Last updated: 11/03/2018 21:45:38
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
Drug-drug Interaction Study of Eltrombopag and Cyclosporine in Healthy Subjects
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
Official title: A Phase I, Open-label, Randomized, Three-period Cross-over Study Evaluating the Effect of Cyclosporine on the Pharmacokinetics of Eltrombopag in Healthy Adult Subjects
Trial description: A drug-drug interaction study between eltrombopag and cyclosporine is being conducted to support the use of these drugs together in subjects, such as those with severe aplastic anemia or immune thrombocytopenia purpura. The primary objective of the study is to evaluate the effect of cyclosporine on the pharmacokinetics of eltrombopag. This is a Phase I, open-label, randomized, three-period cross-over study in healthy adult subjects. The study consists of a screening visit and three treatment periods. All subjects will be randomized to receive one of the three treatments in each treatment period separated by washout periods of 3-10 days. The total duration of a subject’s participation in the study from screening to final discharge is up to approximately 6 weeks (assuming 3 day washouts between treatment periods). Approximately 39 healthy subjects will be enrolled with the goal of completing at least 10 subjects per sequence (total 30).
Primary purpose:
Other
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Plasma eltrombopag area under time-concentration curve from time zero to infinity (AUC[0-inf])
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose in each treatment period
Plasma eltrombopag maximum observed concentration (Cmax)
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose in each treatment period
Secondary outcomes:
Composite of plasma eltrombopag pharmacokinetic (PK) parameters
Timeframe: Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 16, 24, 36, 48, and 72 hours post-dose in each treatment period
Vital signs assessment
Timeframe: Up to 6 weeks
Composite clinical laboratory assessments including hematology, clinical chemistry and urinalysis parameters
Timeframe: Up to 6 weeks
Number of participants with adverse events (AEs)
Timeframe: From the start of study treatment until the end of treatment period 3 (assessed up to 18 days)
Electrocardiogram (ECG) assessment
Timeframe: Up to 6 weeks
Interventions:
Enrollment:
39
Primary completion date:
Not applicable
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Purpura, Thrombocytopenic, Idiopathic
Product
ciclosporin, eltrombopag
Collaborators
Not applicable
Study date(s)
November 2014 to December 2014
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 64 years
Accepts healthy volunteers
Yes
- Between 18 and 64 years of age inclusive.
- Healthy subjects.
- Alanine aminotransferase (ALT) and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Inclusion and exclusion criteria
Inclusion criteria:
- Between 18 and 64 years of age inclusive.
- Healthy subjects.
- Body weight >=60 kilograms (kg) for men and women and body mass index (BMI) within the range 24.7-32.0 kg/meter squared (m^2) inclusive.
- Male: Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception during the study.
- Female of non-child bearing potential.
- Female of child-bearing potential who has a negative serum or urine pregnancy test and is willing to practice acceptable methods of birth control during the study.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Exclusion criteria:
- Alanine aminotransferase (ALT) and bilirubin >1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- QT interval corrected (QTc) > 450 millisecond (msec): The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Fridericia’s formula (QTcF), and/or another method, machine-read or manually over-read. For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used.
- Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St. John's Wort) within 7 days.
- Requiring the use of oral or injectable strong Cytochrome P3A4 (CYP3A4) and Breast cancer resistance protein (BRCP) inhibitors or use of other CYP3A4 and BCRP inhibitors/inducers within 14 days prior to dosing.
- History of regular alcohol consumption within 1 month of the study.
- Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 30 days prior to screening.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- Platelet counts or creatinine levels that exceed the upper limit of the normal range.
- Presence of hepatitis B surface antigen (HBsAg) or presence of hepatitis B core antibody (HBcAb), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment
- A positive pre-study drug/alcohol screen.
- A positive test for human immune virus (HIV) antibody.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
- The subject has participated in a clinical trial and has received an investigational product within 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Trial location(s)
Location
GSK Investigational Site
Overland Park, Kansas, United States, 66211
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
No longer a GSK study
Actual primary completion date
Not applicable
Actual study completion date
2014-24-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 201583 can be found on the GSK Clinical Study Register.
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