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)

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05677347

Enrollment

Registered

2023-01-10

Start date

2023-01-23

Completion date

2023-07-20

Last updated

2024-10-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Single ascending dose, Repeat dose, Phosphatidylinositol 4-kinase beta (PI4KB) inhibitor, Chronic Obstructive Pulmonary Disease (COPD)

Brief summary

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.

Interventions

DRUGGSK3923868

GSK3923868 will be administered

DRUGPlacebo

Placebo will be administered

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Masking description

The participants and investigators will be blinded.

Intervention model description

The same cohort of participants will move from Part 1 (single ascending doses treatment periods 1 and 2) to Part 2 (repeat dose treatment period 3)

Eligibility

Sex/Gender

ALL

Age

40 Years to 70 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Clinically Significant Changes in Spirometry Measurements Following Repeat Dose of GSK3923868	Up to 29 days	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.
Number of Participants With Non-SAEs and SAEs Following Repeat Dose of GSK3923868	Up to 29 days	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.
Number of Participants With Clinically Significant Changes in Hematology and Clinical Chemistry Laboratory Parameters Following Single Dose of GSK3923868	Up to 18 days	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.
Number of Participants With Clinically Significant Changes in Hematology and Clinical Chemistry Laboratory Parameters Following Repeat Dose of GSK3923868	Up to 29 days	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.
Number of Participants With Clinically Significant Changes in Urinalysis Parameters Following Repeat Dose of GSK3923868	Up to 29 days	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.
Number of Participants With Clinically Significant Changes in Vital Signs and 12-lead Electrocardiogram (ECG) Findings Following Single Dose of GSK3923868	Up to 18 days	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.
Number of Participants With Clinically Significant Changes in Vital Signs and 12-lead Electrocardiogram (ECG) Findings Following Repeat Dose of GSK3923868	Up to 29 days	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.
Number of Participants With Clinically Significant Changes in Spirometry Measurements Following Single Dose of GSK3923868	Up to 18 days	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.
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) Following Single Dose of GSK3923868	Up to 18 days	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.

Secondary

Measure	Time frame	Description
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	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	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.
Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to 6 Hours (AUC [0-6]) of GSK3923868 for Repeat Dose	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	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.
Maximum Observed Plasma Concentration (Cmax) of GSK3923868 for Single Dose	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	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.
Time to Reach Cmax (Tmax) of GSK3923868 for Single Dose	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	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.
Cmax of GSK3923868 for Repeat Dose	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	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.
Tmax of GSK3923868 for Repeat Dose	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	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.
Area Under the Plasma-concentration Time Curve From Time Zero (Pre-dose) to 24 Hours (AUC [0-24]) of GSK3923868 for Single Dose	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	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.

Countries

Germany

Participant flow

Pre-assignment details

All the 12 participants were enrolled and randomized in the study.

Participants by arm

Arm	Count
GSK3923868 500 mcg SD/Placebo SD/GSK3923868 1500 mcg RD Eligible participants received 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 also received a repeat dose (RD) of GSK3923868 1500 mcg in Treatment Period 3. There was a washout period between each treatment period. Participants had a follow-up of 14 days after the last dose of GSK3923868.	3
GSK3923868 500 mcg SD/GSK3923868 1000 mcg SD/Placebo RD Eligible participants received a single dose of GSK3923868 500 mcg in Treatment Period 1 followed by GSK3923868 1000 mcg in Treatment Period 2. Participants also received a repeat dose of placebo matching GSK3923868 in Treatment Period 3. There was a washout period between each treatment period. Participants had a follow-up of 14 days after the last dose of GSK3923868.	3
GSK3923868 500 mcg SD/GSK3923868 1000 mcg SD/GSK3923868 1500 mcg RD Eligible participants received a single dose of GSK3923868 500 mcg in Treatment Period 1 followed by GSK3923868 1000 mcg in Treatment Period 2. Participants also received repeat dose of GSK3923868 1500 mcg in Treatment Period 3. There was a washout period between each treatment period. Participants had a follow-up of 14 days after the last dose of GSK3923868.	3
Placebo SD/GSK3923868 1000 mcg SD/GSK3923868 1500 mcg RD Eligible participants received a single dose of placebo matching GSK3923868 in Treatment Period 1 followed by GSK3923868 1000 mcg in Treatment Period 2. Participants also received a repeat dose of GSK3923868 1500 mcg in Treatment Period 3. There was a washout period between each treatment period. Participants had a follow-up of 14 days after the last dose of GSK3923868.	3
Total	12

Baseline characteristics

Characteristic	GSK3923868 500 mcg SD/Placebo SD/GSK3923868 1500 mcg RD	GSK3923868 500 mcg SD/GSK3923868 1000 mcg SD/Placebo RD	GSK3923868 500 mcg SD/GSK3923868 1000 mcg SD/GSK3923868 1500 mcg RD	Placebo SD/GSK3923868 1000 mcg SD/GSK3923868 1500 mcg RD	Total
Age, Continuous	67.7 YEARS STANDARD_DEVIATION 2.31	59.3 YEARS STANDARD_DEVIATION 5.69	63.3 YEARS STANDARD_DEVIATION 7.23	68.0 YEARS STANDARD_DEVIATION 1	64.6 YEARS STANDARD_DEVIATION 5.5
Race/Ethnicity, Customized De-identified	3 Participants	3 Participants	3 Participants	3 Participants	12 Participants
Sex/Gender, Customized De-identified	3 Participants	3 Participants	3 Participants	3 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 9	0 / 9	0 / 3	0 / 9
other Total, other adverse events	1 / 6	2 / 9	1 / 9	2 / 3	4 / 9
serious Total, serious adverse events	0 / 6	0 / 9	0 / 9	0 / 3	0 / 9

Outcome results

Primary

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.

Time frame: Up to 29 days