Drug interaction assessment of GSK3882347 in healthy participants aged 18 to 65 years
- Conditions
- Healthy volunteer drug interaction studyNot Applicable
- Registration Number
- ISRCTN16147016
- Lead Sponsor
- GlaxoSmithKline (United Kingdom)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- All
- Target Recruitment
- 30
1. Participants must be =18 years of age and =65 years of age at the time of signing the informed consent.
2. 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.
3. Body weight at least 50.0 kg (110 lbs) for males and 45.0 kg (99 lbs) for females; and body mass index (BMI) within the range 18.5 – 32.0 kg/m² (inclusive).
4. Male and female participants
4.1. Male Participants: 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:
4.1.1. 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
4.1.2. Must agree to use contraception/barrier as detailed below:
- Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant
- Agree to use a male condom when engaging in any activity that allows for the passage of ejaculate to another person.
4.2. Female Participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
4.2.1. Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4 Contraceptive and Barrier Guidance. OR
4.2.2. Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 10.4 during the study intervention Period and for at least 3 days after the last dose of study (or for intervention). For WOCBP choosing hormonal contraceptives, the required duration for hormonal contraceptive use is during the study intervention period and for at least 14 days [with a double barrier as described in Section 10.4]) after the last dose of the study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of the study intervention
4.2.3. A WOCBP must have a negative highly sensitive pregnancy test [urine or serum] as required by local regulations) within 24 hrs before the first dose of the study intervention. See Section 8.3.6 Pregnancy Testing.
- If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Additional requirements for pregnancy testing during and after study intervention are located in Section 8.3.6 Pregnancy Testing.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk of inclusion of a woman with an early undetected pregnancy.
5. Capable of giving si
1. 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 subject 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.
2. Abnormal blood pressure, as determined by the investigator.
3. Alanine transferase (ALT) value >1.5 × ULN.
4. Bilirubin value >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
5. 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)
6. The participant has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.
7. The participant has any history of heart failure.
8. The participant has a family history of QT prolongation or sudden death.
9. The participant has any current or previous history of episodes of symptomatic bradycardia or bradyarrhythmia.
10. The participant has a QTc >450 msec. Note: The QTc is the QT interval corrected for heart rate according to the Fridericia formula, machine, or manual overread.
11. The participant has anuria, oliguria, or impairment of renal function (GFR by MDRDa<90 mL/min/1.73m2 or serum creatinine > upper limit of normal [ULN] or urine albumin-creatinine ratio [ACR] of =30 mg/g at screening).
12. The participant must agree to and adhere to the concomitant therapy (including nondrug therapies) restrictions as described in Section 6.9 from the Screening Visit through to the end of the study (including telephone visit).
13. Participation in the study would result in loss of blood or blood products in excess of 500 ml within 56 days.
14. Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
15. 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.
16. Current enrolment or past participation in this clinical study.
17. Positive human immunodeficiency virus (HIV) antibody test.
18. Presence of Hepatitis B surface antigen (HbsAg) at screening or within 3 months prior to the first dose of the study intervention.
19. Hepatitis C antibody test result at screening or within 3 months prior to the first dose of the study intervention.NOTE: Participants with a positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if there is a history of a confirmatory negative Hepatitis C RNA. Positive Hepatitis C RNA test result within 3 months prior to the first dose of the study intervention.
20. A positive confirmation of COVID-19 infection, or high clinical index of suspicion for COVID-19.
21. The participant, in the judgment of the investigator, would not be able or willing to comply with the protocol or complete the study.
22. Regular alcohol consumption within 6 months prior to the study, defined as a
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Plasma pharmacokinetics of midazolam with GSK3882347, midazolam (MDZ) and 1-hydroxy-MDZ: AUC(0-24), AUC(0-t), AUC(0-inf), Cmax, tmax, tlag and t½ measured using noncompartmental PK analysis methods in Period 2 compared to Period 1 following 14 days dosing of GSK3882347
- Secondary Outcome Measures
Name Time Method Measured throughout the study up to the telephone follow-up visit:<br>1. Occurrence of adverse events (AEs) and serious adverse events (SAEs) measured using AE and SAE reports submitted by the investigator in the study eCRF, or via paper reporting forms<br>2. Occurrence of clinically significant changes in laboratory values (hematology, chemistry, and urinalysis), vital signs and 12-lead electrocardiogram (ECG) readings<br>3. GSK3882347 AUC(0-24), Ctau, CL/F, Vd/F and MRT AUC(0-inf) and Cmax for single dose (Day 2) and AUC(0-tau) and Cmax for repeat dose (Day 15) measured using noncompartmental PK analysis methods<br>4. Ro (accumulation ratio) using AUC(0-tau) for repeat dose measured using the ratio of AUC(0-24)Day15/AUC(0-24)Day1<br>5. Time invariance using AUC(0-tau) (repeat dose) and AUC(0-inf) (single dose) measured using the ratio of AUC(0-24)Day15/AUC(0-inf)Day1<br>6. Achievement of steady-state (Ctau collected on multiple days) measured using the ratio of Ctau,Day15/Ctau,Day1