Pulmonary Disease, Chronic ObstructivePhase 2NCT02522299
A Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 in Chronic Obstructive Pulmonary Disease (COPD) Subjects With Acute Exacerbation
A Phase 2 study testing GSK2269557, DISKUS and ELLIPTA in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 6 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate specific alterations in immune cell mechanisms related to neutrophil function as detected by PI3Kdelta-dependent changes in messenger ribonucleic acid (mRNA) extracted from induced sputum in patients experiencing an exacerbation of COPD, with or without treatment with… Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- GSK2269557, DISKUS and ELLIPTA
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 4 Nov 2015to 22 Jun 2018
- 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 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between 40 and 80 years of age inclusive, at the time of signing the informed consent.
- The subject has a confirmed and established diagnosis of COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for at least 6 months prior to entry.
- The subject is able to produce >100 milligram (mg) of sputum at screening for processing, (ie, total weight of sputum plugs).
- The subject has a post-bronchodilator FEV1/FVC <0.7 and FEV1 <=80 % of predicted.
- Disease severity: Acute exacerbation of COPD requiring an escalation in therapy to include both corticosteroid and antibiotics. Acute exacerbation to be confirmed by an experienced physician and represent a recent change in at least two major and one minor symptoms, one major and two minor symptoms, or all 3 major symptoms. Major symptoms: Subjective increase in dyspnea; Increase in sputum volume; Change in sputum colour. Minor symptoms: Cough; Wheeze; Sore throat
- The subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (pack years = [cigarettes per day smoked/20 x number of years smoked]).
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- Body weight >= 45 kilogram (kg) and body mass index (BMI) within the range 16 to 35 kilogram per meter square (kg/m^2) (inclusive)
- Male
- 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: (1)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. Females whose menopausal status is in doubt will be required to use, or have been using, one of the highly effective contraception methods as specified below from 30 days prior to the first dose of study medication and until completion of the follow-up visit. 2)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. GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP. 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. 1) Contraceptive subdermal implant that meets GSK standard criteria including a <1% rate of failure per year, as stated in the product label. 2) Intrauterine device or intrauterine system that meets GSK standard criteria including a <1% rate of failure per year, as stated in the product label. 3) Oral Contraceptive, either combined or progestogen alone. 4) Injectable progestogen. 5) Contraceptive vaginal ring. 6) Percutaneous contraceptive patches. 7) 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. 8) Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository). 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. Specific inclusion criteria for Male subjects with female partners of reproductive potential is outlined below: 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 after the completion of the follow up visit. 1) Vasectomy with documentation of azoospermia. 2) Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant that meets GSK standard criteria including a <1% rate of failure per year, as stated in the product label. Intrauterine device or intrauterine system that meets GSK standard 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 which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.
Who cannot join
- To avoid recruitment of subjects with a severe COPD exacerbation, the presence of any one of the following severity criteria will render the subject ineligible for inclusion in the study: Need for invasive mechanical ventilation (short term [<48 hour] Non-invasive ventilation [NIV] or continuous positive airway pressure [CPAP] is acceptable); Haemodynamic instability or clinically significant heart failure; Confusion; Clinically significant pneumonia, identified by chest X-ray at screening, and as judged by the Investigator.
- Subjects who have current medical conditions or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions (e.g. hypertension or noninsulin-dependent diabetes mellitus [NIDDM]) are permitted to be entered into the study).
- Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the subject or affect the interpretation of the results.
- ALT >2xupper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the exclusion criteria, outside of the reference range for the population being studied may be included if the Investigator [in consultation with the GSK Medical Monitor if required] documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- 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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- ECG indicative of an acute cardiac event (e.g. Myocardial Infarction) or demonstrating a clinically significant arrhythmia requiring treatment.
- QTcF > 450 msec or QTcF > 480 msec in subjects with Bundle Branch Block, based on single QTcF value.
- Subjects who have undergone lung volume reduction surgery.
- Subject is currently on chronic treatment with macrolides or long term antibiotics.
- Subject is being treated with long term oxygen therapy (LTOT) (>15 hours/day).
- The subject has been on chronic treatment with anti-Tumour Necrosis Factor (anti-TNF), or any other immunosuppressive therapy (except corticosteroid) within 60 days prior to dosing
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >28 units for males or >21 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (~240 milliliter [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 (such as lactose) or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
- A known (historical) positive test for human immunodeficiency virus (HIV) antibody.
- 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. NOTE: Because of the short window for screening, treatment with GSK2269557 may start before receiving the result of the hepatitis tests. If subsequently the test is found to be positive, the subject may be withdrawn, as judged by the Principal Investigator in consultation with the Medical Monitor.
- 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 4 investigational medicinal products within 12 months prior to the first dosing day.
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
Canada5 sites
GSK Investigational Site
Hamilton, Ontario, L8N 3Z5
GSK Investigational Site
Montreal, Ontario, H4A 3J1
GSK Investigational Site
Montreal, Quebec, H2W1T8
GSK Investigational Site
Québec, Quebec, G1V 4G5
GSK Investigational Site
Vancouver, British Columbia, V5Z 1M9
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 for 12 Weeks in Adult Subjects Diagnosed With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)
The purpose of this study is to evaluate specific alterations in immune cell mechanisms related to neutrophil function as detected by PI3Kdelta-dependent changes in messenger ribonucleic acid (mRNA) extracted from induced sputum in patients experiencing an exacerbation of COPD, with or without treatment with GSK2269557. The efficacy of treatment with GSK2269557 will also be measured using functional respiratory imaging (FRI) and spirometry. This is a randomised, double-blind, placebo-controlled, parallel-group study. The study consisted of Screening Phase (up to 3 days prior to Day 1), Treatment Phase (Days 1 to 84) and Follow phase (7 to 14 days after last dose). The total duration of the study is 13-14 weeks including the screening visit. DISKUS TM and ELLIPTA TM are registered trademark of GSK group of companies.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- GSK2269557, Placebo, DISKUS, ELLIPTA
- Keywords
- double-blind, PI3Kdelta, GSK2269557, exacerbation, Chronic Obstructive Pulmonary Disease, randomised, placebo-controlled
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK2269557Drug
GSK2269557 500 mcg blended with lactose per blister and will be administered using a DISKUS dry powder inhaler device. Since GSK2269557 will no longer be manufactured for use with the DISKUS device, it will be replaced with ELLIPTA Device. Subjects will receive GSK2269557 700 mcg once daily for 84 consecutive days via ELLIPTA.
PlaceboDrug
Lactose will be administered using a DISKUS and ELLIPTA dry powder inhaler device
DISKUSDevice
It is multi-dose dry powder inhaler containing one foil strip of drug with 60 blisters
ELLIPTADevice
It is multi-dose dry powder inhaler containing one foil strip of drug with 30 blisters
| Study group | Role | What they receive |
|---|---|---|
| GSK2269557 1000 microgram (mcg) | Experimental | Subjects will receive 2 inhalations of GSK2269557 (30 seconds apart, 2 x 500 mcg, total dose of 1000 mcg) once daily for 84 consecutive days via DISKUS™ device. Receives: Drug: GSK2269557; Device: DISKUS |
| Placebo via DISKUS | Placebo comparator | Subjects will receive 2 inhalations of placebo once daily for 84 days via DISKUS device. Receives: Drug: Placebo; Device: DISKUS |
| GSK2269557 700 mcg | Experimental | Subjects will receive 2 inhalations of GSK2269557 700 mcg once daily for 84 consecutive days via ELLIPTA. Receives: Device: ELLIPTA |
| Placebo via ELLIPTA | Placebo comparator | Subjects will receive Placebo once daily for 84 consecutive days via ELLIPTA. Receives: Drug: Placebo; Device: ELLIPTA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in NEMI Treatment Group
Saline-induced sputum samples were collected at the indicated time-points to determine the alterations in previously identified immune cell mechanisms specifically related to neutrophil function by identifying the changes in mRNA transcriptome in induced sputum. Baseline was defined as screening visit. The log2 transformed mRNA intensities for each probe set were analyzed in a separate repeated measures model. Back transformed baseline-adjusted ratios and two-sided unadjusted p-values were calculated for each visit as the specified time-point value/baseline value. These ratios were converted to fold change values; if ratio >= 1 then fold change=ratio or if ratio < 1 then fold change = -1/ratio. Data for pre-specified probe sets that meet the criteria fold change >1.5 or <-1.5 and p<0.05 for All NEMI, All Placebo and All NEMI/All Placebo group is presented in outcome measure 1, 2 and 3 respectively. In the categories column we have included time-point, Probe ID and Gene label.
Measured: Baseline (Screening) and Days 12, 28 and 84
Change in mRNA Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in Placebo Treatment Group
Saline-induced sputum samples were collected at the indicated time-points to determine the alterations in previously identified immune cell mechanisms specifically related to neutrophil function by identifying the changes in mRNA transcriptome in induced sputum. Baseline was defined as screening visit. The log2 transformed mRNA intensities for each probe set were analysed in a separate repeated measures model. Back transformed baseline-adjusted ratios and two-sided unadjusted p-values were calculated for each visit as the specified time-point value/baseline value. These ratios were converted to fold change values; if ratio >= 1 then fold change=ratio or if ratio < 1 then fold change = -1/ratio. Data for pre-specified probe sets that meet the criteria fold change >1.5 or <-1.5 and p<0.05 for All NEMI, All Placebo and All NEMI/All Placebo group is presented in outcome measure 1, 2 and 3 respectively. In the categories column we have included time-point, Probe ID and Gene label.
Measured: Baseline (Screening) and Days 12, 28 and 84
Change in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in All NEMI/All Placebo Comparison Treatment Group
Saline-induced sputum samples were collected at the indicated time-points to determine the alterations in previously identified immune cell mechanisms specifically related to neutrophil function by identifying the changes in mRNA transcriptome in induced sputum. For each probe set, the log2 transformed mRNA intensities were analyzed in separate repeated measures models. The models included a Treatment, Visit and Treatment*Visit term. The Visit consisted of 4 levels: Screening (Baseline), Day 12, Day 28 and Day 84, and the Treatment consisted of three levels: Null (when Visit = Screening), All Placebo and All NEMI. The fold changes were derived from the back transformed ratio from Baselines as fold change = ratio if ratio is >=1, else if ratio <1 then fold change = -1/ratio. Data for pre-specified probe sets that meet the criteria fold change >1.5 and p<0.05 for All NEMI, All Placebo and All NEMI/All Placebo group is presented in outcome measure 1, 2 and 3 respectively.
Measured: Baseline (Screening) and Days 12, 28 and 84
Secondary outcomes (30)
Change From Baseline in Specific Imaging Airway Volume (siVaw) at Functional Residual Capacity (FRC) and Total Lung Capacity (TLC) for Individual Lobes
siVaw was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Baseline (Screening), Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (n=X1, X2 in the category title). This table presents the untrimmed data (in rows with categories containing untrimmed), SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening), Days 12 and 28
Change From Baseline (Day 12) in siVaw at FRC and TLC for Individual Lobes at Day 28
siVaw is a measure of the volume in an individual's airway corrected for their lobar volume derived from the high resolution computed tomography (HRCT). It was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Baseline (Screening), Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in siVaw at FRC and TLC for Individual Regions
siVaw was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Baseline (Screening), Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (n=X1, X2 in the category title).This table presents the untrimmed data (in rows with categories containing untrimmed), SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening), Days 12 and 28
Change From Baseline (Day 12) in siVaw at FRC and TLC for Individual Regions at Day 28
siVaw is a measure of the volume in an individual's airway corrected for their lobar volume derived from the high resolution computed tomography (HRCT). It was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Baseline (Screening), Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in Imaging Airway Volume (iVaw) at FRC and TLC for Individual Lobes
iVaw was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Screening, Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (n=X1, X2 in the category title). This table presents the untrimmed data (in rows with categories containing untrimmed), SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iVaw at FRC and TLC for Individual Lobes at Day 28
iVaw is a measure of the volume in an individual's airway derived from the HRCT. It was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Screening, Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in iVaw at FRC and TLC for Individual Regions
iVaw was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Screening, Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (n=X1, X2 in the category title). This table presents the untrimmed data (in rows with categories containing untrimmed), SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iVaw at FRC and TLC for Individual Regions at Day 28
iVaw is a measure of the volume in an individual's airway derived from the HRCT. It was measured at FRC and TLC. Data was collected at longitudinal time points (Untrimmed data): Screening, Day 12 \& Day 28 and at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For Untrimmed data and SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in Imaging Airway Resistance (iRaw) at FRC and TLC for Individual Lobes
iRaw is a measure of the resistance in an individual's airway derived from HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (represented by n=X1, X2 in the category title). • This table presents the SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iRaw at FRC and TLC for Individual Lobes at Day 28
iRaw is a measure of the resistance in an individual's airway derived from HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in iRaw at FRC and TLC for Individual Regions
iRaw is a measure of the resistance in an individual's airway derived from HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (n=X1, X2 in the category title). This table presents the SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iRaw at FRC and TLC for Individual Regions at Day 28
iRaw is a measure of the resistance in an individual's airway derived from HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analyzed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Lobes
siRaw is a measure of the resistance in an individual's airway corrected for their lobar volume derived from the HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analysed (represented by n=X1, X2 in the category title). This table presents the SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Lobes at Day 28
siRaw is a measure of the resistance in an individual's airway corrected for their lobar volume derived from the HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analysed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Regions
siRaw is a measure of the resistance in an individual's airway corrected for their lobar volume derived from the HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analysed (represented by n=X1, X2 in the category title). This table presents the SCRD12 scan trim pair data (in rows with categories containing Scan Trimmed and Day 12) and SCRD28 scan trim pair data (in rows with categories containing Scan Trimmed and Day 28) only.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Regions at Day 28
siRaw is a measure of the resistance in an individual's airway corrected for their lobar volume derived from the HRCT. It was measured at FRC and TLC. Data was collected at each time point for scan trimmed pairs: SCRD12, SCRD28 \& D12D28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe) and 5 Regions (Upper, Lower, Central, Distal \& Total). For SCRD12 \& SCRD28 scan trimmed pairs the baseline is screening, for D12D28 scan trimmed pair the baseline is D12. Change from baseline is the post-Baseline value minus the Baseline value. Only participants available at the specified time point were analysed (represented by n=X1, X2 in the category title). This table presents the D12D28 scan trim pair data only.
Measured: Baseline (Day 12) and Day 28
Change From Baseline in Lung Lobar Volume (iVlobe) at FRC and TLC for Individual Lobes
Change from Baseline in lung lobar volumes was measured at FRC and TLC scan conditions. Data was collected at longitudinal time points: Baseline (Screening), Day 12 and Day 28. At each time point it was measure at 5 lobes (right upper lobe, left upper lobe, right middle lobe, right lower lobe \& left lower lobe). The value at Screening was considered as Baseline. Change from baseline is the post-Baseline value minus the Baseline value. The study had a protocol amendment to reflect changes in manufacturing device from DISKUS to ELLIPTA after study had been initiated, but the 2 treatment arms remained the same i.e. Placebo and NEMI.There was no intent to compare two devices.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline in Lung Lobar Volume (iVlobe) at FRC and TLC for Individual Regions
Change from Baseline in lung lobar volumes was measured at FRC and TLC scan conditions. Data was collected at longitudinal time points: Baseline (Screening), Day 12 and Day 28. At each time point it was measure at 5 Regions (Upper, Lower, Central, Distal \& Total). The value at Screening was considered as Baseline. Change from Baseline is the post-Baseline value minus the Baseline value. The study had a protocol amendment to reflect changes in manufacturing device from DISKUS to ELLIPTA after study had been initiated, but the 2 treatment arms remained the same i.e. Placebo and NEMI.There was no intent to compare two devices.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline in Trachea Length and Diameter at FRC and TLC
Trachea length and diameter was derived from HRCT. It was measured at both FRC and TLC scan conditions. The value at Screening was considered as Baseline. Change from Baseline is the post-Baseline value minus the Baseline value. The change from Baseline data is presented for Day 12 and Day 28 for trachea length and diameter. The study had a protocol amendment to reflect changes in manufacturing device from DISKUS to ELLIPTA after study had been initiated, but the 2 treatment arms remained the same i.e. Placebo and NEMI.There was no intent to compare two devices.
Measured: Baseline (Screening) and Days 12 and 28
Change From Baseline (Average Day 1 to 3) Peak Expiratory Flow (PEF)
PEF measurements were taken (in triplicate) daily in the morning before dose administration, as soon as it is safe for the participant to do so. The best/highest result was recorded. Participants were provided with a handheld device. Baseline here is defined as average of Day 1 to Day 3. Change from Baseline is the post-Baseline value minus the Baseline value. The study had a protocol amendment to reflect changes in manufacturing device from DISKUS to ELLIPTA after study had been initiated, but the 2 treatment arms remained the same i.e. Placebo and NEMI. There was no intent to compare two devices.
Measured: Baseline and up to Day 84
Mean Number of Occasions of Rescue Usage Per Day
For reliever/rescue use, bronchodilator use recorded in the diary was summarized as the mean number of occasions of rescue use per day.where a rescue-free day was defined as a 24-hour period in which the number of occasions of bronchodilator use was zero. Number of occasions bronchodilator taken in the last 24 hours were collected in the daily diary. The mean number of occasions of rescue use per day, were calculated for each participant during the four weekly periods (Weeks 1 to 4; Weeks 5-8 and Weeks 9-12). The study had a protocol amendment to reflect changes in manufacturing device from DISKUS to ELLIPTA after study had been initiated, but the 2 treatment arms remained the same i.e. Placebo and NEMI.There was no intent to compare two devices.
Measured: Weeks 1 to 4; Weeks 5 to 8 and Weeks 9 to 12
Mean Rescue Medication Free Days
For reliever/rescue use, bronchodilator use recorded in the diary was summarized as the mean number of occasions of rescue use per day, where a rescue-free day was defined as a 24-hour period in which the number of occasions of bronchodilator use was zero. Number of occasions bronchodilator taken in the last 24 hours were collected in the daily diary. The mean number of rescue free days were calculated for each participant during the four weekly periods (Weeks 1 to 4; Weeks 5-8 and Weeks 9-12). The study had a protocol amendment to reflect changes in manufacturing device from DISKUS to ELLIPTA after study had been initiated, but the 2 treatment arms remained the same i.e. Placebo and NEMI. There was no intent to compare two devices.
Measured: Weeks 1 to 4; Weeks 5 to 8 and Weeks 9 to 12
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC)
FEV1 is the volume of air that can forcibly be blown out in one second. A triplicate FEV1 measurement were taken daily in the morning before dose administration using the site's spirometer as soon as it was safe to do so. FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. Baseline is the latest available measurement from Day 2 Within 48 hours /discharge (On Treatment) and Day 1 (Pre-Treatment). Change from Baseline is the post-Baseline value minus Baseline value. The study had a protocol amendment to reflect changes in manufacturing device from DISKUS to ELLIPTA after study had been initiated, but the 2 treatment arms remained the same i.e. Placebo and NEMI.There was no intent to compare two devices.
Measured: Baseline and Days 12, 28, 56, 84
Number of Participants With Worst Case Hematology Results Post-Baseline Relative to Baseline
Blood samples were collected to analyze the following s hematology parameters: Hemoglobin, Hematocrit, Mean Corpuscle Hemoglobin (MCH), Mean Corpuscle Volume (MCV), Platelet count, Red Blood Cell (RBC) count, White Blood Cell (WBC) count, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils. Participants were counted in the worst case category that their value changes to (low or high), unless there is no change in their category. Participants whose lab value category was unchanged (example given [e.g.],High to High), or whose value became normal, were not recorded. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. The value at Screening was considered as Baseline. Data for Worst Case Laboratory Hematology values Post-Baseline Relative to Baseline has been presented.
Measured: Baseline (Screening) and up to 14 weeks
Number of Participants With Worst Case Chemistry Results Post-Baseline Relative to Baseline
Blood samples were collected to analyze the following Chemistry parameters: Albumin, Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Direct Bilirubin, Total Bilirubin, Calcium, C-Reactive protein, Creatinine, Glucose, Potassium, Sodium, Total Protein and Urea/Blood urea nitrogen. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose lab value category was unchanged e.g. High to High), or whose value became normal, were not recorded. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. The value at Screening was considered as Baseline. Data for Worst Case Laboratory chemistry values Post-Baseline Relative to Baseline has been presented.
Measured: Baseline (Screening) and up to 14 weeks
Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Vital signs were measured in semi-supine position after 5 minutes rest and included Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Heart rate (HR). Data for number of participants with Post-Baseline worst case Vital Sign results relative to PCI Criteria relative to Baseline was presented. PCI ranges were: SBP (lower: <85 and upper: >160 mmHg), DBP (lower: <45 and upper: >100 mmHg), and HR (lower: <40 and upper: >110 bpm). The value at Screening was considered as Baseline.
Measured: Baseline (Screening) and up to 14 weeks
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
A Single 12-lead ECGs was obtained at screening and at each other timepoint during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. Data for number of participants with worst case post-Baseline abnormal ECG findings was reported. The value at Screening was considered as Baseline.
Measured: Up to 14 weeks
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is any untoward medical occurrence in a clinical investigation participant, or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that at any dose, resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, is associated with liver injury and impaired liver function or any other situation according to medical or scientific judgment was categorized as SAE. Number of participants with AEs and SAEs have been reported.
Measured: Up to 14 weeks
Maximum Plasma Concentration (Cmax) Following Administration of NEMI
Blood samples for pharmacokinetic (PK) analysis was collected at the indicated time points following administration of NEMI via DISKUS and ELLIPTA.
Measured: Day 1: 5 minutes Post-dose on Day 1
Trough Concentration Following Administration of NEMI
Blood samples for pharmacokinetic (PK) analysis was collected at the indicated time points following administration of NEMI via DISKUS and ELLIPTA.
Measured: Day 1: 24 Hours post-dose; Days 12, 28, 56, 84: Pre-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2015 (estimated)
- Study start4 Nov 2015
- Primary completion15 Jun 2018
- Study completion22 Jun 2018
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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 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
- NCT02522299
- Sponsor's protocol ID
- 201928
- Other IDs
- 2015-003696-30, 2015
- Status last verified
- Aug 2021
- First submitted
- 3 Aug 2015
- Last updated
- 5 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD for this study is available via the Clinical Study Data Request site
Publications
Begg M, Hamblin JN, Jarvis E, Bradley G, Mark S, Michalovich D, Lennon M, Wajdner HE, Amour A, Wilson R, Saunders K, Tanaka R, Arai S, Tang T, Van Holsbeke C, De Backer J, Vos W, Titlestad IL, FitzGerald JM, Killian K, Bourbeau J, Poirier C, Maltais F, Cahn A, Hessel EM. Exploring PI3Kdelta Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials. Int J Chron Obstruct Pulmon Dis. 2021 Jun 3;16:1621-1636. doi: 10.2147/COPD.S309303. eCollection 2021.
PubMed 34113094
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Efficacy and Changes in Induced Sputum and Blood Biomarkers Following Daily Repeat Doses of Inhaled GSK2269557 for 12 Weeks in Adult Subjects Diagnosed With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD)
- ClinicalTrials.gov ID
- NCT02522299
- Acronym / sponsor ID
- 201928
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- double-blind, PI3Kdelta, GSK2269557, exacerbation, Chronic Obstructive Pulmonary Disease, randomised, placebo-controlled
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2015 (actual)
- Primary completion
- 15 Jun 2018 (actual)
- Study completion
- 22 Jun 2018 (actual)
- First posted
- 13 Aug 2015 (estimated)
- Results
- Posted 25 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate specific alterations in immune cell mechanisms related to neutrophil function as detected by PI3Kdelta-dependent changes in messenger ribonucleic acid (mRNA) extracted from induced sputum in patients experiencing an exacerbation of COPD, with or without treatment with GSK2269557. The efficacy of treatment with GSK2269557 will also be measured using functional respiratory imaging (FRI) and spirometry. This is a randomised, double-blind, placebo-controlled, parallel-group study. The study consisted of Screening Phase (up to 3 days prior to Day 1), Treatment Phase (Days 1 to 84) and Follow phase (7 to 14 days after last dose). The total duration of the study is 13-14 weeks including the screening visit. DISKUS TM and ELLIPTA TM are registered trademark of GSK group of companies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| GSK2269557 1000 microgram (mcg) | Experimental | Drug: GSK2269557, Device: DISKUSSubjects will receive 2 inhalations of GSK2269557 (30 seconds apart, 2 x 500 mcg, total dose of 1000 mcg) once daily for 84 consecutive days via DISKUS™ device. |
| Placebo via DISKUS | Placebo comparator | Drug: Placebo, Device: DISKUSSubjects will receive 2 inhalations of placebo once daily for 84 days via DISKUS device. |
| GSK2269557 700 mcg | Experimental | Device: ELLIPTASubjects will receive 2 inhalations of GSK2269557 700 mcg once daily for 84 consecutive days via ELLIPTA. |
| Placebo via ELLIPTA | Placebo comparator | Drug: Placebo, Device: ELLIPTASubjects will receive Placebo once daily for 84 consecutive days via ELLIPTA. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Between 40 and 80 years of age inclusive, at the time of signing the informed consent.
- The subject has a confirmed and established diagnosis of COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for at least 6 months prior to entry.
- The subject is able to produce >100 milligram (mg) of sputum at screening for processing, (ie, total weight of sputum plugs).
- The subject has a post-bronchodilator FEV1/FVC <0.7 and FEV1 <=80 % of predicted.
- Disease severity: Acute exacerbation of COPD requiring an escalation in therapy to include both corticosteroid and antibiotics. Acute exacerbation to be confirmed by an experienced physician and represent a recent change in at least two major and one minor symptoms, one major and two minor symptoms, or all 3 major symptoms. Major symptoms: Subjective increase in dyspnea; Increase in sputum volume; Change in sputum colour. Minor symptoms: Cough; Wheeze; Sore throat
Key exclusion criteria (19 listed)
- To avoid recruitment of subjects with a severe COPD exacerbation, the presence of any one of the following severity criteria will render the subject ineligible for inclusion in the study: Need for invasive mechanical ventilation (short term [<48 hour] Non-invasive ventilation [NIV] or continuous positive airway pressure [CPAP] is acceptable); Haemodynamic instability or clinically significant heart failure; Confusion; Clinically significant pneumonia, identified by chest X-ray at screening, and as judged by the Investigator.
- Subjects who have current medical conditions or diseases that are not well controlled and, which as judged by the Investigator, may affect subject safety or influence the outcome of the study. (Note: Patients with adequately treated and well controlled concurrent medical conditions (e.g. hypertension or noninsulin-dependent diabetes mellitus [NIDDM]) are permitted to be entered into the study).
- Subject has a diagnosis of active tuberculosis, lung cancer, clinically overt bronchiectasis, pulmonary fibrosis, asthma or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the subject or affect the interpretation of the results.
- ALT >2xupper limit of normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the exclusion criteria, outside of the reference range for the population being studied may be included if the Investigator [in consultation with the GSK Medical Monitor if required] documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
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 |
|---|---|---|
| GSK2269557GSK2269557 500 mcg blended with lactose per blister and will be administered using a DISKUS dry powder inhaler device. Since GSK2269557 will no longer be manufactured for use with the DISKUS device, it will be replaced with ELLIPTA Device. Subjects will receive GSK2269557 700 mcg once daily for 84 consecutive days via ELLIPTA. | Drug | GSK2269557 1000 microgram (mcg) |
| PlaceboLactose will be administered using a DISKUS and ELLIPTA dry powder inhaler device | Drug | Placebo via DISKUS, Placebo via ELLIPTA |
| DISKUSIt is multi-dose dry powder inhaler containing one foil strip of drug with 60 blisters | Device | GSK2269557 1000 microgram (mcg), Placebo via DISKUS |
| ELLIPTAIt is multi-dose dry powder inhaler containing one foil strip of drug with 30 blisters | Device | GSK2269557 700 mcg, Placebo via ELLIPTA |
Primary outcome
Change in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in NEMI Treatment Group
Time frame: Baseline (Screening) and Days 12, 28 and 84
Saline-induced sputum samples were collected at the indicated time-points to determine the alterations in previously identified immune cell mechanisms specifically related to neutrophil function by identifying the changes in mRNA transcriptome in induced sputum. Baseline was defined as screening visit. The log2 transformed mRNA intensities for each probe set were analyzed in a separate repeated measures model. Back transformed baseline-adjusted ratios and two-sided unadjusted p-values were calculated for each visit as the specified time-point value/baseline value. These ratios were converted to fold change values; if ratio >= 1 then fold change=ratio or if ratio < 1 then fold change = -1/ratio. Data for pre-specified probe sets that meet the criteria fold change >1.5 or <-1.5 and p<0.05 for All NEMI, All Placebo and All NEMI/All Placebo group is presented in outcome measure 1, 2 and 3 respectively. In the categories column we have included time-point, Probe ID and Gene label.
Change in mRNA Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in Placebo Treatment Group
Time frame: Baseline (Screening) and Days 12, 28 and 84
Saline-induced sputum samples were collected at the indicated time-points to determine the alterations in previously identified immune cell mechanisms specifically related to neutrophil function by identifying the changes in mRNA transcriptome in induced sputum. Baseline was defined as screening visit. The log2 transformed mRNA intensities for each probe set were analysed in a separate repeated measures model. Back transformed baseline-adjusted ratios and two-sided unadjusted p-values were calculated for each visit as the specified time-point value/baseline value. These ratios were converted to fold change values; if ratio >= 1 then fold change=ratio or if ratio < 1 then fold change = -1/ratio. Data for pre-specified probe sets that meet the criteria fold change >1.5 or <-1.5 and p<0.05 for All NEMI, All Placebo and All NEMI/All Placebo group is presented in outcome measure 1, 2 and 3 respectively. In the categories column we have included time-point, Probe ID and Gene label.
Change in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in All NEMI/All Placebo Comparison Treatment Group
Time frame: Baseline (Screening) and Days 12, 28 and 84
Saline-induced sputum samples were collected at the indicated time-points to determine the alterations in previously identified immune cell mechanisms specifically related to neutrophil function by identifying the changes in mRNA transcriptome in induced sputum. For each probe set, the log2 transformed mRNA intensities were analyzed in separate repeated measures models. The models included a Treatment, Visit and Treatment*Visit term. The Visit consisted of 4 levels: Screening (Baseline), Day 12, Day 28 and Day 84, and the Treatment consisted of three levels: Null (when Visit = Screening), All Placebo and All NEMI. The fold changes were derived from the back transformed ratio from Baselines as fold change = ratio if ratio is >=1, else if ratio <1 then fold change = -1/ratio. Data for pre-specified probe sets that meet the criteria fold change >1.5 and p<0.05 for All NEMI, All Placebo and All NEMI/All Placebo group is presented in outcome measure 1, 2 and 3 respectively.
30 secondary outcomes
Change From Baseline in Specific Imaging Airway Volume (siVaw) at Functional Residual Capacity (FRC) and Total Lung Capacity (TLC) for Individual Lobes
Time frame: Baseline (Screening), Days 12 and 28
Change From Baseline (Day 12) in siVaw at FRC and TLC for Individual Lobes at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in siVaw at FRC and TLC for Individual Regions
Time frame: Baseline (Screening), Days 12 and 28
Change From Baseline (Day 12) in siVaw at FRC and TLC for Individual Regions at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in Imaging Airway Volume (iVaw) at FRC and TLC for Individual Lobes
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iVaw at FRC and TLC for Individual Lobes at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in iVaw at FRC and TLC for Individual Regions
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iVaw at FRC and TLC for Individual Regions at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in Imaging Airway Resistance (iRaw) at FRC and TLC for Individual Lobes
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iRaw at FRC and TLC for Individual Lobes at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in iRaw at FRC and TLC for Individual Regions
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in iRaw at FRC and TLC for Individual Regions at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Lobes
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Lobes at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Regions
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline (Day 12) in Specific Imaging Airway Resistance (siRaw) at FRC and TLC for Individual Regions at Day 28
Time frame: Baseline (Day 12) and Day 28
Change From Baseline in Lung Lobar Volume (iVlobe) at FRC and TLC for Individual Lobes
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline in Lung Lobar Volume (iVlobe) at FRC and TLC for Individual Regions
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline in Trachea Length and Diameter at FRC and TLC
Time frame: Baseline (Screening) and Days 12 and 28
Change From Baseline (Average Day 1 to 3) Peak Expiratory Flow (PEF)
Time frame: Baseline and up to Day 84
Mean Number of Occasions of Rescue Usage Per Day
Time frame: Weeks 1 to 4; Weeks 5 to 8 and Weeks 9 to 12
Mean Rescue Medication Free Days
Time frame: Weeks 1 to 4; Weeks 5 to 8 and Weeks 9 to 12
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC)
Time frame: Baseline and Days 12, 28, 56, 84
Number of Participants With Worst Case Hematology Results Post-Baseline Relative to Baseline
Time frame: Baseline (Screening) and up to 14 weeks
Number of Participants With Worst Case Chemistry Results Post-Baseline Relative to Baseline
Time frame: Baseline (Screening) and up to 14 weeks
Number of Participants With Worst Case Vital Sign Results Relative to Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Time frame: Baseline (Screening) and up to 14 weeks
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Time frame: Up to 14 weeks
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
Time frame: Up to 14 weeks
Maximum Plasma Concentration (Cmax) Following Administration of NEMI
Time frame: Day 1: 5 minutes Post-dose on Day 1
Trough Concentration Following Administration of NEMI
Time frame: Day 1: 24 Hours post-dose; Days 12, 28, 56, 84: Pre-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34113094Begg M, Hamblin JN, Jarvis E, Bradley G, Mark S, Michalovich D, Lennon M, Wajdner HE, Amour A, Wilson R, Saunders K, Tanaka R, Arai S, Tang T, Van Holsbeke C, De Backer J, Vos W, Titlestad IL, FitzGerald JM, Killian K, Bourbeau J, Poirier C, Maltais F, Cahn A, Hessel EM. Exploring PI3Kdelta Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials. Int J Chron Obstruct Pulmon Dis. 2021 Jun 3;16:1621-1636. doi: 10.2147/COPD.S309303. eCollection 2021.
- Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request 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
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GSK2269557, DISKUS and ELLIPTA in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 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 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Canada, Denmark. 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 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 25 Nov 2019). 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 in Messenger Ribonucleic Acid (mRNA) Transcriptome in Induced Sputum After 12, 28 and 84 Days of Treatment (Selected Probe Sets With Fold Change >1.5 or <-1.5 and p<0.05) in NEMI Treatment Group (time frame: Baseline (Screening) and Days 12, 28 and 84). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02522299, 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 5 Sep 2021.