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AnaemiaPhase 1NCT02371603

Drug-drug Interaction Study of GSK1278863 With Pioglitazone, Rosuvastatin and Trimethoprim in Healthy Adult Volunteers

A Phase 1 study testing GSK1278863 25 mg Tablet, Pioglitazone 15 mg Tablet and Rosuvastatin 10 mg Tablet in people with Anaemia, 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

This study will be a two-part with an open-label, single oral dose, two-way crossover study design. Part A and Part B of the study are independent and may be conducted in parallel. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Anaemia
What is being tested?
GSK1278863 25 mg Tablet, Pioglitazone 15 mg Tablet and Rosuvastatin 10 mg Tablet
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
11 Feb 2015to 12 Aug 2015
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 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Subjects who are between 18 and 65 years of age, inclusive at the time of signing the informed consent form.
  • Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and ECG monitoring obtained at the screening visit. The determination of clinical significance will be made by the investigator and the GlaxoSmithKline (GSK) Medical Monitor and will require that the finding is unlikely to introduce additional risk factors or interfere with the study procedures, or the integrity of the study.
  • Hemoglobin values at screening greater than the lower limit of the laboratory reference range and less than or equal to 16.0 grams (g)/ deciliter (dL) for males and less than or equal to 14.0 g/dL for females.
  • Body weight >=50 Kilogram (kg) and Body Mass Index (BMI) within the range 19-29.9 kg/meter (m)^2 (inclusive).
  • Female or Male. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine or serum human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: a) Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation and Documented hysteroscopic tubal occlusion procedure with follow-up, confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy, b) Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 International units (IU)/ liter (L) and estradiol levels consistent with menopause (<32 picogram (pg)/ milliliter [mL]) are confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrolment. c) Reproductive potential and agrees to follow the contraception requirement for Female Subjects from 30 days prior to the first dose of study treatment and until at least five terminal half-lives or until any continuing pharmacologic effect has ended, whichever is longer after the last dose of study treatment and completion of the follow-up visit.
  • 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 transaminase (ALT), alkaline phosphatase and bilirubin >1.5xUpper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Corrected QT interval(QTc): QT interval corrected for heart rate according to Bazetts formula (QTcB) >450 milliseconds (msec), The QTc must be the QT interval corrected for heart rate according to Bazetts formula (QTcB). For purposes of data analysis, QTcB will be used.
  • Hypertensive (diastolic Blood pressure (BP) >90 millimetre of mercury (mmHg) or systolic BP >140 mmHg at Screening.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of deep vein thrombosis, stroke, transient ischemic attack, pulmonary embolism or other thrombosis related condition.
  • History of myocardial infarction or acute coronary syndrome.
Show all 25Show fewer
  • Subjects with a pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or hepatic function that could interfere with the absorption, metabolism, and/or excretion of GSK1278863, trimethoprim, pioglitazone or rosuvastatin. Examples of conditions that could interfere with normal gastrointestinal anatomy or motility include gastrointestinal bypass surgery, partial or total gastrectomy, small bowel resection, vagotomy, malabsorption, Crohn's disease, ulcerative colitis, or celiac sprue.
  • Evidence of active peptic, duodenal or esophageal ulcer disease at Screening or history of clinically significant Gastrointestine (GI) bleeding.
  • Subjects with chronic inflammatory joint disease (example [e.g.]., scleroderma, systemic lupus erythematosis, rheumatoid arthritis).
  • Subjects with a history of pulmonary artery hypertension.
  • Subjects with a history of malignancy within the prior five years, who are receiving treatment for cancer, or who have a strong family history of cancer (e.g., familial cancer disorders); with the exception of squamous cell or basal cell carcinoma of the skin that has been definitively treated prior to screening through Day -1 (Randomization).
  • History of proliferative vascular eye disease (e.g., choroidal or retinal disease, such as neovascular age-related macular degeneration, proliferative diabetic retinopathy or macular edema).
  • Subjects with heart failure, as defined by the New York Heart Association (NYHA) functional classification system, including known right heart failure
  • Subjects must abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) except occasional usage of acetaminophen, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment until completion of the follow-up visit, unless in the opinion of the investigator and GSK Medical Monitor the medication will not interfere with the study.
  • History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco or nicotine-containing products prior to screening.
  • History of drug abuse or dependence within 6 months of the study.
  • History of sensitivity to any of the study treatments (e.g., GSK1278863, pioglitazone, rosuvastatin, trimethoprim), or their components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Consumption of >3 servings/day of red wine, grapefruit (juice), blood orange (juice), star fruit, onions, kale, broccoli, green beans, or apples from 7 days prior to the first dose of investigational product until the follow-up visit, unless in the opinion of the investigator and GSK Medical Monitor this will not interfere with the study procedures or compromise subject safety.
  • A positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • A positive test for Human Immunodeficiency 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 the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the study treatment (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Unwillingness or inability to follow the procedures outlined in the protocol.

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: An Open Label, Randomized, Two Part Study to Evaluate the CYP2C8- and OATP1B1-Mediated Drug-Drug Interaction Potential of GSK1278863 With Pioglitazone and Rosuvastatin as Victims and Trimethoprim as Perpetrator in Healthy Adult Volunteers

This study will be a two-part with an open-label, single oral dose, two-way crossover study design. Part A and Part B of the study are independent and may be conducted in parallel. The Part A of the study will assess the effect of an oral dose of GSK1278863 on the pharmacokinetics of a CYP2C8 (pioglitazone) and OATP1B1 (rosuvastatin) probe substrate in order to determine the potential for clinically-significant drug interactions with CYP2C8 and OATP1B1 substrates. The Part B of the study will assess the effect of a weak CYP2C8 inhibitor (trimethoprim) on the pharmacokinetics of GSK1278863 and its six predominant metabolites. Part A will be conducted in approximately 30 healthy subjects, having a randomized study design. There will be approximate 7-day washout period between each dosing period. Part B will be conducted in approximately 20 healthy subjects, having single sequence study design. Follow up will be conducted within 7 to 10 days after the last dose in both Part A and B. The total duration of a subject's involvement in the part A of the study will be approximately 8 weeks (Screening to Follow-up) and in part B will be approximately 7 weeks (Screening to Follow-up).

Conditions
Anaemia
Being tested
GSK1278863 25 mg Tablet, Pioglitazone 15 mg Tablet, Rosuvastatin 10 mg Tablet, Trimethoprim 100 mg Tablet
Keywords
Prolyl hydroxylase inhibitor, GSK1278863, Anemia, Drug interaction
Medical subject headings
Anemia

What participants receive

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

  • GSK1278863 25 mg TabletDrug

    A round, biconvex, white film coated tablet to be taken orally in the fasted state in the morning

  • Pioglitazone 15 mg TabletDrug

    White to off-white, round, convex, non scored tablet with "ACTOS" on one side, and "15" on the other, to be taken orally in the fasted state in the morning

  • Rosuvastatin 10 mg TabletDrug

    Pink, round, biconvex, coated tablets. Debossed "CRESTOR" and "10" on one side, to be taken orally in the fasted state in the morning

  • Trimethoprim 100 mg TabletDrug

    White, round, scored, convex tablet, debossed "93" above the score and debossed "2159" below the score on one side and plain on the other, to be taken orally as two tablets once in the morning and once in the evening

Study groups in NCT02371603
Study groupRoleWhat they receive
Part A: GSK1278863, pioglitazone and rosuvastatinExperimentalSubjects will receive single, oral 15 milligram (mg) pioglitazone, 10 mg rosuvastatin and 25 mg dose of GSK1278863 (Treatment A) or 15 mg pioglitazone and 10 mg rosuvastatin (Treatment B) on Day 1 and a 25 mg dose of GSK1278863 alone on Day 2 in two treatment periods as per treatment sequence AB or BA. The 2 treatment periods will be separated by a wash out period of approximately 7 days
Receives: Drug: GSK1278863 25 mg Tablet; Drug: Pioglitazone 15 mg Tablet; Drug: Rosuvastatin 10 mg Tablet
Part B: GSK1278863 and trimethoprimExperimentalSubjects will receive a single, oral 25 mg dose of GSK1278863 on Day 1 and Day 6 morning. The subjects will also receive 200 mg dose of trimethoprim twice daily from Day 3 to 6, with Day 6 dosing being concomitant with morning dosing of GSK1278863
Receives: Drug: GSK1278863 25 mg Tablet; Drug: Trimethoprim 100 mg Tablet

What is being measured

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

  1. Composite of pharmacokinetic (PK) parameters for pioglitazone following oral administration of pioglitazone alone and in combination with GSK1278863, evaluated by measurement of plasma Cmax and AUC (0-infinity) for Part A

    The effect of an oral dose of GSK1278863 on the pharmacokinetics of pioglitazone will be assessed using the following PK parameters: maximum observed concentration (Cmax), area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC (0-infinity)

    Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (h) post-dose in each treatment period

  2. Composite of PK parameters for rosuvastatin following oral administration of rosuvastatin alone and in combination with GSK1278863 evaluated by measurement of plasma Cmax and AUC (0-infinity) for Part A

    The effect of an oral dose of GSK1278863 on the pharmacokinetics of rosuvastatin will be assessed using the following PK parameters: Cmax and AUC (0-infinity)

    Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 h post-dose in each treatment period

  3. Composite of PK parameters for GSK1278863 and its 6 predominant metabolites following oral administration of GSK1278863 alone and in combination with steady-state trimethoprim evaluated by measurement of plasma Cmax and AUC (0-infinity) for Part B

    The effect of trimethoprim on the pharmacokinetics of GSK1278863 and six predominant metabolites (GSK2391220 [M2], GSK2506104 [M3], GSK2487818 [M4], GSK2506102 [M5], GSK2531398 [M6], GSK2531401 [M13]) will be assessed using the following PK parameters: Cmax and AUC (0-infinity)

    Measured: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, and 48 h post-dose of GSK1278863 on day 1 and day 6

Secondary outcomes (7)

  1. Composite of PK parameters for pioglitazone following oral administration of pioglitazone alone and in combination with GSK1278863 evaluated by measurement of plasma AUC(0-t), tmax and t1/2 for Part A

    Additional plasma PK parameters for characterizing the effect of co-administration of GSK1278863 on the pharmacokinetics of pioglitazone are the following: area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC[0-t]), time of occurrence of Cmax (tmax) and terminal phase half-life (t1/2)

    Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 h post-dose in each treatment period

  2. Composite of PK parameters for rosuvastatin following oral administration of rosuvastatin alone and in combination with GSK1278863 evaluated by measurement of plasma AUC(0-t), tmax and t1/2 for Part A

    Additional plasma PK parameters for characterizing the effect of co-administration of GSK1278863 on the pharmacokinetics of rosuvastatin are the following: AUC[0-t], tmax) and t1/2

    Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 h post-dose in each treatment period

  3. Composite of PK parameters for GSK1278863 and its 6 predominant metabolites following oral administration ofGSK1278863 alone and in combination withsteady-state trimethoprim evaluated by measurement of plasma AUC(0-t), tmax and t1/2 for Part B

    Additional plasma PK parameters for characterizing the effect of co-administration of steady-state trimethoprim on the pharmacokinetics of GSK1278863 and six predominant metabolites (GSK2391220 [M2], GSK2506104 [M3], GSK2487818 [M4],GSK2506102 [M5], GSK2531398 [M6],GSK2531401 [M13]) are the following: AUC[0-ttmax and t1/2

    Measured: Pre-dose, 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 18, 24, and 48 h post-dose of GSK1278863 on day 1 and day 6

  4. Number of participants with adverse events as a measure of safety and tolerability of GSK1278863 alone and co-administered with pioglitazone and rosuvastatin or steady-state trimethoprim

    Adverse events will be collected from Day -1 and until the final follow-up visit. Intensity of AEs will be categorized as mild, moderate or severe

    Measured: Up to 4 weeks for Part A and up to 3 weeks for Part B

  5. Composite of clinical laboratory tests assessed by measuring hematology, clinical chemistry and urinalysis

    Clinical laboratory tests will include hematology, clinical chemistry and urinalysis

    Measured: Up to 4 weeks for Part A and up to 3 weeks for Part B

  6. Safety and tolerability of single oral dose of GSK1278863 alone and co-administered with pioglitazone and rosuvastatin or steady-state trimethoprim assessed by12-lead electrocardiogram (ECG)

    Triplicate 12-lead ECGs will be obtained at each timepoint during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals

    Measured: Up to 4 weeks for Part A and up to 3 weeks for Part B

  7. Composite of vital signs assessed by measuring temperature, systolic and diastolic blood pressure and pulse rate

    Vital signs will be measured in supine position after 5 minutes rest and will include temperature, systolic and diastolic blood pressure and pulse rate

    Measured: Up to 4 weeks for Part A and up to 3 weeks for Part B

Timeline

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

  1. First posted25 Feb 2015 (estimated)
  2. Study start11 Feb 2015
  3. Primary completion12 Aug 2015
  4. Study completion12 Aug 2015

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
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02371603
Sponsor's protocol ID
200229
Status last verified
Nov 2017
First submitted
19 Feb 2015
Last updated
17 Nov 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1278863 25 mg Tablet, Pioglitazone 15 mg Tablet and Rosuvastatin 10 mg Tablet in people with Anaemia, 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 6 inclusion and 25 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 17 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?

Composite of pharmacokinetic (PK) parameters for pioglitazone following oral administration of pioglitazone alone and in combination with GSK1278863, evaluated by measurement of plasma Cmax and AUC (0-infinity) for Part A (time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (h) post-dose in each treatment period). The study lists 3 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 NCT02371603.

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 17 Nov 2017.

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