Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Doravirine
Doravirine, Tenofovir, Lamivudine- Blinded · 2 trials · 2 indications
The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL at Week 48 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.
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach.
| Arm | Type | Description |
|---|---|---|
| Doravirine 100 mg | EXPERIMENTAL | Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. |
| Darunavir 800 mg and Ritonavir 100 mg | ACTIVE_COMPARATOR | Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. |
| Immediate Switch to Doravirine, Tenofovir, Lamivudine | EXPERIMENTAL | Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded doravirine, tenofovir, lamivudine orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for an additional 12 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 216 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 312 weeks. |
| Deferred Switch to Doravirine, Tenofovir, Lamivudine | EXPERIMENTAL | Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for 24 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 228 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 324 weeks. |
| Name | Type | Description |
|---|---|---|
| Doravirine | DRUG | Doravirine 100 mg tablet administered p.o. q.d. |
| Darunavir | DRUG | Darunavir 800 mg tablet administered p.o. q.d. |
| Ritonavir | DRUG | Ritonavir 100 mg tablet administered p.o. q.d. |
| TRUVADA™ or EPZICOM™/KIVEXA™ | DRUG | The investigator selects either TRUVADA™, a tablet containing 200 mg emtricitabine and 300 mg tenofovir disoproxil fumarate p.o. q.d. or EPZICOM™/KIVEXA™, a tablet containing 600 mg abacavir sulfate and 300 mg lamivudine, p.o. q.d. |
| Doravirine, Tenofovir, Lamivudine - Blinded | DRUG | A single tablet FDC containing doravirine 100 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg administered orally, once daily for 12 weeks during the Blinded period |
| Doravirine, Tenofovir, Lamivudine - Open-Label | DRUG | A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; also an additional 96 weeks during the Open-Label extension period 1; a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2; and a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3. |
| ATRIPLA^TM | DRUG | A single tablet FDC containing efavirenz (EFV) 600 mg, emtricitabine (FTC) 200 mg, and TDF 300 mg administered orally, once daily for 12 weeks during the Blinded period |
| Placebo to ATRIPLA™ | DRUG | A single placebo to ATRIPLA™ tablet administered orally, once daily for 12 weeks during the Blinded period |
| Placebo to Doravirine, Tenofovir, Lamivudine | DRUG | A single placebo to doravirine, tenofovir, lamivudine tablet administered orally, once daily for 12 weeks during the Blinded period |
Inclusion Criteria: * Is HIV-1 positive and has HIV treatment indicated based on physician assessment. * Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents. * Is considered clinically stable with no signs or symptoms of active infection for at ...
Doravirine is an investigational small molecule being studied for the treatment of HIV-1 infection, including in patients with renal impairment. It is being developed as a single agent and in combination with tenofovir DF and lamivudine for virologically suppressed HIV-1-infected adults.
Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that targets the reverse transcriptase enzyme of HIV-1. By inhibiting this enzyme, it interferes with viral replication. The drug is being studied in combination with other antiretrovirals to maintain viral suppression in HIV-1-infected patients.
Doravirine is being developed by Merck & Company, Inc. (NYSE: MRK). The company is conducting clinical trials to evaluate the drug's safety and efficacy in HIV-1-infected participants, including those switching from other antiretroviral regimens.
Doravirine is in Phase 2 clinical development. While some completed trials were Phase 1 and Phase 3, the most recent completed trial was a Phase 2 study evaluating a switch to doravirine, tenofovir, and lamivudine in virologically suppressed participants.
Doravirine has been studied in several clinical trials, including NCT01466985, a Phase 1 study in HIV-1-infected participants; NCT02089659, a Phase 1 hepatic impairment study; NCT02397096, a Phase 3 switch study; and NCT02652260, a Phase 2 switch study from efavirenz-based therapy.
Doravirine is the single-agent form, while doravirine plus tenofovir DF and lamivudine is a fixed-dose combination being studied under the code MK-1439A. Clinical trials have evaluated both the single agent and the combination in HIV-1-infected patients.