Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2269557 to Japanese Healthy Subjects

NCT ID: NCT02972905

Last Updated: 2017-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2016-12-31

Brief Summary

GSK2269557 is a potent and highly selective inhaled Phosphoinositide 3-Kinase (PI3K) delta inhibitor being developed as an anti-inflammatory and anti-infective agent for the treatment of inflammatory airway diseases, such as chronic obstructive pulmonary disease (COPD). The purpose of the study is to assess the safety, tolerability and pharmacokinetics (PK) of single and repeat doses of GSK2269557 administered via the ELLIPTA dry powder inhaler (DPI) to healthy Japanese subjects. This is the first time for Japanese subjects that GSK2269557 will be administered via the ELLIPTA DPI with the addition of magnesium stearate.

In each group of this study, subjects will receive a single dose of either GSK2269557 or placebo in Session 1 and receive daily dose of GSK2269557 or placebo for 10 days in Session 2. Session 1 of the next dose strength may be run in parallel with the Session 2 of the previous dose. The doses planned for the study are 200 micrograms (mcg), 500 mcg and 700 mcg. There will be at least 10 days washout between the two dosing sessions. Follow up period will start 10 days (+-1 day) after the last dose of Session 2. A total number of 36 subjects will be enrolled for the study with 27 subjects receiving a dose strength of GSK2269557 and 9 subjects will receive each dose strength of GSK2269557. ELLIPTA is a trademark of the GSK group of companies.

Conditions

Pulmonary Disease, Chronic Obstructive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Session 1: Placebo

Subjects will receive a single dose inhalation of GSK2269557 matching placebo via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days.

Group Type: PLACEBO_COMPARATOR

Placebo ELLIPTA DPI

Intervention Type: DRUG

Placebo ELLIPTA DPI contains lactose

Session 1: GSK2269557 200 mcg

Subjects will receive a single dose inhalation of GSK2269557 200 mcg via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days.

Group Type: EXPERIMENTAL

GSK2269557 ELLIPTA DPI

Intervention Type: DRUG

GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.

Session 1: GSK2269557 500 mcg

Subjects will receive a single dose inhalation of GSK2269557 500 mcg via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days.

Group Type: EXPERIMENTAL

GSK2269557 ELLIPTA DPI

Intervention Type: DRUG

GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.

Session 1: GSK2269557 700 mcg

Subjects will receive a single dose inhalation of GSK2269557 700 mcg via the ELLIPTA DPI. The washout period between the two dosing sessions will be at least 10 days.

Group Type: EXPERIMENTAL

GSK2269557 ELLIPTA DPI

Intervention Type: DRUG

GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.

Session 2: Placebo

Subjects will receive repeated doses of GSK2269557 matching Placebo once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days.

Group Type: PLACEBO_COMPARATOR

Placebo ELLIPTA DPI

Intervention Type: DRUG

Placebo ELLIPTA DPI contains lactose

Session 2: GSK2269557 200 mcg

Subjects will receive repeated doses of GSK2269577 200mcg once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days.

Group Type: EXPERIMENTAL

GSK2269557 ELLIPTA DPI

Intervention Type: DRUG

GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.

Session 2: GSK2269557 500 mcg

Subjects will receive repeated doses of GSK2269577 500mcg once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days.

Group Type: EXPERIMENTAL

GSK2269557 ELLIPTA DPI

Intervention Type: DRUG

GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.

Session 2: GSK2269557 700 mcg

Subjects will receive repeated doses of GSK2269577 700mcg once daily via the ELLIPTA DPI for 10 days. The washout period between the two dosing sessions will be at least 10 days.

Group Type: EXPERIMENTAL

GSK2269557 ELLIPTA DPI

Intervention Type: DRUG

GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.

Interventions

GSK2269557 ELLIPTA DPI

GSK2269557 ELLIPTA DPI contains GSK2269557 blended with lactose and magnesium stearate. This will be supplied in two strength of 100 mcg per blister and 500 mcg per blister.

Intervention Type: DRUG

Placebo ELLIPTA DPI

Placebo ELLIPTA DPI contains lactose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be 20 to 64 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• Normal spirometry (forced expiratory volume in 1 second >=80% of predicted) at Screening.
• Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 18.5 to 24.9 kg/square meter (m^2) (inclusive).
• Japanese Male: A male participant must agree to use contraception of this protocol during the treatment period and until follow up visit.
• Capable of giving signed informed consent as described in restrictions listed in the informed consent form (ICF).

• History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data
• Abnormal blood pressure as determined by the investigator
• ALT >1.5x upper limit of normal (ULN)
• 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)
• QTcF >450 milliseconds (msec).
• Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing.
• History of donation of blood or blood products >=400 milliliters (mL) within 3 months or >=200 mL within 1 month prior to screening
• Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
• Current enrollment or past participation within the last 30 days before signing of consent in this clinical study involving an investigational study treatment or any other type of medical research
• The subject is positive Serological test for syphilis (rapid plasma reagin and Treponema pallidum), Human immunodeficiency virus (HIV) Antigen/Antibody, Hepatitis B surface antigen (HbsAg), Hepatitis C virus (HCV) antibody, or Human T-cell lymphotropic virus type 1 (HTLV-1) antibody at screening.
• Positive pre-study drug screen
• Regular use of known drugs of abuse
• Regular alcohol consumption within 6 months prior to the study defined as: for an average weekly intake of >14 units for males. One unit is equivalent to 350 ml of beer, 150 ml of wine or 45 ml of 80 proof distilled spirits
• Smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening
• Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Fukuoka, , Japan

Countries

Japan

Other Identifiers

205759

Identifier Type: -

Identifier Source: org_study_id