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The aim of the study is to gather information on how the drug behaves in healthy adults, how it is absorbed, and how it interacts when taken with other medicines.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1A_VH4524184 (Sequence 1) | Experimental | Participants will receive VH4524184 tablet(s) of Dose level 1 followed by Dose level 2 in fasted condition. |
|
| Part 1A_VH4524184 (Sequence 2) | Experimental | Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 1 in fasted condition. |
|
| Part 1A_VH4524184 (Sequence 3) | Experimental | Participants will receive VH4524184 tablet(s) of Dose level 3 followed by Dose level 2 in fasted condition. |
|
| Part 1A_VH4524184 (Sequence 4) | Experimental | Participants will receive VH4524184 tablet(s) of Dose level 2 followed by Dose level 3 in fasted condition. |
|
| Part 1B_VH4524184 (Sequence 5) | Experimental | Participants will receive VH4524184 tablet of Dose level 2 in fasted condition and then followed by intake of a high fat meal. |
|
| Part 1B_VH4524184 Sequence 6) |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VH4524184 | Drug | VH4524184 will be administered. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Maximum plasma concentration (Cmax) for VH4524184 | Up to Day 18 | |
| Part 1: Area under the concentration-time curve from 0 to tau (AUC0-t) for VH4524184 | Up to day 18 | |
| Part 1: Area under the concentration-time curve from 0 to infinity (AUC0-inf) for VH4524184 | Up to day 18 | |
| Part 2: Cmax for VH4524184 | At Day 1, Day 14, Day 19 and Day 22 | |
| Part 2: AUC0-t of VH4524184 | At Day 1, Day 14, Day 19 and Day 22 | |
| Part 2: AUC0-inf of VH4524184 | At Day 1, Day 14, Day 19 and Day 22 | |
| Part 2: Cmax for metformin | At Day 1 and Day 15 | |
| Part 2: AUC0-t for metformin | At Day 1 and Day 15 | |
| Part 2: Cmax for Digoxin | At Day 1 and Day 15 | |
| Part 2: AUC0-t for Digoxin | At Day 1 and Day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events (AEs) and severity of AEs | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Severity of grades are defined as Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Potentially Life- Threatening. | From Day 1 up to Day 42 |
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Inclusion Criteria:
1. Participants must be 18 to 60 years of age inclusive at the time of signing the Informed consent form (ICF).
2. Male or female
Male Participants: No restrictions for male participants
A female participant (female sex assigned at birth) is eligible to participate if she is not pregnant, or breastfeeding and the following condition applies: She is a woman of nonchildbearing potential (WONCBP).
3. Participants who are overtly healthy as determined by medical evaluation 4. AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) 6. Capable of giving signed informed consent.
Exclusion Criteria:
13. Use of medications/supplements affecting cytochrome P450 enzymes within 7 to 14 days prior to dosing.
14. Contraindications based on selected drug prescribing information. 15. Exposure to more than 4 new investigational products within 12 months 16. Current enrollment or past participation in another investigational study in which an investigational intervention was administered within the last 30 days.
17. Estimated glomelular filtration rate (eGFR) < 90 mL/min or serum creatinine >1.1×ULN [Inker, 2021].
18. Hemoglobin <12.5 g/dL for men and <11 g/dL for women. 19. Presence of Hepatitis B surface antigen (HBsAg) [and Hepatitis B core antibody (HBcAb)] at screening 20. Positive Hepatitis C antibody test result at screening 21. Positive SARS-CoV-2 test, having signs and symptoms which in the opinion of the investigator are suggestive of COVID-19.
22.Positive pre- study drug/alcohol screen. 23. Poor metabolizers of CYP2C9 and / or CYP2C19 as assessed by genotype testing. HLA-B*1502 positive as applicable to specified cohort.
Other exclusion criteria 24. Regular alcohol consumption exceeding specified limits. 25. Regular use of known drugs of abuse. 26. Nicotine use within 6 months. 27. Sensitivity or allergy to the study drug. 28. ALT >1.5×ULN. 29. Total bilirubin >1.5×ULN. 30. Significant arrhythmias or ECG findings that may compromise participant safety according to the investigator or VH Medical Monitor's assessment.
31. For eligibility determination, triplicate ECGs are required. The criteria are:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Lenexa | Kansas | 66219 | United States | ||
| GSK Investigational Site |
Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.viiv-studyregister.com/documents/About\_ViiV\_Patient\_Level\_Data\_Sharing\_Final\_25Sep2023.pdf
Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| D017964 | Itraconazole |
| D017828 | Rifabutin |
| D010672 | Phenytoin |
| D008687 | Metformin |
| D004077 | Digoxin |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Experimental |
Participants will receive VH4524184 tablet of Dose level 2 following a high fat meal and then in fasted condition. |
|
| Part 1B_VH4524184 (Sequence 7) | Experimental | Participants will receive VH4524184 tablet of Dose level 3 in fasted condition and then followed by intake of a high fat meal. |
|
| Part 1B_VH4524184 (Sequence 8) | Experimental | Participants will receive VH4524184 tablet of Dose level 3 following a high fat meal and then in a fasted condition. |
|
| Part 2_Cohort 1 | Experimental | Participants will receive VH4524184 tablet and Itraconazole. |
|
| Part 2_Cohort 2A | Experimental | Participants will receive VH4524184 and Rifabutin. |
|
| Part 2_Cohort 2B | Experimental | Participants will receive VH4524184 tablet and Phenytoin. |
|
| Part 2_ Cohort 3 | Experimental | Participants will receive Metformin, Digoxin and VH4524184 tablets. |
|
| Itraconazole | Drug | Itraconazole will be administered. |
|
|
| Rifabutin | Drug | Rifabutin will be administered. |
|
|
| Phenytoin | Drug | Extended phenytoin sodium will be administered. |
|
|
| Metformin | Drug | Metformin will be administered. |
|
|
| Digoxin | Drug | Digoxin will be administered. |
|
|
| Number of participants with AEs leading to discontinuation of study intervention | Throughout the study treatment period (from Day 1 up to Day 33) |
| Number of participants with Change in laboratory parameters | From Day 1 up to Day 42 |
| Number of participants with maximum toxicity grade increase from baseline in laboratory parameters | Toxicity is graded using the DAIDS criteria Version 2.1 where grades were defined based on numeric criteria as follows Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: potentially life-threatening. A higher grade indicates greater severity. | From Day 1 up to Day 42 |
| Part 1: Time to maximum concentration (Tmax) of VH4524184 | At Day 1 |
| Part 1: Apparent Terminal Half Life (T1/2) of VH4524184 | At Day 1 |
| Part 1: Apparent oral clearance (CL/F) of VH4524184 | At Day 1 |
| Part 2: Tmax of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin) | At Day 1, Day 14, Day 19 and Day 22 |
| Part 2: T1/2 of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin) | At Day 1, Day 14, Day 19 and Day 22 |
| Part 2: CL/F of VH4524184 Following Single-Dose Administration with CYP3A4 Inhibitors and Inducers (Itraconazole, Rifabutin, Phenytoin) | At Day 1, Day 14, Day 19 and Day 22 |
| Part 2: Cmax for VH5424184 Following Comedication with Transporter Substrates with metformin and digoxin | At Day 1 and Day 15 |
| Part 2: AUC0-t for VH5424184 Following Comedication with Transporter Substrates metformin and digoxin | At Day 1 and Day 15 |
| Part 2: Cmax for Itraconazole Following Comedication with VH4524184 | At Day 1 and Day 14 |
| Part 2: AUC0-t for Itraconazole Following Comedication with VH4524184 | At Day 1 and Day 14 |
| Part 2: Cmax for Rifabutin Following Comedication with VH4524184 | At Day 1 and Day 11 |
| Part 2: AUC0-t for Rifabutin Following Comedication with VH4524184 | At Day 1 and Day 19 |
| Part 2: Cmax for Phenytoin Following Comedication with VH4524184 | Day 1 and Day 22 |
| Part 2: AUC0-t for Phenytoin Following Comedication with VH4524184 | Day 1 and Day 22 |
| Salt Lake City |
| Utah |
| 84124 |
| United States |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D010879 |
| Piperazines |
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D006827 | Hydantoins |
| D048289 | Imidazolidines |
| D007093 | Imidazoles |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |