Phase 1
N=12
Safety, Tolerability and Pharmacokinetics of GSK3923868 Inhalation Powder in Healthy Participants and Stable Asthmatics
Pulmonary Disease, Chronic Obstructive
Bottom Line
View on ClinicalTrials.gov: NCT04585009 ↗Enrolled (actual)
12
Serious AEs
0.0%
Results posted
Feb 2024
Primary outcome: Primary: Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) — 3; 3; 3; 6 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- GSK3923868 (Drug); Matching placebo (Drug); Monodose RS01 (Device)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jun 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A, Cohort-1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
3; 3; 3; 6; 0; 0 | — |
| PRIMARY Part A, Cohort 2: Number of Participants With AEs and SAEs |
5; 5; 5; 3; 0; 0 | — |
| PRIMARY Part B: Number of Participants With AEs and SAEs |
4; 12; 0; 0 | — |
| PRIMARY Part C: Number of Participants With AEs and SAEs |
3; 8; 0; 0 | — |
| PRIMARY Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Laboratory Parameters |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters |
1; 0; 0; 0 | — |
| PRIMARY Part C: Number of Participants With Clinically Significant Changes in Clinical Chemistry and Hematology Lab Parameters |
1; 1; 0; 0 | — |
| PRIMARY Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead Electrocardiogram (ECG) Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings |
1; 6; 0; 0 | — |
| PRIMARY Part C: Number of Participants With Clinically Significant Changes in Vital Signs and 12-Lead ECG Findings |
0; 0; 0; 0 | — |
| PRIMARY Part A, Cohort-1: Number of Participants With Clinically Significant Changes in Spirometry Measurements |
0; 0; 0; 0 | — |
| PRIMARY Part A, Cohort-2: Number of Participants With Clinically Significant Changes in Spirometry Measurements |
0; 0; 0; 0 | — |
| PRIMARY Part B: Number of Participants With Clinically Significant Changes in Spirometry Measurements |
0; 0 | — |
| PRIMARY Part C: Number of Participants With Clinically Significant Changes in Spirometry Measurements |
0; 0 | — |
| SECONDARY Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Last Quantifiable Concentration (AUC[0-t]) |
1774.65; 3810.3; 8111.1; 22550.14; 49756.36; 144519.79 | — |
| SECONDARY Part A, Cohort 1 and 2: Area Under the Plasma GSK3923868 Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-inf]) |
1964.21; 4125.22; 8656.56; 22941.62; 50504.33; 146453.53 | — |
| SECONDARY Part A, Cohort 1 and 2: Maximum Observed GSK3923868 Plasma Concentration (Cmax) |
370.84; 772.49; 1811.8; 4284.89; 9583.02; 30985.12 | — |
| SECONDARY Part A, Cohort 1 and 2: Time to Maximum Observed Plasma Drug Concentration (Tmax) |
1; 1; 1; 1; 1; 0.75 | — |
| SECONDARY Part B, Cohort 3 and 4: AUC From Time Zero (Predose) to Time Tau (AUC [0-tau]) (Tau=24hours for Once a Day Dosing Regimen) of GSK3923868 |
128045.03; 144211.68 | — |
| SECONDARY Part B, Cohort 3 and 4: Cmax of GSK3923868 |
32342.47; 31270.98 | — |
| SECONDARY Part B, Cohort 3 and 4: Tmax of GSK3923868 |
0.75; 1 | — |
| SECONDARY Part C: AUC (0-tau) (Tau=24 Hours for Once a Day Dosing Regimen) of GSK3923868 |
97412.11; 136461.8 | — |
| SECONDARY Part C: Cmax of GSK3923868 |
27799.34; 35484.07 | — |
| SECONDARY Part C: Tmax of GSK3923868 |
0.758; 0.75 | — |
Summary
This is a first time in human (FTIH) study designed to evaluate the safety, tolerability and pharmacokinetic (PK) profile of single and repeat doses of GSK3923868 inhalation powder in both healthy participants and asthmatics. This is a 3-part, randomized, double blind, placebo controlled study of GSK3923868, administered as an inhalation powder blend (GSK3923868 capsules for inhalation) via Mono-dose inhaler in healthy participants (Parts A and B) and in participants with asthma (Part C). The duration of study participation for each part A, B and C will be 11, 9 and 8 weeks, respectively.
Eligibility Criteria
Inclusion Criteria: For Parts A and B
- Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
- Participants who are generally healthy as determined by medical evaluation based on screening medical history, physical examination, vital signs, ECG assessment, pulmonary function testing, laboratory tests and cardiac monitoring.
- Body weight at least 50.0 kilograms (kg) (110 pounds [lbs]) and body mass index (BMI) within the range 18.5 to 32.0 kilograms per meter square (kg/m^2) (inclusive).
- Male Participants: A male participant is eligible to participate if they agree to the following during the intervention period and for at least 10 days after the last dose of study intervention: Refrain from donating sperm. Plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remaining abstinent OR must agree to use contraception as detailed below when having sexual intercourse with a woman of childbearing potential who is not currently pregnant: Agree to use a male condom AND female partner to use an additional highly effective contraceptive method with a failure rate of = 65 percent predicted normal value.
- Positive bronchodilator reversibility test defined as an increase in FEV1 of > 12 percent and > 200 milliliter (mL) from Baseline, 10 to 15 minutes after administration of 400 micrograms (μg) salbutamol (or equivalent).
- Participants with maintained control of their asthma using the permitted medications: short-acting beta agonist (SABA) use only (n=8 participants) and regular treatment with inhaled corticosteroid (ICS) or ICS/long-acting beta agonist (LABA) (including use of Leukotriene Receptor Agonist [LTRA]) (n=8 participants).
- Body weight at least 50.0 kg (110 lbs) and BMI within the range 18.5 to 32.0 kg/m^2 (inclusive).
- Male Participants: A male participant is eligible to participate if they agree to the following during the intervention period and for at least 10 days after the last dose of study intervention: Refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remaining abstinent OR must agree to use contraception as detailed below when having sexual intercourse with a woman of childbearing potential who is not currently pregnant: Agree to use a male condom AND female partner to use an additional highly effective contraceptive method with a failure rate of 450 milliseconds (msec) at screening visit based on the average of triplicate ECGs.
- Screening ECG measurements meets the following criteria for exclusion: heart rate: males- 100 beats per minute (bpm); females- 100 bpm; PR interval: 220 msec; QRS duration: 120 msec; QTcF: >450 msec.
- Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
- Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).
- Signs and symptoms suggestive of COVID-19.
- Past or intended use of over-the-counter or prescription medication, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days before the first dose of study intervention, unless in the opinion of the Investigator and the GlaxoSmithKline (GSK) Medical Monitor, the medication will not interfere with the study procedures or compromise participant safety.
- Participation in this study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 56 days.
- Exposure to more than 4 new chemical entities within 12 months before the first dosing day.
- Current enrolment or past participation in a clinical trial and has received an investigational product within the following time period before the first dosing day in this study: 30 days, 5 half-lives or twice the duration of the biological effect of the
Data sourced from ClinicalTrials.gov (NCT04585009). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.