A Study to Investigate the Efficacy, Safety, and Tolerability of Repeat Doses of Inhaled GSK2269557 in Adults With Persistent, Uncontrolled Asthma

NCT02567708 | Completed Phase 2 Results

• 1 other identifier: 201543
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 12

Brief Summary

This study is a multi-centre, randomised, double-blind, placebo-controlled (with rescue medication), two period crossover study in subjects with persistent uncontrolled asthma, currently not treated with an inhaled corticosteroid (ICS) or long acting beta 2 agonist (LABA). This study is the first administration of GSK2269557 to asthmatic subjects, and the aims of the study are to investigate the efficacy, safety, tolerability, and pharmacokinetics of four weeks of treatment with orally inhaled GSK2269557 1000 microgram (mcg) in subjects with persistent uncontrolled asthma. In a sub-study, biological mediators will be measured from induced sputum and blood. Approximately 50 subjects will be randomised into the study (including approximately 16 subjects in the sputum sub-study). Each subject will complete two treatment periods: subjects will be randomised to receive GSK2269557 1000 mcg in one treatment period, and matching placebo in the other treatment period. Each treatment will be administered once daily for 28 days (+/- 2 days) via the DISKUS™ dry powder inhaler (DPI). The study will consist of a Screening Visit; a Run-in Period (approximately 2 weeks in duration); two 28-day Treatment Periods (each with 4 clinic visits); a 4-week Washout Period (between the Treatment Periods); and a Follow-up Visit. The total duration of the study for each subject will be approximately 16 weeks. DISKUS is a registered trademark of the GlaxoSmithKline group of companies.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

GSK2269557; Asthma; Pharmacokinetics; Safety; Adults; DISKUS Dry Powder Inhaler; Efficacy

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Intent-To-Treat (ITT) Population

  FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose).

  Baseline and Day 28 for each treatment period

• Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 in Per Protocol (PP) Population

  FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is the maximum volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. FEV1 was measured using a spirometer. Change from Baseline is calculated as post-Baseline value minus Baseline value where Baseline is defined as Day 1 (pre-dose). The analysis was performed on the PP Population which comprised of all participants in the ITT Population not identified as major protocol violators.

  Baseline and Day 28 for each treatment period

Secondary Outcomes (16)

• Weighted Mean (0-4 Hours) FEV1 at Day 28

  Day 28 for each treatment period

• Change From Baseline in Trough FEV1 at Day 7 and Day 14

  Baseline, Day 7 and Day 14 for each treatment period

• Change From Baseline in Forced Vital Capacity (FVC) at Day 7, Day 14 and Day 28

  Baseline, Day 7, Day 14 and Day 28 for each treatment period

• Change From Baseline in FEV1/FVC at Day 7, Day 14 and Day 28

  Baseline, Day 7, Day 14 and Day 28 for each treatment period

• Change From Baseline in Asthma Control Test (ACT) Score at Day 28

  Baseline and Day 28 for each treatment period

Study Arms (1)

GSK2269557 and Placebo

EXPERIMENTAL

Each subject will complete two treatment periods: GSK2269557 1000 mcg in one treatment period, and matching placebo in the other treatment period. Each treatment will be administered once daily for 28 days (+/- 2 days) via the DISKUS DPI. The treatment periods will be separated by a washout of at least 4 weeks.

Drug: GSK2269557 DPI; Drug: Placebo DPI

Interventions

GSK2269557 DPI DRUG

GSK2269557 will be supplied as a lactose blend in a DISKUS DPI with a unit dose strength of 500 mcg. 2 inhalations will be taken every morning before breakfast.

GSK2269557 and Placebo

Placebo DPI DRUG

Placebo will be lactose in a DISKUS DPI. 2 inhalations will be taken every morning before breakfast.

GSK2269557 and Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 18 and 70 years of age inclusive, at the time of signing the informed consent.
• Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with an intermittent short acting beta 2 agonist (SABA) or other non-corticosteroid controllers. Non corticosteroid controllers (e.g. leukotriene receptor antagonists \[LTRAs\]) must be discontinued from Screening until the end of Treatment Period 2.
• Able to replace current SABA treatment with salbutamol metered dose inhaler (MDI) at Screening for use as needed for the duration of the study. Judged capable of withholding salbutamol for at least 4 hours prior to FEV1 assessments.
• No use of an ICS or LABA for at least 12 weeks prior to first dose of study medication.
• A best pre-bronchodilator FEV1 \>=60 percent (%) of the predicted normal value at screening.
• FEV1 increase by \>=12% and \>=200 milliliter (mL) over baseline value within 10-40 minutes of inhalation of 400 mcg salbutamol MDI (a spacer device may be used if required).
• Positive skin prick test to common aero-allergen(s) at screening (not historical).
• Sputum sub-study only: Able to produce \>100 milligram (mg) of sputum at screening or during the run-in period.
• Body weight \>=45 kilogram (kg) and body mass index (BMI) within the range 18-32 kilogram per meter square (kg/m\^2) (inclusive).
• Male subject: Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the first dose of study medication until completion of the follow-up visit.
• Vasectomy with documentation of azoospermia.
• Male condom plus partner use of one of the contraceptive options below:
• Contraceptive subdermal implant with a \<1% rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system with a \<1% rate of failure per year, as stated in the product label; Oral contraceptive, either combined or progestogen alone, injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches.
• Female subject: is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies:
• Non-reproductive potential defined as pre-menopausal females with one of the following: Documented tubal ligation Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion Hysterectomy Documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone \[FSH\] and estradiol levels consistent with menopause \[refer to laboratory reference ranges for confirmatory levels\]). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

You may not qualify if:

• History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures.
• Any severe asthma exacerbation, defined as deterioration of asthma requiring the use of systemic corticosteroids (oral, parenteral or depot) within 12 weeks of screening, or an inpatient hospitalisation or emergency department visit due to asthma that required systemic corticosteroids within 6 months of screening.
• Respiratory Infection: culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that has not resolved within 4 weeks of screening and led to a change in asthma management or, in the opinion of the investigator, is expected to affect the subject's asthma status or the subject's ability to participate in the study.
• Concurrent Respiratory Disease: current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, lung cancer, or other respiratory abnormalities other than asthma.
• Alanine aminotransferase (ALT) \>2x upper limit of normal (ULN) and bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• QTc \>450 millisecond (msec) or QTc \>480 msec in subjects with bundle branch block.
• Other laboratory abnormalities or concurrent diseases/clinical: clinically significant laboratory abnormality, uncontrolled condition or disease state that, in the opinion of the investigator (in consultation with the GSK Medical Monitor, if required), would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
• Use of any of the prohibited medications listed in the protocol.
• Current smokers or subjects with a history of smoking within 6 months of screening, or with a total pack year history of \>5 pack years.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• History of sensitivity to any of the study medications, or components thereof (including lactose) or a history of drug or other allergy (including a milk protein allergy) that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• Sputum sub-study only: History of sensitivity to the induced sputum procedure.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study medication.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (12)

GSK Investigational Site

Munich, Bavaria, 80539, Germany

Location

GSK Investigational Site

Rüdersdorf, Brandenburg, 15562, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60389, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Homburg, Saarland, 66421, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04275, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04357, Germany

Location

GSK Investigational Site

Lübeck, Schleswig-Holstein, 23552, Germany

Location

GSK Investigational Site

Berlin, 10119, Germany

Location

GSK Investigational Site

Berlin, 10717, Germany

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Magdeburg, 39120, Germany

Location

Related Publications (1)

• Khindri S, Cahn A, Begg M, Montembault M, Leemereise C, Cui Y, Hogg A, Wajdner H, Yang S, Robertson J, Hamblin JN, Ludwig-Sengpiel A, Kornmann O, Hessel EM. A Multicentre, Randomized, Double-Blind, Placebo-Controlled, Crossover Study To Investigate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Repeat Doses of Inhaled Nemiralisib in Adults with Persistent, Uncontrolled Asthma. J Pharmacol Exp Ther. 2018 Dec;367(3):405-413. doi: 10.1124/jpet.118.249516. Epub 2018 Sep 14.

  PMID: 30217958 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Asthma

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2015
• First Posted: October 5, 2015
• Study Start: October 1, 2015
• Primary Completion: September 21, 2016
• Study Completion: September 28, 2016
• Last Updated: August 1, 2018
• Results First Posted: August 1, 2018

Record last verified: 2018-02

Locations

DE (12)