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Colitis, UlcerativePhase 1NCT05999708

A First Time in Human Study to Evaluate the Safety and Tolerability of GSK4381406 in Healthy Participants

A Phase 1 study testing GSK4381406 and Indomethacin in people with Colitis, Ulcerative, run by GlaxoSmithKline at 1 site in United Kingdom.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is a 3-part First Time in Human (FTIH) study to evaluate the safety, tolerability, and pharmacokinetics (PK) profile of GSK4381406 following administration of single ascending doses (Part 1), repeat ascending doses (Part 2), and repeat doses with an indomethacin challenge (Part 3) in healthy adult participants. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Colitis, Ulcerative
What is being tested?
GSK4381406 and Indomethacin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited Kingdom
Study dates
31 Oct 2023to 5 Dec 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Body weight greater than (>)50 kg and body mass index (BMI) within the range 18-29.9 kilogram per meter square (kg/m^2) (inclusive)
  • Male and female participants
  • A female participant is eligible to participate if she is of non-childbearing potential
  • Capable of giving signed informed consent

Who cannot join

  • Medical history of cardiovascular, cerebrovascular (including transient ischemic attack (TIA), ischemic and hemorrhagic stroke), respiratory, hepatic, renal (including chronic kidney disease), gastrointestinal (including IBD and IBS), endocrine, hematologic (including anemia and coagulopathies), or neurological disorders
  • Abnormal blood pressure (BP) (defined as systolic BP greater than or equal to [≥]130 millimetres of mercury (mmHg) or diastolic BP ≥85 mmHg) measured (based on the average of triplicate BP readings)
  • Medical history of antihypertensive drugs
  • Presence, or history within the past 14 days, of irregularities in bowel movements, including diarrhea (the passage of 3 or more loose or liquid stools per day) and constipation (3 or fewer bowel movements per week or requiring the use of laxatives).
  • Symptomatic herpes zoster within 3 months prior to screening.
  • Clinically significant multiple or severe drug allergies, intolerance to corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
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  • Any history or presence of malignancy except for basal cell or squamous epithelial carcinomas of the skin.
  • Alanine transaminase (ALT) >1.5x Upper limit of normal (ULN)
  • Total bilirubin >1.5x ULN (isolated total bilirubin >1.5xULN is acceptable if total bilirubin is fractionated and direct bilirubin lesser than [<]35 percentage [%]).
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
  • QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 millisecond (msec)
  • Unable to refrain from the use of over-the-counter or prescription medication, including herbal medications and vitamins within 7 days or 5 half-lives (whichever is longer) prior to dosing until after follow-up visit, unless in the opinion of the Investigator and the GSK medical monitor, the medication will not interfere with the study procedures or compromise participant safety
  • Use of a systemic antimicrobial within 30 days of screening
  • The use of NSAIDs, including aspirin, are not permitted throughout the study (except on Part 3 Indomethacin challenge) and should not have been taken within 14 days immediately preceding the first dose of study intervention. For analgesia, paracetamol (acetaminophen) at doses of less than or equal to (≤)4 gram per day (g/day) is permitted
  • Unable to refrain from consumption of red wine, Seville oranges, grapefruit, or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to first dose of study intervention until completion of the follow up period
  • Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study
  • Participation in the study would result in loss of blood or blood products in excess of 450 millilitre (mL) within the last 3 months prior to the Screening Visit. Blood donation during the study is not permitted
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day
  • Current enrolment or past participation in another investigational study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within the last 40 days or 5 half-lives, whichever is longer, before the first day of dosing (Day 1)
  • Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study intervention
  • Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
  • Positive hepatitis C ribo nucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
  • Positive pre-study drug/alcohol screen
  • Regular use of known drugs of abuse, including tetrahydrocannabinol.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, and TB testing: a positive (not indeterminate) TB test such as QuantiFERON-TB Gold Plus test
  • Positive smoke breathalyzer levels indicative of smoking history at screening and each in-house admission to the clinical research unit or regular use of tobacco- or nicotine-containing products (e.g., nicotine patches or vaporizing devices) within 6 months prior to screening.
  • Estimated glomerular filtration rate (eGFR) of <90 millilitre per minute per 1.73 meter square (mL/min/1.73 m^2) and / or UACR of >30 milligram per gram (mg/g) (>3 milligram per millimoles [mg/mmol]) at screening.
  • Electrocardiogram (ECG) evidence of ischemic heart disease as determined by the Investigator.
  • Positive test for Coronavirus disease 2019 (COVID-19) infection or signs and symptoms suggestive of COVID-19
  • Regular excess alcohol consumption within 6 months prior to the study defined as an average weekly intake of >14 units for males and females
  • Hypersensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study Additional exclusions for part 3 cohort only -
  • Medical history of NSAIDs hypersensitivities, bronchial asthma, psychiatric and neurologic disorders, gastrointestinal disorders (including gastroesophageal reflux disease [GORD], gastritis, peptic ulcer disease and previous GI bleeding), cardiac or renal disease, coagulation defects and who are not on concomitant medication that may potentiate the potential harmful effects of indomethacin.
  • Medical history of diabetes, defined as an HbA1c >5.6%, >39 mmol/mol.
  • History of severe lactose intolerance or galactosaemia

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • GSK Investigational Site

    Cambridge, CB2 0GG

Other trials in United Kingdom

About this study

Official title: A Randomized, Double-Blind, Placebo-Controlled, Single, Repeat Dose Escalation and Indomethacin Challenge Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK4381406 in Healthy Participants

This is a 3-part First Time in Human (FTIH) study to evaluate the safety, tolerability, and pharmacokinetics (PK) profile of GSK4381406 following administration of single ascending doses (Part 1), repeat ascending doses (Part 2), and repeat doses with an indomethacin challenge (Part 3) in healthy adult participants. Part 1 consists of 4 planned cohorts with up to 2 treatment periods in each and is expected to have 6 doses (but can accommodate up to 7 doses). The impact of food on PK of GSK4381406 will also be assessed. Part 2 will investigate 14 days of repeat dosing in 3 cohorts with 3 dose levels. Part 3 will evaluate the impact of repeat doses of GSK4381406 versus placebo on indomethacin induced changes in small intestinal permeability in healthy participants.

Being tested
GSK4381406, Placebo, Indomethacin
Keywords
Gastrointestinal (GI), Intestinal permeability, First time in human (FTIH), Safety, Pharmacokinetics, Indomethacin challenge, Food effect
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK4381406Drug

    GSK4381406 will be administered.

  • PlaceboDrug

    Placebo will be administered.

  • IndomethacinDrug

    Indomethacin will be administered.

Study groups in NCT05999708
Study groupRoleWhat they receive
Part 1: Cohort 1 - GSK4381406 or placeboExperimentalParticipants in Part 1 Cohort 1 will receive a single dose of GSK4381406 dose level 1 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 3 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose.
Receives: Drug: GSK4381406; Drug: Placebo
Part 1: Cohort 2 - GSK4381406 or placeboExperimentalParticipants in Part 1 Cohort 2 will receive a single dose of GSK4381406 dose level 2 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 4 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose.
Receives: Drug: GSK4381406; Drug: Placebo
Part 1: Cohort 3 - GSK4381406 or placeboExperimentalParticipants in Part 1 Cohort 3 will receive a single dose of GSK4381406 dose level 5 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 7 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose. Note: Requirement for Treatment Period 2 (dose level 7) will be determined by PK data of previous doses.
Receives: Drug: GSK4381406; Drug: Placebo
Part 1: Cohort 4 - GSK4381406 or placeboExperimentalParticipants in Part 1 Cohort 4 will receive a single dose of GSK4381406 dose level 6 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 6 in Treatment Period 2 in fed state with washout period of at least 40 days between each dose.
Receives: Drug: GSK4381406; Drug: Placebo
Part 2: Cohort 5 - GSK4381406 or placeboExperimentalParticipants in Part 2 Cohort 5 will receive 14 days of once daily repeat dosing of GSK4381406 dose level A or placebo in fasted state.
Receives: Drug: GSK4381406; Drug: Placebo
Part 2: Cohort 6 - GSK4381406 or placeboExperimentalParticipants in Part 2 Cohort 6 will receive 14 days of once daily repeat dosing of GSK4381406 dose level B or placebo in fasted state.
Receives: Drug: GSK4381406; Drug: Placebo
Part 2: Cohort 7 - GSK4381406 or placeboExperimentalParticipants in Part 2 Cohort 7 will receive 14 days of once daily repeat dosing of GSK4381406 dose level C or placebo in fasted state.
Receives: Drug: GSK4381406; Drug: Placebo
Part 3 - GSK4381406 or Placebo and IndomethacinExperimentalParticipants in Part 3 will receive 3 days of once daily repeat dosing of GSK4381406 in Treatment Period 1 followed by placebo in Treatment Period 2, or placebo in Treatment Period 1 and GSK4381406 in Treatment Period 2 in a cross-over design with a washout period of at least 14 days between each dosing period. Participants will be dosed in fasted state. The participants will be challenged with indomethacin during the final 2 days of each dosing period.
Receives: Drug: GSK4381406; Drug: Placebo; Drug: Indomethacin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    Measured: Up to Day 40

  2. Part 2 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    Measured: Up to Day 54

  3. Part 3 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)

    Measured: Up to Day 34

  4. Part 1 - Number of participants with clinically significant changes in hematology laboratory values

    Measured: Up to Day 40

  5. Part 2 - Number of participants with clinically significant changes in hematology laboratory values

    Measured: Up to Day 54

  6. Part 3 - Number of participants with clinically significant changes in hematology laboratory values

    Measured: Up to Day 34

  7. Part 1 - Number of participants with clinically significant changes in chemistry laboratory values

    Measured: Up to Day 40

  8. Part 2 - Number of participants with clinically significant changes in chemistry laboratory values

    Measured: Up to Day 54

  9. Part 3 - Number of participants with clinically significant changes in chemistry laboratory values

    Measured: Up to Day 34

  10. Part 1 - Number of participants with clinically significant changes in urinalysis

    Measured: Up to Day 40

  11. Part 2 - Number of participants with clinically significant changes in urinalysis

    Measured: Up to Day 54

  12. Part 3 - Number of participants with clinically significant changes in urinalysis

    Measured: Up to Day 34

  13. Part 1 - Number of participants with clinically significant changes in vital signs

    Measured: Up to Day 40

  14. Part 2 - Number of participants with clinically significant changes in vital signs

    Measured: Up to Day 54

  15. Part 3 - Number of participants with clinically significant changes in vital signs

    Measured: Up to Day 34

  16. Part 1 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings

    Measured: Up to Day 40

  17. Part 2 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings

    Measured: Up to Day 54

  18. Part 3 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings

    Measured: Up to Day 34

Secondary outcomes (20)

  1. Part 1 - Area under the plasma concentration-time curve (AUC) from time zero to 24-hour post-dose [AUC(0-24)

    Measured: Up to 24 hours post dose

  2. Part 1 - AUC from time zero to last quantifiable concentration [AUC(0-t)

    Measured: Up to Day 40

  3. Part 1 - AUC from time zero to infinity [AUC(0-inf)

    Measured: Up to Day 40

  4. Part 1 - Maximum observed plasma drug concentration (Cmax)

    Measured: Up to Day 40

  5. Part 1 - Time to maximum observed plasma drug concentration (tmax)

    Measured: Up to Day 40

  6. Part 1 - Time of last quantifiable concentration (tlast)

    Measured: Up to Day 40

  7. Part 1 - Apparent terminal phase half-life (t½)

    Measured: Up to Day 40

  8. Part 2 - AUC from time zero to last quantifiable concentration [AUC(0-t)

    Measured: Day 1 and Day 14

  9. Part 2 - AUC over the dosing interval [AUC(0-tau)

    Measured: Day 1 and Day 14

  10. Part 2 - Maximum observed plasma drug concentration (Cmax)

    Measured: Day 1 and Day 14

  11. Part 2 - Time to maximum observed plasma drug concentration (tmax)

    Measured: Day 1 and Day 14

  12. Part 2 - AUC from time zero to infinity [AUC(0-inf)

    Measured: Day 14 to Day 54

  13. Part 2 - Apparent terminal phase half-life (t½)

    Measured: Day 14 to Day 54

  14. Part 2 - Pre-dose (trough) plasma concentrations (Ctau)

    Measured: Day 1 to Day 14

  15. Part 2 - Accumulation ratios for Cmax (R)

    Measured: Day 1 and Day 14

  16. Part 2 - Accumulation ratios for AUC(0-tau) (Ro)

    Measured: Day 1 and Day 14

  17. Part 1: Cohort 4 - AUC from time zero to infinity [AUC(0-inf)

    Measured: Up to Day 40

  18. Part 1: Cohort 4 - Maximum observed plasma drug concentration (Cmax)

    Measured: Up to Day 40

  19. Part 1: Cohort 4 - Time to maximum observed plasma drug concentration (tmax)

    Measured: Up to Day 40

  20. Part 3 - Lactulose:rhamnose ratio over 0-5 hour in urine

    Lactulose and rhamnose concentrations in urine will be collected over 0-2 hour and 2-5 hour, which will be used to derive the ratio over 0-5 hour

    Measured: At Day 1, 3, 17 and 20

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2023
  2. Study start31 Oct 2023 (estimated)
  3. Primary completion5 Dec 2024 (estimated)
  4. Study completion5 Dec 2024 (estimated)

Why it stopped: Study terminated prior to FSFV for strategic business reasons.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05999708
Sponsor's protocol ID
218680
Status last verified
Dec 2023
First submitted
11 Aug 2023
Last updated
15 Dec 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK4381406 and Indomethacin in people with Colitis, Ulcerative, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 - Number of participants with adverse events (AEs) and serious adverse events (SAEs) (time frame: Up to Day 40). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05999708.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.

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