Study of AKR-501 Tablets Taken Orally Once Daily for 28 Days in Patients With Chronic Idiopathic Thrombocytopenic Purpura (ITP)
Condition: Chronic Idiopathic Thrombocytopenic Purpura; Purpura, Thrombocytopenic, Idiopathic
MeSH terms: Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic
Intervention: Placebo; Avatrombopag tablets
Intervention description: Placebo tablets 2.5, 5, 10 and 20 mg taken orally once daily for 28 days.; Avatrombopag tablets 2.5, 5, 10 and 20 mg taken orally once daily for 28 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic Idiopathic Thrombocytopenic Purpura; Idiopathic Thrombocytopenic Purpura; ITP

Summary:

      The purpose of this study is to determine the efficacy, safety and tolerability, of AKR-501
      (avatrombopag) tablets, as compared to placebo, in the treatment of participants with chronic
      Idiopathic Thrombocytopenic Purpura (ITP).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men and women ≥ 18 years of age.

          2. Confirmed diagnosis of ITP according to American Society of Hematology (ASH)
             Guidelines ≥ 3 months prior to Day 1.

          3. If ≥ 60 years old, must have had either a bone marrow biopsy consistent with ITP
             within past 3 years or a good response (platelet count > 100,000/mm^3) to a previous
             ITP treatment.

          4. Are refractory or relapsed after at least one prior ITP therapy (patients who are
             refractory and failed to achieve a platelet count ≥ 50,000/mm^3 despite steroids or ≥
             30,000/mm^3 to other prior ITP therapies, such as splenectomy, danazol, or
             immunosuppressive drugs. For patients who are relapsed, the platelet counts must be
             below 50,000/mm^3 if using steroids or 30,000/mm^3 if not prescribed steroids.)

          5. Patients receiving maintenance corticosteroids may be enrolled, as long as the
             corticosteroids have been administered at a stable dose (same milligram amount ± 10%)
             for ≥ 2 weeks prior to Screening Visit A and the investigator does not foresee the
             need to change the steroid dose during study participation. Patients should remain on
             this stable corticosteroid dose during study participation.

          6. Patients receiving stable dosages of cyclosporine A, mycophenolate mofetil,
             azathioprine or danazol may also be enrolled. The dosages of all these medications
             must be stable for at least 3 months prior to AKR-501 administration.

          7. Platelet count:

               -  Patients not receiving steroids (no steroid treatment for > 2 weeks prior to the
                  Screening Visit A): platelets < 30,000/mm^3 at Screening Visit A and within 96
                  hours prior to Day 1 (Screening Visit B)

               -  Patients receiving steroids: platelets < 50,000/mm^3 at Screening Visit A and
                  within 96 hours prior to Day 1 (Screening Visit B).

          8. Women of child-bearing potential must have a negative pregnancy test at Screening
             Visit A and Screening Visit B. (Childbearing potential is defined as any woman who has
             not been surgically sterilized and is premenopausal or peri-menopausal i.e., any
             menstrual flow within 12 months of Screening Visit A).

          9. Women of child-bearing potential and all men must agree to practice a medically
             approved form of contraception (one of the following must be used: condoms (male or
             female) with a spermicidal agent, diaphragm, or cervical cap with a spermicidal agent,
             IUD, hormonal contraception, abstinence).

         10. Willing and able to provide written informed consent before any study-related
             procedure.

        Exclusion Criteria:

          1. Women who are pregnant and/or lactating.

          2. Splenectomy procedure performed 4 weeks prior to AKR-501 administration.

          3. Use of the following drugs or treatments prior to Day 1:

               -  Within 3 months - Rituximab;

               -  Within 2 weeks - Aspirin or Aspirin-containing compounds, Salicylates,
                  Anticoagulants, clopidogrel, ticlopidine, Rh0(D) Immune Globulin (WinRho®), or
                  intravenous immunoglobulin (IVIG).

          4. Participation in a clinical trial involving any investigational agent within 4 weeks
             of Day 1.

          5. Exposure to eltrombopag or AMG -531.

          6. Significant medical conditions or diseases as determined by the Investigator (e.g.,
             clinically active systemic lupus erythematosus; known or suspected HIV infection;
             acute hepatitis or clinically active chronic hepatitis; lymphoproliferative disease;
             congestive heart failure).

          7. History of cardiovascular disease (e.g., angina, unstable angina, myocardial
             infraction, coronary artery stent placement, angioplasty, coronary artery bypass
             grafting).

          8. History of thromboembolic disease (e.g., transient ischemic attack [TIA], stroke
             [CVA], pulmonary embolism [PE]).

          9. History of deep venous thrombosis (DVT).

         10. History of lupus anticoagulant or anticardiolipin antibody syndrome or positive anti
             b2 glycoprotein antibody.

         11. History of any medical condition where systemic anticoagulation was required for more
             than 6 months.

         12. Laboratory abnormalities:

               -  Hemoglobin < 12.5 g/dL for men and < 11.5 g/dL for women. If anemia is clearly
                  related to ITP, for example excessive blood loss, then that patient may be
                  enrolled without the need for a waiver after discussion with the Sponsor's
                  medical monitor

               -  White blood cell count (WBC) < lower limit of normal

               -  Absolute neutrophil count (ANC) < 1000/mm^3

               -  Prothrombin time (PT) > 1.25 x upper limit of normal

               -  Partial thromboplastin time (PTT) > 1.25 x upper limit of normal

               -  Total bilirubin > 3 x upper normal limit

               -  Alanine transaminase (ALT) > 3 x upper normal limit

               -  Aspartate transaminase (AST) > 3 x upper normal limit

               -  Creatinine > 1.5x upper normal limit

               -  Blood urea nitrogen (BUN) > 1.5 x upper normal limit

               -  HIV positive

               -  IgM HAV positive, Hepatitis B surface antigen (HBsAg) or hepatitis C antibody
                  (HCV) positive.

         13. History of, or current alcohol or drug abuse likely to interfere with ability to
             comply with protocol.

             requirements or give informed consent, as determined by the Investigator.

         14. History of, or current psychiatric illness likely to interfere with ability to comply
             with protocol requirements or give informed consent, as determined by the
             Investigator.

         15. Currently taking any of the following medications: Rituximab, Aspirin or
             Aspirin-containing compounds, Salicylates, Anticoagulants, clopidogrel, ticlopidine,
             Rh0(D) Immune Globulin (WinRho®), or intravenous immunoglobulin (IVIG).