Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MK-8527 · 16 trials · 9 indications
The number of participants with adjudicated HIV-1 infection will be presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experienced AEs will be presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that discontinued study intervention due to an AE will be presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Blood samples will be collected to determine the AUC0-inf of MK-8527 in plasma.
Blood samples will be collected at multiple time points to estimate AUC0-inf of MK-8527 in plasma.
Blood samples will be collected at multiple time points to estimate AUC0-inf of MK-8527 in plasma.
Blood samples will be collected at multiple time points to estimate AUC0-inf of MK-8527 in plasma.
The dose-normalized AUC0-24hr of R-methadone will be determined on Day 1.
The dose-normalized AUC0-24hr of S-methadone will be determined on Day 1.
Plasma samples will be collected at pre-specified timepoints to determine the AUC0-last of MK-8527.
Plasma samples will be collected at pre-specified timepoints to determine the AUC0-inf of MK-8527.
Plasma samples will be collected at pre-specified timepoints to determine the Cmax of MK-8527.
Plasma samples will be collected at pre-specified timepoints to determine the Tmax of MK-8527.
Plasma samples will be collected at pre-specified timepoints to determine the t1/2 of MK-8527.
Plasma samples will be collected at pre-specified timepoints to determine the CL/F of MK-8527.
Plasma samples will be collected at pre-specified timepoints to determine the Vz/F of MK-8527.
Change from Baseline in QTc following MK-8527 administration will be reported.
Blood samples will be collected to determine the AUC0-inf of MK-8527 in plasma
Blood samples will be collected to determine the AUC0-last of MK-8527 in plasma
Blood samples will be collected to determine the AUC0-24 of MK-8527 in plasma
Blood samples will be collected to determine the AUC0-168 of MK-8527 in plasma
Blood samples will be collected to determine the Cmax of MK-8527 in plasma
Blood samples will be collected to determine the Tmax of MK-8527 in plasma
Breast milk samples will be collected to determine the AUC0-120hrs after administration of a single oral dose of MK-8527.
Breast milk samples will be collected to determine the Cmax after administration of a single oral dose of MK-8527.
Breast milk samples will be collected to determine the Tmax after administration of a single oral dose of MK-8527.
Urine and fecal samples will be collected to determine the cumulative percentage of radioactivity recovered from both urine and feces.
Urine samples will be collected to determine the percent of total radioactivity recovered from urine.
Fecal samples will be collected to determine the percent of total radioactivity recovered from feces.
Plasma samples will be collected to determine the AUC0-24 of MK-8527.
Plasma samples will be collected to determine the Cmax of MK-8527.
Plasma samples will be collected to determine the C24 of MK-8527.
Plasma samples will be collected to determine the Tmax of MK-8527.
Plasma samples will be collected to determine the AUC0-24 of total radioactivity.
Plasma samples will be collected to determine the Cmax of total radioactivity.
Plasma samples will be collected to determine the C24 of total radioactivity.
Plasma samples will be collected to determine the Tmax of total radioactivity.
Whole blood samples will be collected to determine the AUC0-24 of total radioactivity.
Whole blood samples will be collected to determine the Cmax of total radioactivity.
Whole blood samples will be collected to determine the C24 of total radioactivity.
Whole blood samples will be collected to determine the Tmax of total radioactivity.
Urine samples will be collected to determine the cumulative amount of radioactivity recovered from urine.
Urine samples will be collected to determine the percent of the total radioactive dose recovered from urine.
Fecal samples will be collected to determine the cumulative amount of radioactivity recovered from feces.
Fecal samples will be collected to determine the percent of the total radioactive dose recovered from feces.
Plasma samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.
Urine samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.
Fecal samples will be collected at pre-specified timepoints and used to determine the total number of metabolites that represent at least 10% of the dose of radioactivity. Metabolites will be determined using liquid scintillation and high-resolution mass spectrometry.
Blood samples will be collected to determine the AUC0-Inf of MK-8527-TP in PBMC.
Blood samples will be collected to determine the AUC0-last of MK-8527-TP in PBMC.
Blood samples will be collected to determine the C672 of MK-8527-TP in PBMC.
Blood samples will be collected to determine the Cmax of MK-8527-TP in PBMC.
Blood samples will be collected to determine the Tmax of MK-8527-TP in PBMC.
Blood samples will be collected to determine the t1/2 of MK-8527-TP in PBMC.
Blood samples were collected at pre-specified time points to determine the AUC0-last of MK-8527 in participant's plasma. AUC0 to last of MK-8527 was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration. AUC0-last was calculated using noncompartmental analysis.
Blood samples were collected at pre-specified time points to determine the AUC0-inf of MK-8527 in participant's plasma. AUC0-inf was defined as AUC0-last + (Cest,last/λz) where Cest,last was the estimated last measurable concentration, and λz was the apparent first-order terminal elimination rate constant.
Blood samples were collected at pre-specified time points to determine the Cmax of MK-8527 in participant's plasma. Cmax was defined as the maximum observed concentration of MK-8527 in plasma after the administration of a given dose.
Blood samples were collected at pre-specified time points to determine the tmax of MK-8527 in participant's plasma. Tmax of MK-8527 in plasma was determined by deriving the difference between the time of the blood draw associated with the Cmax and the time of study drug administration
Blood samples were collected at pre-specified time points to determine the t1/2 of MK-8527 in participant's plasma. t1/2 was defined as 0.693/Apparent terminal elimination rate constant (λz).
Blood samples were collected at pre-specified time points to determine the CL/F of MK-8527 in participant's plasma. CL/F was defined as dose/(AUC0-inf).
Blood samples were collected at pre-specified time points to determine the Vz/F of MK-8527 in participant's plasma. Vz/F of MK-8527 in plasma was determined using the formula Dose/(AUC0-inf × λz).
The mean change from baseline in HIV-1 RNA counts at 168 hours after a single doses of MK-8527 is reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Blood samples were taken to determine HIV-1 RNA levels at Predose (baseline) and 168 hours postdose. Data were fitted with a longitudinal data analysis (LDA) model containing fixed effects for treatment, time and treatment by time interaction, and a random effect for participant.The change from baseline in plasma HIV-1 RNA in participants administered MK-8527 was calculated and results were compared with historical placebo data.
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that reported at least 1 AE will be summarized.
An AE is defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it is considered related to the medicinal product. The percentage of participants that were discontinued from the study due to an AE will be summarized.
| Arm | Type | Description |
|---|---|---|
| MK-8527 + Placebo to FTC/TDF | EXPERIMENTAL | Participants will receive 11 mg MK-8527 once monthly (QM) and placebo matched to Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) once daily (QD) for up to approximately 2 years. Participants will then receive open-label 200 mg FTC/245 mg TDF QD for an additional 28 days. |
| FTC/TDF + Placebo to MK-8527 | ACTIVE_COMPARATOR | Participants will receive 200 mg FTC/245 mg TDF QD and placebo matched to MK-8527 QM for up to approximately 2 years. Participants will then receive open-label 200 mg FTC/245 mg TDF QD for an additional 28 days. |
| MK-8527 | EXPERIMENTAL | Participants will receive 11 mg MK-8527 once monthly (QM) and placebo to FTC/TDF once daily (QD) for up to approximately 2 years. Participants will then receive open-label 200 mg FTC/245 mg TDF QD for an additional 28 days. |
| FTC/TDF | ACTIVE_COMPARATOR | Participants will receive 200 mg FTC/245 mg TDF QD and placebo to MK-8527 QM for up to approximately 2 years. Participants will then receive open-label 200 mg FTC/245 mg TDF QD for an additional 28 days. |
| MK-8527 Low Dose QM | EXPERIMENTAL | Participants receive oral MK-8527 low dose QM for 6 months, followed by an 8-week blinded safety follow-up period. |
| MK-8527 Medium Dose QM | EXPERIMENTAL | Participants receive oral MK-8527 medium dose QM for 6 months, followed by an 8-week blinded safety follow-up period. |
| MK-8527 High Dose QM | EXPERIMENTAL | Participants receive oral MK-8527 high dose QM for 6 months, followed by an 8-week blinded safety follow-up period. |
| Placebo to MK-8527 | PLACEBO_COMPARATOR | Participants receive oral placebo matched to MK-8527 QM for 6 months, followed by an 8-week blinded safety follow-up period. |
| MK-8527 + Rifampin | EXPERIMENTAL | Participants receive single doses of MK-8527 alone and in combination with daily doses of rifampin. |
| Part 1: MK-8527 | EXPERIMENTAL | Participants will receive a single dose of MK-8527 with food and a single dose of MK-8527 without food. |
| Part 2: MK-8527 + Probenecid | EXPERIMENTAL | Participants will receive a single dose of MK-8527 alone and a single dose of MK-8527 in combination with probenecid. |
| Part 3: MK-8527 + Itraconazole | EXPERIMENTAL | Participants will receive a single dose of MK-8527 alone and a single dose of MK-8527 in combination with itraconazole. |
| Methadone + MK-8527 | EXPERIMENTAL | Participants will receive methadone and MK-8527. |
| Mild Hepatic Impairment (Group 1) | EXPERIMENTAL | All participants will receive a single dose of MK-8527 on Day 1. |
| Moderate Hepatic Impairment (Group 2) | EXPERIMENTAL | All participants will receive a single dose of MK-8527 on Day 1. |
| Healthy (Group 3) | EXPERIMENTAL | All participants will receive a single dose of MK-8527 on Day 1. |
| MK-8527 PLUS Moxifloxacin and Placebo | EXPERIMENTAL | Participants receive a single dose of MK-8527 followed by a single dose of moxifloxacin and a single dose of placebo depending on randomization. |
| Moxifloxacin PLUS MK-8527 and Placebo | EXPERIMENTAL | Participants receive a single dose of moxifloxacin followed by a single dose of MK-8527 and a single dose of placebo depending on randomization. |
| Placebo PLUS MK-8527 and Moxifloxacin | EXPERIMENTAL | Participants receive a single dose of placebo followed by a single dose of MK-8527 and a single dose of moxifloxacin depending on randomization. |
| MK-8527 + CBZ | EXPERIMENTAL | Treatment A (Period 1): Participants will receive a single dose of MK-8527 on Day 1. Treatment B (Period 2): Participants will receive CBZ twice a day on Days 1 to 20 and a single dose of MK-8527 coadministered with the morning dose of CBZ on Day 14. A washout period will separate Treatments A and B. |
| [14C]MK-8527 | EXPERIMENTAL | Participants will receive a single oral dose of \[14C\]MK-8527 on Day 1 |
| Treatment A: MK-8527 | EXPERIMENTAL | Participants receive a single dose of MK-8527. |
| Treatment B: MK-8527 + FTC/TDF | EXPERIMENTAL | Participants receive FTC/TDF then MK-8527. |
| Moderate Renal Impairment | EXPERIMENTAL | Participants with moderate renal impairment receive a single dose of MK-8527 on Day 1. |
| Severe Renal Impairment | EXPERIMENTAL | Participants with severe renal impairment receive a single dose of MK-8527 on Day 1. |
| Healthy | EXPERIMENTAL | Healthy participants receive a single dose of MK-8527 on Day 1. |
| Arm 1: All Participants | EXPERIMENTAL | Participants receive single doses of LNG/EE alone and in combination with a single dose of MK-8527. |
| Panel A: MK-8527 1.0 mg | EXPERIMENTAL | Participants receive a single oral dose of MK-8527 1.0 mg. |
| Panel B: MK-8527 0.5 mg | EXPERIMENTAL | Participants receive a single oral dose of MK-8527 0.5 mg. |
| Panel C: MK-8527 0.25 mg | EXPERIMENTAL | Participants receive a single oral dose of MK-8527 0.25 mg. |
| Panel A: 10 mg MK-8527 | EXPERIMENTAL | Single oral dose of 10 mg MK-8527 capsule after an 8-hour fast |
| Panel B: 3 mg MK-8527 | EXPERIMENTAL | Single oral dose of 3 mg MK-8527 capsule after an 8-hour fast |
| Panel C: 1 mg MK-8527 | EXPERIMENTAL | Single oral dose of 1 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels. |
| Panel D: ≤50 mg MK-8527 | EXPERIMENTAL | Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels. |
| Panel E: ≤50 mg MK-8527 | EXPERIMENTAL | Single oral dose of ≤50 mg MK-8527 capsule after an 8-hour fast. Dose level determined by results of previous panels. |
| Name | Type | Description |
|---|---|---|
| MK-8527 | DRUG | Oral tablet |
| Emtricitabine/tenofovir disoproxil (FTC/TDF) | DRUG | Oral tablet |
| Placebo matched to MK-8527 | DRUG | Placebo oral tablet matched to MK-8527 |
| Placebo matched to FTC/TDF | DRUG | Placebo oral tablet matched to FTC/TDF |
| FTC/TDF | DRUG | Oral tablet |
| Placebo to MK-8527 | DRUG | Placebo tablet matched to MK-8527 |
| Placebo to FTC/TDF | DRUG | Placebo tablet matched to FTC/TDF |
| Rifampin | DRUG | Administered orally |
| Probenecid | DRUG | Oral tablet |
| Itraconazole | DRUG | Oral solution |
| Methadone | DRUG | Formulated per local guidelines, administered orally. |
| Moxifloxacin | DRUG | Oral administration |
| Placebo | DRUG | Oral administration |
| CBZ | DRUG | Oral Extended-release Capsule |
| [14C]MK-8527 | DRUG | Oral Dose |
| LNG/EE | DRUG | LNG/EE combination tablet taken by mouth. |
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Is confirmed Human Immunodeficiency Virus (HIV)-uninfected based on negative HIV-1/HIV-2 test results * Has been sexually active (2 vaginal intercourse encounters with cisgender male individual(s) withi...
MK-8527 is an investigational small molecule being developed for HIV, including HIV pre-exposure prophylaxis (PrEP). It is also studied in healthy participants and in people with renal or hepatic impairment to assess safety and pharmacokinetics. It is not approved and remains in clinical development.
MK-8527 is developed by Merck & Company, Inc., traded on the New York Stock Exchange under the ticker MRK. The company is conducting clinical trials of MK-8527 across multiple phases for HIV-related indications.
MK-8527 is in Phase 2 clinical development for HIV pre-exposure prophylaxis, based on a completed Phase 2 trial (NCT06045507). Additional Phase 1 studies have been completed in renal impairment, hepatic impairment, and drug-drug interaction settings. It is investigational and not FDA approved.
MK-8527 has completed a Phase 2 trial (NCT06045507) in participants at low risk for HIV-1 infection, and Phase 1 trials in renal impairment (NCT06295796), hepatic impairment (NCT07025551), and a drug-drug interaction study with an oral contraceptive (NCT06783192). All trials are completed.
MK-8527 is a distinct investigational compound developed by Merck. No alternative names are provided in the available data. It is being studied as a potential oral pre-exposure prophylaxis for HIV, but it is not yet approved.