Chronic Idiopathic Thrombocytopenic Purpura, Purpura, Thrombocytopenic, Idiopathic
Conditions
Keywords
Chronic Idiopathic Thrombocytopenic Purpura, Idiopathic Thrombocytopenic Purpura, ITP
Brief 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).
Detailed description
This is a Phase 2, multi-center, double-blind, randomized, placebo-controlled, dose-ranging, parallel-group study. The pharmacokinetic (PK) and pharmacokinetic/pharmacodynamic (PK/PD) relationship of avatrombopag will also be studied. Approximately 65 eligible participants will be randomized in a 3:3:3:3:1 ratio in a double-blinded fashion into one of five parallel treatment groups to receive daily doses of either avatrombopag 2.5, 5, 10 or 20 mg or placebo for 28 days, respectively. Each avatrombopag dosing group will consist of 15 participants while the placebo group will consist of 5 participants. All study participants will be evaluated weekly (Days 3, 5, 7, 14, 21 and 28) for safety, efficacy, and (Days 7, 14, 21, and 28) avatrombopag PK while receiving study treatment with a final assessment for safety and effectiveness to be done 2 weeks after the last study dose (Day 42). At the completion of Visit Day 28±1, participants who complete 28±1 days of study dosing will be assessed for eligibility to enroll into the rollover Study 501-CL-004 (NCT00625443) based on this visit.
Interventions
DRUGPlacebo
Placebo tablets 2.5, 5, 10 and 20 mg taken orally once daily for 28 days.
DRUGAvatrombopag tablets
Avatrombopag tablets 2.5, 5, 10 and 20 mg taken orally once daily for 28 days.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responder Rate (RR) to Avatrombopag on Day 28 | Day-4 to Day 1, Baseline, Day 28 | Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Day 28. The RR was defined as the percentage of participants with a Day 1 platelet count of less than 30,000/milliliter (mL) who reached a platelet count of greater than or equal to 50,000/mL on Day 28 of study medication, together with the percentage of participants using steroids who had a Day 1 platelet count greater than or equal to 30,000/mL but less than 50,000/mL who reached a platelet count of greater than or equal to 20,000/mL higher than their Day 1 platelet count on Day 28 of study medication. The RR was summarized by treatment group using the method of last observation carried forward (LOCF). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Platelet Count From Baseline | Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, Day 28 | Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28. The unit of measure was K/mm\^3, where K = platelets x 1000 = platelets x 10\^3 and mm\^3 = cubic milliliter= microliter. |
| Responder Rate to Avatrombopag by Visit | Day -4 to Day 1, Baseline, Day 7, Day 14, and Day 21 | Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, and 21. The RR was summarized by treatment group using the method of LOCF. Day 28 was not included with this data because it was reported as a primary outcome measure. |
| Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28 | Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28. |
| Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28 | Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28. |
| Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28 | Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28. |
Other
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Pharmacokinetics (PK) and the Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship of Avatrombopag in Patients With ITP. | Days 7, 14, 21 and 28 | Given the sparse PK sampling in this study, PK data from outside studies, which includes healthy subjects, were included to assist in PK model development. As a result this data was not reported with these study results. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2.5 mg Avatrombopag 2.5 mg tablet taken orally once daily for 28 days | 15 |
| 5.0 mg Avatrombopag 5.0 mg tablet taken orally once daily for 28 days | 15 |
| 10.0 mg Avatrombopag 10.0 mg tablet taken orally once daily for 28 days | 14 |
| 20.0 mg Avatrombopag 20.0 mg tablet taken orally once daily for 28 days | 15 |
| Placebo 3:3:3:3:1 ratio to avatrombopag tablet taken orally once daily for 28 days | 5 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Platelet increase;more than 500,000 mm^3 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 2.5 mg Avatrombopag | 5.0 mg Avatrombopag | 10.0 mg Avatrombopag | 20.0 mg Avatrombopag | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 52.9 Years STANDARD_DEVIATION 17.84 | 55.6 Years STANDARD_DEVIATION 18.03 | 57.5 Years STANDARD_DEVIATION 17.88 | 47.9 Years STANDARD_DEVIATION 16.54 | 39.6 Years STANDARD_DEVIATION 20.63 | 52.3 Years STANDARD_DEVIATION 17.81 |
| Sex: Female, Male Female | 9 Participants | 9 Participants | 8 Participants | 11 Participants | 3 Participants | 40 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 2 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 15 | 13 / 15 | 11 / 14 | 14 / 15 | 4 / 5 |
| serious Total, serious adverse events | 2 / 15 | 0 / 15 | 1 / 14 | 0 / 15 | 0 / 5 |
Outcome results
Primary
Responder Rate (RR) to Avatrombopag on Day 28
Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Day 28. The RR was defined as the percentage of participants with a Day 1 platelet count of less than 30,000/milliliter (mL) who reached a platelet count of greater than or equal to 50,000/mL on Day 28 of study medication, together with the percentage of participants using steroids who had a Day 1 platelet count greater than or equal to 30,000/mL but less than 50,000/mL who reached a platelet count of greater than or equal to 20,000/mL higher than their Day 1 platelet count on Day 28 of study medication. The RR was summarized by treatment group using the method of last observation carried forward (LOCF).
Time frame: Day-4 to Day 1, Baseline, Day 28
Population: Full analysis population, LOCF, included participants who were randomly assigned to treatment and had at least one post-baseline platelet count assessment. The randomized, full analysis, and safety populations were identical for this study. No participants were excluded from the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2.5 mg Avatrombopag | Responder Rate (RR) to Avatrombopag on Day 28 | 13.3 Percentage of participants |
| 5.0 mg Avatrombopag | Responder Rate (RR) to Avatrombopag on Day 28 | 53.3 Percentage of participants |
| 10.0 mg Avatrombopag | Responder Rate (RR) to Avatrombopag on Day 28 | 50.0 Percentage of participants |
| 20.0 mg Avatrombopag | Responder Rate (RR) to Avatrombopag on Day 28 | 80.0 Percentage of participants |
| Placebo | Responder Rate (RR) to Avatrombopag on Day 28 | 0 Percentage of participants |
Secondary
Change in Platelet Count From Baseline
Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28. The unit of measure was K/mm\^3, where K = platelets x 1000 = platelets x 10\^3 and mm\^3 = cubic milliliter= microliter.
Time frame: Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, Day 28
Population: Full Analysis population, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 2.5 mg Avatrombopag | Change in Platelet Count From Baseline | Day 7 | 13.6 platelets x 10^3/mm^3 | Standard Deviation 22.37 |
| 2.5 mg Avatrombopag | Change in Platelet Count From Baseline | Day 14 | 12.5 platelets x 10^3/mm^3 | Standard Deviation 22.64 |
| 2.5 mg Avatrombopag | Change in Platelet Count From Baseline | Day 21 | 7.5 platelets x 10^3/mm^3 | Standard Deviation 18.38 |
| 2.5 mg Avatrombopag | Change in Platelet Count From Baseline | Day 28 | 7.3 platelets x 10^3/mm^3 | Standard Deviation 23.74 |
| 5.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 7 | 46.7 platelets x 10^3/mm^3 | Standard Deviation 55.22 |
| 5.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 28 | 43.7 platelets x 10^3/mm^3 | Standard Deviation 50.35 |
| 5.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 14 | 57.5 platelets x 10^3/mm^3 | Standard Deviation 74.72 |
| 5.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 21 | 47.1 platelets x 10^3/mm^3 | Standard Deviation 54.54 |
| 10.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 28 | 81.0 platelets x 10^3/mm^3 | Standard Deviation 124.55 |
| 10.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 14 | 103.1 platelets x 10^3/mm^3 | Standard Deviation 119.55 |
| 10.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 21 | 80.6 platelets x 10^3/mm^3 | Standard Deviation 129.98 |
| 10.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 7 | 68.3 platelets x 10^3/mm^3 | Standard Deviation 81.23 |
| 20.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 7 | 168.8 platelets x 10^3/mm^3 | Standard Deviation 114.59 |
| 20.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 14 | 332.4 platelets x 10^3/mm^3 | Standard Deviation 278.96 |
| 20.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 28 | 200.2 platelets x 10^3/mm^3 | Standard Deviation 292.36 |
| 20.0 mg Avatrombopag | Change in Platelet Count From Baseline | Day 21 | 261.3 platelets x 10^3/mm^3 | Standard Deviation 278.17 |
| Placebo | Change in Platelet Count From Baseline | Day 28 | -1.8 platelets x 10^3/mm^3 | Standard Deviation 7.73 |
| Placebo | Change in Platelet Count From Baseline | Day 21 | 8.4 platelets x 10^3/mm^3 | Standard Deviation 13.72 |
| Placebo | Change in Platelet Count From Baseline | Day 14 | -1.4 platelets x 10^3/mm^3 | Standard Deviation 4.16 |
| Placebo | Change in Platelet Count From Baseline | Day 7 | 5.0 platelets x 10^3/mm^3 | Standard Deviation 9.54 |
Secondary
Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit
Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28.
Time frame: Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Population: Full analysis population, LOCF, included participants who were randomly assigned to treatment and had at least one post-baseline platelet count assessment. The randomized, full analysis, and safety populations were identical for this study. No participants were excluded from the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 7 | 33.3 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 14 | 26.7 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 21 | 6.7 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 28 | 13.3 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 7 | 60.0 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 28 | 53.3 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 14 | 60.0 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 21 | 60.0 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 28 | 57.1 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 14 | 71.4 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 21 | 64.3 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 7 | 78.6 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 7 | 93.3 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 14 | 93.3 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 28 | 86.7 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 21 | 86.7 Percentage of participants |
| Placebo | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 28 | 20.0 Percentage of participants |
| Placebo | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 21 | 20.0 Percentage of participants |
| Placebo | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 14 | 0 Percentage of participants |
| Placebo | Percentage of Participants Whose Platelet Counts Doubled From Baseline by Visit | Day 7 | 20.0 Percentage of participants |
Secondary
Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit
Platelet counts were measured from the participant's, blood which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28.
Time frame: Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Population: Full analysis population, LOCF, included participants who were randomly assigned to treatment and had at least one post-baseline platelet count assessment. The randomized, full analysis, and safety populations were identical for this study. No participants were excluded from the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 7 | 6.7 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 14 | 0 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 21 | 0 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 28 | 6.7 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 7 | 20.0 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 28 | 33.3 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 14 | 26.7 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 21 | 20.0 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 28 | 28.6 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 14 | 42.9 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 21 | 21.4 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 7 | 28.6 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 7 | 80.0 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 14 | 86.7 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 28 | 53.3 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 21 | 73.3 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 28 | 0 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 21 | 0 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 14 | 0 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 100,000/mL by Visit | Day 7 | 0 Percentage of participants |
Secondary
Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit
Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, 21, and 28.
Time frame: Day -4 to Day 1, Baseline, Day 7, Day 14, Day 21, and Day 28
Population: Full analysis population, LOCF, included participants who were randomly assigned to treatment and had at least one post-baseline platelet count assessment. The randomized, full analysis, and safety populations were identical for this study. No participants were excluded from the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 7 | 6.7 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 14 | 20.0 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 21 | 13.3 Percentage of participants |
| 2.5 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 28 | 13.3 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 7 | 66.7 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 28 | 53.3 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 14 | 60.0 Percentage of participants |
| 5.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 21 | 60.0 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 28 | 50.0 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 14 | 78.6 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 21 | 50.0 Percentage of participants |
| 10.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 7 | 64.3 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 7 | 93.3 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 14 | 93.3 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 28 | 80.0 Percentage of participants |
| 20.0 mg Avatrombopag | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 21 | 86.7 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 28 | 0 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 21 | 20.0 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 14 | 0 Percentage of participants |
| Placebo | Percentage of Participants With Platelet Counts Greater Than or Equal to 50,000/mL by Visit | Day 7 | 0 Percentage of participants |
Secondary
Responder Rate to Avatrombopag by Visit
Platelet counts were measured from the participant's blood, which was drawn at their Screening Visit B (Day -4 to Day 1, Baseline), and on study drug treatment Days 7, 14, and 21. The RR was summarized by treatment group using the method of LOCF. Day 28 was not included with this data because it was reported as a primary outcome measure.
Time frame: Day -4 to Day 1, Baseline, Day 7, Day 14, and Day 21
Population: Full analysis population, LOCF, included participants who were randomly assigned to treatment and had at least one post-baseline platelet count assessment. The randomized, full analysis, and safety populations were identical for this study. No participants were excluded from the efficacy analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2.5 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 7 | 6.7 Percentage of participants |
| 2.5 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 21 | 13.3 Percentage of participants |
| 2.5 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 14 | 20.0 Percentage of participants |
| 5.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 14 | 60.0 Percentage of participants |
| 5.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 7 | 66.7 Percentage of participants |
| 5.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 21 | 60.0 Percentage of participants |
| 10.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 14 | 78.6 Percentage of participants |
| 10.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 7 | 64.3 Percentage of participants |
| 10.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 21 | 50.0 Percentage of participants |
| 20.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 7 | 93.3 Percentage of participants |
| 20.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 21 | 86.7 Percentage of participants |
| 20.0 mg Avatrombopag | Responder Rate to Avatrombopag by Visit | Day 14 | 93.3 Percentage of participants |
| Placebo | Responder Rate to Avatrombopag by Visit | Day 14 | 0 Percentage of participants |
| Placebo | Responder Rate to Avatrombopag by Visit | Day 7 | 0 Percentage of participants |
| Placebo | Responder Rate to Avatrombopag by Visit | Day 21 | 0 Percentage of participants |
Other Pre-specified
To Evaluate the Pharmacokinetics (PK) and the Pharmacokinetic/Pharmacodynamic (PK/PD) Relationship of Avatrombopag in Patients With ITP.
Given the sparse PK sampling in this study, PK data from outside studies, which includes healthy subjects, were included to assist in PK model development. As a result this data was not reported with these study results.
Time frame: Days 7, 14, 21 and 28
Population: Given the sparse PK sampling in this study, PK data from outside studies, which includes healthy subjects, were included to assist in PK model development. As a result this data was not reported with these study results.