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Purpura, Thrombocytopenic, IdiopathicPhase 1NCT02281370

Drug-drug Interaction Study of Eltrombopag and Cyclosporine in Healthy Subjects

A Phase 1 study testing Eltrombopag and Cyclosporine in people with Purpura, Thrombocytopenic, Idiopathic, run by GlaxoSmithKline at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 64 yearsHealthy volunteers can take part
Conditions the study is for
Purpura, Thrombocytopenic, Idiopathic
What is being tested?
Eltrombopag and Cyclosporine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
1 siteUnited States
Study dates
5 Nov 2014to 24 Dec 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 64 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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 locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Overland Park, Kansas, 66211

Other trials in United States

About this study

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

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).

Being tested
Eltrombopag, Cyclosporine
Keywords
cyclosporine, drug-drug interaction, pharmacokinetics, eltrombopag, SB-497115
Medical subject headings
Purpura, Thrombocytopenic, Idiopathic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EltrombopagDrug

    White to off white bi-convex round tablets containing eltrombopag 50 mg for oral administration

  • CyclosporineDrug

    Soft gelatine capsule containing cyclosporine 100 mg for oral administration. Cyclosporine will be administered at the doses of 200 mg (2 x 100 mg capsules) or 600 mg (6 x 100 mg capsules)

Study groups in NCT02281370
Study groupRoleWhat they receive
SEQUENCE D0, D1, D2ExperimentalParticipants will receive treatment D0 in treatment period 1, D1 in treatment period 2 and D2 in treatment period 3 (one treatment per period). Where D0=eltrombopag 50 milligram (mg), D1= cyclosporine 200 mg + eltrombopag 50 mg, and D2= cyclosporine 600 mg + eltrombopag 50 mg. Treatment periods will be separated by washout periods of 3-10 days
Receives: Drug: Eltrombopag; Drug: Cyclosporine
SEQUENCE D1, D0, D2ExperimentalParticipants will receive treatment D1 in treatment period 1, D0 in treatment period 2 and D2 in treatment period 3 (one treatment per period). Where D0=eltrombopag 50 mg, D1= cyclosporine 200 mg + eltrombopag 50 mg, and D2= cyclosporine 600 mg + eltrombopag 50 mg. Treatment periods will be separated by washout periods of 3-10 days
Receives: Drug: Eltrombopag; Drug: Cyclosporine
SEQUENCE D1, D2, D0ExperimentalParticipants will receive treatment D1 in treatment period 1, D2 in treatment period 2 and D0 in treatment period 3 (one treatment per period). Where D0=eltrombopag 50 mg, D1= cyclosporine 200 mg + eltrombopag 50 mg, and D2= cyclosporine 600 mg + eltrombopag 50 mg. Treatment periods will be separated by washout periods of 3-10 days
Receives: Drug: Eltrombopag; Drug: Cyclosporine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma eltrombopag area under time-concentration curve from time zero to infinity (AUC[0-inf])

    Measured: 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

  2. Plasma eltrombopag maximum observed concentration (Cmax)

    Measured: 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 (5)

  1. Composite of plasma eltrombopag pharmacokinetic (PK) parameters

    PK parameters include: area under time-concentration curve from time zero to the time of last quantifiable concentration (AUC[0-t]), the percentage of AUC(0-inf) obtained by extrapolation (%AUCex), time to occurrence of Cmax (tmax), terminal phase half-life (t1/2), and apparent oral clearance (CL/F)

    Measured: 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

  2. Vital signs assessment

    Vital signs will include temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate

    Measured: Up to 6 weeks

  3. Composite clinical laboratory assessments including hematology, clinical chemistry and urinalysis parameters

    Measured: Up to 6 weeks

  4. Number of participants with adverse events (AEs)

    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product

    Measured: From the start of study treatment until the end of treatment period 3 (assessed up to 18 days)

  5. Electrocardiogram (ECG) assessment

    Single 12-lead ECG will be obtained following eltrombopag dosing using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT interval (QTc)

    Measured: Up to 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Nov 2014 (estimated)
  2. Study start5 Nov 2014
  3. Primary completion24 Dec 2014
  4. Study completion24 Dec 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02281370
Sponsor's protocol ID
201583
Status last verified
Nov 2017
First submitted
30 Oct 2014
Last updated
13 Nov 2017
Results posted
No
Data monitoring committee
No

Publications

  • Aslanis V, Zhang J, Lomeli B, Grosch K, Ouatas T. Effect of cyclosporine coadministration on the pharmacokinetics of eltrombopag in healthy volunteers. Cancer Chemother Pharmacol. 2018 Nov;82(5):847-855. doi: 10.1007/s00280-018-3677-6. Epub 2018 Aug 31.

    PubMed 30171280

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Eltrombopag and Cyclosporine in people with Purpura, Thrombocytopenic, Idiopathic, run by GlaxoSmithKline at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma eltrombopag area under time-concentration curve from time zero to infinity (AUC[0-inf]) (time frame: 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02281370, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2017.

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