A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)

Immune Thrombocytopenia (ITP) Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Efficacy and Safety of S-888711 Tablets Administered Once-daily for 42 Days to Adult Subjects With Relapsed Persistent or Chronic Immune Thrombocytopenia With or Without Prior Splenectomy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01054443
• Other study ID #: 0913M0621
• Status: Terminated
• Phase: Phase 2
• Start date: March 18, 2010
• Est. completion date: November 24, 2010

Study information

• Verified date: February 2021
• Source: Shionogi Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to assess the efficacy of 3 dose levels of lusutrombopag (0.5 mg, 0.75 mg, and 1.0 mg) and placebo on platelet count.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: November 24, 2010
• Est. primary completion date: November 24, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• A signed and dated written informed consent
• Males and females = 18 years of age
• All subjects must agree to use barrier contraception
• Diagnosis of ITP
• Subjects > 60 years must have had a diagnostic bone marrow aspiration
• Relapsed persistent or chronic ITP status, with or without prior splenectomy (exception: in Hungary only splenectomized subjects will be enrolled), after having failed at least 1 prior ITP therapy (excluding TPO agonists) and have a platelet count < 30,000/µL if not taking medications or < 50,000/µL despite concomitant steroids or other ITP therapies, such as danazol or immunosuppressive drugs
• Subjects receiving steroid therapy must be on a stable dose
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT) within 20% of the upper limit of normal (ULN)
• Subjects receiving stable dosages of cyclosporine A, mycophenolate mofetil, azathioprine, or danazol are allowed. The dosages of all these medications must be stable for at least 4 weeks prior to Visit 1 (Day 1)

Exclusion Criteria:

• History of clinically important hemorrhagic clotting disorder
• Females who are pregnant, lactating, or taking oral contraceptives
• History of alcohol/drug abuse or dependence within 1 year
• Use of the following drugs or treatment prior to Visit 1 (Day 1):
• Within 12 weeks - alemtuzumab, multi-drug systemic chemotherapy, stem cell therapy;
• Within 8 weeks - rituximab
• Within 2 weeks - platelet transfusions or plasmapheresis treatment
• Within 4 weeks - use of anti-platelet or anti-coagulant drugs
• Within 1 week - Rho(D) immune globulin or intravenous immunoglobulin
• History of clinically significant cardiovascular or thromboembolic disease within 26 weeks prior to Screening
• Splenectomy within 4 weeks prior to Screening
• Clinically significant laboratory abnormalities
• Hemoglobin < 10.0 g/dL for men or women, not clearly related to ITP
• Absolute neutrophil count < 1000/mm^3
• Abnormal peripheral blood smear
• Total bilirubin > 1.5 x upper limit of normal
• Alanine aminotransferase (ALT) > 1.5 x upper limit of normal
• Aspartate aminotransferase (AST) > 1.5 x upper limit of normal
• Creatinine > 1.5 x upper limit of normal
• Human immunodeficiency virus (HIV) positive
• Hepatitis A immunoglobulin M antibody (IgM HAV) positive, hepatitis B surface antigen (HbsAg) or hepatitis C antibody (HCV) positive
• Thyroid stimulating hormone (TSH) > 1.5 x upper limit of normal
• Free thyroxine (T4) > 1.5 x upper limit of normal
• Exposure to previous thrombopoietin (TPO) mimetics/agonists (e.g., eltrombopag,romiplostim, E5501 [AKR-501] or LGD-4665) within 4 weeks prior to Screening
• Subjects unresponsive to previous TPO mimetics/agonists (e.g., eltrombopag, romiplostim, E5501 [AKR-501] or LGD-4665)
• Exposure to an investigative medication within the past 30 days

Related Conditions & MeSH terms

• Immune Thrombocytopenia (ITP)
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Placebo
Tablet
• Lusutrombopag
Tablet

Locations

Country	Name	City	State
United States	Investigator	Anaheim	California
United States	Investigator	Atlanta	Georgia
United States	Investigator	Bethesda	Maryland
United States	Investigator	Boston	Massachusetts
United States	Investigator	Boynton Beach	Florida
United States	Investigator	Cleveland	Ohio
United States	Investigator	Jacksonville	Florida
United States	Investigator	Jefferson City	Missouri
United States	Investigator	Kansas City	Missouri
United States	Investigator	Los Angeles	California
United States	Investigator	Metairie	Louisiana
United States	Investigator	New Brunswick	New Jersey
United States	Investigator	New York	New York
United States	Investigator	New York	New York
United States	Investigator	Riverdale	Georgia
United States	Investigator	Salt Lake City	Utah
United States	Investigator	San Antonio	Texas
United States	Investigator	Seattle	Washington
United States	Investigator	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Shionogi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Response	Responders were participants with one of the following: achieved a platelet count of = 50,000 cells/µL after 6 weeks of dosing; or; prematurely withdrawn due to a platelet count > 400,000 cells/µL prior to Day 42.; Participants were counted as non-responders if any of the following conditions held: The above conditions were not satisfied; They received rescue medications; They satisfied the above conditions after receiving restricted medications during the treatment period; They had achieved a platelet count of = 50,000 cells/µL before Week 6 but not after Week 6; or; They withdrew for any reason other than a platelet count > 400,000 cells/µL.	Week 6
Secondary	Change From Baseline in Platelet Count at Week 6		Baseline and Week 6
Secondary	Duration of Response	Duration of response was defined as the percentage of the cumulative time a platelet count was = 50,000 cells/µL during the treatment period.	6 weeks
Secondary	Percentage of Participants Who Achieved a Platelet Count of = 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing		Week 6
Secondary	Percentage of Participants Who Achieved a Platelet Count of = 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing		Week 6
Secondary	Number of Participants With Worst Severity of Bleeding Associated With ITP During the Treatment Period,	Bleeding assessments were performed by the Investigator according to the World Health Organization (WHO) criteria bleeding scale: Grade 0: no bleeding; Grade 1: petechial bleeding; Grade 2: mild blood loss (clinically significant); Grade 3: gross blood loss, requires transfusion (severe); Grade 4: debilitating blood loss, retinal or cerebral associated with fatality.; For each participant, the most severe WHO bleeding grade observed during the 6-week treatment period is reported.	6 weeks
Secondary	Number of Participants Who Received Rescue Medication During the Treatment Period		6 weeks
Secondary	Number of Participants With Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a subject administered a pharmaceutical product during the course of a clinical investigation, including any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product (IP), whether or not thought to be related to the IP. AEs reported after initial study drug administration were considered treatment-emergent.; A serious adverse event is defined as any AE that resulted in death, was life-threatening, hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect or an important medical event that, based upon medical judgment, may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above.; A treatment-related AE is any AE determined by the investigator to be possibly related, probably related, or definitely related to study drug.	6 weeks
Secondary	Lusutrombopag Plasma Concentration	Plasma concentrations of lusutrombopag were determined using a validated liquid chromatography mass spectrometry method. The lower limit of quantification (LOQ) for the plasma assay for lusutrombopag was 0.1 ng/mL.	Days 8, 22, and 36, after dosing
Secondary	Plasma Concentration of Metabolite S-888711 Deshexyl	Plasma concentrations of the major metabolite S-888711 deshexyl were determined using a validated liquid chromatography mass spectrometry method. The lower limit of quantification (LOQ) for the plasma assay for S-888711 deshexyl was 0.1 ng/mL.	Days 8, 22, and 36, after dosing