Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02397096 | Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcriptase Inhibitors (MK-1439A-024) | PHASE3 | COMPLETED | 673 | — | — | Jun 9, 2015 | Sep 5, 2023 | Nov 20, 2024 | - | — |
| NCT02089659 | A Study to Investigate the Influence of Hepatic Insufficiency on the Pharmacokinetics of Doravirine (MK-1439) (MK-1439-019) | PHASE1 | COMPLETED | 16 | — | — | Mar 26, 2014 | May 12, 2014 | Dec 28, 2018 | - | — |
| NCT01466985 | A Study of Doravirine (MK-1439) in Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439-005) | PHASE1 | COMPLETED | 18 | — | — | Oct 21, 2011 | Apr 10, 2012 | Feb 15, 2019 | - | — |
The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach and all missing data were considered treatment failures, regardless of the reason.
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
Blood was collected for the determination of plasma doravirine using a liquid chromatographic tandem mass spectrometric method
The change from baseline to Day 7 in plasma HIV RNA viral load was determined for each arm. Results are expressed as change in HIV RNA log10 copies/mL after 7 daily doses of doravirine or placebo. It was hypothesized that at least 1 dose of doravirine would be superior to placebo as documented by the upper bound of the 90% confidence interval \<-1. Plasma HIV RNA levels were determined using the Abbott RealTime HIV assay which has a linear range from 40 to 10 million copies/mL.
| Arm | Type | Description |
|---|---|---|
| Immediate Switch to Doravirine, Tenofovir, Lamivudine | EXPERIMENTAL | Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will switch on Day 1 to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions |
| Delayed Switch to Doravirine, Tenofovir, Lamivudine | ACTIVE_COMPARATOR | Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions |
| Part 1: Moderate Hepatic Insufficiency | EXPERIMENTAL | Participants with moderate hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have moderate hepatic insufficiency based on the Child-Pugh scale. |
| Part 1: Healthy Matched Control | EXPERIMENTAL | Healthy participants matched for age and weight receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. |
| Part 2: Mild Hepatic Insufficiency | EXPERIMENTAL | Participants with mild hepatic insufficiency receive a single oral dose of 100 mg doravirine on Day 1 of Part 1. All participants in this arm were to have mild hepatic insufficiency based on the Child-Pugh scale. This arm was to be enrolled and investigated only if a clinically meaningful increase in exposure of doravirine was observed in participants with moderate hepatic insufficiency in Part 1. |
| Panel A: Doravirine 25 mg or Placebo | EXPERIMENTAL | Participants will receive oral doses of doravirine 25 mg or placebo once daily for 7 days. |
| Panel B: Doravirine 200 mg or Placebo | EXPERIMENTAL | Panel B (doravirine 200 mg or placebo once daily for 7 days) will initiate upon satisfactory review of safety and tolerability from Panel A, and all safety, tolerability and pharmacokinetic data from the study MK-1439-001. |
| Panel C: Doravirine or Placebo | EXPERIMENTAL | Panel C is optional. If conducted, the dose will be confirmed after review of data from prior panels. |
| Name | Type | Description |
|---|---|---|
| Doravirine, Tenofovir, Lamivudine | DRUG | Single tablet containing MK-1439 (doravirine) 100 mg, lamivudine 300 mg, and tenofovir disoproxil fumarate 300 mg |
| Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor | DRUG | Baseline regimen of antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) administered according to the product circular |
| Baseline regimen of cobicistat-boosted elvitegravir | DRUG | Baseline regimen of antiretroviral therapy with cobicistat-boosted elvitegravir administered according to the product circular |
| Baseline regimen of a non-nucleoside reverse transcriptase inhibitor | DRUG | Baseline regimen of antiretroviral therapy with a NNRTI (efavirenz, nevirapine, or rilpivirine) administered according to the product circular |
| Baseline regimen of two nucleoside reverse transcriptase inhibitors | DRUG | Baseline regimen of antiretroviral therapy with two NRTIs administered according to the product circular |
| Doravirine | DRUG | Following an overnight fast, a single tablet of 100 mg doravirine was be administered orally |
| Placebo | DRUG | Placebo tablets once daily for 7 days. |
Inclusion Criteria: Inclusion Criteria include, but are not limited to: * Have plasma Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) levels below the limit of quantification (BLoQ) (\<40 copies/mL by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the scree...