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

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 1

Conditions

Coeliac Disease

Celiac Disease

Treatments

Other: Grape fruit juice

Drug: Itraconazole

Other: Water

Drug: GSK3915393 Capsules

Drug: Placebo capsules

Drug: GSK3915393 Solution for Infusion

Study type

Interventional

Funder types

Industry

Identifiers

NCT04604795

213585

Details and patient eligibility

About

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.

Enrollment

65 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

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 design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

65 participants in 12 patient groups, including a placebo group

Part A:GSK3915393 DLs 1,3,4,intravenous (IV) microdose and placebo (Sequence A)

Experimental group

Description:

In Part A, participants will receive dose levels (DLs) 1, 3, 4, IV microdose of GSK3915393, and placebo in a pre-determined sequence (Sequence A). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.

Treatment:

Drug: Placebo capsules

Drug: GSK3915393 Capsules

Drug: GSK3915393 Solution for Infusion

Part A:GSK3915393 DLs 1,2,4,IV microdose and placebo (Sequence B)

Experimental group

Description:

In Part A, participants will receive dose levels 1, 2, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence B). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.

Treatment:

Drug: Placebo capsules

Drug: GSK3915393 Capsules

Drug: GSK3915393 Solution for Infusion

Part A:GSK3915393 DLs 1,2,3,IV microdose and placebo (Sequence C)

Experimental group

Description:

In Part A, participants will receive dose levels 1, 2, 3, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence C). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.

Treatment:

Drug: Placebo capsules

Drug: GSK3915393 Capsules

Drug: GSK3915393 Solution for Infusion

Part A:GSK3915393 DLs 2,3,4,IV microdose and placebo (Sequence D)

Experimental group

Description:

In Part A, participants will receive dose levels 2, 3, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence D). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.

Treatment:

Drug: Placebo capsules

Drug: GSK3915393 Capsules

Drug: GSK3915393 Solution for Infusion

Part B: Cohort 1: Participants receiving GSK3915393 DL X

Experimental group

Description:

Participants will receive GSK3915393 dose level X twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A.

Treatment:

Drug: GSK3915393 Capsules

Part B: Cohort 1: Participants receiving placebo

Placebo Comparator group

Description:

Participants will receive placebo matching GSK3915393 dose level X during Part B of the study.

Treatment:

Drug: Placebo capsules

Part B: Cohort 2: Participants receiving GSK3915393 DL Y

Experimental group

Description:

Participants will receive GSK3915393 dose level Y twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B.

Treatment:

Drug: GSK3915393 Capsules

Part B: Cohort 2: Participants receiving placebo

Placebo Comparator group

Description:

Participants will receive placebo matching GSK3915393 dose level Y twice daily during Part B of the study

Treatment:

Drug: Placebo capsules

Part B: Cohort 3: Participants receiving GSK3915393 DL Z

Experimental group

Description:

Participants will receive GSK3915393 dose level Z twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B.

Treatment:

Drug: GSK3915393 Capsules

Part B: Cohort 3: Participants receiving placebo

Placebo Comparator group

Description:

Participants will receive placebo matching GSK3915393 dose level Z twice daily during Part B of the study.

Treatment:

Drug: Placebo capsules

Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)

Experimental group

Description:

Participants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and itraconazole (ITZ) in period 2. Participants will then receive oral GSK3915393 plus water in period 3, oral GSK3915393 plus grape fruit juice (GFJ) in period 4 and oral GSK3915393 plus ITZ in period 5.

Treatment:

Other: Grape fruit juice

Other: Water

Drug: Itraconazole

Drug: GSK3915393 Capsules

Drug: GSK3915393 Solution for Infusion

Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B)

Experimental group

Description:

Participants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and ITZ in period 2. Participants will then receive oral GSK3915393 plus GFJ in period 3, oral GSK3915393 plus water in period 4 and oral GSK3915393 plus ITZ in period 5.

Treatment:

Other: Grape fruit juice

Other: Water

Drug: Itraconazole

Drug: GSK3915393 Capsules

Drug: GSK3915393 Solution for Infusion

Trial documents