Pulmonary Disease, Chronic ObstructivePhase 1NCT02262689
To Evaluate Effects of GSK2256294 on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions
A Phase 1 study testing GSK2256294 in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 1 site in United States.
Trial summary
The study evaluates the effect of GSK2256294 exposure at steady state on pulmonary artery systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of dosing. It is single centre, double blind, randomized, placebo-controlled study to be conducted in approximately 30 healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- GSK2256294
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2015to 24 Apr 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
- AGE: Between 18 and 65 years of age inclusive, at the time of signing the informed consent
- Screening echocardiogram of at least good quality, without clinically significant abnormalities, and with mild-moderate tricuspid regurgitation sufficient for the reliable estimation of PASP, as determined by the echocardiography core laboratory or responsible cardiologist.
- Screening PASP within the normal range according to site standards
- Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator [in consultation with the Medical Monitor if required] agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body weight >= 60 kilogram and body mass index within the range 19 - 35 kilogram per square meter (inclusive)
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- Female subject is eligible to participate if she is of non-reproductive potential defined as: 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, and documented bilateral oophorectomy. Postmenopausal criteria is 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) must discontinue their HRT before the start of the study; for those whose menopausal status is in doubt, they will be required to use one of the highly effective contraception methods and may need to have a blood sample taken to check FSH/estradiol levels.
- 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 two weeks after the last dose of study medication; vasectomy with documentation of azoospermia; male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant that meets the Standard Operating Procedure (SOP)effectiveness criteria including a <1% rate of failure per year, as stated in the product label, Intrauterine device or intrauterine system that meets SOP effectiveness criteria including a <1% rate of failure per year, as stated in the product label, Oral Contraceptive, either combined or progestogen alone, Injectable progestogen, Contraceptive vaginal ring; percutaneous contraceptive patches. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
- Capable of giving signed informed consent as described in protocol, which includes compliance with the requirements and restrictions listed in the consent form and in protocol
Who cannot join
- Subjects with sickle cell trait.
- History of pulmonary hypertension.
- 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).
- QTcF > 450 milliseconds (msec) NOTE: The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF). The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis, QTcF will be used as specified in the Reporting and Analysis Plan (RAP).
- Permitted Medications and Non-Drug Therapies: Acetaminophen, at doses of =< 2 grams/day is permitted for use any time during the study. Other concomitant medication may be considered on a case by case basis by the investigator in consultation with the GSK Medical Monitor. All concomitant medications taken during the study will be recorded in the case report form. The minimum requirement is that drug name, dose administered and the dates of administration be recorded.
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- Prohibited Medications and Non-Drug Therapies: Subjects must abstain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), 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 until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study. - History of regular alcohol consumption within 6 months of the study defined as: For US sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 grams of alcohol: 12 ounces (360 milliliter [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 within 6 months prior to screening
- 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
- Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. For potent immunosuppressive agents, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded.
- A positive pre-study drug/alcohol screen.
- 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 56 days.
- 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 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.
About this study
Official title: A Randomised Placebo-controlled Study to Evaluate the Effects of GSK2256294 Following Repeat Dosing on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions
The study evaluates the effect of GSK2256294 exposure at steady state on pulmonary artery systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of dosing. It is single centre, double blind, randomized, placebo-controlled study to be conducted in approximately 30 healthy volunteers. Subjects will be screened no more than 30 days. Subject will be admitted in clinical unit on Day -1. Subject will be dosed for 7 days in unit in morning on all days except for dosing on Days 3 -6. Dosing on Days 3 -6 will occur at home. Subjects will return to the unit on the evening of Day 6 and remain there until Day 8. Subjects will undergo echocardiography under normoxic and hypoxic on Day 1 pre-dose and on Day 7 post-dose. Subject will be followed up for 28- 32 days after discharge. The maximum estimated time that a subject will be enrolled in the study is 62 days from the screening visit to follow up.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- GSK2256294, Placebo
- Keywords
- GSK2256294, normoxic, hypoxic, Pulmonary artery systolic pressure (PASP)
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2256294Drug
GSK2256294 will be supplied as gelatin capsule to be administered orally with the unit dose 5 mg / dose level 15 mg
PlaceboDrug
Matched Placebo will be supplied as gelatin capsule to be administered orally
| Study group | Role | What they receive |
|---|---|---|
| GSK2256294 15 mg | Experimental | Randomised subjects will be instructed to take three capsules of GSK2256294 15 mg, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose. Receives: Drug: GSK2256294 |
| Placebo | Placebo comparator | Randomised subjects will be instructed to take three capsules of matching placebo, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline of PASP under hypoxic conditions
PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under hypoxic conditions following 7 days of GSK2256294 15 milligrams (mg) once daily. Change from baseline was calculated as the Day 7 value minus the Day1 value.
Measured: Day 1 and Day 7
Secondary outcomes (6)
Change from baseline of PASP under normoxic conditions
The PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under normoxic conditions following 7 days of GSK2256294 15 mg once daily. Change from baseline was calculated as the Day 7 value minus Day 1 value.
Measured: Day 1 and Day 7
Number of subjects with Adverse events (AEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Measured: Up to Day 32
Assessment of 12-lead electrocardiogram (ECG)
Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals
Measured: Up to Day 32
Assessment of vital sign measurements
Vital sign assessments includes temperature, blood pressure (systolic and diastolic) and pulse rate. measurements
Measured: Up to Day 32
Assessment of physical examination findings
A complete physical examination will include, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height and weight will also be measured and recorded. A brief physical examination will include, at a minimum assessments of the lungs, cardiovascular system, and abdomen (liver and spleen).
Measured: Up to Day 32
Assessment of clinical laboratory parameters
Clinical laboratory parameters includes haematology, clinical chemistry and urinalysis
Measured: Up to Day 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2014 (estimated)
- Study start8 Jan 2015
- Primary completion24 Apr 2015
- Study completion24 Apr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02262689
- Sponsor's protocol ID
- 201402
- Status last verified
- May 2017
- First submitted
- 9 Oct 2014
- Last updated
- 9 May 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 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Placebo-controlled Study to Evaluate the Effects of GSK2256294 Following Repeat Dosing on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions
- ClinicalTrials.gov ID
- NCT02262689
- Acronym / sponsor ID
- 201402
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- GSK2256294, normoxic, hypoxic, Pulmonary artery systolic pressure (PASP)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 8 Jan 2015 (actual)
- Primary completion
- 24 Apr 2015 (actual)
- Study completion
- 24 Apr 2015 (actual)
- First posted
- 13 Oct 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.
The study evaluates the effect of GSK2256294 exposure at steady state on pulmonary artery systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of dosing. It is single centre, double blind, randomized, placebo-controlled study to be conducted in approximately 30 healthy volunteers. Subjects will be screened no more than 30 days. Subject will be admitted in clinical unit on Day -1. Subject will be dosed for 7 days in unit in morning on all days except for dosing on Days 3 -6. Dosing on Days 3 -6 will occur at home. Subjects will return to the unit on the evening of Day 6 and remain there until Day 8. Subjects will undergo echocardiography under normoxic and hypoxic on Day 1 pre-dose and on Day 7 post-dose. Subject will be followed up for 28- 32 days after discharge. The maximum estimated time that a subject will be enrolled in the study is 62 days from the screening visit to follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GSK2256294 15 mg | Experimental | Drug: GSK2256294Randomised subjects will be instructed to take three capsules of GSK2256294 15 mg, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose. |
| Placebo | Placebo comparator | Drug: PlaceboRandomised subjects will be instructed to take three capsules of matching placebo, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- AGE: Between 18 and 65 years of age inclusive, at the time of signing the informed consent
- Screening echocardiogram of at least good quality, without clinically significant abnormalities, and with mild-moderate tricuspid regurgitation sufficient for the reliable estimation of PASP, as determined by the echocardiography core laboratory or responsible cardiologist.
- Screening PASP within the normal range according to site standards
- Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
- A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator [in consultation with the Medical Monitor if required] agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Key exclusion criteria (15 listed)
- Subjects with sickle cell trait.
- History of pulmonary hypertension.
- 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).
- QTcF > 450 milliseconds (msec) NOTE: The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF). The specific formula that will be used to determine eligibility and discontinuation for an individual subject should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual subject and then the lowest QTc value used to include or discontinue the subject from the trial. For purposes of data analysis, QTcF will be used as specified in the Reporting and Analysis Plan (RAP).
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 |
|---|---|---|
| GSK2256294GSK2256294 will be supplied as gelatin capsule to be administered orally with the unit dose 5 mg / dose level 15 mg | Drug | GSK2256294 15 mg |
| PlaceboMatched Placebo will be supplied as gelatin capsule to be administered orally | Drug | Placebo |
Primary outcome
Change from baseline of PASP under hypoxic conditions
Time frame: Day 1 and Day 7
PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under hypoxic conditions following 7 days of GSK2256294 15 milligrams (mg) once daily. Change from baseline was calculated as the Day 7 value minus the Day1 value.
6 secondary outcomes
Change from baseline of PASP under normoxic conditions
Time frame: Day 1 and Day 7
Number of subjects with Adverse events (AEs)
Time frame: Up to Day 32
Assessment of 12-lead electrocardiogram (ECG)
Time frame: Up to Day 32
Assessment of vital sign measurements
Time frame: Up to Day 32
Assessment of physical examination findings
Time frame: Up to Day 32
Assessment of clinical laboratory parameters
Time frame: Up to Day 32
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 9 May 2017.
- Results for study 201402 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 GSK2256294 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 9 inclusion and 15 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 9 May 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. Some participants in this study may receive a placebo. 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?
Change from baseline of PASP under hypoxic conditions (time frame: Day 1 and Day 7). 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 9 May 2017.