A Rollover Study to Provide Continued Treatment With Eltrombopag

NCT ID: NCT01957176

Last Updated: 2022-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-15
• Study Completion Date: 2022-02-23

Brief Summary

The objective of this study was to provide continued treatment with eltrombopag for subjects who were participating in a Novartis-sponsored investigational study with eltrombopag (parent studies 114968/ASPIRE (NCT01440374), PMA112509 (NCT00903422), and TRA105325/EXTEND (NCT00351468), receiving clinical benefit without unacceptable toxicity and to collect long-term safety data.

Detailed Description

This Phase IV, multicenter, non-randomized, open-label, uncontrolled, rollover study was designed to provide continued access to eltrombopag to eligible subjects. As this study was a rollover study, the subjects were enrolled into this study from the parent studies.

There were 3 cohorts in this study:

Cohort A: Adult subjects who have completed study treatment with eltrombopag during their participation in a parent study for MDS/AML (i.e., 114968/ASPIRE and PMA112509).

Cohort B: Adult subjects who have completed study treatment with eltrombopag during their participation in a parent study for ITP (i.e., TRA105325/EXTEND).

Cohort C: Pediatric subjects who have completed study treatment with eltrombopag during their participation in a parent study for ITP. Once a subject turned 18 years of age, they might remain in the study and follow the Cohort B procedures. No pediatric subjects were enrolled in this cohort/study.

The study consisted of a transition visit, study treatment visits, and a follow-up visit. Subjects in Cohort A and Cohort B completed the Transition visit assessments and then returned for their next schedule visit as per the Visit schedule. In the study treatment visit, subjects received a starting dose of eltrombopag at the same dose and administration that they were receiving at the time of their last study treatment visit in the parent study.

Safety was evaluated through physical examinations, clinical laboratory tests, and monitoring of adverse events. Additional safety assessments were done as per standard of care and/or when medically indicated.

Assessment of clinical benefit was performed throughout the study using local standard of care as determined by the Investigator to determine continued study participation and treatment with eltrombopag. Only subjects considered by the Investigator to be receiving clinical benefit without unacceptable toxicity may continue on study treatment. Once treatment with eltrombopag was permanently discontinued, the subject would attend the follow-up visit.

Conditions

Thrombocytopaenia

Keywords

myelodysplastic syndromes; thrombocytopenia; acute myeloid leukemia; idiopathic thrombocytopenic purpura; Eltrombopag; pediatrics

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A (Myelodysplastic syndrome (MDS)/ Acute myeloid leukemia (AML) adult subjects)

All subjects in this cohort received eltrombopag (ELT) at the dose that they were receiving at the time of the transition visit, except in the case where the subject required a dose modification. The range of doses of ELT that were used in this cohort were from 50 to 300 mg once daily (OD) for subjects of non-East Asian heritage. The dose ranges for subjects of East Asian heritage (i.e., Japanese, Chinese, Taiwanese, Thai and Korean) were 25 to 150 mg. Dose adjustments (if required) were done depending on each subject's platelet counts.

Group Type: EXPERIMENTAL

Eltrombopag (ELT)

Intervention Type: DRUG

Subjects were dosed with ELT tablets or powder for oral suspension (PfOS) based on the dosage form used in the parent study. ELT tablets were white, round film coated tablets containing ELT olamine equivalent to 12.5 mg, 25 mg, 50 mg, 75 mg and 100 mg of ELT. ELT PfOS was a reddish-brown to yellow powder contained inside an elongated sachet. Each sachet contained ELT olamine equivalent to 20 mg of ELT per gram of powder.

Cohort B (Idiopathic thrombocytopenic purpura (ITP) adult subjects)

All subjects in this cohort received ELT at the dose that they were receiving at the time of the transition visit, except in the case where the subject required a dose modification. The range of doses of ELT that were used in this cohort were from 12.5 to 75 mg. Dose adjustments (if required) were done depending on each subject's platelet counts.

Group Type: EXPERIMENTAL

Eltrombopag (ELT)

Intervention Type: DRUG

Subjects were dosed with ELT tablets or powder for oral suspension (PfOS) based on the dosage form used in the parent study. ELT tablets were white, round film coated tablets containing ELT olamine equivalent to 12.5 mg, 25 mg, 50 mg, 75 mg and 100 mg of ELT. ELT PfOS was a reddish-brown to yellow powder contained inside an elongated sachet. Each sachet contained ELT olamine equivalent to 20 mg of ELT per gram of powder.

Cohort C (Idiopathic thrombocytopenic purpura (ITP) pediatric subjects)

All subjects in this cohort received ELT at the dose that they were receiving at the time of the transition visit, except in the case where the subject required a dose modification. The range of doses of ELT that were used in this cohort were from 12.5 to 75 mg. Dose adjustments (if required) were done depending on each subject's platelet counts.

Group Type: EXPERIMENTAL

Eltrombopag (ELT)

Intervention Type: DRUG

Subjects were dosed with ELT tablets or powder for oral suspension (PfOS) based on the dosage form used in the parent study. ELT tablets were white, round film coated tablets containing ELT olamine equivalent to 12.5 mg, 25 mg, 50 mg, 75 mg and 100 mg of ELT. ELT PfOS was a reddish-brown to yellow powder contained inside an elongated sachet. Each sachet contained ELT olamine equivalent to 20 mg of ELT per gram of powder.

Interventions

Eltrombopag (ELT)

Subjects were dosed with ELT tablets or powder for oral suspension (PfOS) based on the dosage form used in the parent study. ELT tablets were white, round film coated tablets containing ELT olamine equivalent to 12.5 mg, 25 mg, 50 mg, 75 mg and 100 mg of ELT. ELT PfOS was a reddish-brown to yellow powder contained inside an elongated sachet. Each sachet contained ELT olamine equivalent to 20 mg of ELT per gram of powder.

Intervention Type: DRUG

Other Intervention Names

SB-497115

Eligibility Criteria

Inclusion Criteria

• Written informed consent has been obtained from the subject (or subject's legally acceptable representative) prior to performance of any study-specific procedure.
• The subject is participating in a GSK sponsored investigational study of eltrombopag (parent study) within the past 28 days and is receiving clinical benefit without unacceptable toxicity as determined by the investigator.
• Subjects with a QTc <450 millisecond (msec) or <480 msec for subjects with bundle branch block. The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF) or another method, machine or manual overread. For subject eligibility and withdrawal QTcF will be used. For purposes of data analysis, QTcF will be used. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
• Women must be either of non-child bearing potential or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study.
• Women of childbearing potential must have a negative serum pregnancy test within 14 days of the first dose of study treatment and agree to use effective contraception, during the study and for 4 weeks following the last dose of study treatment.
• Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of first dose until 16 weeks after the last dose of study treatment.
• In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.

Exclusion Criteria

• Permanent discontinuation of eltrombopag in the parent study based upon the study treatment discontinuation or study withdrawal criteria from the parent study. Subjects who permanently discontinued treatment because they completed all study related treatments remain eligible.
• The subject is pregnant or a lactating female.
• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions at the time of transition to this study that could interfere with subject's safety, obtaining informed consent or compliance with the study procedures, in the opinion of the investigator or GSK Medical Monitor.
• French subjects: The French subject has participated in any study using an investigational drug during the previous 30 days, with the exception of eltrombopag, in the parent study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

Shanghai, , China

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Athens, , Greece

Novartis Investigative Site

Heraklion, Crete, , Greece

Novartis Investigative Site

Shatin, , Hong Kong

Novartis Investigative Site

Tullamore, , Ireland

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

San Isidro, Lima region, Peru

Novartis Investigative Site

Chorzów, , Poland

Novartis Investigative Site

Bucharest, , Romania

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Sousse, , Tunisia

Countries

Argentina; Brazil; Hungary; Israel; Mexico; Russia; Spain; Thailand; Belgium; China; France; Greece; Hong Kong; Ireland; Netherlands; Peru; Poland; Romania; South Korea; Tunisia

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2013-001371-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CETB115A2X01B

Identifier Type: OTHER

Identifier Source: secondary_id

200170

Identifier Type: -

Identifier Source: org_study_id