A Rollover Study to Provide Continued Treatment With Eltrombopag

Study 200170: A Rollover Study to Provide Continued Treatment With Eltrombopag

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.

Study Overview

• Status: Completed
• Conditions: Thrombocytopaenia
• Intervention / Treatment: Drug: Eltrombopag (ELT)

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• China
  • Shanghai, China, 200025
    • Novartis Investigative Site
• France
  • Paris Cedex 12, France, 75571
    • Novartis Investigative Site
• Greece
  • Athens, Greece, 11527
    • Novartis Investigative Site
  • Heraklion, Crete, Greece, 71201
    • Novartis Investigative Site
• Hong Kong
  • Shatin, Hong Kong
    • Novartis Investigative Site
• Ireland
  • Tullamore, Ireland
    • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 02841
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Novartis Investigative Site
• Peru
  • Lima
    • San Isidro, Lima, Peru, Lima 27
      • Novartis Investigative Site
• Poland
  • Chorzow, Poland, 41-500
    • Novartis Investigative Site
• Romania
  • Bucharest, Romania, 022328
    • Novartis Investigative Site
• Tunisia
  • Sousse, Tunisia, 4000
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.; Other Names: SB-497115
Experimental: 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.	Drug: 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.; Other Names: SB-497115
Experimental: 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.	Drug: 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.; Other Names: SB-497115

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	The distribution of adverse events was done via the analysis of frequencies for Adverse Events (AEs) and Serious Adverse Events (SAEs), through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive analysis performed.	From the time of transition visit until 30 days after last dose of study treatment, assessed up to approximately 100 months.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2013
• Primary Completion (Actual): February 23, 2022
• Study Completion (Actual): February 23, 2022

Study Registration Dates

• First Submitted: October 4, 2013
• First Submitted That Met QC Criteria: October 4, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): December 30, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: pediatrics; acute myeloid leukemia; thrombocytopenia; Eltrombopag; myelodysplastic syndromes; idiopathic thrombocytopenic purpura
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia
• Other Study ID Numbers: 200170; 2013-001371-20 (EudraCT Number); CETB115A2X01B (Other Identifier: Novartis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No