AsthmaPhase 1NCT02224521
GSK2190915A - Bioavailability Study
A Phase 1 study testing GSK2190915 Solution., GSK2190915 Granule Capsule (A) and GSK2190915 Semi-solid Lipid Capsule (B) in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that reduces inflammation in cells. This study will evaluate three capsule and two tablet formulations to select the optimal formulation for further development. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthma
- What is being tested?
- GSK2190915 Solution., GSK2190915 Granule Capsule (A) and GSK2190915 Semi-solid Lipid Capsule (B)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Apr 2009to 8 Jun 2010
- 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
- A subject will be eligible for inclusion in cohorts 1, 2, 3, 5 and 6 of this study only if all of the following criteria apply:
- Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5 times Upper Limit of Normal, ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent).
- Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, laboratory tests and Electrocardiogram (ECG). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study objectives.
- Male or female (of non child-bearing potential) between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate only if she is of:
- •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation (in which case the male partner should use an acceptable form of contraception as specified in section 8.1) or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units, MlU/ml and estradiol less than 40 picogrammes per millilitre (less than 140 picomoles per litre) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 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 enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.]
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- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 5 terminal half-lives post-last dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- 6.12 lead ECG without any clinically significant abnormality as judged by the Investigator, and QTc intervals corrected for Bazett ror Fredericia (QTcB and QTcF) less than450 milliseconds (msec)
- 7.Body weight greater than or equal to 50 kilogrammes (kg) (110 pounds, lbs) for men and greater than or equal to 45 kg (99 lbs) for women and Body Mass Index, BMI within the range 18-30 kilogrammes per squared metre (kg/m2) inclusive.
- 8.Non-smokers only- Negative urine cotinine test at screening, no history of smoking within 6 months of the start of the study, and with a total pack year history of less than or equal to 1 pack years.
- A subject will be eligible for inclusion in cohort 4 of this study only if all of the following criteria apply:
- Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, laboratory tests, ECG and Holter assessment at screening. A subject with a clinical abnormality or laboratory parameter outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study objectives. A subject with a well controlled or mild medical condition (eg controlled hypertension, hypothyroidism adequately treated with replacement therapy, mild chronic obstructive pulmonary disease (COPD) requiring short acting bronchodilators only) may be included only if the Investigator and the GSK Medical Monitor agree that the condition is unlikely to introduce additional risk factors and will not interfere with the study objectives.
- Male or female (of non child-bearing potential) over 65 years of age inclusive, at the time of signing the informed consent.
- A female subject is eligible to participate only if she is of:
- •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation (in which case the male partner should use an acceptable form of contraception as specified in section 8.1) or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units, MlU/ml and estradiol less than 40 picogrammes per millilitre (less than 140 picomoles per litre) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 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 enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.]
- Male subjects must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 5 terminal half-lives post-last dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- 5.12 lead ECG without any clinically significant abnormality as judged by the Investigator and QTcB and QTcF less than 450 msec
- 6.Body weight greater than or equal to 50 kg (110 lbs) for men and greater than or equal to 45 kg (99lbs) for women and BMI within the range 18-35 kg/m2 inclusive.
- 7.For non-smokers only - negative urine cotinine test at screening, no history of smoking within 6 months of the start of the study, and with a total pack year history of less than or equal to 1 pack years.
- 8.For smokers only - a smoking history of greater than or equal to 5 pack years and currently smoking at least 5 cigarettes/day for the last 6 months
Who cannot join
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Significant cardiac, pulmonary, metabolic, renal, gastrointestinal or other conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus (HIV) antibody.
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- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units for males or less than14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
- 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 or 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.
- Use of prescription or non-prescription drugs, including 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 medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- 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 GSK Medical Monitor, contraindicates their participation.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Pregnant females as determined by positive serum or urine human Chorionic Gonadotrophin (hCG) test at screening or prior to dosing.
- Lactating females.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
- For non-smokers only - urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- Blood pressure persistently greater than 150 over 90 (150/90) millimetres of mercury (mmHg) at screening.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomised, Single-dose, Multi-cohort, Crossover Bioavailability Study of a Solution Formulation and Three Capsule Formulations of GSK2190915 in Healthy Adult Subjects Followed by a Repeat-dose, Randomized, Parallel Group, Double-blinded Study of One Selected Capsule Formulation and Matched Placebo in Elderly Healthy Subjects
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that reduces inflammation in cells.
This study will evaluate three capsule and two tablet formulations to select the optimal formulation for further development. Safety will be assessed through clinical laboratory testing, 12-lead electrocardiogram (ECG), vital signs and Adverse Event/ Serious Adverse Event (AE/ SAE) recording.
Read the detailed description
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5 lipoxygenase (5-LO) activation. Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli.
Clinical studies conducted to date with GSK2190915 have utilised an aqueous formulation of the compound. However, to progress the compound further in clinical development, a solid dose formulation is necessary. This study will evaluate the optimal capsule formulation from a selection of three available capsule formulations, and a dose, that can be taken forward for future clinical development. Since it is expected that the compound will be developed for Chronic Obstructive Pulmonary Disease (COPD), the study will also include a repeat-dose cohort with elderly subjects (smokers and non-smokers over 65 years of age) in order to evaluate the repeat-dose derived pharmacokinetic parameters of the selected capsule formulation in this population.
This is a multi-cohort study and upto 6 cohorts will be performed.
In cohort 1, the bioavailability of single doses of 50 milligrammes (50 mg) of three capsule formulations (capsule formulations A, B and C) in the fasted state will be assessed. Depending on the bioavailability data obtained from cohort 1, one, two or three capsule formulations may be taken forward into cohort 2.
If only one formulation is deemed to be suitable for progression, cohort 2 will be a single-dose, 4-way complete crossover study to investigate both food-effect and dose proportionality in 10 healthy adult subjects. The decision to progress this formulation to the final (repeat-dose) cohort (cohort 4) will be made based on favourable food interaction and proportionality in bioavailability between high and low doses in cohort 2.
If more than one capsule formulation fulfils the bioavailability criteria following cohort 1, cohort 2 will be a food-effect study with a 100mg single dose of two or three selected capsule formulations in healthy adult subjects. Progression to Cohort 3 will be dependent on the formulation/s meeting predetermined pharmacokinetic (PK) criteria. Cohort 3 will be a complete crossover study with single doses of 20mg and 200mg of each of upto two capsule formulations taken forward from cohort 2 in 10 healthy adult subjects in the fasted state. The aim of performing this cohort is to explore the dose proportionality between low and high doses of the two selected capsule formulations.
Cohort 4 is a 12-day repeat-dose, double-blinded, placebo-controlled study in 12 healthy elderly subjects (>65 years) in the fed or fasted state with once-daily dosing of the highest dose (200mg) of the capsule formulation (A, B or C) taken forward from the previous cohorts. The aim of this cohort is to investigate the accumulation of the selected formulation during repeat dosing.
Cohort 5 will be a 4-way complete crossover study with single doses of 100mg of two tablet formulations (milled and micronised) administered to healthy volunteers in the fed and fasted states. The aim of performing this cohort is to explore the single-dose pharmacokinetics of the two tablet formulations with a view to assessing their suitability for use in subsequent late- phase studies.
Cohort 6 will be a 4-way complete crossover study with single doses of 100mg of two modified tablet formulations (different from Cohort 5 formulations) administered to healthy volunteers in the fed and fasted states. The aim of performing this cohort is to explore the single-dose pharmacokinetics of the two modified tablet formulations with a view to assessing their suitability for use in subsequent late- phase studies.
- Conditions
- Asthma
- Being tested
- GSK2190915 Solution., GSK2190915 Granule Capsule (A), GSK2190915 Semi-solid Lipid Capsule (B), GSK2190915 Liquid Lipid Capsule (C), GSK2190915 Milled Tablet
- Keywords
- FLAP inhibitor, Chronic Obstructive Pulmonary Disease (COPD), COPD, Bioavailability
- Medical subject headings
- Asthma, Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2190915 Solution.Drug
Aqueous Solution, 10mg/mL.
GSK2190915 Granule Capsule (A)Drug
GSK2190915A granule filled in to Gelatin capsules
GSK2190915 Semi-solid Lipid Capsule (B)Drug
GSK2190915A dispersed in a lipid vehicle and filled in to HPMC capsules
GSK2190915 Liquid Lipid Capsule (C)Drug
GSK2190915A dissolved in lipid vehicle milled and filled in to Gelatin capsules
GSK2190915 Milled TabletDrug
GSK2190915A granule is blended, compressed into tablets and aqueous film coated
GSK2190915 Micronised TabletDrug
GSK2190915A granule is blended, compressed into tablets and aqueous film coated
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects will be assigned to any of the 4 dosage regimen (A, B, C, D) in four periods. A= GSK2190915 Solution, 50mg single dose, fasted; B = GSK2190915 Capsule Formulation A, 50mg single dose (1 x 50mg capsule), fasted; C= GSK2190915 Capsule Formulation B, 50mg single dose (1 x 50mg capsule), fasted; D= GSK2190915 Capsule Formulation C, 50mg single dose (1 x 50mg capsule), fasted. Receives: Drug: GSK2190915 Solution.; Drug: GSK2190915 Granule Capsule (A); Drug: GSK2190915 Semi-solid Lipid Capsule (B); Drug: GSK2190915 Liquid Lipid Capsule (C) |
| Cohort 2 | Experimental | The selected formulation will be dosed with GSK2190915 capsule formulation at 20mg (fasted), 100mg (fasted), 100mg (fed) and 200mg (fasted). Receives: Drug: GSK2190915 Solution.; Drug: GSK2190915 Granule Capsule (A); Drug: GSK2190915 Semi-solid Lipid Capsule (B); Drug: GSK2190915 Liquid Lipid Capsule (C) |
| Cohort 3 | Experimental | Cohort 3 will be a 4-way complete crossover study with single doses of 20mg and 200mg of up to two capsule formulations taken forward from cohort 2 in 10 healthy adult subjects in the fasted state. Receives: Drug: GSK2190915 Solution.; Drug: GSK2190915 Granule Capsule (A); Drug: GSK2190915 Semi-solid Lipid Capsule (B); Drug: GSK2190915 Liquid Lipid Capsule (C) |
| Cohort 4 | Experimental | The regimen for Cohort 4 will be either the highest dose (200mg) of the capsule formulation (A, B or C) taken forward from the previous cohorts or the solution formulation (200mg). Receives: Drug: GSK2190915 Solution.; Drug: GSK2190915 Granule Capsule (A); Drug: GSK2190915 Semi-solid Lipid Capsule (B); Drug: GSK2190915 Liquid Lipid Capsule (C) |
| Cohort 5 | Experimental | Subjects will take milled and micronised tablet formulations of GSK2190915 in the fasted state in periods 1 and 2, and will take milled and micronised tablet formulations of GS2190915 in the fed state in periods 3 and 4. Receives: Drug: GSK2190915 Milled Tablet; Drug: GSK2190915 Micronised Tablet |
| Cohort 6 | Experimental | Tablet formulations (milled and micronised, different to the Cohort 5 formulations) of GSK2190915 will be dosed in the fasted and fed (after a light breakfast) states. Receives: Drug: GSK2190915 Milled Tablet; Drug: GSK2190915 Micronised Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite of plasma pharmacokinetic (PK) parameters of GSK2190915 in Cohort 1, 2 and 3
PK parameters including area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-∞]), 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]), concentrations at 24h post dose (C24), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), terminal half-life (t1/2) and oral clearance (CL/F) for Cohort 1, 2, 3 will be measured.
Measured: PK samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 hours post dose in each period up to 36 days
Composite of PK parameters in Cohort 4
PK parameters including area under the plasma concentration-time curve over the dosing interval (AUC [0-tau]), trough C24, Cmax, Tmax, and accumulation for Cohort 4 will be measured.
Measured: Up to 12 days
Composite of PK parameters in Cohort 5 and 6
PK parameters including AUC (0-∞), AUC (0-t), C24, Cmax, Tmax, t1/2 and CL/F for Cohort 5 and 6 will be measured.
Measured: PK samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post dose in each period up to 36 days
Secondary outcomes (16)
Blood pressure measurement for Cohorts 1, 2, and 3 after GSK2190915 administration
Measured: Up to 36 days
Blood pressure measurement for Cohorts 4 after GSK2190915 administration
Measured: Up to 12 days
Blood pressure measurement for Cohorts 5 and 6 after GSK2190915 administration
Measured: Up to 36 days
Pulse rate measurement for Cohorts 1, 2, and 3 after GSK2190915 administration
Measured: Up to 36 days
Pulse rate measurement for Cohort 4 after GSK2190915 administration
Measured: Up to 12 days
Pulse rate measurement for Cohorts 5 and 6 after GSK2190915 administration
Measured: Up to 36 days
ECG measurement for Cohorts 1, 2, 3 after GSK2190915 administration
Measured: Up to 36 days
ECG measurement for Cohort 4 after GSK2190915 administration
Measured: Up to 12 days
ECG measurement for Cohort 5 and 6 after GSK2190915 administration
Measured: Up to 36 days
Holter monitoring for Cohort 4 only after GSK2190915 administration
Measured: Up to 12 days
Laboratory assessment for Cohorts 1, 2, 3 after GSK2190915 administration
Laboratory parameters including hematology, clinical chemistry, and urinalysis
Measured: Up to 36 days
Laboratory assessment for Cohort 4 after GSK2190915 administration
Laboratory parameters including hematology, clinical chemistry, and urinalysis
Measured: Up to 12 days
Laboratory assessment for Cohort 5 and 6 after GSK2190915 administration
Laboratory parameters including hematology, clinical chemistry, and urinalysis
Measured: Up to 36 days
Adverse Event reporting for Cohorts 1, 2, and 3 after GSK2190915 administration
Measured: Up to 36 days
Adverse Event reporting for Cohort 4 after GSK2190915 administration
Measured: Up to 12 days
Adverse Event reporting for Cohorts 5 and 6 after GSK2190915 administration
Measured: Up to 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2014 (estimated)
- Study start20 Apr 2009
- Primary completion8 Jun 2010
- Study completion8 Jun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02224521
- Sponsor's protocol ID
- 112071
- Status last verified
- Jun 2017
- First submitted
- 23 Jun 2011
- Last updated
- 14 Jun 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.
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomised, Single-dose, Multi-cohort, Crossover Bioavailability Study of a Solution Formulation and Three Capsule Formulations of GSK2190915 in Healthy Adult Subjects Followed by a Repeat-dose, Randomized, Parallel Group, Double-blinded Study of One Selected Capsule Formulation and Matched Placebo in Elderly Healthy Subjects
- ClinicalTrials.gov ID
- NCT02224521
- Acronym / sponsor ID
- 112071
- Conditions
- Asthma
- Keywords
- FLAP inhibitor, Chronic Obstructive Pulmonary Disease (COPD), COPD, Bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2009 (actual)
- Primary completion
- 8 Jun 2010 (actual)
- Study completion
- 8 Jun 2010 (actual)
- First posted
- 25 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that reduces inflammation in cells.
This study will evaluate three capsule and two tablet formulations to select the optimal formulation for further development. Safety will be assessed through clinical laboratory testing, 12-lead electrocardiogram (ECG), vital signs and Adverse Event/ Serious Adverse Event (AE/ SAE) recording.
Detailed description
GSK2190915 is a high affinity 5-lipoxygenase-activating protein (FLAP) inhibitor that attenuates the production of leukotrienes, through the blockage of the first committed step in the leukotriene pathway, 5 lipoxygenase (5-LO) activation. Leukotrienes are potent inflammatory molecules produced mainly by mast cells, eosinophils, monocytes/macrophage and neutrophils in response to allergic or inflammatory stimuli.
Clinical studies conducted to date with GSK2190915 have utilised an aqueous formulation of the compound. However, to progress the compound further in clinical development, a solid dose formulation is necessary. This study will evaluate the optimal capsule formulation from a selection of three available capsule formulations, and a dose, that can be taken forward for future clinical development. Since it is expected that the compound will be developed for Chronic Obstructive Pulmonary Disease (COPD), the study will also include a repeat-dose cohort with elderly subjects (smokers and non-smokers over 65 years of age) in order to evaluate the repeat-dose derived pharmacokinetic parameters of the selected capsule formulation in this population.
This is a multi-cohort study and upto 6 cohorts will be performed.
In cohort 1, the bioavailability of single doses of 50 milligrammes (50 mg) of three capsule formulations (capsule formulations A, B and C) in the fasted state will be assessed. Depending on the bioavailability data obtained from cohort 1, one, two or three capsule formulations may be taken forward into cohort 2.
If only one formulation is deemed to be suitable for progression, cohort 2 will be a single-dose, 4-way complete crossover study to investigate both food-effect and dose proportionality in 10 healthy adult subjects. The decision to progress this formulation to the final (repeat-dose) cohort (cohort 4) will be made based on favourable food interaction and proportionality in bioavailability between high and low doses in cohort 2.
If more than one capsule formulation fulfils the bioavailability criteria following cohort 1, cohort 2 will be a food-effect study with a 100mg single dose of two or three selected capsule formulations in healthy adult subjects. Progression to Cohort 3 will be dependent on the formulation/s meeting predetermined pharmacokinetic (PK) criteria. Cohort 3 will be a complete crossover study with single doses of 20mg and 200mg of each of upto two capsule formulations taken forward from cohort 2 in 10 healthy adult subjects in the fasted state. The aim of performing this cohort is to explore the dose proportionality between low and high doses of the two selected capsule formulations.
Cohort 4 is a 12-day repeat-dose, double-blinded, placebo-controlled study in 12 healthy elderly subjects (>65 years) in the fed or fasted state with once-daily dosing of the highest dose (200mg) of the capsule formulation (A, B or C) taken forward from the previous cohorts. The aim of this cohort is to investigate the accumulation of the selected formulation during repeat dosing.
Cohort 5 will be a 4-way complete crossover study with single doses of 100mg of two tablet formulations (milled and micronised) administered to healthy volunteers in the fed and fasted states. The aim of performing this cohort is to explore the single-dose pharmacokinetics of the two tablet formulations with a view to assessing their suitability for use in subsequent late- phase studies.
Cohort 6 will be a 4-way complete crossover study with single doses of 100mg of two modified tablet formulations (different from Cohort 5 formulations) administered to healthy volunteers in the fed and fasted states. The aim of performing this cohort is to explore the single-dose pharmacokinetics of the two modified tablet formulations with a view to assessing their suitability for use in subsequent late- phase studies.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: GSK2190915 Solution., Drug: GSK2190915 Granule Capsule (A), Drug: GSK2190915 Semi-solid Lipid Capsule (B), Drug: GSK2190915 Liquid Lipid Capsule (C)Subjects will be assigned to any of the 4 dosage regimen (A, B, C, D) in four periods. A= GSK2190915 Solution, 50mg single dose, fasted; B = GSK2190915 Capsule Formulation A, 50mg single dose (1 x 50mg capsule), fasted; C= GSK2190915 Capsule Formulation B, 50mg single dose (1 x 50mg capsule), fasted; D= GSK2190915 Capsule Formulation C, 50mg single dose (1 x 50mg capsule), fasted. |
| Cohort 2 | Experimental | Drug: GSK2190915 Solution., Drug: GSK2190915 Granule Capsule (A), Drug: GSK2190915 Semi-solid Lipid Capsule (B), Drug: GSK2190915 Liquid Lipid Capsule (C)The selected formulation will be dosed with GSK2190915 capsule formulation at 20mg (fasted), 100mg (fasted), 100mg (fed) and 200mg (fasted). |
| Cohort 3 | Experimental | Drug: GSK2190915 Solution., Drug: GSK2190915 Granule Capsule (A), Drug: GSK2190915 Semi-solid Lipid Capsule (B), Drug: GSK2190915 Liquid Lipid Capsule (C)Cohort 3 will be a 4-way complete crossover study with single doses of 20mg and 200mg of up to two capsule formulations taken forward from cohort 2 in 10 healthy adult subjects in the fasted state. |
| Cohort 4 | Experimental | Drug: GSK2190915 Solution., Drug: GSK2190915 Granule Capsule (A), Drug: GSK2190915 Semi-solid Lipid Capsule (B), Drug: GSK2190915 Liquid Lipid Capsule (C)The regimen for Cohort 4 will be either the highest dose (200mg) of the capsule formulation (A, B or C) taken forward from the previous cohorts or the solution formulation (200mg). |
| Cohort 5 | Experimental | Drug: GSK2190915 Milled Tablet, Drug: GSK2190915 Micronised TabletSubjects will take milled and micronised tablet formulations of GSK2190915 in the fasted state in periods 1 and 2, and will take milled and micronised tablet formulations of GS2190915 in the fed state in periods 3 and 4. |
| Cohort 6 | Experimental | Drug: GSK2190915 Milled Tablet, Drug: GSK2190915 Micronised TabletTablet formulations (milled and micronised, different to the Cohort 5 formulations) of GSK2190915 will be dosed in the fasted and fed (after a light breakfast) states. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- A subject will be eligible for inclusion in cohorts 1, 2, 3, 5 and 6 of this study only if all of the following criteria apply:
- Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase and bilirubin less than or equal to 1.5 times Upper Limit of Normal, ULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percent).
- Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, laboratory tests and Electrocardiogram (ECG). A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study objectives.
- Male or female (of non child-bearing potential) between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation (in which case the male partner should use an acceptable form of contraception as specified in section 8.1) or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 million international units, MlU/ml and estradiol less than 40 picogrammes per millilitre (less than 140 picomoles per litre) is confirmatory]. [Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 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 enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.]
Key exclusion criteria (19 listed)
- A subject will not be eligible for inclusion in this study if any of the following criteria apply:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Significant cardiac, pulmonary, metabolic, renal, gastrointestinal or other conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.
- A positive pre-study drug/alcohol screen.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK2190915 Solution.Aqueous Solution, 10mg/mL. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| GSK2190915 Granule Capsule (A)GSK2190915A granule filled in to Gelatin capsules | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| GSK2190915 Semi-solid Lipid Capsule (B)GSK2190915A dispersed in a lipid vehicle and filled in to HPMC capsules | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| GSK2190915 Liquid Lipid Capsule (C)GSK2190915A dissolved in lipid vehicle milled and filled in to Gelatin capsules | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| GSK2190915 Milled TabletGSK2190915A granule is blended, compressed into tablets and aqueous film coated | Drug | Cohort 5, Cohort 6 |
| GSK2190915 Micronised TabletGSK2190915A granule is blended, compressed into tablets and aqueous film coated | Drug | Cohort 5, Cohort 6 |
Primary outcome
Composite of plasma pharmacokinetic (PK) parameters of GSK2190915 in Cohort 1, 2 and 3
Time frame: PK samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 hours post dose in each period up to 36 days
PK parameters including area under the plasma concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-∞]), 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]), concentrations at 24h post dose (C24), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), terminal half-life (t1/2) and oral clearance (CL/F) for Cohort 1, 2, 3 will be measured.
Composite of PK parameters in Cohort 4
Time frame: Up to 12 days
PK parameters including area under the plasma concentration-time curve over the dosing interval (AUC [0-tau]), trough C24, Cmax, Tmax, and accumulation for Cohort 4 will be measured.
Composite of PK parameters in Cohort 5 and 6
Time frame: PK samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post dose in each period up to 36 days
PK parameters including AUC (0-∞), AUC (0-t), C24, Cmax, Tmax, t1/2 and CL/F for Cohort 5 and 6 will be measured.
16 secondary outcomes
Blood pressure measurement for Cohorts 1, 2, and 3 after GSK2190915 administration
Time frame: Up to 36 days
Blood pressure measurement for Cohorts 4 after GSK2190915 administration
Time frame: Up to 12 days
Blood pressure measurement for Cohorts 5 and 6 after GSK2190915 administration
Time frame: Up to 36 days
Pulse rate measurement for Cohorts 1, 2, and 3 after GSK2190915 administration
Time frame: Up to 36 days
Pulse rate measurement for Cohort 4 after GSK2190915 administration
Time frame: Up to 12 days
Pulse rate measurement for Cohorts 5 and 6 after GSK2190915 administration
Time frame: Up to 36 days
ECG measurement for Cohorts 1, 2, 3 after GSK2190915 administration
Time frame: Up to 36 days
ECG measurement for Cohort 4 after GSK2190915 administration
Time frame: Up to 12 days
ECG measurement for Cohort 5 and 6 after GSK2190915 administration
Time frame: Up to 36 days
Holter monitoring for Cohort 4 only after GSK2190915 administration
Time frame: Up to 12 days
Laboratory assessment for Cohorts 1, 2, 3 after GSK2190915 administration
Time frame: Up to 36 days
Laboratory assessment for Cohort 4 after GSK2190915 administration
Time frame: Up to 12 days
Laboratory assessment for Cohort 5 and 6 after GSK2190915 administration
Time frame: Up to 36 days
Adverse Event reporting for Cohorts 1, 2, and 3 after GSK2190915 administration
Time frame: Up to 36 days
Adverse Event reporting for Cohort 4 after GSK2190915 administration
Time frame: Up to 12 days
Adverse Event reporting for Cohorts 5 and 6 after GSK2190915 administration
Time frame: Up to 36 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Results for study 112071 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK2190915 Solution., GSK2190915 Granule Capsule (A) and GSK2190915 Semi-solid Lipid Capsule (B) in people with Asthma, run by GlaxoSmithKline at 1 site in United Kingdom.
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 22 inclusion and 19 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 14 Jun 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 Kingdom. 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 plasma pharmacokinetic (PK) parameters of GSK2190915 in Cohort 1, 2 and 3 (time frame: PK samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48 and 72 hours post dose in each period up to 36 days). 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?
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 14 Jun 2017.