Last updated: 06/27/2022 08:00:12

Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to evaluate the interaction between GSK3915393 and grapefruit juice and itraconazole

GSK study ID
213585
See study documents
Clinicaltrials.gov ID
NCT04604795
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Randomized, Placebo Controlled, Double Blind, Single and Repeat Dose Escalation Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and open label assessment of coadministration of GSK3915393 with grapefruit juice and itraconazole on the pharmacokinetics of GSK3915393
Trial description: This is a 3-part first time into human study (FTIH) study for GSK3915393. Parts A and B of the study will evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending and repeat oral doses of GSK3915393 in healthy adult participants. Part C will evaluate the impact of co-administration of GSK3915393 with grapefruit juice and itraconazole on the PK of GSK3915393.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Part A: Number of participants with adverse events (AEs), serious AEs (SAEs), and treatment related AEs following oral dosing

Timeframe: Up to Week 11

Part B: Number of participants with AEs, SAEs and treatment related AEs

Timeframe: Up to Week 4

Part A: Number of participants with clinically significant changes in physical examination, vital signs, laboratory parameters and 12-lead electrocardiogram (ECG) following oral dosing

Timeframe: Up to Week 11

Part B: Number of participants with clinically significant changes in physical examination, vital signs, laboratory parameters and 12-lead ECG

Timeframe: Up to Week 4

Part C: Maximum observed plasma drug concentration (Cmax) of GSK3915393

Timeframe: Pre-dose to Day 3 in Treatment Periods 1, 2, 3, 4 and 5 (Period 1, 3 and 4 are 3 days each, Period 2 and 5 are 6 days each)

Part C: Time to maximum observed plasma drug concentration (Tmax) of GSK3915393

Timeframe: Pre-dose to Day 3 in Treatment Periods 1, 2, 3, 4 and 5 (Period 1, 3 and 4 are 3 days each, Period 2 and 5 are 6 days each)

Part C: Area under the plasma drug concentration versus time curve from time zero to last quantifiable concentration (AUC[0-t]) of GSK3915393

Timeframe: Pre-dose to Day 3 in Treatment Periods 1, 2, 3, 4 and 5 (Period 1, 3 and 4 are 3 days each, Period 2 and 5 are 6 days each)

Part C: AUC from time zero to infinity (AUC[0-inf]) of GSK3915393

Timeframe: Pre-dose to Day 3 in Treatment Periods 1 and 2 (Period 1 is 3 days and Period 2 is 6 days

Part C: Apparent terminal half-life (t1/2) of GSK3915393

Timeframe: Pre-dose to Day 3 in Treatment Periods 1 and 2, (Period 1 is 3 days and Period 2 is 6 days)

Secondary outcomes:

Part A: Maximum observed plasma drug concentration (Cmax) following single oral dose of GSK3915393

Timeframe: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days)

Part A: Cmax following single intravenous (IV) dose of GSK3915393

Timeframe: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days)

Part A: Time to maximum observed plasma concentration (Tmax) following single oral dose of GSK3915393

Timeframe: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days)

Part A: Tmax following single IV dose of GSK3915393

Timeframe: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days)

Part A: AUC(0 to t) following single oral dose of GSK3915393

Timeframe: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days)

Part A: AUC(0 to t) following single IV dose of GSK3915393

Timeframe: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days)

Part A: AUC(0 to inf) following single oral dose of GSK3915393

Timeframe: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days)

Part A: AUC(0 to inf) following single IV dose of GSK3915393

Timeframe: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days)

Part A: T1/2 following single IV dose of GSK3915393

Timeframe: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days)

Part A: Clearance (CL) following single IV dose of GSK3915393

Timeframe: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days)

Part A: Volume of distribution (Vd) following single IV dose of GSK3915393

Timeframe: Pre-dose to Day 1 in Treatment Period 3 (Each period is 4 days)

Part A: Absolute bioavailability (F) following single oral dose of GSK3915393

Timeframe: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days)

Part A: Fraction of drug escaping hepatic metabolism

Timeframe: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days)

Part A: Product of fraction of drug absorbed and fraction of drug escaping gut

Timeframe: Pre-dose to Day 2 in Treatment Periods 1, 2, 4 and 5 (Each period is 4 days)

Part A: Number of participants with AEs and SAEs following IV dosing

Timeframe: Up to Week 11

Part A: Number of participants with clinically significant changes in physical examination, vital signs, laboratory parameters and ECG following IV dosing

Timeframe: Up to Week 11

Part B: Cmax of GSK3915393

Timeframe: Pre-dose and up to 24 hours post-dose on Days 1 and 14; Pre-dose and up to 10 hours post-dose on Days 3, 5, and 7

Part B: Tmax of GSK3915393

Timeframe: Pre-dose and up to 24 hours post-dose on Days 1 and 14; Pre-dose and up to 10 hours post-dose on Days 3, 5, and 7

Part B: AUC (0-t) of GSK3915393

Timeframe: Pre-dose and up to 24 hours post-dose on Days 1 and 14; Pre-dose and up to 10 hours post-dose on Days 3, 5, and 7

Part B: AUC over the dosing interval (AUC[0 to tau]) of GSK3915393

Timeframe: Pre-dose and up to 24 hours post-dose on Days 1 and 14; Pre-dose and up to 10 hours post-dose on Days 3, 5, and 7

Part B: Cmax following first dose of GSK3915393

Timeframe: Pre-dose and up to 10 hours post-dose on Days 1, 3, 5, 7 and 15

Part B: Tmax following first dose of GSK3915393

Timeframe: Pre-dose and up to 10 hours post-dose on Days 1, 3, 5, 7 and 15

Part B: AUC(0 to tau) following first dose of GSK3915393

Timeframe: Pre-dose and up to 10 hours post-dose on Days 1, 3, 5, 7 and 15

Part B: Trough concentration (Ctrough) following repeat dose of GSK3915393

Timeframe: Pre first dose on Days 2, 3, 5, 7 and 14

Part C: Number of participants with AEs, SAEs and treatment related AEs

Timeframe: Up to Week 10

Part C: Number of participants with clinically significant changes in physical examination, vital signs, laboratory parameters and ECG

Timeframe: Up to Week 10

Part C: Fraction of drug escaping hepatic metabolism

Timeframe: Pre-dose to Day 3 in Treatment Periods 1, 2, 3, 4 and 5 (Period 1, 3 and 4 are 3 days each, Period 2 and 5 are 6 days each)

Part C: Product of fraction of drug absorbed

Timeframe: Pre-dose to Day 3 in Treatment Periods 1, 2, 3, 4 and 5 (Period 1, 3 and 4 are 3 days each, Period 2 and 5 are 6 days each)

Interventions:
  • Drug: GSK3915393 Capsules
  • Drug: GSK3915393 Solution for Infusion
  • Drug: Placebo capsules
  • Drug: Itraconazole
  • Other: Water
  • Other: Grape fruit juice
    • Enrollment:
    65
    Primary completion date:
    2021-29-06
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Celiac Disease, Coeliac Disease
    Product
    Not applicable
    Collaborators
    Not applicable
    Study date(s)
    November 2020 to June 2021
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 50 Years
    Accepts healthy volunteers
    Yes
    • Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
    • Healthy participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
    • History or current evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (Irritable bowel syndrome [IBS], Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), endocrine, hematological, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
    • Current evidence of active infection.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
    • Healthy participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
    • Negative coronavirus disease of 2019 (COVID-19) test on admission.
    • Body weight >=40 kilograms (kg) and body mass index (BMI) within the range 18.5-29.9 kilograms per square meter (kg/m^2) (inclusive).
    • Male or females: No restrictions for male participants. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method from 30 days prior to first dose until follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). A WOCBP must have a negative highly sensitive pregnancy test (serum) at screening and on admission to the clinical unit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
    • Capable of giving signed informed consent.
    Exclusion criteria:
    • History or current evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (Irritable bowel syndrome [IBS], Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), endocrine, hematological, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
    • Current evidence of active infection.
    • Participants with signs/symptoms suggestive of COVID-19 (i.e. fever, cough, etc) within the past 14 days prior to screening and admission to clinical unit.
    • Participants with known COVID-19 positive contacts in the past 14 days prior to screening and admission to clinical unit.
    • Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a participant’s lifetime.
    • Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).
    • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
    • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
    • History of gastrointestinal (GI) surgery (with exception of appendectomy).
    • Average QT interval corrected using Fridericia’s formula (QTcF) >450 milliseconds (msec) at screening.
    • Any clinically relevant abnormality on the screening medical assessment, laboratory examination, or electrocardiogram.
    • History of QTc prolongation, symptomatic cardiac arrhythmias or cardiac arrest.
    • For Part C only, history of liver toxicity resulting from drug administration.
    • For Part C only, history of intolerance to itraconazole.
    • History of sensitivity to any of the study medication, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.
    • Use of any immunosuppressive medications within 6 months prior to entry.
    • Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, probiotics, antacids, herbal and dietary supplements (including Saint [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 medication for each dosing, unless in the opinion of the Investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. (Paracetamol is acceptable at a dose of no more than 500 milligrams [mg] at a time and no more than 2 grams [g] per day).
    • Participants who have received a COVID-19 vaccine within 7 days of admission (or readmission) to the clinical unit or who are demonstrating signs/symptoms attributed to a COVID-19 vaccination that occurred greater than 7 days earlier.
    • Recent donation of blood or blood products such that participation in the study would result in loss of blood in excess of 500 milliliter (mL) within 56 days.
    • The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
    • Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
    • Unwillingness or inability to follow the procedures outlined in the protocol or any other type of medical research within 30 days of randomization.
    • Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment.
    • Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
    • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
    • A positive pre-study drug/alcohol screen.
    • Positive human immunodeficiency virus (HIV) antibody test.
    • History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
    • Regular alcohol consumption within 6 months prior to screening: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
    • Urinary cotinine levels indicative of smoking or use of tobacco or nicotine-containing products (e.g. nicotine patches or vaporizing devices) at screening or on admission to the unit.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    London, United Kingdom, NW10 7EW
    Status
    Study Complete
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    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2021-29-06
    Actual study completion date
    2021-29-06

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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