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This study is designed to investigate the safety, tolerability and PK of VH4524184 (GSK4524184) and the potential of VH4524184 to inhibit or induce CYP3A activity in healthy participants.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1: Cohort 1: Participants receiving VH4524184 DL1 | Experimental | Eligible participants will receive VH4524184 Dose Level 1 (DL1) during Cohort 1 of Part 1 of the study. |
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| Part 1: Cohort 1: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 DL1 during Cohort 1 of Part 1 of the study. |
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| Part 1: Cohort 2: Participants receiving VH4524184 DL2 | Experimental | Eligible participants will receive VH4524184 DL2 during Cohort 2 of Part 1 of the study. |
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| Part 1: Cohort 2: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 DL2 during Cohort 2 of Part 1 of the study. |
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| Part 1: Cohort 3: Participants receiving VH4524184 DL3 | Experimental | Eligible participants will receive VH4524184 DL3 during Cohort 3 of Part 1 of the study. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VH4524184 | Drug | VH4524184 will be administered. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of participants with serious adverse events (SAE) and non-serious adverse events (non-SAE) | Up to 4 weeks | |
| Part 2: Number of participants with SAE and non-SAE | Up to 6.5 weeks | |
| Part 3: Number of participants with SAE and non-SAE | Up to 6.5 weeks | |
| Part 1: Number of participants with adverse events based on severity | Up to 4 weeks | |
| Part 2: Number of participants with adverse events by severity | Up to 6.5 weeks | |
| Part 3: Number of participants with adverse events based on severity | Up to 6.5 weeks | |
| Part 1: Percentage of participants who discontinue treatment due to adverse events (AE) | Up to 4 weeks | |
| Part 2: Percentage of participants who discontinue treatment due to AE | Up to 6.5 weeks | |
| Part 3: Percentage of participants who discontinue treatment due to AE | Up to 6.5 weeks | |
| Part 1: Change from Baseline in Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and Alkaline phosphatase (ALP) (International units per liter) |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities | Up to 4 weeks | |
| Part 2: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities | Up to 6.5 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | ViiV Healthcare | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Baltimore | Maryland | 21225 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40117383 | Derived | Rogg L, Underwood M, Hanan N, Castillo-Mancilla JR, Kahl L, Halliday F, Ghita GL, Jeffrey JL, Byrne S, Onodera T, Horton J, Gartland M. Phase 1 Evaluation of VH4524184, a Third-Generation Integrase Strand Transfer Inhibitor With an Enhanced Resistance Profile. Clin Infect Dis. 2025 Oct 6;81(3):510-520. doi: 10.1093/cid/ciaf135. |
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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/
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 terminated asset(s) 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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Participants will receive escalating doses of VH4524184 or placebo in Part 1 and Part 2 of the study. In Part 3, participants will receive VH4524184 under fasted and fed conditions.
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This will be a double blind study.
| Part 1: Cohort 3: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 DL3 during Cohort 3 of Part 1 of the study. |
|
| Part 1: Cohort 4: Participants receiving VH4524184 DL4 | Experimental | Eligible participants will receive VH4524184 DL4 during Cohort 4 of Part 1 of the study. |
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| Part 1: Cohort 4: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 DL4 during Cohort 4 of Part 1 of the study. |
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| Part 1: Cohort 5: Participants receiving VH4524184 DL5 | Experimental | Eligible participants will receive VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study. |
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| Part 1: Cohort 5: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 DL5 during Cohort 5 (optional) of Part 1 of the study. |
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| Part 1: Cohort 6: Participants receiving VH4524184 DL6 | Experimental | Eligible participants will receive VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study. |
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| Part 1: Cohort 6: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 DL6 during Cohort 6 (optional) of Part 1 of the study. |
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| Part 2: Cohort 7: Participants receiving VH4524184 RL1 | Experimental | Eligible participants will receive VH4524184 Repeat dose Level 1 (RL1) during Cohort 7 (Part 2) of the study. |
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| Part 2: Cohort 7: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 RL1 during Cohort 7 (Part 2) of the study. |
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| Part 2: Cohort 8: Participants receiving VH4524184 RL2 | Experimental | Eligible participants will receive VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184 |
|
| Part 2: Cohort 8: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 RL2 during Cohort 8 (Part 2) of the study. If Cohort 8 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184. |
|
| Part 2: Cohort 9: Participants receiving VH4524184 RL3 | Experimental | Eligible participants will receive VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of VH4524184. |
|
| Part 2: Cohort 9: Participants receiving Placebo | Placebo Comparator | Eligible participants will receive Placebo matching VH4524184 RL3 during Cohort 9 (Part 2) (optional) of the study. If Cohort 9 is the highest Part 2 dose cohort, participants may also receive midazolam probe before and following repeat dose administration of Placebo matching VH4524184. |
|
| Part 3: Cohort 10: VH4524184 Fasted/ VH4524184 Fed | Experimental | Eligible participants will receive VH4524184 under fasted condition in Treatment Period 1 followed by VH4524184 under fed condition in Treatment Period 2 during Cohort 10 (Part 3) of the study. Treatment Periods will be separated by a washout period. |
|
| Midazolam | Drug | Midazolam will be administered in the highest dose cohort in Part 2 (Cohorts 8 or 9). |
|
| Placebo | Drug | Placebo will be administered. |
|
| Baseline (Day 1) and up to 4 weeks |
| Part 2: Change from Baseline in AST, ALT and ALP (International units per liter) | Baseline (Day 1) and up to 6.5 weeks |
| Part 3: Change from Baseline in AST, ALT and ALP (International units per liter) | Baseline (Day 1) and up to 6.5 weeks |
| Part 1: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter) | Baseline (Day 1) and up to 4 weeks |
| Part 2: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter) | Baseline (Day 1) and up to 6.5 weeks |
| Part 3: Change from Baseline in Total bilirubin and Direct bilirubin (Micromoles per liter) | Baseline (Day 1) and up to 6.5 weeks |
| Part 1: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds) | Baseline (Day 1) and up to 4 weeks |
| Part 2: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds) | Baseline (Day 1) and up to 6.5 weeks |
| Part 3: Change from Baseline in Prothrombin time and Partial Thromboplastin Time (Seconds) | Baseline (Day 1) and up to 6.5 weeks |
| Part 1: Change from Baseline in International normalized ratio (INR) (Ratio) | Baseline (Day 1) and up to 4 weeks |
| Part 2: Change from Baseline in INR (Ratio) | Baseline (Day 1) and up to 6.5 weeks |
| Part 3: Change from Baseline in INR (Ratio) | Baseline (Day 1) and up to 6.5 weeks |
| Part 1: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR | Baseline (Day 1) and up to 4 weeks |
| Part 2: Number of participants with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR | Baseline (Day 1) and up to 6.5 weeks |
| Part 3: Number of participant with maximum toxicity grade increase from Baseline in liver panel laboratory parameters; AST, ALT, ALP, Total bilirubin, Direct bilirubin, Prothrombin time, Partial Thromboplastin Time and INR | Baseline (Day 1) and up to 6.5 weeks |
| Part 1: Area under the plasma-concentration time curve from zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) following dosing of VH4524184 | Up to 4 weeks |
| Part 2: Area under the plasma concentration-time curve from zero (pre-dose) to the end of the dosing interval at steady state (AUC[0-tau]) following dosing of VH4524184 | Up to 6.5 weeks |
| Part 1: Maximum observed plasma drug concentration (Cmax) following dosing of VH4524184 | Up to 4 weeks |
| Part 2: Cmax following dosing of VH4524184 | Up to 6.5 weeks |
| Part 1: Time to maximum observed plasma drug concentration (tmax) following dosing of VH4524184 | Up to 4 weeks |
| Part 2: Tmax following dosing of VH4524184 | Up to 6.5 weeks |
| Part 1: Apparent terminal half-life (t1/2) following dosing of VH4524184 | Up to 4 weeks |
| Part 2: T1/2 following dosing of VH4524184 | Up to 6.5 weeks |
| Part 3: Number of participants with treatment emergent Grade 3 or Grade 4 laboratory abnormalities | Up to 6.5 weeks |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| 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 |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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