Idiopathic Pulmonary FibrosisPhase 1NCT01725139

A Proof of Mechanism Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

A Phase 1 study testing GSK2126458 in people with Idiopathic Pulmonary Fibrosis, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 45 years and older
Conditions the study is for: Idiopathic Pulmonary Fibrosis
What is being tested?: GSK2126458
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 17 participants
Where: 1 siteUnited Kingdom
Study dates: 8 Mar 2013to 12 Jul 2016
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 45 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Diagnosis of IPF as determined by a responsible and experienced chest physician and based on established criteria defined by the American Thoracic Society/European Respiratory Society: American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias.
FVC greater than (>) 40% predicted and Diffusing capacity of the Lung for Carbon Monoxide (DLCO) >30% predicted
Alanine aminotransferase (ALT) less than (<) 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin less than or equal to (<=) 1.5xULN.
QTcB <450 milliseconds (msec) and QTc interval <=480 msec; or QTc <480 msec in subjects with Bundle Branch Block.
Male over 45 years of age inclusive, or female over 50 years of age inclusive at the time of signing the informed consent
A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhoea. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception, 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. For most forms of HRT, at least 2 to 4 weeks should elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.

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Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until the follow-up contact.
Body weight >=40 kilogram (kg) (female), >=50 kg (male), and body mass index (BMI) between 20 and 35 kg/meter squared (m^2) inclusive.
Subjects must have left ventricular ejection fraction (LVEF) >=50 % as demonstrated by a recent echocardiogram (at screening or within 3 months prior to screening).

Who cannot join

Current IPF exacerbation
History of acute coronary syndromes, atrial fibrillation, coronary angioplasty, or stenting within the past 24 weeks.
Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
Uncontrolled hypertension or a history of conditions which could increase the risk of complications from hypertension
Current upper or lower respiratory tract infection
Repeated systolic BP >=160 millimeters of mercury (mmHg) and/or diastolic BP >=90 mmHg unless they are diabetic, in which case subjects with repeated systolic BP >=145 mmHg and/or diastolic >=85 mmHg

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Poorly controlled diabetes (HbA1c [glycated hemoglobin (hemoglobin A1c)] >7.5%).
Clinically significant laboratory assessment outside the reference range unless the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Current or chronic history of liver disease, or known hepatic or biliary abnormalities
Previous exposure to ionising radiation >5 millisievert (mSv) in the 3 years prior to enrolment
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 g of alcohol: a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
Subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day
Currently taking Pirfenidone or have received Pirfenidone within the previous 30 days
Unable to refrain from the use of prohibited prescription or non-prescription drugs, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety
History of sensitivity to any of the study medications, or components there of or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period
History of sensitivity to heparin or heparin-induced thrombocytopenia

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
London, SW3 6NP

Other trials in United Kingdom

About this study

Official title: A Randomised, Placebo-controlled, Double-blind, Repeat Dose Escalation Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

This is a dose escalation/dose finding, double-blind, placebo-controlled, parallel study of GSK2126458 in subjects with IPF. The study is designed to explore a number of doses of GSK2126458 for engagement of pharmacology after short term dosing. It is anticipated that approximately 24 subjects will be enrolled in this study. Actual number of cohorts in this study could vary up to a maximum of 6 cohorts (n=4/cohort; 3 on active and 1 on placebo).

Each cohort will consist of four subjects who will be randomised to receive GSK2126458 (three subjects) or placebo (one subject) for approximately 8 days (7 to 10 days). On Day 1 they will receive their first dose of GSK2126458 (or placebo) and safety, tolerability and PK/PD in the blood will be measured for up to 8 hours post-dose. Subjects will then be discharged from the site with study drug until the last day of dosing. They will also receive hand held spirometers and instructions on action to be taken in case of deterioration in pulmonary function or any other adverse events (AEs). On the last day of dosing they will return to the site for a repeat of the Day 1 procedures.

A bronchoalveolar lavage (BAL) and [18F]-fluoro-deoxyglucose (FDG)- positron emission tomography / computed tomography (PET/CT) scan will be conducted twice during the study; once, at least 2 days before dosing commences and again during the course of the dosing period.

After the final subject in each cohort has completed dosing, a dose escalation meeting will take place. Safety and tolerability and PK data will be reviewed during this meeting and decisions made may include but are not limited to: escalate the dose, decrease the dose or repeat the same dose in the next cohort; stop the study.

Conditions: Idiopathic Pulmonary Fibrosis
Being tested: GSK2126458, Placebo
Medical subject headings: Idiopathic Pulmonary Fibrosis

What participants receive

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

GSK2126458Drug
GSK2126458 will be available as film coated tablet of dose strength 0.25 mg and 0.5 mg
PlaceboDrug
Matching placebo will be available

Study groups in NCT01725139
Study group	Role	What they receive
Cohort 1-GSK2126458	Experimental	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 (0.25 mg twice daily [bid]) or placebo for approximately 8 days (7 to 10 days dosing) Receives: Drug: GSK2126458
Cohort 1-Placebo	Placebo comparator	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing) Receives: Drug: Placebo
Cohort 2-GSK2126458	Experimental	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 1 and which could be escalated or deescalated or repeated from Cohort 1 dosing. Receives: Drug: GSK2126458
Cohort 2-Placebo	Placebo comparator	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing). Receives: Drug: Placebo
Cohort 3- GSK2126458	Experimental	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 2 and which could be escalated or deescalated or repeated from Cohort 2 dosing. Receives: Drug: GSK2126458
Cohort 3-Placebo	Placebo comparator	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing). Receives: Drug: Placebo
Cohort 4- GSK2126458	Experimental	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 3 and which could be escalated or deescalated or repeated from Cohort 3 dosing. Receives: Drug: GSK2126458
Cohort 4- Placebo	Placebo comparator	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing). Receives: Drug: Placebo
Cohort 5- GSK2126458	Experimental	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 4 and which could be escalated or deescalated or repeated from Cohort 4 dosing. Receives: Drug: GSK2126458
Cohort 5- Placebo	Placebo comparator	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing). Receives: Drug: Placebo
Cohort 6- GSK2126458	Experimental	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 4 and which could be escalated or deescalated or repeated from Cohort 5 dosing. Receives: Drug: GSK2126458
Cohort 6- Placebo	Placebo comparator	Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing). Receives: Drug: Placebo

What is being measured

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

Pharmacodynamic (PD) endpoints pAKT/AKT in platelet-rich plasma and BAL cells, [18F]-FDG-PET/CT
Pharmacodynamic will be measured by inhibition of pAKT/AKT in platelet-rich plasma and BAL cells, as well as inhibition of glucose uptake as measured by thoracic[18F]-FDG-PET/CT
Measured: Baseline, Day 1, mid-study BAL visit (Day 5-9) and final dosing day (Day 7, 8, 9 or 10) for each cohort
Area under the curve (AUC) in blood for GSK2126458
GSK2126458 PK parameters in blood in order to define the blood and pulmonary PK/PD relationship for GSK2126458 in IPF subjects
Measured: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort
Maximum observed concentration (Cmax) in blood for GSK2126458
GSK2126458 PK parameters in blood in order to define the blood and pulmonary PK/PD relationship for GSK2126458 in IPF subjects
Measured: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort
Pre-dose (trough) concentration at the end of the dosing interval (Ctrough) in blood for GSK2126458
GSK2126458 PK parameters in blood in order to define the blood and pulmonary PK/PD relationship for GSK2126458 in IPF subjects
Measured: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort
Concentration of GSK2126458 in bronchoalveolar lavage fluid (BALF)
GSK2126458 concentration in BALF in order to define the pulmonary PK/PD relationship for GSK2126458 in IPF subjects
Measured: Baseline BAL visit and mid-study BAL visit (Day 5-9).

Secondary outcomes (8)

Safety and tolerability of GSK2126458 as assessed by number of subjects with adverse events (AE)s
Safety and tolerability parameters will include recording of AEs, throughout the study in subjects with IPF
Measured: Baseline up to final dosing day (Day 7, 8, 9 or 10) for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in vital signs
Vital sign measurement will be done in a semi-supine position and will include systolic and diastolic blood pressure, pulse rate and tympanic temperature
Measured: Day 1, final dosing day (Day 7, 8, 9 or 10) and follow-up (10-14 days post last dose), for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in clinical laboratory parameters
Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and additional parameters
Measured: Day 1, mid-study BAL visit (Day 5-9), final dosing day (Day 7, 8, 9 or 10) and follow-up (10-14 days post last dose) for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in pulmonary function
Pulmonary function will be assessed by spirometry to test the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)
Measured: Recorded daily from screening until final dosing day (Day 7, 8, 9 or 10) for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in electrocardiogram (ECG)
Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTc intervals
Measured: Screening, Day 1 and final dosing day (Day 7, 8, 9 or 10) for each study cohort
Assessment of subject's breathlessness using MRC dyspnoea scale
The Medical Research Council (MRC) dyspnoea scale is a 5-point scale used for grading the degree of a patient's breathlessness.
Measured: Day 1 and final dosing day (Day 7, 8, 9 or 10) for each study cohort
Assessment of FEV1 and FVC using daily hand-held spirometry
Subjects will be required to record their daily spirometry scores (FEV1 and FVC) using hand-held spirometers, at approximately the same time each morning between Screening and the Final Dosing Day
Measured: Recorded daily from screening until final dosing day (Day 7, 8, 9 or 10) for each cohort
Investigate the effect of GSK2126458 on the frequency and or severity of chronic cough using Leicester Cough Questionnaire (LCQ) in IPF subjects
Subjects will be required to complete the 19 questions - LCQ, which is a symptom specific questionnaire designed to assess the impact of cough severity, a major symptom of IPF. Subjects will be required to complete the 19 questions of the LCQ on Day 1 and the Final Dosing Day
Measured: Day 1 and final dosing day (Day 7, 8, 9 or 10) for each cohort

Timeline

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

8 Mar 201312 Jul 2016

First posted12 Nov 2012 (estimated)
Study start8 Mar 2013
Primary completion12 Jul 2016
Study completion12 Jul 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01725139
Sponsor's protocol ID: 116711
Other IDs: 2012-001376-11
Status last verified: Nov 2019
First submitted: 8 Nov 2012
Last updated: 21 Nov 2019
Results posted: No
Data monitoring committee: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

Lukey PT, Harrison SA, Yang S, Man Y, Holman BF, Rashidnasab A, Azzopardi G, Grayer M, Simpson JK, Bareille P, Paul L, Woodcock HV, Toshner R, Saunders P, Molyneaux PL, Thielemans K, Wilson FJ, Mercer PF, Chambers RC, Groves AM, Fahy WA, Marshall RP, Maher TM. A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis. Eur Respir J. 2019 Mar 18;53(3):1801992. doi: 10.1183/13993003.01992-2018. Print 2019 Mar.
PubMed 30765508
Mercer PF, Woodcock HV, Eley JD, Plate M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Blanchard AD, Marshall RP, Lukey PT, Chambers RC. Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF. Thorax. 2016 Aug;71(8):701-11. doi: 10.1136/thoraxjnl-2015-207429. Epub 2016 Apr 21.
PubMed 27103349

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Idiopathic Pulmonary Fibrosis trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Placebo-controlled, Double-blind, Repeat Dose Escalation Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
ClinicalTrials.gov ID: NCT01725139
Acronym / sponsor ID: 116711
Conditions: Idiopathic Pulmonary Fibrosis
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 8 Mar 2013 (actual)
Primary completion: 12 Jul 2016 (actual)
Study completion: 12 Jul 2016 (actual)
First posted: 12 Nov 2012 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 12

Arm	Type	Receives
Cohort 1-GSK2126458	Experimental	Drug: GSK2126458Subjects will be randomized in 3:1 ratio to receive either GSK2126458 (0.25 mg twice daily [bid]) or placebo for approximately 8 days (7 to 10 days dosing)
Cohort 1-Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing)
Cohort 2-GSK2126458	Experimental	Drug: GSK2126458Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 1 and which could be escalated or deescalated or repeated from Cohort 1 dosing.
Cohort 2-Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing).
Cohort 3- GSK2126458	Experimental	Drug: GSK2126458Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 2 and which could be escalated or deescalated or repeated from Cohort 2 dosing.
Cohort 3-Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing).
Cohort 4- GSK2126458	Experimental	Drug: GSK2126458Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 3 and which could be escalated or deescalated or repeated from Cohort 3 dosing.
Cohort 4- Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing).
Cohort 5- GSK2126458	Experimental	Drug: GSK2126458Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 4 and which could be escalated or deescalated or repeated from Cohort 4 dosing.
Cohort 5- Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing).
Cohort 6- GSK2126458	Experimental	Drug: GSK2126458Subjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or placebo for approximately 8 days (7 to 10 days dosing). GSK2126458 dose will be decided from Cohort 4 and which could be escalated or deescalated or repeated from Cohort 5 dosing.
Cohort 6- Placebo	Placebo comparator	Drug: PlaceboSubjects will be randomized in 3:1 ratio to receive either GSK2126458 bid or matching placebo for approximately 8 days (7 to 10 days dosing).

Who may qualify

Ages: 45 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Diagnosis of IPF as determined by a responsible and experienced chest physician and based on established criteria defined by the American Thoracic Society/European Respiratory Society: American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias.
FVC greater than (>) 40% predicted and Diffusing capacity of the Lung for Carbon Monoxide (DLCO) >30% predicted
Alanine aminotransferase (ALT) less than (<) 2x upper limit of normal (ULN); alkaline phosphatase and bilirubin less than or equal to (<=) 1.5xULN.
QTcB <450 milliseconds (msec) and QTc interval <=480 msec; or QTc <480 msec in subjects with Bundle Branch Block.
Male over 45 years of age inclusive, or female over 50 years of age inclusive at the time of signing the informed consent

Key exclusion criteria (19 listed)

Current IPF exacerbation
History of acute coronary syndromes, atrial fibrillation, coronary angioplasty, or stenting within the past 24 weeks.
Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
Uncontrolled hypertension or a history of conditions which could increase the risk of complications from hypertension
Current upper or lower respiratory tract infection

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
GSK2126458GSK2126458 will be available as film coated tablet of dose strength 0.25 mg and 0.5 mg	Drug	Cohort 1-GSK2126458, Cohort 2-GSK2126458, Cohort 3- GSK2126458, Cohort 4- GSK2126458, Cohort 5- GSK2126458, Cohort 6- GSK2126458
PlaceboMatching placebo will be available	Drug	Cohort 1-Placebo, Cohort 2-Placebo, Cohort 3-Placebo, Cohort 4- Placebo, Cohort 5- Placebo, Cohort 6- Placebo

Primary outcome

Pharmacodynamic (PD) endpoints pAKT/AKT in platelet-rich plasma and BAL cells, [18F]-FDG-PET/CT
Time frame: Baseline, Day 1, mid-study BAL visit (Day 5-9) and final dosing day (Day 7, 8, 9 or 10) for each cohort
Pharmacodynamic will be measured by inhibition of pAKT/AKT in platelet-rich plasma and BAL cells, as well as inhibition of glucose uptake as measured by thoracic[18F]-FDG-PET/CT
Area under the curve (AUC) in blood for GSK2126458
Time frame: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort
GSK2126458 PK parameters in blood in order to define the blood and pulmonary PK/PD relationship for GSK2126458 in IPF subjects
Maximum observed concentration (Cmax) in blood for GSK2126458
Time frame: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort
GSK2126458 PK parameters in blood in order to define the blood and pulmonary PK/PD relationship for GSK2126458 in IPF subjects
Pre-dose (trough) concentration at the end of the dosing interval (Ctrough) in blood for GSK2126458
Time frame: Day 1, mid-study PET visit (Day 4-8), mid-study BAL visit (Day 5-9) and final dosing day post-dose (Day 7, 8, 9 or 10) for each cohort
GSK2126458 PK parameters in blood in order to define the blood and pulmonary PK/PD relationship for GSK2126458 in IPF subjects
Concentration of GSK2126458 in bronchoalveolar lavage fluid (BALF)
Time frame: Baseline BAL visit and mid-study BAL visit (Day 5-9).
GSK2126458 concentration in BALF in order to define the pulmonary PK/PD relationship for GSK2126458 in IPF subjects

8 secondary outcomes

Safety and tolerability of GSK2126458 as assessed by number of subjects with adverse events (AE)s
Time frame: Baseline up to final dosing day (Day 7, 8, 9 or 10) for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in vital signs
Time frame: Day 1, final dosing day (Day 7, 8, 9 or 10) and follow-up (10-14 days post last dose), for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in clinical laboratory parameters
Time frame: Day 1, mid-study BAL visit (Day 5-9), final dosing day (Day 7, 8, 9 or 10) and follow-up (10-14 days post last dose) for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in pulmonary function
Time frame: Recorded daily from screening until final dosing day (Day 7, 8, 9 or 10) for each cohort
Safety and tolerability of GSK2126458 as assessed by change from baseline in electrocardiogram (ECG)
Time frame: Screening, Day 1 and final dosing day (Day 7, 8, 9 or 10) for each study cohort
Assessment of subject's breathlessness using MRC dyspnoea scale
Time frame: Day 1 and final dosing day (Day 7, 8, 9 or 10) for each study cohort
Assessment of FEV1 and FVC using daily hand-held spirometry
Time frame: Recorded daily from screening until final dosing day (Day 7, 8, 9 or 10) for each cohort
Investigate the effect of GSK2126458 on the frequency and or severity of chronic cough using Leicester Cough Questionnaire (LCQ) in IPF subjects
Time frame: Day 1 and final dosing day (Day 7, 8, 9 or 10) for each cohort

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2019.
Background: PubMed 30765508Lukey PT, Harrison SA, Yang S, Man Y, Holman BF, Rashidnasab A, Azzopardi G, Grayer M, Simpson JK, Bareille P, Paul L, Woodcock HV, Toshner R, Saunders P, Molyneaux PL, Thielemans K, Wilson FJ, Mercer PF, Chambers RC, Groves AM, Fahy WA, Marshall RP, Maher TM. A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis. Eur Respir J. 2019 Mar 18;53(3):1801992. doi: 10.1183/13993003.01992-2018. Print 2019 Mar.
Derived from this study: PubMed 27103349Mercer PF, Woodcock HV, Eley JD, Plate M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Blanchard AD, Marshall RP, Lukey PT, Chambers RC. Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF. Thorax. 2016 Aug;71(8):701-11. doi: 10.1136/thoraxjnl-2015-207429. Epub 2016 Apr 21.
Results for study 116711 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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An Extension Study of Subjects Who Received an Avalyn Inhaled Antifibrotic Agent (SAIL)
Progressive Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis (IPF)
RecruitingObservational study
Real-world Study of Nerandomilast in Patients With Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis (IPF), Progressive Pulmonary Fibrosis
RecruitingPhase 2
A Phase 2 Study of LTI-03 in Patients With Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis (IPF)
Not yet recruitingPhase 2
A Phase 2 Study of HB0056 in Patients With Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis (IPF)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2126458 in people with Idiopathic Pulmonary Fibrosis, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 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 21 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacodynamic (PD) endpoints pAKT/AKT in platelet-rich plasma and BAL cells, [18F]-FDG-PET/CT (time frame: Baseline, Day 1, mid-study BAL visit (Day 5-9) and final dosing day (Day 7, 8, 9 or 10) for each cohort). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01725139, which also lists 2 linked publications.

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 21 Nov 2019.