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Efficacy and Safety of Oral E5501 Plus Standard of Care for the Treatment of Thrombocytopenia in Adults With Chronic Immune Thrombocytopenia (Amendment 02)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01438840
Recruitment Status : Completed
First Posted : September 22, 2011
Results First Posted : January 5, 2018
Last Update Posted : February 5, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Chronic Thrombocytopenia
Immune Thrombocytopenia
Interventions Drug: Avatrombopag
Drug: Placebo
Drug: Standard of care
Enrollment 49
Recruitment Details  
Pre-assignment Details A total of 100 participants were screened in study. Of these 100 participants, 51 were screen failures and 49 were randomized into the study.
Arm/Group Title Placebo (Core Study) Avatrombopag (Core Study) Avatrombopag (Extension Phase)
Hide Arm/Group Description Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. Participants who met all the eligibility criteria requirements of extension phase and who discontinued the core study because of lack of treatment effect continued into the extension phase. Avatrombopag was administered to participants who entered extension phase, with a starting dose of 20 mg avatrombopag, once daily for 76 weeks and underwent dose titration.
Period Title: Core Study
Started 17 32 0
Completed 1 22 0
Not Completed 16 10 0
Reason Not Completed
Adverse Event             0             3             0
Lack of Efficacy             15             7             0
Withdrawal of consent             1             0             0
Period Title: Extension Phase
Started 0 0 39 [1]
Completed 0 0 29
Not Completed 0 0 10
Reason Not Completed
Adverse Event             0             0             3
Lost to Follow-up             0             0             1
Withdrawal by Subject             0             0             3
Lack of Efficacy             0             0             2
Not specified             0             0             1
[1]
39 participants met eligibility criteria for the Extension Phase.
Arm/Group Title Placebo (Core Study) Avatrombopag (Core Study) Total
Hide Arm/Group Description Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. Total of all reporting groups
Overall Number of Baseline Participants 17 32 49
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Geometric Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 32 participants 49 participants
41.2  (14.7) 46.4  (14.2) 44.6  (14.44)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 32 participants 49 participants
Female
8
  47.1%
23
  71.9%
31
  63.3%
Male
9
  52.9%
9
  28.1%
18
  36.7%
1.Primary Outcome
Title Number of Weeks With Platelet Count Greater Than or Equal to 50 x 10^9/L During 6-Month Treatment Period
Hide Description The cumulative number of weeks of platelet response is defined as the total numbers of weeks in which the platelet count is greater than or equal to 50 x 10^ 9/L during 6 months of treatment of core study in the absence of rescue therapy.
Time Frame Week 1 to Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (Core Study): All participants who were randomized into the study.
Arm/Group Title Placebo (Core Study) Avatrombopag (Core Study)
Hide Arm/Group Description:
Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind.
Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug.
Overall Number of Participants Analyzed 17 32
Median (Full Range)
Unit of Measure: Weeks
0
(0 to 2)
12.4
(0 to 25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Core Study), Avatrombopag (Core Study)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With a Reduction in Use of Concomitant Immune/Idiopathic Thrombocytopenic Purpura (ITP) Medication
Hide Description Only participants on concomitant ITP medications at baseline were included.
Time Frame Week 1 through Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (Core Study): All participants who were randomized into the study.
Arm/Group Title Placebo (Core Study) Avatrombopag (Core Study)
Hide Arm/Group Description:
Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind.
Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug.
Overall Number of Participants Analyzed 7 15
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
0
   0.0%
5
  33.3%
No
7
 100.0%
10
  66.7%
3.Secondary Outcome
Title Number of Participants With Platelet Count Greater Than or Equal to 50 x 10^9/L at Day 8
Hide Description Participants with platelet response at Day 8 are defined as those who had a platelet count greater than or equal to 50 x 10^9/L at day 8 in the absence of rescue therapy on or before Day 8.
Time Frame Week 1 (Day 8)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (Core Study): All participants who were randomized into the study.
Arm/Group Title Placebo (Core Study) Avatrombopag (Core Study)
Hide Arm/Group Description:
Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind.
Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug.
Overall Number of Participants Analyzed 17 32
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
0
   0.0%
21
  65.6%
No
17
 100.0%
11
  34.4%
Time Frame Core Study: up to 39 Weeks (including Screening, Titration, Treatment, Dose Taper, and Follow-up for those who did not enter the Extension Phase). Extension Phase: up to 104 weeks (including Conversion, Maintenance Period, Dose Taper, and Follow-up).
Adverse Event Reporting Description Treatment emergent adverse events were collected. Core Study Safety Analysis Set (SAS): All participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment. Extension Phase SAS: All participants who received at least 1 dose of avatrombopag (either Core or Extension Phase) and had a postdose safety assessment.
 
Arm/Group Title Placebo (Core Study) Avatrombopag (Core Study) Avatrombopag (Extension Phase)
Hide Arm/Group Description Placebo was administered as 5 mg, 10 mg, 20 mg, 30 mg or 40 mg in a flexible dose design for 26 weeks. Placebo was administered orally at a starting dose of 20 mg, once daily. Afterwards the dose could be titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on the participant's response to the study drug; placebo titration was used to maintain the blind. Avatrombopag was administered orally as 5 mg, 10 mg, 20 mg, 30 mg, or 40 mg in a flexible dose design for 26 weeks. Participants received blinded therapy at a starting dose of 20 mg avatrombopag, one daily and they were allowed to have their dose titrated up (maximum dose of 40 mg avatrombopag) or down (minimum dose of 5 mg avatrombopag) depending on their response to study drug. Participants who met all eligibility criteria requirements of extension phase and who discontinued the core study because of lack of treatment effect continued into the extension phase. Avatrombopag was administered to participants who entered extension phase, with a starting dose of 20 mg avatrombopag, once daily for 76 weeks and underwent dose titration.
All-Cause Mortality
Placebo (Core Study) Avatrombopag (Core Study) Avatrombopag (Extension Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo (Core Study) Avatrombopag (Core Study) Avatrombopag (Extension Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/17 (5.88%)   9/32 (28.13%)   15/47 (31.91%) 
Blood and lymphatic system disorders       
Idiopathic thrombocytopenic purpura  1  1/17 (5.88%)  0/32 (0.00%)  0/47 (0.00%) 
Thrombocytopenia  2  0/17 (0.00%)  1/32 (3.13%)  3/47 (6.38%) 
Gastrointestinal disorders       
Food poisoning  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Mouth haemorrhage  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Nausea  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Vomiting  2  0/17 (0.00%)  2/32 (6.25%)  2/47 (4.26%) 
Erosive duodenitis  1  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Gastritis haemorrhagic  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Gingival bleeding  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
General disorders       
Polyserositis  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Infections and infestations       
Urinary tract infection  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Investigations       
Platelet count decreased  2  0/17 (0.00%)  1/32 (3.13%)  2/47 (4.26%) 
Alanine aminotransferase increased  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Aspartate aminotransferase increased  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Gamma-glutamyltransferase increased  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc disorder  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Chronic myelomonocytic leukaemia  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Nervous system disorders       
Cerebrovascular accident  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Headache  2  0/17 (0.00%)  2/32 (6.25%)  2/47 (4.26%) 
Dizziness  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Reproductive system and breast disorders       
Uterine haemorrhage  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Respiratory, thoracic and mediastinal disorders       
Epistaxis  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Skin and subcutaneous tissue disorders       
Petechiae  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Vascular disorders       
Deep vein thrombosis  2  0/17 (0.00%)  1/32 (3.13%)  1/47 (2.13%) 
Jugular vein thrombosis  2  0/17 (0.00%)  0/32 (0.00%)  1/47 (2.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA VERSION 16.1
2
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (Core Study) Avatrombopag (Core Study) Avatrombopag (Extension Phase)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/17 (58.82%)   31/32 (96.88%)   45/47 (95.74%) 
Blood and lymphatic system disorders       
Anaemia  1  0/17 (0.00%)  2/32 (6.25%)  2/47 (4.26%) 
Idiopathic thrombocytopenic purpura  2  1/17 (5.88%)  0/32 (0.00%)  0/47 (0.00%) 
Iron deficiency anaemia  2  1/17 (5.88%)  0/32 (0.00%)  0/47 (0.00%) 
Thrombocytopenia  2  0/17 (0.00%)  2/32 (6.25%)  9/47 (19.15%) 
Gastrointestinal disorders       
Dyspepsia  2  1/17 (5.88%)  1/32 (3.13%)  1/47 (2.13%) 
Gingival bleeding  2  0/17 (0.00%)  4/32 (12.50%)  8/47 (17.02%) 
Mouth Haemorrhage  2  0/17 (0.00%)  3/32 (9.38%)  4/47 (8.51%) 
Nausea  2  0/17 (0.00%)  3/32 (9.38%)  3/47 (6.38%) 
Vomiting  2  0/17 (0.00%)  2/32 (6.25%)  2/47 (4.26%) 
General disorders       
Fatigue  2  1/17 (5.88%)  4/32 (12.50%)  7/47 (14.89%) 
Infections and infestations       
Influenza  2  0/17 (0.00%)  2/32 (6.25%)  4/47 (8.51%) 
Nasopharyngitis  2  0/17 (0.00%)  3/32 (9.38%)  5/47 (10.64%) 
Pharyngitis  2  1/17 (5.88%)  0/32 (0.00%)  6/47 (12.77%) 
Upper respiratory tract infection  2  1/17 (5.88%)  6/32 (18.75%)  11/47 (23.40%) 
Urinary tract infection  2  0/17 (0.00%)  1/32 (3.13%)  3/47 (6.38%) 
Injury, poisoning and procedural complications       
Contusion  2  4/17 (23.53%)  10/32 (31.25%)  19/47 (40.43%) 
Joint injury  2  1/17 (5.88%)  0/32 (0.00%)  0/47 (0.00%) 
Investigations       
Blood gastrin increased  2  0/17 (0.00%)  2/32 (6.25%)  2/47 (4.26%) 
Blood urine present  2  1/17 (5.88%)  0/32 (0.00%)  0/47 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/17 (0.00%)  4/32 (12.50%)  5/47 (10.64%) 
Back pain  2  0/17 (0.00%)  3/32 (9.38%)  4/47 (8.51%) 
Pain in extremity  2  1/17 (5.88%)  1/32 (3.13%)  3/47 (6.38%) 
Nervous system disorders       
Dizziness  2  1/17 (5.88%)  0/32 (0.00%)  2/47 (4.26%) 
Headache  2  2/17 (11.76%)  12/32 (37.50%)  14/47 (29.79%) 
Somnolence  2  1/17 (5.88%)  0/32 (0.00%)  0/47 (0.00%) 
Psychiatric disorders       
Insomnia  2  1/17 (5.88%)  3/32 (9.38%)  3/47 (6.38%) 
Respiratory, thoracic and mediastinal disorders       
Cough  2  0/17 (0.00%)  2/32 (6.25%)  3/47 (6.38%) 
Epistaxis  2  3/17 (17.65%)  4/32 (12.50%)  8/47 (17.02%) 
Skin and subcutaneous tissue disorders       
Petechiae  2  1/17 (5.88%)  4/32 (12.50%)  7/47 (14.89%) 
Vascular disorders       
Hypertension  2  1/17 (5.88%)  2/32 (6.25%)  5/47 (10.64%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA VERSION 16.1
2
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Inc.
Organization: Eisai Call Center
Phone: 888-422-4743
Layout table for additonal information
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01438840     History of Changes
Other Study ID Numbers: E5501-G000-302
First Submitted: September 19, 2011
First Posted: September 22, 2011
Results First Submitted: December 5, 2017
Results First Posted: January 5, 2018
Last Update Posted: February 5, 2018