Pulmonary Disease, Chronic ObstructivePhase 2NCT02567708
A Study to Investigate the Efficacy, Safety, and Tolerability of Repeat Doses of Inhaled GSK2269557 in Adults With Persistent, Uncontrolled Asthma
A Phase 2 study testing GSK2269557 DPI in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 12 sites in Germany.
Trial summary
This study is a multi-centre, randomised, double-blind, placebo-controlled (with rescue medication), two period crossover study in subjects with persistent uncontrolled asthma, currently not treated with an inhaled corticosteroid (ICS) or long acting beta 2 agonist (LABA). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- GSK2269557 DPI
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 12 sitesGermany
- Study dates
- 1 Oct 2015to 28 Sep 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between 18 and 70 years of age inclusive, at the time of signing the informed consent.
- Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with an intermittent short acting beta 2 agonist (SABA) or other non-corticosteroid controllers. Non corticosteroid controllers (e.g. leukotriene receptor antagonists [LTRAs]) must be discontinued from Screening until the end of Treatment Period 2.
- Able to replace current SABA treatment with salbutamol metered dose inhaler (MDI) at Screening for use as needed for the duration of the study. Judged capable of withholding salbutamol for at least 4 hours prior to FEV1 assessments.
- No use of an ICS or LABA for at least 12 weeks prior to first dose of study medication.
- A best pre-bronchodilator FEV1 >=60 percent (%) of the predicted normal value at screening.
- FEV1 increase by >=12% and >=200 milliliter (mL) over baseline value within 10-40 minutes of inhalation of 400 mcg salbutamol MDI (a spacer device may be used if required).
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- Positive skin prick test to common aero-allergen(s) at screening (not historical).
- Sputum sub-study only: Able to produce >100 milligram (mg) of sputum at screening or during the run-in period.
- Body weight >=45 kilogram (kg) and body mass index (BMI) within the range 18-32 kilogram per meter square (kg/m^2) (inclusive).
- Male subject: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the first dose of study medication until completion of the follow-up visit.
- Vasectomy with documentation of azoospermia.
- Male condom plus partner use of one of the contraceptive options below:
- Contraceptive subdermal implant with a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with 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.
- 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 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; 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.
- Reproductive potential and agrees to follow one of the options listed below in the GlaxoSmithKline (GSK) modified list of highly effective methods for avoiding pregnancy in females of reproductive potential (FRP) requirements from 30 days prior to the first dose of study medication and until completion of the follow-up visit.
- Contraceptive subdermal implant that meets the effectiveness criteria including a <1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the 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; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject; Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository).
- This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis. 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 the protocol which includes compliance with the requirements and restrictions listed in the consent form and the protocol. The informed consent must be signed prior to any study related procedure, including change in asthma medication.
Who cannot join
- History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures.
- Any severe asthma exacerbation, defined as deterioration of asthma requiring the use of systemic corticosteroids (oral, parenteral or depot) within 12 weeks of screening, or an inpatient hospitalisation or emergency department visit due to asthma that required systemic corticosteroids within 6 months of screening.
- Respiratory Infection: culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that has not resolved within 4 weeks of screening and led to a change in asthma management or, in the opinion of the investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
- Concurrent Respiratory Disease: current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, lung cancer, or other respiratory abnormalities other than asthma.
- Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) and bilirubin >1.5xULN (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).
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- QTc >450 millisecond (msec) or QTc >480 msec in subjects with bundle branch block.
- Other laboratory abnormalities or concurrent diseases/clinical: clinically significant laboratory abnormality, uncontrolled condition or disease state that, in the opinion of the investigator (in consultation with the GSK Medical Monitor, if required), would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
- Use of any of the prohibited medications listed in the protocol.
- Current smokers or subjects with a history of smoking within 6 months of screening, or with a total pack year history of >5 pack years.
- 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 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- History of sensitivity to any of the study medications, or components thereof (including lactose) or a history of drug or other allergy (including a milk protein allergy) that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- Sputum sub-study only: History of sensitivity to the induced sputum procedure.
- 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 medication.
- 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 dose of study medication 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 4 investigational medicinal products within 12 months prior to the first dose of study medication.
- Affiliation with investigator site: subject is an investigator; sub-investigator; study co-ordinator; employee of a participating investigator or study site; or, an immediate family member of the aforementioned, that is involved in this study.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
Germany12 sites
GSK Investigational Site
Berlin, 10119
GSK Investigational Site
Berlin, 10717
GSK Investigational Site
Berlin, 10787
GSK Investigational Site
Frankfurt am Main, Hesse, 60389
GSK Investigational Site
Frankfurt am Main, Hesse, 60596
GSK Investigational Site
Homburg, Saarland, 66421
GSK Investigational Site
Leipzig, Saxony, 04275
GSK Investigational Site
Leipzig, Saxony, 04357
GSK Investigational Site
Lübeck, Schleswig-Holstein, 23552
GSK Investigational Site
Magdeburg, 39120
GSK Investigational Site
Munich, Bavaria, 80539
GSK Investigational Site
Rüdersdorf, Brandenburg, 15562
About this study
Official title: A Multi-centre, Randomised, Double-blind, Placebo-controlled, Crossover Study to Investigate the Efficacy, Safety, and Tolerability of Repeat Doses of Inhaled GSK2269557 in Adults With Persistent, Uncontrolled Asthma
This study is a multi-centre, randomised, double-blind, placebo-controlled (with rescue medication), two period crossover study in subjects with persistent uncontrolled asthma, currently not treated with an inhaled corticosteroid (ICS) or long acting beta 2 agonist (LABA). This study is the first administration of GSK2269557 to asthmatic subjects, and the aims of the study are to investigate the efficacy, safety, tolerability, and pharmacokinetics of four weeks of treatment with orally inhaled GSK2269557 1000 microgram (mcg) in subjects with persistent uncontrolled asthma. In a sub-study, biological mediators will be measured from induced sputum and blood.
Approximately 50 subjects will be randomised into the study (including approximately 16 subjects in the sputum sub-study). Each subject will complete two treatment periods: subjects will be randomised to receive GSK2269557 1000 mcg in one treatment period, and matching placebo in the other treatment period. Each treatment will be administered once daily for 28 days (+/- 2 days) via the DISKUS™ dry powder inhaler (DPI).
The study will consist of a Screening Visit; a Run-in Period (approximately 2 weeks in duration); two 28-day Treatment Periods (each with 4 clinic visits); a 4-week Washout Period (between the Treatment Periods); and a Follow-up Visit. The total duration of the study for each subject will be approximately 16 weeks. DISKUS is a registered trademark of the GlaxoSmithKline group of companies.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- GSK2269557 DPI, Placebo DPI
- Keywords
- GSK2269557, Asthma, Pharmacokinetics, Safety, Adults, DISKUS Dry Powder Inhaler, Efficacy
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2269557 DPIDrug
GSK2269557 will be supplied as a lactose blend in a DISKUS DPI with a unit dose strength of 500 mcg. 2 inhalations will be taken every morning before breakfast.
Placebo DPIDrug
Placebo will be lactose in a DISKUS DPI. 2 inhalations will be taken every morning before breakfast.
| Study group | Role | What they receive |
|---|---|---|
| GSK2269557 and Placebo | Experimental | Each subject will complete two treatment periods: GSK2269557 1000 mcg in one treatment period, and matching placebo in the other treatment period. Each treatment will be administered once daily for 28 days (+/- 2 days) via the DISKUS DPI. The treatment periods will be separated by a washout of at least 4 weeks. Receives: Drug: GSK2269557 DPI; Drug: Placebo DPI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Intent-To-Treat (ITT) Population
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose).
Measured: Baseline and Day 28 for each treatment period
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Per Protocol (PP) Population
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose). The analysis was performed on the PP Population which comprised of all participants in the ITT Population not identified as major protocol violators.
Measured: Baseline and Day 28 for each treatment period
Secondary outcomes (16)
Weighted Mean (0-4 Hours) FEV1 at Day 28
The weighted mean FEV1 on Day 28 was calculated using data collected pre-dose and at 1 hour, 2 hours, 3 hours, and 4 hours post-dose. The weighted mean FEV1 was derived by calculating the average area under the curve using the trapezoidal rule, and then dividing by the relevant time interval.
Measured: Day 28 for each treatment period
Change From Baseline in Trough FEV1 at Day 7 and Day 14
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hrs after the last administration of study drug. Change from Baseline values were calculated as post-Baseline values minus Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Measured: Baseline, Day 7 and Day 14 for each treatment period
Change From Baseline in Forced Vital Capacity (FVC) at Day 7, Day 14 and Day 28
FVC is defined as the total amount of air exhaled during the FEV test. Data was collected pre-dose at Baseline (Day 1), Day 7, Day 14 and Day 28. Change from Baseline was calculated as the post-Baseline value minus the Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Measured: Baseline, Day 7, Day 14 and Day 28 for each treatment period
Change From Baseline in FEV1/FVC at Day 7, Day 14 and Day 28
FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the total amount of air exhaled during the FEV test. Change from Baseline in FEV1/FVC at Day 7, Day 14 and Day 28 was calculated as post-Baseline value minus Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Measured: Baseline, Day 7, Day 14 and Day 28 for each treatment period
Change From Baseline in Asthma Control Test (ACT) Score at Day 28
The total ACT score is the sum of five-item questionnaires developed as a measurement of asthma control. Total score can range from five (worse control) to 25 (full control), with higher scores reflecting greater asthma control. Total ACT score at Day 1 (Baseline) and Day 28 in both Treatment Periods was used for this analysis. Change from Baseline in ACT was calculated as post-Baseline value minus Baseline value where Baseline was defined as Day 1 (pre-dose).
Measured: Baseline and Day 28 for each treatment period
Change From Baseline in Daily FEV1 Averaged Over the Treatment Period
Triplicate measurements of FEV1 were collected in an eDiary pre-dose before breakfast [ante meridiem (AM)], and approximately 12 hours later at evening [post-meridiem (PM)]. The average change from Baseline was calculated by summing the total value of the endpoint (i.e. change from Baseline) within the time period of interest and dividing by the number of days with non-missing data for that endpoint to obtain an average for each subject. The AM Baseline is the Day 1 AM value, the PM Baseline is the last PM reading prior to taking the first dose of blinded study medication within that Treatment Period. The number of participants with data available at the specified time points are represented by n=X in the category titles.
Measured: Baseline and up to Day 28 for each treatment period
Change From Baseline in Daily Peak Expiratory Flow (PEF) Averaged Over the Treatment Period
Triplicate measurements of PEF were collected in an eDiary pre-dose before breakfast (AM), and approximately 12 hours later at evening (PM). The average change from Baseline was calculated by summing the total value of the endpoint (i.e. change from Baseline) within the time period of interest and dividing by the number of days with non-missing data for that endpoint to obtain an average for each subject. The AM Baseline is the Day 1 AM value, the PM Baseline is the last PM reading prior to taking the first dose of blinded study medication within that Treatment Period. The number of participants with data available at the specified time points are represented by n=X in the category titles.
Measured: Baseline and up to Day 28 for each treatment period
Change From Baseline in Trough Fractional Exhaled Nitric Oxide (FeNO) at Day 7, Day 14 and Day 28
Participants with asthma have high levels of NO in their exhaled breath. Evaluation of FeNO is a quantitative, noninvasive method of measuring airway inflammation to assess airway diseases including asthma. FeNO was measured in the clinic using a handheld electronic device. Change from Baseline for Day 7, Day 14 and Day 28 was calculated as the post-Baseline value minus the Baseline value where Baseline was defined as Day 1 (pre-dose). The number of participants with data available at the specified time points are represented by n=X in the category titles.
Measured: Baseline, Day 7, Day 14 and Day 28 for each treatment period
Mean Number of Inhalations Per Day of Rescue Medication (Salbutamol) Over the Treatment Period
Daily recordings of rescue medication use were collected in an eDiary by participants. The mean number of inhalations per day of rescue medication was calculated for each participant as number of inhalations over the time period of interest divided by number of days when rescue medication was taken over the time period of interest.
Measured: Up to Day 28 for each treatment period
Percentage of Rescue Free Days Over the Treatment Period
Daily recordings of rescue medication use were collected in an eDiary by participants. Percentage of rescue free days was calculated as the number of rescue free days divided by length of treatment period.
Measured: Up to Day 28 for each treatment period
Number of Participants With On-treatment Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. The analysis was performed on Safety Population which comprised of all participants who were randomized into the study.
Measured: From the Start of IP up to Week 14
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Blood samples were collected from participants for evaluation of clinical chemistry parameters by Potential Clinical Importance Criteria. The clinical chemistry parameters included albumin, calcium, creatinine, glucose, potassium and sodium. Participants were counted in the category that their value changes to (low, normal or high), unless there is no change in their category. The number of participants with data available at the specified data points are represented by n=X in the category titles.
Measured: From start of IP up to Week 14
Number of Participants With Abnormal Values of Hematology Parameters
Blood samples were collected from participants for evaluation of hematology parameters by Potential Clinical Importance Criteria. The hematology parameters included hematocrit, hemoglobin, lymphocytes, total neutrophils, platelets and white blood cells (WBC). Participants were counted in the category that their value changes to (low, normal or high), unless there is no change in their category. The number of participants with data available at the specified data points are represented by n=X in the category titles.
Measured: From start of IP up to Week 14
Number of Participants With Abnormal Vital Sign Values
Number of participants with abnormal values of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were evaluated. Vital signs outside the range of potential clinical importance are presented at the indicated timepoints: Day 7, Day 14, Day 28 and follow-up/Early withdrawal. The number of participants with data available at the specified data points are represented by n=X in the category titles.
Measured: From start of IP up to Week 14
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Single measurements of 12-lead ECGs were obtained after 5 minutes rest in a semi-supine position at Baseline (Day 1 pre dose) , Day 7, Day 28 pre-dose in each treatment period using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc). ECG values were recorded as abnormal not clinically significant (NCS) and abnormal clinically significant (CS). The number of participants with data available at the specified data points are represented by n= X in the category titles.
Measured: Up to Day 28 for each treatment period
Plasma Concentration of GSK2269557
Blood samples were collected from participants for pharmacokinetic (PK) analysis at Day 7, Day 14 and Day 28 pre dose. On Day 28 samples were also collected between 5-10 minutes post dose and between 2.5-3.5 hours post dose. The analysis was performed on PK Population which comprised of participants in the ITT Population for whom a PK sample was obtained and analyzed. The number of participants with data available at the specified data points are represented by n= X in the category titles.
Measured: Pre dose at Day 7 and Day 14. At Day 28 pre dose, 5-10 minutes and 2.5-3.5 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2015 (estimated)
- Study start1 Oct 2015
- Primary completion21 Sep 2016
- Study completion28 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 50 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
- NCT02567708
- Sponsor's protocol ID
- 201543
- Status last verified
- Feb 2018
- First submitted
- 20 Jul 2015
- Last updated
- 1 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Khindri S, Cahn A, Begg M, Montembault M, Leemereise C, Cui Y, Hogg A, Wajdner H, Yang S, Robertson J, Hamblin JN, Ludwig-Sengpiel A, Kornmann O, Hessel EM. A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Repeat Doses of Inhaled Nemiralisib in Adults with Persistent, Uncontrolled Asthma. J Pharmacol Exp Ther. 2018 Dec;367(3):405-413. doi: 10.1124/jpet.118.249516. Epub 2018 Sep 14.
PubMed 30217958
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Randomised, Double-blind, Placebo-controlled, Crossover Study to Investigate the Efficacy, Safety, and Tolerability of Repeat Doses of Inhaled GSK2269557 in Adults With Persistent, Uncontrolled Asthma
- ClinicalTrials.gov ID
- NCT02567708
- Acronym / sponsor ID
- 201543
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- GSK2269557, Asthma, Pharmacokinetics, Safety, Adults, DISKUS Dry Powder Inhaler, Efficacy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Oct 2015
- Primary completion
- 21 Sep 2016 (actual)
- Study completion
- 28 Sep 2016 (actual)
- First posted
- 5 Oct 2015 (estimated)
- Results
- Posted 1 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multi-centre, randomised, double-blind, placebo-controlled (with rescue medication), two period crossover study in subjects with persistent uncontrolled asthma, currently not treated with an inhaled corticosteroid (ICS) or long acting beta 2 agonist (LABA). This study is the first administration of GSK2269557 to asthmatic subjects, and the aims of the study are to investigate the efficacy, safety, tolerability, and pharmacokinetics of four weeks of treatment with orally inhaled GSK2269557 1000 microgram (mcg) in subjects with persistent uncontrolled asthma. In a sub-study, biological mediators will be measured from induced sputum and blood.
Approximately 50 subjects will be randomised into the study (including approximately 16 subjects in the sputum sub-study). Each subject will complete two treatment periods: subjects will be randomised to receive GSK2269557 1000 mcg in one treatment period, and matching placebo in the other treatment period. Each treatment will be administered once daily for 28 days (+/- 2 days) via the DISKUS™ dry powder inhaler (DPI).
The study will consist of a Screening Visit; a Run-in Period (approximately 2 weeks in duration); two 28-day Treatment Periods (each with 4 clinic visits); a 4-week Washout Period (between the Treatment Periods); and a Follow-up Visit. The total duration of the study for each subject will be approximately 16 weeks. DISKUS is a registered trademark of the GlaxoSmithKline group of companies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GSK2269557 and Placebo | Experimental | Drug: GSK2269557 DPI, Drug: Placebo DPIEach subject will complete two treatment periods: GSK2269557 1000 mcg in one treatment period, and matching placebo in the other treatment period. Each treatment will be administered once daily for 28 days (+/- 2 days) via the DISKUS DPI. The treatment periods will be separated by a washout of at least 4 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Between 18 and 70 years of age inclusive, at the time of signing the informed consent.
- Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with an intermittent short acting beta 2 agonist (SABA) or other non-corticosteroid controllers. Non corticosteroid controllers (e.g. leukotriene receptor antagonists [LTRAs]) must be discontinued from Screening until the end of Treatment Period 2.
- Able to replace current SABA treatment with salbutamol metered dose inhaler (MDI) at Screening for use as needed for the duration of the study. Judged capable of withholding salbutamol for at least 4 hours prior to FEV1 assessments.
- No use of an ICS or LABA for at least 12 weeks prior to first dose of study medication.
- A best pre-bronchodilator FEV1 >=60 percent (%) of the predicted normal value at screening.
Key exclusion criteria (18 listed)
- History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures.
- Any severe asthma exacerbation, defined as deterioration of asthma requiring the use of systemic corticosteroids (oral, parenteral or depot) within 12 weeks of screening, or an inpatient hospitalisation or emergency department visit due to asthma that required systemic corticosteroids within 6 months of screening.
- Respiratory Infection: culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that has not resolved within 4 weeks of screening and led to a change in asthma management or, in the opinion of the investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
- Concurrent Respiratory Disease: current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, lung cancer, or other respiratory abnormalities other than asthma.
- Alanine aminotransferase (ALT) >2x upper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
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 |
|---|---|---|
| GSK2269557 DPIGSK2269557 will be supplied as a lactose blend in a DISKUS DPI with a unit dose strength of 500 mcg. 2 inhalations will be taken every morning before breakfast. | Drug | GSK2269557 and Placebo |
| Placebo DPIPlacebo will be lactose in a DISKUS DPI. 2 inhalations will be taken every morning before breakfast. | Drug | GSK2269557 and Placebo |
Primary outcome
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Intent-To-Treat (ITT) Population
Time frame: Baseline and Day 28 for each treatment period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose).
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Per Protocol (PP) Population
Time frame: Baseline and Day 28 for each treatment period
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose). The analysis was performed on the PP Population which comprised of all participants in the ITT Population not identified as major protocol violators.
16 secondary outcomes
Weighted Mean (0-4 Hours) FEV1 at Day 28
Time frame: Day 28 for each treatment period
Change From Baseline in Trough FEV1 at Day 7 and Day 14
Time frame: Baseline, Day 7 and Day 14 for each treatment period
Change From Baseline in Forced Vital Capacity (FVC) at Day 7, Day 14 and Day 28
Time frame: Baseline, Day 7, Day 14 and Day 28 for each treatment period
Change From Baseline in FEV1/FVC at Day 7, Day 14 and Day 28
Time frame: Baseline, Day 7, Day 14 and Day 28 for each treatment period
Change From Baseline in Asthma Control Test (ACT) Score at Day 28
Time frame: Baseline and Day 28 for each treatment period
Change From Baseline in Daily FEV1 Averaged Over the Treatment Period
Time frame: Baseline and up to Day 28 for each treatment period
Change From Baseline in Daily Peak Expiratory Flow (PEF) Averaged Over the Treatment Period
Time frame: Baseline and up to Day 28 for each treatment period
Change From Baseline in Trough Fractional Exhaled Nitric Oxide (FeNO) at Day 7, Day 14 and Day 28
Time frame: Baseline, Day 7, Day 14 and Day 28 for each treatment period
Mean Number of Inhalations Per Day of Rescue Medication (Salbutamol) Over the Treatment Period
Time frame: Up to Day 28 for each treatment period
Percentage of Rescue Free Days Over the Treatment Period
Time frame: Up to Day 28 for each treatment period
Number of Participants With On-treatment Serious Adverse Events (SAEs) and Non-serious Adverse Events (AEs)
Time frame: From the Start of IP up to Week 14
Number of Participants With Abnormal Values of Clinical Chemistry Parameters
Time frame: From start of IP up to Week 14
Number of Participants With Abnormal Values of Hematology Parameters
Time frame: From start of IP up to Week 14
Number of Participants With Abnormal Vital Sign Values
Time frame: From start of IP up to Week 14
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to Day 28 for each treatment period
Plasma Concentration of GSK2269557
Time frame: Pre dose at Day 7 and Day 14. At Day 28 pre dose, 5-10 minutes and 2.5-3.5 hours post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30217958Khindri S, Cahn A, Begg M, Montembault M, Leemereise C, Cui Y, Hogg A, Wajdner H, Yang S, Robertson J, Hamblin JN, Ludwig-Sengpiel A, Kornmann O, Hessel EM. A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Repeat Doses of Inhaled Nemiralisib in Adults with Persistent, Uncontrolled Asthma. J Pharmacol Exp Ther. 2018 Dec;367(3):405-413. doi: 10.1124/jpet.118.249516. Epub 2018 Sep 14.
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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
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK2269557 DPI in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 12 sites in Germany.
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 19 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 1 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Intent-To-Treat (ITT) Population (time frame: Baseline and Day 28 for each treatment period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02567708, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2018.