A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Parallel Group Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3915393 Administered as a Single Dose to Healthy Participants of Chinese, Japanese and European Ancestry, and to Assess the Effects of GSK3915393, on the Pharmacokinetics of Nintedanib
Overview
- Phase
- Phase 1
- Intervention
- GSK3915393
- Conditions
- Idiopathic Pulmonary Fibrosis
- Sponsor
- GlaxoSmithKline
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Part A: Maximum Observed Plasma Concentration (Cmax) of GSK3915393
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
GSK3915393 is a new medicine which is being developed for a chronic lung disease called Idiopathic Pulmonary Fibrosis (IPF). This is a healthy participant study which has two parts. Part A will assess the safety, tolerability, and blood levels of GSK3915393 given as a single dose to healthy participants of Chinese, Japanese, and European ancestries. Part B is a drug-drug interaction (DDI) study that examines the effect of a single dose of GSK3915393 on the blood levels of a single dose of nintedanib, which is an approved drug for IPF.
Investigators
Eligibility Criteria
Inclusion Criteria
- •For Part A and Part B:
- •Participants who are generally healthy as determined by medical evaluation based on screening medical history, physical examination, vital signs, electrocardiogram (ECG) assessments, and laboratory tests Body weight at least 50.0 kilograms (kg) (110 pounds \[lbs\]) for male participants (Part A and Part B) or at least 45.0 kg (99 lbs) for female participants (Part A only) Body mass index (BMI) within the range of 18.0 to 28.0 kilogram per square meter (kg/m\^2) (inclusive) Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF)
- •For Part A:
- •Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- •Is a woman of non-childbearing potential (WONCBP) Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method prior to and during the study intervention period (at a minimum until after the last dose of study intervention). The investigator should evaluate the potential for contraceptive method failure (for example, noncompliance, recently initiated in relationship to the first dose of study intervention) A WOCBP must have a negative highly sensitive pregnancy test within 30 days before the first dose of study intervention Participants of Chinese ancestry are eligible if born in mainland China, Hong Kong or Taiwan; descendant of four ethnic Chinese grandparents and two ethnic Chinese parents; and have lived outside China, Hong Kong or Taiwan for less than 10 years at the time of screening Participants of Japanese ancestry are eligible if born in Japan; Descendant of four ethnic Japanese grandparents and two ethnic Japanese parents; and have lived outside Japan for less than 10 years at the time of screening Participants of European ancestry are eligible if Self-identified as being of European ancestry (i.e. from the original peoples of Europe) irrespective of current place of residence; and descendant of four grandparents and two parents of European ancestry
Exclusion Criteria
- •History or presence of 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 intervention or interfering with the interpretation of data Participants with systolic blood pressure (BP) greater than (\>) 140 millimeter of mercury (mmHg) or diastolic BP \> 90 mmHg at screening or pulse rate outside the range of 40 to 100 beats per minute (bpm) will be excluded from the study Alanine transaminase (ALT) or aspartate aminotransferase (AST) \>1× upper limit of normal (ULN) Total bilirubin \>1.5×ULN; Participants with Gilbert's syndrome can be included with total bilirubin \>1.5×ULN as long as direct bilirubin is less than or equal to (≤) 1.5×ULN Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) QT interval corrected (QTc) \>450 milliseconds (msec) at Screening visit based on the average of triplicate ECGs Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, probiotics, antacids, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention, unless in the opinion of the Investigator and the Medical Monitor, the medication will not interfere with the study procedures or compromise participant safety
Arms & Interventions
Part A: GSK3915393
Participants from Chinese, Japanese, and European ancestries will be randomized to receive GSK3915393 under fasting condition.
Intervention: GSK3915393
Part B: Nintedanib followed by Nintedanib plus GSK3915393
Male participants will be randomized to receive Nintedanib in Period 1 followed by co-administration of Nintedanib and GSK3915393 in Period 2 under fed conditions. There will be a washout period of minimum 5 days post last dose between Period 1 and Period 2.
Intervention: Nintedanib
Part B: Nintedanib followed by Nintedanib plus GSK3915393
Male participants will be randomized to receive Nintedanib in Period 1 followed by co-administration of Nintedanib and GSK3915393 in Period 2 under fed conditions. There will be a washout period of minimum 5 days post last dose between Period 1 and Period 2.
Intervention: GSK3915393
Part B: Nintedanib plus GSK3915393 followed by Nintedanib
Male participants will be randomized to receive co-administration of Nintedanib and GSK3915393 in Period 1 followed by Nintedanib in Period 2 under fed conditions. There will be a washout period of minimum 5 days post last dose between Period 1 and Period 2.
Intervention: Nintedanib
Part B: Nintedanib plus GSK3915393 followed by Nintedanib
Male participants will be randomized to receive co-administration of Nintedanib and GSK3915393 in Period 1 followed by Nintedanib in Period 2 under fed conditions. There will be a washout period of minimum 5 days post last dose between Period 1 and Period 2.
Intervention: GSK3915393
Outcomes
Primary Outcomes
Part A: Maximum Observed Plasma Concentration (Cmax) of GSK3915393
Time Frame: Up to 36 hours post dose
Blood sample will be collected to evaluate plasma concentration of GSK3915393.
Part A: Time to Cmax (Tmax) of GSK3915393
Time Frame: Up to 36 hours post dose
Blood sample will be collected to evaluate time of maximum plasma concentration of GSK3915393.
Part A: Apparent Terminal Half-life (T1/2) of GSK3915393
Time Frame: Up to 36 hours post dose
Blood sample will be collected to evaluate plasma concentration of GSK3915393.
Part B: AUC (0-t) of Nintedanib
Time Frame: Up to 48 hours post dose
Blood sample will be collected to evaluate plasma concentration of Nintedanib.
Part B: AUC (0-inf) of Nintedanib
Time Frame: Up to 48 hours post dose
Blood sample will be collected to evaluate plasma concentration of Nintedanib.
Part B: Cmax of Nintedanib
Time Frame: Up to 48 hours post dose
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
Part A: Number of Participants with Adverse Events (AEs)
Time Frame: Up to Day 10
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.
Part A: Number of Participants with Serious Adverse Events (SAEs)
Time Frame: Up to Day 10
An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect in the offspring of a study participant; abnormal pregnancy outcome; or is a suspected transmission of any infectious agent via an authorized medicinal product.
Part A: Number of Participants with Clinically Significant Changes in Clinical Laboratory Values
Time Frame: Up to Day 10
Number of participants with clinically significant changes in clinical laboratory values (hematology, clinical chemistry, and routine urinalysis) will be assessed.
Part A: Number of Participants with Clinically Significant Changes in Vital Signs
Time Frame: Up to Day 10
Number of participants with clinically significant changes in Vital signs (temperature, systolic and diastolic blood pressure \[BP\], pulse rate and respiratory rate \[RR\]) will be assessed.
Part A: Number of Participants with Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)
Time Frame: Up to Day 10
Number of participants with clinically significant changes in 12-lead ECG will be assessed.
Part A: Area Under the Plasma Concentration Versus Time Curve From Time Zero To t (AUC [0-t]) of GSK3915393
Time Frame: Up to 36 hours post dose
Blood sample will be collected to evaluate plasma concentration of GSK3915393.
Part A: Area Under the Plasma Concentration Versus Time Curve From Time Zero To Infinity (AUC [0-inf]) of GSK3915393
Time Frame: Up to 36 hours post dose
Blood sample will be collected to evaluate plasma concentration of GSK3915393.
Secondary Outcomes
- Part B: Number of Participants with AEs(Up to Day 17)
- Part B: Number of Participants with SAEs(Up to Day 17)
- Part B: Number of Participants with Clinically Significant Changes in Clinically Laboratory Values(Up to Day 17)
- Part B: Number of Participants with Clinically Significant Changes in Vital Signs(Up to Day 17)
- Part B: Number of Participants with Clinically Significant Changes in 12-Lead ECG(Up to Day 17)
- Part B: Tmax of Nintedanib(Up to 48 hours post dose)
- Part B: T1/2 of Nintedanib(Up to 48 hours post dose)