Phase 1, Single and Repeat Dose Study to Assess Safety, Tolerability, and Pharmacokinetics (PK) of GSK3923868 in Participants With Chronic Obstructive Pulmonary Disease (COPD)

A Randomized, Double-blind, Placebo Controlled, Single and Repeat Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of Inhaled GSK3923868 in Participants With Chronic Obstructive Pulmonary Disease (COPD)

This is a two parts study, a single ascending dose followed by 14-days repeat dosing. The single ascending dose part will assess two dose levels of GSK3923868 or placebo across two treatment periods 1 and 2 in a single cohort of participants with a washout period of a minimum of 5 days after each treatment periods. The repeat dose part will assess repeated one dose level of GSK3923868 or placebo in treatment period 3 with up to 14 days of follow up in the same cohort of participants. The duration of study participation for treatment period 1, 2 and 3 will be 6, 6 and up to 29 days (including follow up), respectively.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: GSK3923868

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Between 40 and 70 years of age.
• Confirmed diagnosis of COPD for greater than (>) 6 months.
• Participant is a smoker or an ex-smoker with a smoking history of at least 10 pack years.
• A female participant is eligible to participate if she is not pregnant or breastfeeding and agrees to use contraceptives during the study (for women of childbearing potential only).

Exclusion Criteria:

• Participant has poorly controlled or unstable COPD.
• Participant has a past or current medical condition(s) or disease(s) that is/are not well controlled.
• Participant has had a respiratory tract infection treated with antibiotics within 4 weeks prior to screening.
• Participant requires regular treatment with oral corticosteroids or has received a course of oral or parenteral corticosteroids within 4 weeks prior to screening.
• Participant requires long-term oxygen therapy.
• Current enrolment or past participation in a clinical trial within 30 days before this study starts.
• Positive tests for human immunodeficiency virus (HIV), hepatitis B and C, or Coronavirus disease-19 (COVID-19).
• Positive pre-study drug (except for as results of opioids prescribed for medical reasons and/or inadvertent consumption of poppy seeds) /alcohol screening result.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3923868 500 mcg SD/Placebo SD/GSK3923868 1500 mcg RD; Eligible participants will receive a single dose (SD) of GSK3923868 500 microgram (mcg) in Treatment Period 1 followed by a single dose of placebo matching GSK3923868 in Treatment Period 2. Participants will also receive a repeat dose (RD) of GSK3923868 1500 mcg in Treatment Period 3. There will be a washout period between each treatment period. Participants will have a follow-up of 14 days after the last dose of GSK3923868.	Drug: Placebo; Placebo will be administered; Drug: GSK3923868; GSK3923868 will be administered
Experimental: GSK3923868 500 mcg SD/GSK3923868 1000 mcg SD/Placebo RD; Eligible participants will receive a single dose of GSK3923868 500 mcg in Treatment Period 1 followed by a single dose of GSK3923868 1000 mcg in Treatment Period 2. Participants will also receive a repeat dose of placebo matching GSK3923868 in Treatment Period 3. There will be a washout period between each treatment period. Participants will have a follow-up of 14 days after the last dose of GSK3923868.	Drug: Placebo; Placebo will be administered; Drug: GSK3923868; GSK3923868 will be administered
Experimental: GSK3923868 500 mcg SD/GSK3923868 1000 mcg SD/GSK3923868 1500 mcg RD; Eligible participants will receive a single dose of GSK3923868 500 mcg in Treatment Period 1 followed by a single dose of GSK3923868 1000 mcg in Treatment Period 2. Participants will also receive repeat dose of GSK3923868 1500 mcg in Treatment Period 3. There will be a washout period between each treatment period. Participants will have a follow-up of 14 days after the last dose of GSK3923868.	Drug: GSK3923868; GSK3923868 will be administered
Experimental: Placebo SD/GSK3923868 1000 mcg SD/GSK3923868 1500 mcg RD; Eligible participants will receive a single dose of placebo matching GSK3923868 in Treatment Period 1 followed by a single dose of GSK3923868 1000 mcg in Treatment Period 2. Participants will also receive a repeat dose of GSK3923868 1500 mcg in Treatment Period 3. There will be a washout period between each treatment period. Participants will have a follow-up of 14 days after the last dose of GSK3923868.	Drug: Placebo; Placebo will be administered; Drug: GSK3923868; GSK3923868 will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Following Single Dose of GSK3923868	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Adverse events which were not serious, were considered as non-serious adverse events.	Up to 18 days
Number of Participants With Non-SAEs and SAEs Following Repeat Dose of GSK3923868	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Adverse events which were not serious, were considered as non-serious adverse events.	Up to 29 days
Number of Participants With Clinically Significant Changes in Hematology and Clinical Chemistry Laboratory Parameters Following Single Dose of GSK3923868	The laboratory measurements included hematology and clinical chemistry. The parameters evaluated were Basophil, Eosinophil, Erythrocyte Mean Corpuscular Hemoglobin, Erythrocyte Mean Corpuscular Volume, Erythrocytes, Hematocrit, Hemoglobin, Lymphocyte, Monocyte, Neutrophils, Platelets and Reticulocytes, Alanine Aminotransferase, Albumin, Alkaline phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium, Creatinine, Direct Bilirubin, Glucose, Potassium, Sodium and Urea. Number of participants with clinically significant changes in hematology and clinical chemistry and were reported. Clinical significance was determined by the investigator.	Up to 18 days
Number of Participants With Clinically Significant Changes in Hematology and Clinical Chemistry Laboratory Parameters Following Repeat Dose of GSK3923868	The laboratory measurements included hematology and clinical chemistry. The parameters evaluated were Basophil, Eosinophil, Erythrocyte Mean Corpuscular Hemoglobin, Erythrocyte Mean Corpuscular Volume, Erythrocytes, Hematocrit, Hemoglobin, Lymphocyte, Monocyte, Neutrophils, Platelets and Reticulocytes, Alanine Aminotransferase, Albumin, Alkaline phosphatase, Aspartate Aminotransferase, Bilirubin, Calcium, Creatinine, Direct Bilirubin, Glucose, Potassium, Sodium and Urea. Number of participants with clinically significant changes in hematology and clinical chemistry and were reported. Clinical significance was determined by the investigator.	Up to 29 days
Number of Participants With Clinically Significant Changes in Urinalysis Parameters Following Repeat Dose of GSK3923868	Urine samples were collected at indicated time points for the analysis of urinalysis parameters including specific gravity, potential of hydrogen (pH) of urine, presence of glucose, protein, erythrocytes, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase in urine by dipstick. Number of participants with clinically significant changes in urinalysis parameters were reported. Clinical significance was determined by the investigator.	Up to 29 days
Number of Participants With Clinically Significant Changes in Vital Signs and 12-lead Electrocardiogram (ECG) Findings Following Single Dose of GSK3923868	Vital signs included systolic and diastolic blood pressure, pulse rate and respiratory rate were measured with the participant in semi-supine position after at least 10 minutes rest. Tympanic Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Twelve-lead electrocardiogram were performed in a semi-supine position after at least 10 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, QT and corrected QT intervals (QTc) intervals. Number of participants with clinically significant changes in vital signs and ECG parameters were reported. Clinical significance was determined by the investigator.	Up to 18 days
Number of Participants With Clinically Significant Changes in Vital Signs and 12-lead Electrocardiogram (ECG) Findings Following Repeat Dose of GSK3923868	Vital signs included systolic and diastolic blood pressure, pulse rate and respiratory rate were measured with the participant in semi-supine position after at least 10 minutes rest. Tympanic Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring. Twelve-lead electrocardiogram were performed in a semi-supine position after at least 10 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS duration, QT and corrected QT intervals (QTc) intervals. Number of participants with clinically significant changes in vital signs and ECG parameters were reported. Clinical significance was determined by the investigator.	Up to 29 days
Number of Participants With Clinically Significant Changes in Spirometry Measurements Following Single Dose of GSK3923868	Spirometry included forced expiratory volume in 1 second (FEV1) for lung function assessment. FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. Spirometry assessments were performed in triplicate with the highest value reported. Number of participants with clinically significant changes in spirometry measurements were reported. Clinical significance was determined by the investigator.	Up to 18 days
Number of Participants With Clinically Significant Changes in Spirometry Measurements Following Repeat Dose of GSK3923868	Spirometry included forced expiratory volume in 1 second (FEV1) for lung function assessment. FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. Spirometry assessments were performed in triplicate with the highest value reported. Number of participants with clinically significant changes in spirometry measurements were reported. Clinical significance was determined by the investigator.	Up to 29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to 24 Hours (AUC [0-24]) of GSK3923868 for Single Dose	Blood samples were collected at the indicated time points for pharmacokinetic (PK) analysis of GSK3923868. Pharmacokinetic analysis was conducted using standard non-compartmental method with WinNonlin.	Pre-dose and 5, 15, 30, 45 minutes, 1, 2, 4, 6, 24 hours post-dose on Day 1 in Treatment Periods 1 and 2
Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to Time of the Last Quantifiable Concentration (AUC[0-t]) of GSK3923868 for Single Dose	Blood samples were collected at the indicated time points for PK analysis of GSK3923868. Area under the concentration-time curve from time zero to the time of the last quantifiable concentration values were reported.	Pre-dose and 5, 15, 30, 45 minutes, 1, 2, 4, 6, 24 hours post-dose on Day 1 in Treatment Periods 1 and 2
Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to 6 Hours (AUC [0-6]) of GSK3923868 for Repeat Dose	Blood samples were collected at the indicated time points for pharmacokinetic (PK) analysis of GSK3923868. Pharmacokinetic analysis was conducted using standard non-compartmental method with WinNonlin.	Pre-dose and 5, 15, 30, 45 minutes, 1, 2, 4, 6 hours post-dose on Day 1 and Day 14 in Treatment Period 3
Maximum Observed Plasma Concentration (Cmax) of GSK3923868 for Single Dose	Blood samples were collected at the indicated time points for pharmacokinetic (PK) analysis of GSK3923868. Pharmacokinetic analysis was conducted using standard non-compartmental method with WinNonlin.	Pre-dose and 5, 15, 30, 45 minutes, 1, 2, 4, 6, 24 hours post-dose on Day 1 in Treatment Periods 1 and 2
Time to Reach Cmax (Tmax) of GSK3923868 for Single Dose	Blood samples were collected at the indicated time points for analysis of tmax of GSK3923868. The tmax was obtained directly from the concentration-time data. The tmax was analyzed with the non-compartmental methods with WinNonlin.	Pre-dose and 5, 15, 30, 45 minutes, 1, 2, 4, 6, 24 hours post-dose on Day 1 in Treatment Periods 1 and 2
Cmax of GSK3923868 for Repeat Dose	Blood samples were collected at the indicated time points for pharmacokinetic (PK) analysis of GSK3923868. Pharmacokinetic analysis was conducted using standard non-compartmental method with WinNonlin.	Pre-dose and 5, 15, 30, 45 minutes, 1, 2, 4, 6 hours post-dose on Day 1 and Day 14 in Treatment Period 3
Tmax of GSK3923868 for Repeat Dose	Blood samples were collected at the indicated time points for analysis of tmax of GSK3923868. The tmax was obtained directly from the concentration-time data. The tmax was analyzed with the non-compartmental methods with WinNonlin.	Pre-dose and 5, 15, 30, 45 minutes, 1, 2, 4, 6 hours post-dose on Day 1 and Day 14 in Treatment Period 3

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2023
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Actual): January 10, 2023

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease (COPD); Single ascending dose; Repeat dose; Phosphatidylinositol 4-kinase beta (PI4KB) inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Chronic Disease; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 214075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No