Clinical trial NCT03189589: Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects
Official title: A Randomised, Double-blind, Parallel Group Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Single Dose of GSK2269557 Administered Via the ELLIPTA™ Dry Powder Inhaler to Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Pharmacokinetics
Healthy
ELLIPTA
Safety
GSK2269557
Inhalation
Tolerability
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-06-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Healthy subjects will be randomized to receive GSK2269557 750 µg or GSK2269557 500 µg.
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Mean GSK2269557 Plasma Concentration
timeFrame: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose
measure: Area Under the Plasma Drug Concentration Versus Time Curve (AUC) From Zero to Time t (AUC [0 to t]), AUC From Zero to 24 Hours (AUC [0 to 24]) and AUC From Zero to Infinity (AUC [0 to Inf]) of GSK2269557
timeFrame: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose
measure: Maximum Observed Plasma Drug Concentration (Cmax) and Concentration at Trough (Ctrough) of GSK2269557
timeFrame: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose
measure: Time to Maximum Observed Plasma Drug Concentration (Tmax) and Terminal Half-life (t1/2)
timeFrame: Day 1: Pre-dose, 5 minutes post dose, 30 minutes post-dose, 2 hours post-dose, 6 hours post-dose, 12 hours post-dose; Day 2: 24 hours post-dose; Day 3: 48 hours post-dose and Day 6: 120 hours post-dose
Secondary outcomes:
measure: Number of Participants With Vital Signs of Potential Clinical Importance
timeFrame: Up to Day 2
measure: Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance
timeFrame: Up to Day 2
measure: Change From Baseline in Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline and Day 1
measure: Number of Participants With Hematology Abnormalities of Potential Clinical Importance
timeFrame: Up to Day 2
measure: Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance
timeFrame: Up to Day 2
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to 12 days post-dose
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wilson R, Templeton A, Leemereise C, Eames R, Banham-Hall E, Hessel EM, Cahn A. Safety, Tolerability, and Pharmacokinetics of a New Formulation of Nemiralisib Administered via a Dry Powder Inhaler to Healthy Individuals. Clin Ther. 2019 Jun;41(6):1214-1220. doi: 10.1016/j.clinthera.2019.04.008. Epub 2019 May 7.