Safety, Tolerability and Pharmacokinetics (PK) Study of GSK2269557 in Healthy Subjects

NCT03189589 | Completed Phase 1 Results

• 2 other identifiers: 2076742017-001073-16
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Pharmacokinetics; Healthy; ELLIPTA; Safety; GSK2269557; Inhalation; Tolerability

Outcome Measures

Primary Outcomes (4)

• Mean GSK2269557 Plasma Concentration

  Whole blood samples of approximately 2 milliliters were collected for measurement of plasma concentrations of GSK2269557 at the indicated time points. The pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population which comprised of all randomized participants in the Safety Population and for whom a PK sample was obtained and analyzed.

  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

• 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

  Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles.

  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

• Maximum Observed Plasma Drug Concentration (Cmax) and Concentration at Trough (Ctrough) of GSK2269557

  Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

  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

• Time to Maximum Observed Plasma Drug Concentration (Tmax) and Terminal Half-life (t1/2)

  Blood samples were collected to evaluate the PK of GSK2269557 at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Only those participants with data available at the specified time points were analyzed represented by n=X in the category titles.

  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 (6)

• Number of Participants With Vital Signs of Potential Clinical Importance

  Up to Day 2

• Number of Participants With Electrocardiogram (ECG) Values of Potential Clinical Importance

  Up to Day 2

• Change From Baseline in Forced Vital Capacity (FVC) and Forced Expiratory Volume in 1 Second (FEV1)

  Baseline and Day 1

• Number of Participants With Hematology Abnormalities of Potential Clinical Importance

  Up to Day 2

• Number of Participants With Clinical Chemistry Abnormalities of Potential Clinical Importance

  Up to Day 2

Study Arms (2)

GSK2269557 500 µg receivers

EXPERIMENTAL

Randomized healthy subjects will receive single dose of GSK2269557 500 µg via inhalation route via the ELLIPTA DPI.

Drug: GSK2269557 500 µg

GSK2269557 750 µg receivers

EXPERIMENTAL

Randomized healthy subjects will receive single dose of GSK2269557 750 µg via inhalation route via the ELLIPTA DPI.

Drug: GSK2269557 750 µg

Interventions

GSK2269557 500 µg DRUG

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 500 µg receivers

GSK2269557 750 µg DRUG

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.

GSK2269557 750 µg receivers

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Cambridge, CB2 0GG, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31076203 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration

Interventions

Nemiralisib

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

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 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study and subjects and investigator will be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Healthy subjects will be randomized to receive GSK2269557 750 µg or GSK2269557 500 µg.

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 16, 2017
• Study Start: June 15, 2017
• Primary Completion: July 24, 2017
• Study Completion: July 24, 2017
• Last Updated: August 19, 2019
• Results First Posted: January 14, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

GB (1)