Immune Thrombocytopenia (ITP)Phase 2NCT01054443
A Study to Investigate the Efficacy and Safety of Lusutrombopag (S-888711) Tablets Administered to Adults With Immune Thrombocytopenia (ITP)
A Phase 2 study testing Lusutrombopag in people with Immune Thrombocytopenia (ITP), run by Shionogi at 19 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Thrombocytopenia (ITP)
- What is being tested?
- Lusutrombopag
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 19 sitesUnited States
- Study dates
- 18 Mar 2010to 24 Nov 2010
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
Investigator
Anaheim, California, 92801
Investigator
Atlanta, Georgia, 30341
Investigator
Bethesda, Maryland, 20817
Investigator
Boston, Massachusetts, 02114
Investigator
Boynton Beach, Florida, 33426
Investigator
Cleveland, Ohio, 44106
Investigator
Jacksonville, Florida, 32207
Investigator
Jefferson City, Missouri, 65109
Investigator
Kansas City, Missouri, 64131
Investigator
Los Angeles, California, 90272
Investigator
Metairie, Louisiana, 70006
Investigator
New Brunswick, New Jersey, 08903
Investigator
New York, New York, 10021
Investigator
New York, New York, 10029
Investigator
Riverdale, Georgia, 30274
Investigator
Salt Lake City, Utah, 84132
Investigator
San Antonio, Texas, 78229
Investigator
Seattle, Washington, 98109
Investigator
Washington D.C., District of Columbia, 20007
About this study
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
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.
- Conditions
- Immune Thrombocytopenia (ITP)
- Being tested
- Placebo, Lusutrombopag
- Keywords
- Blood Platelet Disorders, Immune Thrombocytopenia (ITP), Low Platelet Count, Thrombocytopaenia, S-888711, Splenectomy, Thrombopoiesis, Hematologic Disease, Auto-immune thrombocytopenic Purpura, Relapsed Persistent or Chronic ITP, Idiopathic Thrombocytopenic Purpura, Thrombotic Thrombocytopenic Purpura (TTP)
- Medical subject headings
- Purpura, Thrombocytopenic, Idiopathic, Blood Platelet Disorders, Thrombocytopenia, Hematologic Diseases, Purpura, Thrombotic Thrombocytopenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Tablet
LusutrombopagDrug
Also called MULPLETA®, S-888711
Tablet
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Participants received placebo tablets orally once a day for 42 days. Receives: Drug: Placebo |
| Lusutrombopag 0.5 mg | Experimental | Participants received 0.5 mg lusutrombopag orally once a day for 42 days. Receives: Drug: Lusutrombopag |
| Lusutrombopag 0.75 mg | Experimental | Participants received 0.75 mg lusutrombopag orally once a day for 42 days. Receives: Drug: Lusutrombopag |
| Lusutrombopag 1.0 mg | Experimental | Participants received 1.0 mg lusutrombopag orally once a day for 42 days. Receives: Drug: Lusutrombopag |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 6
Secondary outcomes (9)
Change From Baseline in Platelet Count at Week 6
Measured: Baseline and Week 6
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.
Measured: 6 weeks
Percentage of Participants Who Achieved a Platelet Count of ≥ 30,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Measured: Week 6
Percentage of Participants Who Achieved a Platelet Count of ≥ 50,000 Cells/µL and Doubled the Baseline Platelet Count After 6 Weeks of Dosing
Measured: Week 6
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.
Measured: 6 weeks
Number of Participants Who Received Rescue Medication During the Treatment Period
Measured: 6 weeks
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.
Measured: 6 weeks
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.
Measured: Days 8, 22, and 36, after dosing
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.
Measured: Days 8, 22, and 36, after dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2010 (estimated)
- Study start18 Mar 2010
- Primary completion24 Nov 2010
- Study completion24 Nov 2010
Why it stopped: This study was terminated before the planned sample size was enrolled because results indicated that a higher dose was necessary to elicit an efficacy effect.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Immune Thrombocytopenia (ITP)Studies of the same condition, open and under way.
- More trials run by ShionogiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shionogi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shionogi Clinical Trials Administrator Clinical Support Help Line, Study director, Shionogi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01054443
- Sponsor's protocol ID
- 0913M0621
- Status last verified
- Feb 2021
- First submitted
- 20 Jan 2010
- Last updated
- 18 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No