Clinical Trial for Non-responders Who Previously Participated in Eltrombopag Studies TPL 103922 or TPL 108390 (ENABLE-ALL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00996216
First received: October 1, 2009
Last updated: October 10, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to test the safety and tolerability of eltrombopag when used to increase and maintain platelet count. Platelet count to be maintained at a level sufficient to facilitate initiation of antiviral therapy, to minimize antiviral therapy dose reductions, and to avoid permanent discontinuation of antiviral therapy.


Condition Intervention Phase
Hepatitis C
Drug: Eltrombopag
Drug: Antiviral therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Multi-centre Rollover Study to Assess the Safety and Efficacy of Eltrombopag in Thrombocytopenic Subjects With Hepatitis C Virus (HCV) Infection Who Are Otherwise Eligible to Initiate Antiviral Therapy (Peginterferon Alfa-2a or Peginterferon Alfa-2b Plus Ribavirin)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) in Part 1 [ Time Frame: From the start of investigational product up to the start of antiviral therapy (up to 9 weeks; median of 21 days) ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.

  • Number of Participants With Any AE and Any SAE in Part 2 [ Time Frame: From the date of initiation of antiviral therapy (Antiviral Baseline Visit [between Study Day 14 and Study Day 65]) to the completion of the follow-up period (up to Week 96/WD) ] [ Designated as safety issue: No ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs and SAEs.

  • Number of Participants With the Indicated Worst-case Division of Acquired Immune Deficiency Syndrome (DAIDS) Grade Increases From Screening for the Indicated Clinical Chemistry Parameters During Part 1 [ Time Frame: From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days) ] [ Designated as safety issue: No ]
    Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

  • Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Clinical Chemistry Parameter During Part 2 [ Time Frame: From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD) ] [ Designated as safety issue: No ]
    Blood samples were collected for the measurement of clinical chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

  • Number of Participants With the Indicated Worst-case DAIDS Grade Increases From Screening for the Indicated Hematology Parameters During Part 1 [ Time Frame: From Screening up to the start of antiviral therapy (up to 9 weeks; median of 21 days) ] [ Designated as safety issue: No ]
    Blood samples were collected for the measurement of hematology parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

  • Number of Participants With the Indicated Worst-case DAIDS Grade Increases From the Antiviral Baseline Visit for the Indicated Hematology Parameters During Part 2 [ Time Frame: From Day 0 of Part 2 (Antiviral Baseline Visit [between Study Day 14 and Study Day 65) to the completion of the follow-up period (up to Week 96/WD) ] [ Designated as safety issue: No ]
    Blood samples were collected for the measurement of hematology chemistry parameters. The DAIDS grades are utilized for measuring the severity of AEs. Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening.

  • Number of Participants With a Decrease in Visual Acuity During Parts 1 and 2 [ Time Frame: From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks) ] [ Designated as safety issue: No ]
    Visual acuity (VA) is defined as acuteness or clearness of vision.

  • Number of Participants With the Indicated Change in logMAR Scale Values During Parts 1 and 2 [ Time Frame: From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks) ] [ Designated as safety issue: No ]
    LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.

  • Number of Participants With a logMAR Change >=0.15 During Parts 1 and 2 [ Time Frame: From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks) ] [ Designated as safety issue: No ]
    LogMAR (logarithm of the minimum angle of resolution) charts are used to measure an individual's visual acuity. LogMAR, expressed as the (decadic) logarithm of the minimum angle of resolution (range from +1.00 to -0.30), converts the geometric sequence of a traditional chart to a linear scale. As there are 5 letters per line, the total score for a line on the LogMAR chart represents a change of 0.1 log units.


Secondary Outcome Measures:
  • Platelet Counts at the Indicated Time Points [ Time Frame: From the start of investigational product up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks) ] [ Designated as safety issue: No ]
    Blood samples were collected for the measurement of platelet count. For each participant, the duration of Part 1 treatment varies between 2 and 9 weeks.

  • Number of Particpants Who Initiated Antiviral Therapy [ Time Frame: From the start of the investigational product up to 9 weeks (median of 21 days) ] [ Designated as safety issue: No ]
    The number of participants who completed the Pre-antiviral Phase (Part 1) and proceeded to the Antiviral Phase (Part 2) are summarized.

  • Number of Participants Achieving Antiviral Treatment Milestones of Sustained Virological Response (SVR), Rapid Virological Response (RVR), Early Virological Response (EVR), and End of Treatment Response (ETR) [ Time Frame: From the start of investigational product in Part 2 up to the 24-week follow-up visit after the last dose in Part 2 or early withdrawal (up to 96 weeks) ] [ Designated as safety issue: No ]
    SVR is defined as non-detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) at 24 weeks post-completion of the planned treatment period (i.e., Week 48 or 72 for genotype 2/3 or Week 72 for non-genotype 2/3). RVR is defined as undetectable HCV RNA after 4 weeks of antiviral treatment. EVR is defined as clinically significant reduction in HCV RNA (>=2 log10 drop or undetectable) after 12 weeks of antiviral treatment. ETR is defined as undetectable HCV RNA at the end of antiviral treatment.


Enrollment: 27
Study Start Date: September 2009
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open-label eltrombopag
Open-label eltrombopag with dose titrations to support adequate platelet counts.
Drug: Eltrombopag
Eltrombopag starting at 25 mg dose and titrated in Part 1 of study to 50, 75, 100 mg. Platelet count must reach sufficient level to allow initiation of antiviral therapy. Eltrombopag dose may be adjusted during antiviral treatment phase of study to maintain platelet count to continue antiviral therapy without adjustment to antiviral dose.
Other Name: Promacta
Drug: Antiviral therapy
Combination of either peginterferon alfa-2a or alfa-2b with ribavirin at investigator's discretion.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Prior participation in protocol TPL103922 or TPL108390 and completed the Week 24 Follow Up Visit in TPL103922 or TPL108390
  • Male or female ≥18 years old
  • Evidence of chronic HCV infection
  • While participating in TPL103922 or TPL108390, discontinued from study drug due to thrombocytopenia
  • Appropriate candidate for antiviral therapy with pegylated interferon plus ribavirin
  • Platelet count <75,000
  • Fertile males and females must use two forms of effective contraception during treatment and for 24 weeks after treatment
  • Ability to understand and comply with the protocol requirements and instructions
  • Ability to provide written informed consent

Exclusion Criteria:

  • Decompensated liver disease
  • Known hypersensitivity, intolerance, or allergy to interferon, ribavirin, eltrombopag, or their ingredients
  • History of clinically significant bleeding from oesophageal or gastric varices
  • History of arterial or venous thrombosis and two or more of the following risk factors: hereditary thrombophilic disorders; hormone replacement therapy; systemic contraception (containing estrogen); smoking; diabetes; hypercholesterolemia; medication for hypertension or cancer
  • Pre-existing cardiac disease (congestive heart failure Grade III/IV) or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation)
  • Evidence of hepatocellular carcinoma
  • HIV or Hepatitis B infection
  • Therapy with anti-neoplastic or immunomodulatory treatment within six months prior to eltrombopag therapy
  • Malignancy diagnosed or treated within the past five years. Except for localized basal or squamous cell carcinoma treated by local excision or malignancies that were adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival.
  • Pregnant or nursing women
  • Men with a female partner who is pregnant
  • History of alcohol/drug abuse or dependence within six months of the study start unless participating in a controlled rehabilitation programme.
  • Treatment with an investigational drug or interferon within 30 days or 5 half-lives (whichever is longer) of the screening visit
  • History or platelet clumping that prevents reliable measurement of platelet counts
  • Evidence of portal vein thrombosis within three months of baseline visit
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00996216

  Show 28 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00996216     History of Changes
Other Study ID Numbers: 108392
Study First Received: October 1, 2009
Results First Received: October 10, 2013
Last Updated: October 10, 2013
Health Authority: United States: Food and Drug Administration
Europe: European Medicines Agency

Keywords provided by GlaxoSmithKline:
Peginterferon
Platelets
Ribavirin
Hepatitis C-related thrombocytopenia
Thrombocytopenia
Hepatitis C
Thrombopoietin

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Antiviral Agents
Ribavirin
Peginterferon alfa-2a
Peginterferon alfa-2b
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014