Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Islatravir · 8 trials · 4 indications
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. As pre-specified in the protocol and supplemental statistical analysis plan (sSAP), presented here is the percentage of participants who experienced one or more AEs during the Double-blind Treatment Period and includes the 42 days following the final dose of double-blind 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. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who discontinued double-blind study intervention due to an AE during the Double-Blind Treatment Period.
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. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who experienced one or more AEs during the Unblinded Safety Monitoring Period, beginning 42 days following the final dose of double-blind 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.
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.
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy.
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.
An SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').
An drug-related SAE is defined as any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.
A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).
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 collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Blood samples will be collected to determine the C168 of ISL-TP
Blood samples will be collected to determine the C24 of ISL-TP
Blood samples will be collected to determine the AUC0-inf of ISL-TP
Blood samples will be collected to determine the AUClast of ISL-TP
Blood samples will be collected to determine the Cmax of ISL-TP
Blood samples will be collected to determine the Tmax of ISL-TP
Blood samples will be collected to determine the t1/2 of ISL-TP
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Tmax of plasma ISL was expressed as a median.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
The AUC0-24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
The AUC0-24hr of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
Participants were treated with islatravir (ISL), and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Tmax of plasma ISL was expressed as a median.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The Geometric Coefficient of Variation was expressed as a percent (%CV), and is calculated from the square root of corresponding estimated variance obtained for each population in fixed effect model multiplied by 100.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Participants were treated with ISL, and blood samples were collected from pre-dose up to 168 hours post-dose to determine the concentration of plasma ISL. The 95% confidence interval was derived from a fixed effects model performed on natural log-transformed values.
Plasma HIV-1 RNA was measured using the Roche COBAS Ampliprep/COBAS TaqMan HIV-1 test v.2.0, which has a linear range from 20 to 10,000,000 copies/mL. The lower limit of detection has 100% specificity at 20 copies/mL. Additionally, the test increases the probability of detection and expands coverage by targeting two highly conserved regions of the HIV-1 genome to compensate for the possibility of mutations or mismatches.
An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
| Arm | Type | Description |
|---|---|---|
| Group 1: ISL 20 mg + Ulonivirine 100 mg | EXPERIMENTAL | Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART. |
| Group 2: ISL 20 mg + Ulonivirine 200 mg | EXPERIMENTAL | Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART. |
| Group 3: ISL 20 mg + Ulonivirine 400 mg | EXPERIMENTAL | Participants receive ISL 20 mg + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART. |
| Group 4: BIC/FTC/TAF | ACTIVE_COMPARATOR | Participants receive placebo to ISL + placebo to ulonivirine QW and BIC/FTC/TAF 50 mg/200 mg/25 mg QD. |
| Islatravir 60 mg | EXPERIMENTAL | 60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks |
| Islatravir 120 mg | EXPERIMENTAL | 120 mg islatravir administered once monthly, orally in capsule form for 24 weeks |
| Placebo | PLACEBO_COMPARATOR | Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks |
| Islatravir 0.25 mg | EXPERIMENTAL | Participants will be treated once daily (QD) with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
| Islatravir 0.75 mg | EXPERIMENTAL | Participants will be treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
| Islatravir 2.25 mg | EXPERIMENTAL | Participants will be treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
| DOR/3TC/TDF | ACTIVE_COMPARATOR | Participants will be treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments may be discontinued and participants will receive only DOR/3TC/TDF QD open label up to Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
| ISL and 3TC | EXPERIMENTAL | During period 1, participants receive a single dose of islatravir (ISL). During Period 2, participants receive multiple once-daily doses of lamivudine (3TC) for 27 days, and a single dose of ISL co-administered with 3TC on day 6. |
| Moderate Hepatic Impairment | EXPERIMENTAL | Participants receive a single dose of ISL 60 mg. |
| Healthy Controls | EXPERIMENTAL | Participants receive a single dose of ISL 60 mg. |
| Methadone + ISL | EXPERIMENTAL | Methadone-maintained participants (20 to 200 mg \[locally-provided\] once daily \[QD\] from Day -14 to Day -1 and Day 10 to Day 15) receive methadone 20 to 200 mg QD on Day 1 to Day 9; ISL 60 mg is co-administered with methadone on Day 2. |
| Severe Renal Impairment | EXPERIMENTAL | Participants with severe renal impairment received a single oral dose of 60 mg MK-8591 (Islatravir) administered in capsule form. |
| Healthy | EXPERIMENTAL | Healthy participants received a single oral dose of 60 mg Islatravir administered in capsule form. |
| Islatravir 1 mg | EXPERIMENTAL | Single oral dose of islatravir 1 mg |
| Islatravir 2 mg | EXPERIMENTAL | Single oral dose of islatravir 2 mg |
| Islatravir 10 mg | EXPERIMENTAL | Single oral dose of islatravir 10 mg |
| Islatravir 30 mg | EXPERIMENTAL | Single oral dose of islatravir 30 mg |
| Islatravir 0.5 mg | EXPERIMENTAL | Single oral dose of islatravir 0.5 mg |
| Islatravir 30 mg Extended Observation | EXPERIMENTAL | Single oral dose of 30 mg islatravir administered following \>8 hour fast. Participants will be closely monitored for viral load for up to approximately 21 days prior to starting standard of care ART. |
| Name | Type | Description |
|---|---|---|
| Islatravir | DRUG | ISL capsule taken by mouth. |
| Ulonivirine | DRUG | Ulonivirine tablet taken by mouth. |
| BIC/FTC/TAF | DRUG | BIC/FTC/TAF tablet taken by mouth. |
| Placebo to ISL | DRUG | Placebo capsule matched to ISL taken by mouth. |
| Placebo to Ulonivirine | DRUG | Placebo tablet matched to ulonivirine taken by mouth. |
| Placebo to BIC/FTC/TAF | DRUG | Placebo tablet matched to BIC/FTC/TAF taken by mouth. |
| Placebo | DRUG | Placebo capsules taken by mouth. |
| Placebo to Islatravir | DRUG | Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks |
| Doravirine | DRUG | Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks |
| Placebo to Doravirine | DRUG | Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks |
| Lamivudine | DRUG | Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks |
| Placebo to Lamivudine | DRUG | Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks |
| Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate | DRUG | Fixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks. |
| Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate | DRUG | Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks |
| Doravirine/Islatravir | DRUG | Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks |
| Islatravir (ISL) | DRUG | Oral administration of a single dose in period 1 and period 2 |
| Lamivudine (3TC) | DRUG | Oral administration of multiple daily doses for 27 days |
| 1 mg islatravir | DRUG | Single oral dose of 1 mg islatravir administered following ≥8 hour fast |
| 2 mg islatravir | DRUG | Single oral dose of 2 mg islatravir administered following ≥8 hour fast |
| 10 mg islatravir | DRUG | Single oral dose of 10 mg islatravir administered following ≥8 hour fast |
| 30 mg islatravir | DRUG | Single oral dose of 30 mg islatravir administered following ≥8 hour fast |
| 0.5 mg islatravir | DRUG | Single oral dose of 0.5 mg islatravir administered following ≥8 hour fast |
| 0.25 mg islatravir | DRUG | Single oral dose of 0.25 mg islatravir administered following ≥8 hour fast |
Inclusion Criteria: * Is HIV-1 positive with plasma human immunodeficiency virus type 1 (HIV-1) RNA \<50 copies/mL at screening * Has been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for ≥6 months * Has a screening CD4+ T-cell count \>200 cells/mm\^3 (c...
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Islatravir is an investigational small molecule being studied for the prevention and treatment of HIV-1 infection. It is being developed by Merck & Company, Inc. (MRK) and is currently in Phase 2 clinical development. The drug has been evaluated in trials involving participants with HIV-1 infection and healthy volunteers at low risk of HIV-1 infection.
Islatravir is a nucleoside reverse transcriptase inhibitor that targets the HIV-1 reverse transcriptase enzyme. By inhibiting this enzyme, the drug interferes with the replication of the HIV-1 virus. This mechanism is being studied in clinical trials for the treatment and prevention of HIV-1 infection.
Islatravir is being developed by Merck & Company, Inc., a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol MRK. The drug is currently in Phase 2 clinical development for HIV-1 infection and related conditions.
Islatravir is currently in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. The drug has completed four clinical trials, including Phase 1 and Phase 2 studies, with a total enrollment of 540 participants.
Islatravir has completed four clinical trials. These include NCT02217904, a Phase 1 study in treatment-naive HIV-1 infected participants; NCT04003103, a Phase 2 study of once-monthly oral islatravir in participants at low risk of HIV-1 infection; NCT04568603, a Phase 1 study of islatravir and methadone pharmacokinetics; and NCT06811246, a Phase 1 study of islatravir and its interaction with lamivudine.
Yes, Islatravir is also known as MK-8591. Clinical trials for the drug use the MK-8591 designation in their titles, such as NCT02217904 and NCT04003103. This alternative name is used in the context of Merck's development program for the drug.