM001 or placebo.

Condition Intervention Phase
PBC
Primary Biliary Cirrhosis
Drug: LUM001
Drug: Placebo
Drug: Ursodeoxycholic Acid
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi) in Combination With Ursodeoxycholic Acid (UDCA) in Patients With Primary Biliary Cirrhosis

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Change From Baseline in Pruritus Using Adult Itch Reported Outcome (ItchRO) Weekly Sum Score at Week 13/ Early Termination (ET) [ Time Frame: Baseline and Week 13/ET ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Pruritus Using Adult ItchRO Weekly Sum Scores at Weeks 4, 8 and 13 [ Time Frame: Baseline, Weeks 4, 8 and 13 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Pruritus Using Adult ItchRO Average Daily Scores at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET) [ Time Frame: Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Alkaline Phosphatase (ALP) at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET) [ Time Frame: Baseline, Weeks 4, 8, 13 and Last Post-baseline (Week 13/ET) ] [ Designated as safety issue: No ]
    Laboratory serum ALP enzyme levels were evaluated using blood samples collected.

  • Change From Baseline in 5-D Itch Score at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET) [ Time Frame: Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET) ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Fasting Serum Bile Acid Level at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET) [ Time Frame: Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET) ] [ Designated as safety issue: No ]
    Laboratory serum bile acid level levels were evaluated using blood samples collected.

  • 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) [ Time Frame: Baseline, Weeks 4, 8, 13 and Last Post-baseline Visit (Week 13/ET) ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: From the first dose of study drug until the 13 weeks of treatment period (or ET) + 14 days (approximately 15 weeks) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 66
Study Start Date: August 2013
Study Completion Date: April 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LUM001 and Ursodeoxycholic Acid (UDCA)
Administered orally once daily
Drug: LUM001 Drug: Ursodeoxycholic Acid
Other Name: UDCA
Placebo Comparator: Placebo and Ursodeoxycholic Acid (UDCA)
Administered orally once daily
Drug: Placebo Drug: Ursodeoxycholic Acid
Other Name: UDCA

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of Primary Biliary Cirrhosis
  2. Moderate to severe pruritus
  3. Taking ursodeoxycholic acid (UDCA) for at least 6 months, or unable to tolerate UDCA
  4. Ability to understand and willingness to sign informed consent prior to initiation of any study procedures

Exclusion Criteria:

  1. History or presence of other concomitant significant liver disease
  2. Liver transplant
  3. Known HIV infection
  4. Women who are pregnant or lactating
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01904058

  Show 24 Study Locations
Sponsors and Collaborators
Shire
  More Information

Additional Information:
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01904058     History of Changes
Other Study ID Numbers: LUM001-201  2013-000482-36 
Study First Received: July 17, 2013
Results First Received: April 1, 2016
Last Updated: May 24, 2016
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Shire:
PBC

Additional relevant MeSH terms:
Fibrosis
Liver Cirrhosis
Liver Cirrhosis, Biliary
Pathologic Processes
Liver Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents

ClinicalTrials.gov processed this record on September 28, 2016