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Completed

NCT Number: NCT05760261

Drug Interaction Assessment of GSK3882347 in Healthy Participants Aged 18 to 65 Years

The objective of this study is to determine the magnitude and clinical relevance of a potential drug-drug interaction of GSK3882347 with midazolam (MDZ) in healthy participants. This study assesses the effect of GSK3882347 as an inducer of Cytochrome P450 3A4 (CYP3A4) using MDZ, a sensitive substrate of hepatic and intestinal CYP3A4. The study will investigate MDZ pharmacokinetic (PK) effect in two dosing periods:

Period 1: A single dose of MDZ Period 2: 14-days of once daily repeat dosing of GSK3882347 followed by single dose of MDZ co-administered with GSK3882347 on Day 15 (14-days has been selected as this duration is required in order to maximize any potential CYP3A4 enzyme induction).

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Key information

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site

Cambridge, CB2 0GG, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. A participant with a clinical abnormality or laboratory parameter(s) not specifically listed in the exclusion or exclusion criteria that is outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor (if required), agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight at least 50.0 kilogram (kg) (110 pound [lbs.]) for males and 45.0 kg (99 lbs.) for females; and body mass index (BMI) within the range 18.5 - 32.0 kg per meter square (kg/m^2) (inclusive).
  • Male participants are eligible to participate if they agree to the following during the study intervention Period and for at least 3 days, after the last dose of study intervention:
  • Refrain from donating fresh unwashed semen

Plus, either:

  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.

OR

  • Must agree to use contraception/barrier.
  • 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 a contraceptive method that is highly effective, with a failure rate of lesser than (<) 1 percent (%).
  • A WOCBP must have a negative highly sensitive pregnancy test [urine or serum] as required by local regulations) within 24h before the first dose of study intervention.
  • 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 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).

Exclusion criteria

  • History or presence of significant cardiovascular, respiratory, hepatic, renal, urological, gastrointestinal, metabolic, endocrinological, hematological, immunologic, dermatologic, neurological or psychiatric 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 or in the opinion of the investigator places the participants at unacceptable risk or would make adhering to study procedures for the duration of the study difficult. Participants who have had a gastric bypass or a cholecystectomy are excluded from the study.
  • Abnormal blood pressure, as determined by the investigator.
  • Alanine transferase (ALT) value greater than (>)1.5 × upper limit of normal (ULN).
  • Bilirubin value >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • The participant has a current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • The participant has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.
  • The participant has any history of heart failure.
  • The participant has a family history of QT prolongation or sudden death.
  • The participant has any current or previous a history of episodes of symptomatic bradycardia or bradyarrhythmia.
  • The participant has a QTc >450 millisecond (msec). Note: The QTc is the QT interval corrected for heart rate according to Fridericia formula, machine, or manual overread.
  • The participant has anuria, oliguria, or impairment of renal function (GFR by Modification of diet in renal disease [MDRD] <90 milliliter per minute per 1.73 meter square [mL/min/1.73m^2] or serum creatinine > ULN or urine albumin-creatinine ratio [ACR] of ≥300 milligram per gram [mg/g] at screening).
  • The participant must agree to and adhere to the concomitant therapy (including nondrug therapies) restrictions from the Screening Visit through to the end of the end of the study (including telephone visit).
  • Participation in the 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 prior to the first dosing day.
  • Current enrolment or past participation within the last 30 days or 5 half-lives, whichever is longer, before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
  • Current enrolment or past participation in this clinical study.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Presence of Hepatitis B surface antigen (HbsAg) at screening or within 3 months prior to first dose of study intervention.
  • Hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention.
  • A positive confirmation of Coronavirus disease 2019 (COVID-19) infection, or high clinical index of suspicion for COVID-19.
  • The participant, in the judgment of the investigator, would not be able or willing to comply with the protocol or complete the study.
  • Regular alcohol consumption within 6 months prior to the study. An average weekly intake of >14 units for males or females. One unit is equivalent to approximately to 8 g of alcohol: a half-pint (approximately [~]240 mL) of beer, one glass (125 mL) of wine or one (25 mL) measure of spirits.
  • Positive smoke breathalyzer 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 (i.e., nicotine patches or vaporizing devices) within 3 months prior to screening.
  • Regular use of combustible tobacco products, and non-combustible nicotine delivery systems, inclusive of cigarettes, cigars, pipes, and materials used to "vape".
  • Any history of substance abuse or a positive urine test for drugs of abuse/ alcohol breath screen at screening or admission.
  • Known 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.
  • Contraindication for MDZ (i.e., Hypersensitivity to the active substance, benzodiazepines or to any of the excipients, myasthenia gravis, respiratory insufficiency, sleep apnea syndrome, severe hepatic impairment).
  • Use of any products intended to treat medical conditions that are not approved by the governing health authority in a given country or region (for example, herbal medicine, health supplements, traditional medicine, homeopathic remedies, etc.).

Treatment and study plan

midazolam

Drug

Midazolam will be administered.

GSK3882347

Drug

GSK3882347 will be administered.

Primary outcomes

  1. Period 1: Area under the curve from time zero to 24 hours (AUC [0-24]) for plasma concentration of MDZ

    Time frame: Up to 24 hours

  2. Period 1: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ

    Time frame: Up to 24 hours

  3. Period 2: AUC (0-24) for plasma concentration of MDZ

    Time frame: Up to 24 hours

  4. Period 2: AUC (0-24) for plasma concentration of 1-hydroxy-MDZ

    Time frame: Up to 24 hours

  5. Period 1: AUC from time zero to last time of quantifiable concentration (AUC [0-tau]) for plasma concentration of MDZ

    Time frame: Up to Day 2

  6. Period 1: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ

    Time frame: Up to Day 2

  7. Period 2: AUC (0-tau) for plasma concentration of MDZ

    Time frame: Up to Day 15

  8. Period 2: AUC (0-tau) for plasma concentration of 1-hydroxy-MDZ

    Time frame: Up to Day 15

  9. Period 1: AUC from time zero extrapolated to infinite time (AUC [0-inf]) for plasma concentration of MDZ

    Time frame: Up to Day 2

  10. Period 1: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ

    Time frame: Up to Day 2

  11. Period 2: AUC (0-inf) for plasma concentration of MDZ

    Time frame: Up to Day 15

  12. Period 2: AUC (0-inf) for plasma concentration of 1-hydroxy-MDZ

    Time frame: Up to Day 15

  13. Period 1: Maximum plasma concentration (Cmax) of MDZ

    Time frame: Up to Day 2

  14. Period 1: Cmax of 1-hydroxy-MDZ

    Time frame: Up to Day 2

  15. Period 2: Cmax of MDZ

    Time frame: Up to Day 15

  16. Period 2: Cmax of 1-hydroxy-MDZ

    Time frame: Up to Day 15

  17. Period 1: Time to Cmax (Tmax) of MDZ

    Time frame: Up to Day 2

  18. Period 1: Tmax of 1-hydroxy-MDZ

    Time frame: Up to Day 2

  19. Period 2: Tmax of MDZ

    Time frame: Up to Day 15

  20. Period 2: Tmax of 1-hydroxy-MDZ

    Time frame: Up to Day 15

  21. Period 1: Time lag before observation of measurable concentrations (Tlag) of MDZ

    Time frame: Up to Day 2

  22. Period 1: Tlag of 1-hydroxy-MDZ

    Time frame: Up to Day 2

  23. Period 2: Tlag of MDZ

    Time frame: Up to Day 15

  24. Period 2: Tlag of 1-hydroxy-MDZ

    Time frame: Up to Day 15

  25. Period 1: Time to half-life (T1/2) of MDZ

    Time frame: Up to Day 2

  26. Period 1: T1/2 of 1-hydroxy-MDZ

    Time frame: Up to Day 2

  27. Period 2: T1/2 of MDZ

    Time frame: Up to Day 15

  28. Period 2: T1/2 of 1-hydroxy-MDZ

    Time frame: Up to Day 15

Secondary outcomes

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

    Time frame: Up to Day 15

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

    Time frame: Up to Day 15

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

    Time frame: Up to Day 15

  4. Number of participants with clinically significant changes in urinalysis laboratory values

    Time frame: Up to Day 15

  5. Number of participants with clinically significant changes in vital sign values

    Time frame: Up to Day 15

  6. Number of participants with clinically significant changes in 12-lead electrocardiogram (ECG) readings

    Time frame: Up to Day 15

  7. AUC (0-24) for plasma concentration of GSK3882347

    Time frame: Up to 24 hours

  8. Plasma concentrations over the dosing interval tau (Ctau) of GSK3882347

    Time frame: Up to Day 15

  9. Oral clearance (CL/F) of GSK3882347

    Time frame: Up to Day 15

  10. Volume of distribution/ Bioavailability (Vd/F) of GSK3882347

    Time frame: Up to Day 15

  11. Mean residence time (MRT) of GSK3882347

    Time frame: Up to Day 15

  12. AUC(0-inf) for single dose of GSK3882347

    Time frame: Up to Day 2

  13. Cmax for single dose of GSK3882347

    Time frame: Up to Day 2

  14. AUC(0-tau) for repeat dose of GSK3882347

    Time frame: Up to Day 15

  15. Cmax for repeat dose of GSK3882347

    Time frame: Up to Day 15

  16. Accumulation ratio (Ro) using AUC (0-tau) for repeat dose of GSK3882347

    Time frame: Up to Day 15

  17. Time invariance using AUC(0-tau) (repeat dose) of GSK3882347

    Time frame: Up to Day 15

  18. Time invariance using AUC(0-inf) (single dose) of GSK3882347

    Time frame: Up to Day 2

  19. Achievement of steady state of GSK3882347

    Time frame: Up to Day 15

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

A Phase 1, Open-Label Study in Healthy Participants Aged 18 to 65 Years to Investigate the CYP3A4 Induction Potential of GSK3882347

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Mar 8, 2023
Registry last updated
Jan 16, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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