Relative Bioavailibilty for Pediatric Powder for Suspension (PfOS) Formulation and Food Effect

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01072162
First received: February 12, 2010
Last updated: January 27, 2011
Last verified: January 2011
  Purpose

This is a randomized, open-label, five-period, balanced crossover study conducted in approximately 40 healthy adult subjects enrolled at one study center in the USA. Subjects receive five eltrombopag treatments: tablet fasted, Powder for Oral Suspension (PfOS) fasted, PfOS with a high calcium meal, PfOS 2 hours prior to a high calcium meal, and PfOS 2 hours after a high calcium meal, and each treatment is a single 25 mg dose. There is a 10 to 14 day washout between periods, and between the last dose of study drug and the follow-up visit. During each treatment period, subjects undergo serial PK sampling over 72 hours for measurement of plasma eltrombopag concentrations. Safety is assessed by vital signs, clinical safety laboratory assessments, and adverse events reporting.


Condition Intervention Phase
Purpura, Thrombocytopenic, Idiopathic
Drug: Eltrombopag
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Randomized-open-label-five-period-balanced-crossover Study to Evaluate the Relative Bioavailability of an Eltrombopag PfOS Formulation Relative to the 25 mg Tablet Formulation and to Evaluate Administration of the PfOS Formulation With and Separated 2 Hours From a High Calcium Meal in HV

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Evaluate the relative bioavailability of a PfOS formulation relative to the commercial eltrombopag 25 mg tablet formulation in healthy adult subjects. [ Time Frame: 72 hours x 2 periods ] [ Designated as safety issue: No ]
  • Evaluate the effect of a high calcium, moderate fat and calorie meal on the pharmacokinetics of a single oral 25 mg dose of eltrombopag PfOS in healthy adult subjects when eltrombopag is administered concurrently, two hours before, or two hours afte [ Time Frame: 72 hours x 3 periods ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the safety and tolerability of single oral doses of eltrombopag. [ Time Frame: 12-14 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: January 2010
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B
25 mg powder for oral suspension single dose fasted.
Drug: Eltrombopag
25 mg powder for oral suspension
Experimental: C
25 mg powder for oral suspension administered with a meal
Drug: Eltrombopag
25 mg powder for oral suspension
Experimental: D
25 mg powder for oral suspension administered 2 hours prior to meal
Drug: Eltrombopag
25 mg powder for oral suspension
Experimental: E
25 mg powder for oral suspension administered 2 hours after to meal
Drug: Eltrombopag
25 mg powder for oral suspension
A
Commercially available eltrombopag 25 mg tablet
Drug: Eltrombopag
25 mg tablet

Detailed Description:

This is a randomized, open-label, five-period, balanced crossover study conducted in approximately 40 healthy adult subjects enrolled at one study center in the USA. Subjects receive five eltrombopag treatments: tablet fasted, PfOS fasted, PfOS with a high calcium meal, PfOS 2 hours prior to a high calcium meal, and PfOS 2 hours after a high calcium meal, and each treatment is a single 25 mg dose. There is a 10 to 14 day washout between periods, and between the last dose of study drug and the follow-up visit. During each treatment period, subjects undergo serial PK sampling over 72 hours for measurement of plasma eltrombopag concentrations. Safety is assessed by vital signs, clinical safety laboratory assessments, and adverse events reporting.

  Eligibility

Ages Eligible for Study:   18 Years to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy subjects with no clinically significant abnormality identified by physician by evaluation of medical history, physical examination, clinical laboratory tests or electrocardiogram (ECG).
  2. Male and female subjects between the ages of 18 to 64 years of age inclusive, at the time of signing the informed consent.
  3. Subject is able to understand and comply with the protocol requirements, instructions and restrictions.
  4. Capable of giving written informed consent which includes compliance with the requirements and restrictions listed in the consent form.
  5. Body weight ≥ 50kg (110 lbs) for men and ≥ 45 kg (99 lbs) for women and body mass index (BMI) of 18.5 to 29.9 kg/m2 inclusive.
  6. A platelet count within normal range and not > 400,000 plt/uL.
  7. Male subjects, who are not surgically sterile, must agree on abstinence or to use a double barrier method, such as, a condom plus spermicidal agent (foam/gel/film/cream/suppository). This criterion must be followed from the time of the first dose of study medication until 14 days after the last dose of medication.
  8. A female subject is eligible to participate if she is neither pregnant nor lactating, and falls into one of the following categories:

    • non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or bilateral oophorectomy, or post-menopausal females defined as being amenorrheic for greater than one year and having serum estradiol and follicle stimulating hormone levels consistent with menopause.
    • child-bearing potential with negative beta human chorionic gonadotropin (beta/hCG) test and agrees to comply with recognized non-hormonal contraceptive methods from screening or at least two weeks prior to first dose (whichever is earlier) until the follow-up visit. Recognized non-hormonal contraceptive methods include: complete abstinence from intercourse, male partner sterilization, two forms of barrier contraception (e.g. condom and occlusive cap (diaphragm or cervical/vault caps with spermicide), or intrauterine device (IUD), or intrauterine system (IUS) with a < 1% failure rate stated in the product label.

Exclusion Criteria:

  1. History of Gilbert's syndrome.
  2. Any previous history of deep vein thrombosis or any other thromboembolic event.
  3. History of thrombocytopenia or bleeding due to abnormal platelet number or function.
  4. Clotting factor abnormalities associated with hypercoagulability, specifically Factor V Leiden, Protein C or Protein S deficiency or antithrombin III deficiency.
  5. Elevated blood pressure (BP) at screening (systolic > 140 mm Hg, diastolic > 85 mm Hg). If the subject's BP is elevated on the first measurement, complete two additional BP measurements two minutes apart and average the three assessments to evaluate this criteria. If averaged BP exceeds the safety criteria, the subject should be excluded.
  6. History of atrial fibrillation, mitral valve prolapse, significant heart murmur or vascular bruit.
  7. Prolonged QTc interval (Bazett's) at screening (for females > 450 msec and for males > 430 msec). If the QTc interval is prolonged on the initial ECG, then complete two additional ECGs 5 minutes apart and take the average QTc measurements of all three ECGs to evaluate this criteria. If averaged QTc exceeds the safety criteria, the subject should be excluded.
  8. Female subjects currently receiving hormone replacement therapy (HRT).
  9. Positive for HIV, hepatitis B virus or hepatitis C virus assays at screening.
  10. Positive urine drug screen including alcohol at screening or pre-dose (Day -1).
  11. History of alcohol/drug abuse or dependence within 12 months of the study.
  12. History of alcohol consumption in the past six months exceeding 7 units/week for women and 14 units/week for men (where 1 unit = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).
  13. Urinary cotinine levels indicative of smoking at screening or pre-dose (Day -1). History of regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  14. Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
  15. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  16. Use of prescription or non-prescription drugs (including aspirin and non-steroidal anti-inflammatory drugs [NSAIDs]), vitamins, herbal and dietary supplements within seven days (or 14 days if the drug is a potential enzyme inducer, such as St. John's Wort) or five half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the investigator and sponsor the medication will not interfere with the study procedures or compromise subject safety.
  17. Subjects who have donated plasma within seven days prior to the screening visit or where participation in this study would result in donation of blood in excess of 500 mL within a 56-day period.
  18. History of sensitivity to any of the study medications, or components thereof.
  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: NCT01072162

Locations
United States, New York
GSK Investigational Site
Buffalo, New York, United States, 14202
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: E.D. Derilus; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01072162     History of Changes
Other Study ID Numbers: 111718
Study First Received: February 12, 2010
Last Updated: January 27, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
healthy
powder for suspension
tablets
bioavailibility
eltrombopag

Additional relevant MeSH terms:
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Purpura
Blood Coagulation Disorders
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Hemorrhagic Disorders
Autoimmune Diseases

ClinicalTrials.gov processed this record on September 18, 2014