Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia

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ClinicalTrials.gov Identifier: NCT01703169

Recruitment Status : Completed

First Posted : October 10, 2012

Results First Posted : October 19, 2017

Last Update Posted : October 19, 2017

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Novartis

Information provided by (Responsible Party):

University of Utah

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Severe Aplastic Anemia Very Severe Aplastic Anemia Moderate Aplastic Anemia
Intervention	Drug: Eltrombopag
Enrollment	13

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Eltrombopag
Arm/Group Description	Single arm study. Dose Escalation. ...
Arm/Group Description	Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Period Title: Overall Study
Started	13
Completed	13
Not Completed	0

Baseline Characteristics

Arm/Group Title		Eltrombopag
Arm/Group Description		Single arm study. Dose Escalation. ...
Arm/Group Description		Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Overall Number of Baseline Participants		13
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	13 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	8 61.5%
	>=65 years	5 38.5%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	13 participants
	Female	5 38.5%
	Male	8 61.5%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	13 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 7.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	10 76.9%
	More than one race	0 0.0%
	Unknown or Not Reported	2 15.4%
Region of Enrollment Measure Type: Number Unit of measure: Count of Participants
United States	Number Analyzed	13 participants
United States		13

Outcome Measures

1.Primary Outcome


Title	Proportion of Participants With Platelet Response
Description	Defined as a stable platelet count of 50,000/μl or more during an...
Description	Defined as a stable platelet count of 50,000/μl or more during any 4 week period within the possible 12 weeks while on study,and including maximal platelet counts achieved in patients with moderate to very severe aplastic anemia.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Eltrombopag
Arm/Group Description:	Single arm study. Dose Escalation. ...
Arm/Group Description:	Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Overall Number of Participants Analyzed	13
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: proportion of participants
	0.23 (0.05 to 0.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Eltrombopag
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]

Other Statistical Analysis		The proportion of platelet response in a previous study (PMID:22762314) was 0.36 (9/25). The null hypothesis of no difference between the platelet response rate in this study and that of the previous study was tested using a two-sided exact test of binomial proportions. A p-value of 0.40 was obtained. The threshold for significance was 0.05.

2.Secondary Outcome


Title	Platelet Count Twice Baseline.
Description	Proportion of subjects who achieve platelet counts at least twice thei...
Description	Proportion of subjects who achieve platelet counts at least twice their baseline value at any point while on study medication, in patients with moderate to very severe aplastic anemia.
Time Frame	Between weeks 1-12.

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome variable.


Arm/Group Title	Eltrombopag
Arm/Group Description:	Single arm study. Dose Escalation. ...
Arm/Group Description:	Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

3.Secondary Outcome


Title	Hematology Labs
Description	Association between eltrombopag use and response in hemoglobin, hemato...
Description	Association between eltrombopag use and response in hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil count to be evaluate by maximal hemoglobin, hematocrit, total white blood cell count, and absolute neutrophil counts achieved in patients with moderate to very severe aplastic anemia
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome variable.


Arm/Group Title	Eltrombopag
Arm/Group Description:	Single arm study. Dose Escalation. ...
Arm/Group Description:	Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

4.Secondary Outcome


Title	Number of Patients With AE to Measure Toxicity, Using NCI CTCAE
Description	Evaluated weekly, up to 12 weeks. Association between eltrombopag use,...
Description	Evaluated weekly, up to 12 weeks. Association between eltrombopag use, dose, and tolerability in patients with moderate to very severe aplastic anemia
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome variable.


Arm/Group Title	Eltrombopag
Arm/Group Description:	Single arm study. Dose Escalation. ...
Arm/Group Description:	Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

5.Secondary Outcome


Title	Characterization of the PK Profile of Eltrombopag in Patients With Moderate to Very Severe Aplastic Anemia. Evaluated With AUC, Cmax, Cmin, Tmax.
Description	Samples will for PK analysis will collected as a trough level weeks 2,...
Description	Samples will for PK analysis will collected as a trough level weeks 2, 6 and 12, prior to dose of eltrombopag. Additional PK level drawn at 2, 4 and 6 hours post-dose at the scheduled week 2 visit.
Time Frame	Weeks 2, 6 and 12

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome variable.


Arm/Group Title	Eltrombopag
Arm/Group Description:	Single arm study. Dose Escalation. ...
Arm/Group Description:	Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	Approximately 3 years.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Eltrombopag
Arm/Group Description	Single arm study. Dose Escalation. ...
Arm/Group Description	Single arm study. Dose Escalation. Eltrombopag: Oral eltrombopag 150mg/day by mouth starting on Day 1 with dose modification over 12 weeks to a maximum of 300mg/day determined by platelet count
All-Cause Mortality
	Eltrombopag
	Affected / at Risk (%)
Total	2/13 (15.38%)
Serious Adverse Events Serious Adverse Events
	Eltrombopag
	Affected / at Risk (%)	# Events
Total	3/13 (23.08%)
Cardiac disorders
congestive heart failure ^†	1/13 (7.69%)	1
Hepatobiliary disorders
cholecystitis ^†	1/13 (7.69%)	1
Nervous system disorders
syncope ^†	1/13 (7.69%)	1
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Eltrombopag
	Affected / at Risk (%)	# Events
Total	13/13 (100.00%)
Blood and lymphatic system disorders
anemia ^†	3/13 (23.08%)	13
petechiae ^†	11/13 (84.62%)	18
transfusion reaction ^†	1/13 (7.69%)	1
Cardiac disorders
arrhythmia ^†	1/13 (7.69%)	1
chest pain ^†	1/13 (7.69%)	2
Eye disorders
opacity ^†	1/13 (7.69%)	1
scleral icterus ^†	2/13 (15.38%)	2
Gastrointestinal disorders
abdominal pain ^†	1/13 (7.69%)	2
constipation ^†	1/13 (7.69%)	1
diarrhea ^†	2/13 (15.38%)	4
dry mouth ^†	1/13 (7.69%)	1
nausea ^†	2/13 (15.38%)	3
rectal hemorrhage ^†	1/13 (7.69%)	2
General disorders
aches/pains ^†	2/13 (15.38%)	2
chills ^†	1/13 (7.69%)	1
edema ^†	4/13 (30.77%)	10
fatigue ^†	7/13 (53.85%)	8
night sweats ^†	1/13 (7.69%)	1
pain ^†	5/13 (38.46%)	7
port leak ^†	1/13 (7.69%)	1
Hepatobiliary disorders
spelnomegaly ^†	1/13 (7.69%)	1
Infections and infestations
gum hypertrophy ^†	1/13 (7.69%)	1
gum lesions ^†	1/13 (7.69%)	1
otitis externa ^†	1/13 (7.69%)	1
urinary tract infection ^†	2/13 (15.38%)	3
Injury, poisoning and procedural complications
bruising ^†	3/13 (23.08%)	5
Investigations
decreased lymphocyte count ^†	3/13 (23.08%)	22
decreased neutrophil count ^†	3/13 (23.08%)	17
thrombocytopenia ^†	6/13 (46.15%)	24
Alkaline phosphatase increased ^†	1/13 (7.69%)	1
elevated ALT ^†	3/13 (23.08%)	10
elevated AST ^†	3/13 (23.08%)	5
elevated bilirubin ^†	4/13 (30.77%)	7
elevated creatinine ^†	3/13 (23.08%)	8
hypoalbunemia ^†	1/13 (7.69%)	1
weight gain ^†	4/13 (30.77%)	4
Metabolism and nutrition disorders
dehydration ^†	1/13 (7.69%)	1
hyperglycemia ^†	1/13 (7.69%)	2
hypocalcemia ^†	2/13 (15.38%)	5
hyponatremia ^†	2/13 (15.38%)	5
Musculoskeletal and connective tissue disorders
back pain ^†	2/13 (15.38%)	3
cramps ^†	2/13 (15.38%)	2
Nervous system disorders
dizziness ^†	1/13 (7.69%)	1
dysgeusia ^†	2/13 (15.38%)	3
headache ^†	1/13 (7.69%)	1
sciatica ^†	1/13 (7.69%)	1
tremor ^†	1/13 (7.69%)	1
Psychiatric disorders
anxiety ^†	1/13 (7.69%)	1
confusion ^†	1/13 (7.69%)	1
insomnia ^†	2/13 (15.38%)	2
Renal and urinary disorders
dysuria ^†	1/13 (7.69%)	1
pyelonephritis ^†	1/13 (7.69%)	1
renal insufficiency ^†	2/13 (15.38%)	2
Reproductive system and breast disorders
menorrhagia ^†	2/13 (15.38%)	3
Respiratory, thoracic and mediastinal disorders
epistaxis ^†	2/13 (15.38%)	2
hypoxia ^†	2/13 (15.38%)	2
nasal congestion ^†	2/13 (15.38%)	2
respiratory infection ^†	1/13 (7.69%)	1
shortness of breath ^†	1/13 (7.69%)	1
Skin and subcutaneous tissue disorders
purpura ^†	5/13 (38.46%)	8
bronzing of the skin ^†	2/13 (15.38%)	3
dry skin ^†	1/13 (7.69%)	3
ecchymosis ^†	2/13 (15.38%)	2
erythema ^†	1/13 (7.69%)	1
facial hair growth ^†	1/13 (7.69%)	1
jaundice ^†	2/13 (15.38%)	2
mouth sores ^†	2/13 (15.38%)	2
pallor ^†	3/13 (23.08%)	3
rash ^†	3/13 (23.08%)	4
thrush ^†	1/13 (7.69%)	1
Vascular disorders
hematoma ^†	1/13 (7.69%)	1
hot flashes ^†	1/13 (7.69%)	1
hypertension ^†	2/13 (15.38%)	2
† Indicates events were collected by systematic assessment

Limitations and Caveats

Certain data regarding the primary outcome and adverse events were inadvertently not captured during the clinical investigation resulting in insufficient data for statistical analysis and publication.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Kimberlee Taylor
Organization:	Huntsman Cancer Institute
Phone:	8012135673
EMail:	Kimberlee.Taylor@hci.utah.edu

Layout table for additonal information

Responsible Party:	University of Utah
ClinicalTrials.gov Identifier:	NCT01703169
Other Study ID Numbers:	HCI54443 ELT115895 ( Other Identifier: Novartis )
First Submitted:	September 27, 2012
First Posted:	October 10, 2012
Results First Submitted:	June 16, 2017
Results First Posted:	October 19, 2017
Last Update Posted:	October 19, 2017

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