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Pulmonary Disease, Chronic ObstructivePhase 1NCT02453022

A 5-Period, Single Dose, Phase 1 Study in Healthy Elderly Subjects to Assess Relative Bioavailability and Food Effect of Two Oral Formulations of GSK1325756 (Free Base vs HBr Salt) and Food Effect on the HBr Formulation When Given With Omeprazole

A Phase 1 study testing Danirixin HBr 50 mg IR Tablet, Danirixin FB 50 mg IR Tablet and Prilosec (omeprazole) 40mg Delayed-Release capsule in people with Pulmonary Disease, Chronic Obstructive, 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

The current study will help to increase our understanding of the pharmacokinetics (PK) of danirixin. The primary objective of the study is to estimate the relative bioavailability of danirixin Hydrobromide (HBr) tablet, when compared to danirixin free base (FB). Read more about this study

Who is it for?
Ages 65 to 80 yearsHealthy volunteers can take part
Conditions the study is for
Pulmonary Disease, Chronic Obstructive
What is being tested?
Danirixin HBr 50 mg IR Tablet, Danirixin FB 50 mg IR Tablet and Prilosec (omeprazole) 40mg Delayed-Release capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
18 May 2015to 31 Jul 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 65 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • Between 65 and 80 years of age at screening (inclusive)
  • Healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring or a subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives.
  • Body Mass Index between 19 and 34 (inclusive)
  • Male or Female Males: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until a cycle of spermatogenesis following five terminal half- lives after the last dose of study medication. a. Vasectomy with documentation of azoospermia. b. Male condom plus partner use of one of the contraceptive options: Contraceptive subdermal implant, Intrauterine device or intrauterine system, Oral Contraceptive, either combined or progestogen alone Injectable progestogen, Contraceptive vaginal ring, Percutaneous contraceptive patches.
  • This is an all-inclusive list of those methods that meet the following GSK definition of highly effective: having a failure rate of less than 1% per year when used consistently and correctly and, when applicable, in accordance with the product label. For non-product methods (e.g., male sterility), the investigator determines what is consistent and correct use. The GSK definition is based on the definition provided by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
  • Females: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: a. Pre-menopausal females with one of the following: Documented tubal ligation, 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) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. 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 post-menopausal status prior to study enrolment.
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  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in protocol.
  • Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <= 1.5 × Upper limit of normal (ULN) (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
  • Resting Blood pressure (BP) of <=160/90 millimetre (mm) mercury (Hg), irrespective of anti-hypertensive medication status for the subject.
  • Able to consume the Food and Drug Administration (FDA) defined high fat meal within 30 minutes in each of the four treatment periods where study treatment is administered in a fed state

Who cannot join

  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • A positive pre-study Hepatitis B surface antigen (HBsAg) or positive Hepatitis C antibody (HCV Ab) result within 3 months of screening.
  • A positive pre-study drug/alcohol screen, with the exception of a positive result considered by the investigator to be directly attributable to prescription medication approved for subject use during the study.
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • Use of prescription or non-prescription drugs, including proton pump inhibitors, histamine receptor 2 antagonists, systemic antacid medications (unless these can be held during the study), vitamins, herbal and dietary supplements (including St John's Wort) 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 last study assessment for Period 5, unless in the opinion of the investigator and GSK Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety. Some examples of exceptions (permitted medications) are: a. Stable dose of anti-hypertensive medication for at least 3 months prior to the screening visit. b. Stable dose of lipid-lowering medications (statins or fibrates) for at least 3 months prior to the screening visit. c. Antacids up to 24 hours prior to dosing This list is not meant to be all inclusive.
  • 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: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
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  • Exposure to more than four new chemical entities (any investigational, non-marketed, non-FDA-approved medicine) within 12 months prior to the first dosing day.
  • History of regular alcohol consumption within 6 months of the study defined as:
  • An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240 millilitre [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Urine cotinine levels indicative of current smoking, or history or regular use of tobacco- or nicotine-containing products, including e-cigarettes and nicotine patches, within 90 days prior to screening.
  • Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study treatment until collection of the final blood sample.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 3-month period.
  • Unwillingness or inability to follow all of the procedures outlined in the protocol.
  • Subject is mentally or legally incapacitated.
  • Direct involvement in the conduct of the study, or relative of any person directly involved in the conduct of the study.
  • Female Subjects: Positive urine beta-hCG test at screening.
  • Screening QT interval corrected for heart rate according to Fridericia's formula (QTcF)> 450 millisecond (msec) or an ECG that is not suitable for QT measurements (e.g., poorly defined termination of T-wave).
  • History of sensitivity to any of the study treatments, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

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 Single Centre, Open-label, 5-Period, Cross Over, Randomized Study in Healthy Elderly Subjects to Evaluate the Relative Bioavailability of Hydrobromide Salt and Free Base Immediate Release Tablet Formulations of Danirixin in the Fed State, and to Evaluate the Effect of Food and Gastric Acid Secretion Suppression on Danirixin Pharmacokinetics Following Administration of Hydrobromide Salt Tablets

The current study will help to increase our understanding of the pharmacokinetics (PK) of danirixin. The primary objective of the study is to estimate the relative bioavailability of danirixin Hydrobromide (HBr) tablet, when compared to danirixin free base (FB). Safety and tolerability information for oral administration of danrixin HBr tablets in elderly subjects will also be obtained. Secondarily, this study will evaluate effect of food on PK of danirixin HBr, effect of gastric acid suppression, and within-subject PK variability of danirixin HBr. The outcome of this study will contribute to the selection of the most appropriate formulation/dosing regimen for future studies.

This is an open-label, 5-period crossover study. Study will be conducted in 18 healthy elderly subjects. Screening will occur within 42 days prior to Day 1 of period 1. The Treatment Periods will be separated by a washout period of a minimum 5 days. Follow-up will be done within 3 to 10 days post last dose.

Being tested
Danirixin HBr 50 mg IR Tablet, Danirixin FB 50 mg IR Tablet, Prilosec (omeprazole) 40mg Delayed-Release capsule
Keywords
Bioavailability, Omeprazole, Danirixin, Food Effect, Pharmacokinetics
Medical subject headings
Pulmonary Disease, Chronic Obstructive

What participants receive

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

  • Danirixin HBr 50 mg IR TabletDrug

    Danirixin HBr 50 mg IR Tablet is white, film-coated, oval-shaped tablet for oral administration.

  • Danirixin FB 50 mg IR TabletDrug

    Danirixin FB 50 mg IR Tablet is white, film-coated, capsule-shaped tablet for oral administration.

  • Prilosec (omeprazole) 40mg Delayed-Release capsuleDrug

    Prilosec (omeprazole) 40 mg delayed-release capsule is opaque, hard gelatin, apricot, and amethyst colored capsules, coded 743 on cap and PRILOSEC 40 on the body for oral administration.

Study groups in NCT02453022
Study groupRoleWhat they receive
Danirixin HBr + Danirixin FB + OmeprazoleExperimentalSubjects will receive danirixin FB 50 milligram (mg) immediate release (IR) tablet, single dose, in the fed state (treatment A), danirixin HBr 50 mg IR tablet, single dose, in the fed state (treatment B), danirixin HBr 50 mg IR tablet, single dose, in the fasted state (treatment C), or danirixin HBr 50 mg IR tablet, single dose, in the fed state (treatment D) as per randomization in period 1 to 4. In treatment Period 5, subjects will receive danirixin HBr 50 mg IR table, single dose, in the fed state with concomitant, steady state OMP (40 mg once daily for 5 days) (treatment E). Subject will receive treatment with washout period of 5 days in one of the four sequence DCABE, ADBCE, BACDE, CBDAE.
Receives: Drug: Danirixin HBr 50 mg IR Tablet; Drug: Danirixin FB 50 mg IR Tablet; Drug: Prilosec (omeprazole) 40mg Delayed-Release capsule

What is being measured

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

  1. Composite of Danirixin PK parameters

    Danirixin PK parameters area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC[0-inf]) and maximum observed concentration (Cmax) following single dose administration of FB tablet (reference), relative to HBr tablet (test) will be assessed.

    Measured: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours (hrs) post-dose in each period

  2. Number of participants with adverse events (AE) /serious adverse event (SAE) as a measure of safety and tolerability

    AE/SAE will be collected from the start of study treatment and until the follow-up visit or contact for study treatment period 5. Intensity of AEs will be categorized as mild, moderate or severe. 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 is associated with liver injury and impaired liver function.

    Measured: Up to Day 36

  3. Composite of vital signs as a measure of safety and tolerability

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

    Measured: Up to Day 31

  4. Electrocardiogram (ECG) as a measure of safety and tolerability

    ECG will be obtained at selected time-points during the study.

    Measured: Up to Day 29

  5. Composite of clinical laboratory tests as a measure of safety and tolerability

    Clinical laboratory tests will include hematology, clinical chemistry and urinalysis.

    Measured: Up to Day 31

Secondary outcomes (4)

  1. Composite of other Danirixin PK parameters

    Other Danirixin PK parameters area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC[0-t]), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2), time of last quantifiable concentration (tlast) and lag time before observation of drug concentrations in sampled matrix (tlag) following single dose administration of FB tablet (reference), relative to HBr tablet (test) will be assessed.

    Measured: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period

  2. Composite of Danirixin PK parameters to estimate the food effect

    Danirixin PK parameters AUC(0-inf), AUC(0-t), Cmax, tmax, t1/2, tlast and tlag following danirixin HBr tablet formulation under fasting and fed state will be assessed.

    Measured: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period

  3. Composite of Danirixin PK parameters to estimate the effect of Omepazole (OMP)

    Danirixin PK parameters AUC(0-inf), AUC(0-t), Cmax, tmax, t1/2, tlast and tlag following danirixin HBr tablet formulation with or without concomitant, steady state OMP will be assessed.

    Measured: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period

  4. Composite of Danirixin PK parameters to estimate the within-subject variability of danirixin

    Danirixin PK parameters AUC(0-inf), AUC(0-t), Cmax following danirixin HBr tablet formulation under fed conditions will be assessed.

    Measured: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hrs post-dose in each period

Timeline

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

  1. First posted25 May 2015 (estimated)
  2. Study start18 May 2015
  3. Primary completion31 Jul 2015
  4. Study completion31 Jul 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
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02453022
Sponsor's protocol ID
201037
Status last verified
Jul 2018
First submitted
21 May 2015
Last updated
24 Jul 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Danirixin HBr 50 mg IR Tablet, Danirixin FB 50 mg IR Tablet and Prilosec (omeprazole) 40mg Delayed-Release capsule in people with Pulmonary Disease, Chronic Obstructive, 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 10 inclusion and 18 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 24 Jul 2018. 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 Danirixin PK parameters (time frame: Blood samples for PK analysis will be collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48 hours (hrs) post-dose in each period). The study lists 5 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 NCT02453022.

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 24 Jul 2018.

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Clinical Trial NCT02453022 | AzTrials