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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: GSK3923868
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: GSK3923868 or placebo<br>Participants allocation to GSK3923868 and placebo will be in 3:1 ratio. In treatment period 1, participants will receive GSK3923868 (Dose 1) or Placebo; in treatment period 2, GSK3923868 (Dose 2) or Placebo. There will be a washout period of at least 5 days after each treatment periods. | Drug: GSK3923868<br>* GSK3923868 will be administered<br>Drug: Placebo<br>* Placebo will be administered<br>|
| Experimental: Part 2: GSK3923868 or placebo<br>Participants from Part 1 will be allocated to GSK3923868 and placebo in 3:1 ratio to receive single repeat dose of GSK3923868 (Dose 3) or placebo for 14 days in treatment period 3 with up to 14 days of follow up. | Drug: GSK3923868<br>* GSK3923868 will be administered<br>Drug: Placebo<br>* Placebo will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse events (AEs) and Serious Adverse Events (SAEs) |  | Up to Day 5 in treatment period 1 and 2 | 
| Number of participants with AEs and SAEs |  | Up to Day 28 in treatment period 3 | 
| Number of participants with clinically significant changes in laboratory values, vital signs,12-lead Electrocardiogram (ECG) and spirometry measurements up to Follow Up |  | Up to Day 5 in treatment period 1 and 2 | 
| Number of participants with clinically significant changes in laboratory values, vital signs, ECG and spirometry measurements up to Follow Up |  | Up to Day 28 in treatment period 3 | 

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 |  | Up to 24 hours post dose | 
| 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 |  | Up to 24 hours post dose | 
| Area under the plasma-concentration time Curve from time zero (pre-dose) to 6 hours [AUC (0-6)] of GSK3923868 for repeat dose |  | Up to 6 hours post dose | 
| Maximum observed plasma concentration (Cmax) of GSK3923868 for single dose |  | Up to Day 2 | 
| Time of occurrence of Cmax (Tmax) of GSK3923868 for single dose |  | Up to Day 2 | 
| Cmax of GSK3923868 for repeat dose |  | Up to Day 14 | 
| Tmax of GSK3923868 for repeat dose |  | Up to Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single ascending dose, Repeat dose, Phosphatidylinositol 4-kinase beta (PI4KB) inhibitor, Chronic Obstructive Pulmonary Disease (COPD)