Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects
Condition: Pulmonary Disease, Chronic Obstructive
MeSH terms: Pulmonary Disease, Chronic Obstructive
Intervention: GSK2269557 500 µg; GSK2269557 750 µg
Intervention description: GSK2269557 is a potent and highly selective inhaled Phosphoinositide 3 Kinase delta inhibitor. Single dose of GSK2269557 500 µg will be administered to randomized subjects via inhalation route using ELLIPTA DPI.; GSK2269557 is a potent and highly selective inhaled Phosphoinositide 3 Kinase delta inhibitor. Single dose of GSK2269557 750 µg will be administered to randomized subjects via inhalation route using ELLIPTA DPI.
Intervention MeSH terms: Nemiralisib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Healthy subjects will be randomized to receive GSK2269557 750 µg or GSK2269557 500 µg.
Masking: Double (Participant, Investigator)
Masking description: This is a double-blind study and subjects and investigator will be blinded.
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Pharmacokinetics; Healthy; ELLIPTA; Safety; GSK2269557; Inhalation; Tolerability

Summary:

      GSK2269557 is being developed as an anti-inflammatory and anti-infective agent for the
      treatment of inflammatory airways diseases. This is the first study using a new formulation
      of GSK2269557 in healthy subjects and will evaluate the safety, tolerability and PK of a
      single dose of GSK2269557. Data derived from this study will inform on the PK profile and
      systemic exposure expected during Phase 2b. Approximately twelve healthy subjects will be
      randomized to receive a single dose of GSK2269557 750 micrograms (µg) or a single dose of
      GSK2269557 500 µg via the ELLIPTA® dry powder inhaler (DPI) formulated in a blend containing
      0.4 percent magnesium stearate (MgSt) in 1:1 ratio. This randomized, parallel group study
      will be carried out in 3 phases, including screening phase, treatment phase and follow-up
      phase. The total study duration for each subject will be up to 6 weeks. ELLIPTA is a
      registered trademark of GlaxoSmithKline group of companies.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject must be 18 to 75 years of age inclusive, at the time of signing the informed
             consent.

          -  Subjects who are overtly healthy as determined by medical evaluation including medical
             history, physical examination, laboratory tests, and ECG tests. Re-screening will be
             allowed once, at the discretion of the Principal Investigator in consultation with
             GlaxoSmithKline (GSK) medical monitor.

          -  Normal spirometry at Screening FEV1 and FVC >=80 percent of predicted (measurements to
             be taken in triplicate and the highest value for each component must be >=80 percent
             of predicted).

          -  Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 18.0 - 35.0
             kg per square meter (kg/m^2) (inclusive).

          -  Male or female: A male subject must agree to use contraception during the treatment
             period for at least 5 half-lives plus 90 days after the last dose of study treatment
             and refrain from donating sperm during this period. A female subject is eligible to
             participate if she is not pregnant, not breastfeeding, and at least one of the
             following conditions applies: Not a woman of childbearing potential (WOCBP) or A WOCBP
             who agrees to follow the contraceptive guidance during the treatment period for at
             least 5 half-lives plus 90 days after the last dose of study treatment.

          -  Capable of giving signed informed consent.

        Exclusion Criteria:

          -  Asthma or a history of asthma (except in childhood, which has now remitted).

          -  Significant history of or current 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].

          -  Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).

          -  Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin
             is fractionated and direct bilirubin <35 percent).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  QTc interval >450 milliseconds (msec).

          -  Past or intended use of over-the-counter or prescription medication including herbal
             medications within 7 days prior to dosing.

          -  Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines
             during the study.

          -  Participation in the study would result in loss of blood or blood products in excess
             of 500 milliliters (mL) within 56 days.

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day. Consider adding the following criteria if subjects can only be enrolled
             once per study.

          -  Current enrollment or past participation within the last 90 days before signing of
             consent in any other clinical study involving an investigational study treatment or
             any other type of medical research

          -  Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C
             antibody test result at screening. Subjects with positive Hepatitis C antibody due to
             prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C
             Ribonucleic Acid (RNA) test is obtained.

          -  Positive Hepatitis C RNA test result at screening or within 3 months prior to first
             dose of study treatment.

          -  Positive pre-study drug/alcohol screen.

          -  Positive human immunodeficiency virus (HIV) antibody test.

          -  Regular use of known drugs of abuse.

          -  Regular alcohol consumption within 3 months prior to the study defined as: An average
             weekly intake of >14 units for males and females. One unit is equivalent to 8 grams
             (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine
             or 1 (25 mL) measure of spirits.

          -  Current smoker or a history of smoking within 6 months of Screening, or a total pack
             year history of >5 pack years. [Number of pack years = (number of cigarettes per
             day/20) multiplied by number of years smoked]

          -  Sensitivity to any of the study treatments, or components thereof (including lactose
             and MgSt), or drug or other allergy that, in the opinion of the investigator or
             medical monitor, contraindicates participation in the study.