Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Darunavir · 9 trials · 12 indications
The percentage of participants who have plasma human immunodeficiency virus type-1 (HIV-1) ribonucleic acid (RNA) levels \<50 copies/milliliters \[mL\] after 48 weeks of follow-up. Switch = Failure is defined as switch in background nucleoside/nucleotide reverse transcriptase inhibitors (N\[t\]RTIs) not permitted by the trial protocol or plasma HIV-1 RNA assessment closest to target date of the analysis time point window (44-52 weeks) and next/confirmation of Plasma HIV-1 RNA in the analysis time point window above the threshold or discontinuation for any other reason.
Adverse events (AEs): any untoward medical occurrence (any unfavorable and unintended sign \[including an abnormal laboratory finding\], symptom, or disease) that occurred in a participant administered a pharmaceutical product and which did not necessarily have causal relationship with study treatment. Serious adverse events (SAEs): any untoward medical occurrence at any dose resulted: death; was life threatening; requires inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent/significant disability/incapacity or congenital anomaly/birth defect. Adult participants who received either DRV/rtv 800/100 mg once daily or DRV/rtv 600/100 mg twice daily per parent study were included in single arm and combined analysis was performed as planned in protocol because the 2 doses were extensively evaluated in their respective parent studies. Main purpose of this study was to provide continued access and not to compare the 2 doses.
Adverse events (AEs) were defined as any untoward medical occurrence (any unfavorable and unintended sign \[including an abnormal laboratory finding\], symptom, or disease) that occurred in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. Adult participants who received either DRV/rtv 800/100 mg once daily or DRV/rtv 600/100 mg twice daily per parent study were included in single arm and combined analysis was performed as planned in protocol because the 2 doses were extensively evaluated in their respective parent studies. Main purpose of this study was to provide continued access and not to compare the 2 doses.
Number of participants with adverse events possibly related to DRV/rtv treatment were reported. Adult participants who received either DRV/rtv 800/100 mg once daily or DRV/rtv 600/100 mg twice daily per parent study were included in single arm and combined analysis was performed as planned in protocol because the 2 doses were extensively evaluated in their respective parent studies. Main purpose of this study was to provide continued access and not to compare the 2 doses.
C0h is defined as the predose (trough) plasma concentration or concentration just prior to study drug administration.
The Cmin is the minimum observed plasma concentration.
The Cmax is the maximum observed plasma concentration.
The Tmax is defined as actual sampling time to reach maximum observed plasma concentration.
The AUC (0-12) is the area under the plasma concentration-time curve from time zero to 12 hours post dose. The selected arms were based on the dosing frequency (twice daily).
The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours post dose. The selected arms were based on the dosing frequency (once daily).
Virological response is defined as the number of patients in the PP population with a plasma viral load \< 50 HIV RNA copies/ml at Week 48. Treatment failure was defined as two consecutive HIV RNA levels ≥ 50 copies/mL, or discontinuation of randomised treatment (known as TLOVR). In addition, any switch in background nucleoside reverse transcriptase inhibitors (NRTIs) equaled failure\* (referred to as a Switch Equals Failure analysis). \*Discontinuations and rechallenge with NRTIs are taken into account until Week 48
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter.
Cmax is defined as the maximum observed analyte concentration of DRV.
AUC(0-last) is the area under the analyte concentration-time curve from time zero to the time of the last measurable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(0-last) and C(last)/lambda(z), wherein AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) concentration, and lambda(z) is elimination rate constant.
Cmax is defined as the maximum observed plasma concentration.
AUC (0-last) is the area under the Plasma concentration time curve (AUC) from time 0 to the time of the last measurable (non below quantification limit \[non BQL\]) concentration, calculated by linear trapezoidal summation.
The AUC (0-infinity) is the area under the plasma concentration time curve from time zero to infinite time calculated as the sum of AUC (0-last) and C (0-last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration time curve from time zero to last quantifiable time, C(0-last) is the last observed quantifiable concentration, and lambda (z) is elimination rate constant.
The pharmacokinetic parameter (Cmax) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).
The pharmacokinetic parameter (Clast) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).
The pharmacokinetic parameter (tmax) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg) for assessment of bioequivalance.
The pharmacokinetic parameter (AUClast) of darunavir will be compared as a fixed dose combination relative to 2 tablets of darunavir (400 mg), in the presence of cobicistat (150 mg).
| Arm | Type | Description |
|---|---|---|
| Darunavir monotherapy | EXPERIMENTAL | Darunavir (DRV) + ritonavir (rtv): 2 tablets DRV 400 mg should be taken together with 1 tablet rtv 100 mg within 30 minutes after a meal. Following the primary efficacy analysis after Week 48, patients who entered the study with a nadir CD4+ count of \<200 cells/μL will also receive 2 N\[t\]RTIs (ie, triple therapy) as soon as possible |
| Triple therapy containing darunavir | ACTIVE_COMPARATOR | Darunavir (DRV) + ritonavir (rtv) + 2 N\[t\]RTIs: 2 tablets DRV 400 mg should be taken together with 1 tablet rtv 100 mg within 30 minutes after a meal in combination with 2 N\[t\]RTIs (an investigator-selected dual combination of either abacavir (ABC), lamivudine (3TC), zidovudine (AZT), tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) |
| Continued Treatment with DRV in Combination with rtv | EXPERIMENTAL | HIV-1 infected children participants (aged less than \[\<\] 12 years) will continue to receive darunavir (DRV) 200 to 600 milligrams (mg) as oral suspension twice daily (BID) along with ritonavir (rtv) 32 to 100 mg as oral solution/suspension BID. HIV-1 infected adolescent participants (aged 12-17 years) will continue to receive DRV 200 to 600 mg as oral suspension BID along with rtv 32 to 100 mg as oral solution/suspension BID. Dosing for children and adolescent participants will be based on body weight (per parent study TMC114-TiDP29-C232). HIV-1 infected adult participants (aged greater than or equal to \[\>=\] 18 years) will continue to receive DRV 800 mg (2 tablets of 400 mg) orally every day (qd) along with rtv 100 mg tablet (per parent study TMC114-C211) or DRV 600 mg tablet orally BID along with rtv 100 mg tablet (per parent study TMC114-C214 or TMC114-TiDP31-C229). |
| Group 1: Darunavir 600 /Ritonavir 100 | EXPERIMENTAL | TMC114 (darunavir) Two 300 milligram (mg) or one 600 mg tablet twice daily up to 12 weeks postpartum / ritonavir one 100 mg tablet twice daily with darunavir up to 12 weeks postpartum. |
| Group 2: Darunavir 800/Ritonavir 100 | EXPERIMENTAL | TMC114 (darunavir) 800mg tablet once daily up to 12 weeks postpartum/ ritonavir one 100 mg tablet once daily with darunavir up to 12 weeks postpartum. |
| Group 3: Etravirine | EXPERIMENTAL | TMC125 (etravirine) 200 mg (1\*200 mg/2\*100 mg) tablets twice daily up to 12 weeks postpartum. |
| Group 4: Rilpivirine | EXPERIMENTAL | TMC278 (rilpivirine) One 25 mg tablet once daily up to 12 weeks postpartum. |
| Group 5: Darunavir 800/Cobicistat 150 | EXPERIMENTAL | Fixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum. |
| darunavir + 2 NRTI | EXPERIMENTAL | darunavir (DRV, TMC114) 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks |
| 005 | EXPERIMENTAL | Darunavir 400 mg tablet intake of 2 tablets once daily in combination with ritonavir |
| 006 | EXPERIMENTAL | Ritonavir Liquid formulation 80 mg/ml taken in combination with Darunavir |
| 007 | EXPERIMENTAL | Ritonavir 100 mg capsule to be taken once or twice daily in combination with Darunavir and following the Darunavir dosing schedule |
| 008 | EXPERIMENTAL | Ritonavir 100 mg tablet to be taken once or twice daily in combination with Darunavir and following the Darunavir dosing schedule |
| 001 | EXPERIMENTAL | Darunavir Oral suspension 100 mg/ml 20 mg/kg twice daily in combination with ritonavir for body weight between 10 and 20 kg |
| 002 | EXPERIMENTAL | Darunavir 375 mg composed via oral solution or various tablets twice daily in combination with ritonavir for body weight between 20 and 30 kg |
| 003 | EXPERIMENTAL | Darunavir 450 mg composed via oral solution or various tablets twice daily in combination with ritonavir for body weight between 30 and 40 kg |
| 004 | EXPERIMENTAL | Darunavir 600mg composed via oral solution or various tablets twice daily in combination with ritonavir for body weight as of 40 kg |
| 009 | EXPERIMENTAL | Ritonavir powder for oral suspension 10 mg/mL taken in combination with Darunavir. |
| Monotherapy | EXPERIMENTAL | Monotherapy: darunavir/ritonavir (DRV/r) will be administered for 48 weeks. |
| Combination therapy | EXPERIMENTAL | DRV/r along with 2 nucleoside reverse transcriptase inhibitors (NRTIs) will be administered for 48 weeks and whenever possible, participants should take these medications at the same time. Switch of NRTIs will be allowed in the event of suspected toxicity/intolerance, providing this change can be linked to a documented adverse event (AE)/serious AE. |
| Treatment A | EXPERIMENTAL | Participants will receive Treatment A (a single dose of darunavir \[DRV\]/cobicistat \[COBI\] as one fixed dose combination \[FDC\] tablet under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence AB or BA). A washout period of at least 7 days will be maintained between each treatment period. |
| Treatment B | ACTIVE_COMPARATOR | Participants will receive Treatment B (a single dose of DRV/COBI as separate tablets under fed condition on Day 1) as per assigned treatment sequence (Treatment sequence BA or AB). A washout period of at least 7 days will be maintained between each treatment period. |
| Treatment sequence ABC | EXPERIMENTAL | Participants will receive a single oral tablet of darunavir (DRV) 800 milligram (mg)/ cobicistat (COBI) 150 mg/ emtricitabine (FTC) 200 mg/ tenofovir alafenamide (TAF) 10 mg (D/C/F/TAF fixed dose combination \[FDC\]) Treatment A (whole tablet) as reference in session 1 then Treatment B(split tablet) as test in session 2 followed by Treatment C (crushed tablet mixed in applesauce) as test in session 3 under fed conditions (standardized breakfast) on Day 1 of each treatment session. There will be a washout period of at least 7 days between consecutive drug intakes. |
| Treatment sequence ACB | EXPERIMENTAL | Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment A in treatment session 1, then Treatment C in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes. |
| Treatment sequence BCA | EXPERIMENTAL | Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment B in session 1 then Treatment C in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes. |
| Treatment sequence BAC | EXPERIMENTAL | Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment B in session 1 then Treatment A in session 2 followed by Treatment C in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes. |
| Treatment sequence CAB | EXPERIMENTAL | Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment C in session 1 then Treatment A in session 2 followed by Treatment B in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes. |
| Treatment sequence CBA | EXPERIMENTAL | Participants will receive a single oral tablet of D/C/F/TAF \[FDC\] Treatment C in session 1 then Treatment B in session 2 followed by Treatment A in session 3 under fed conditions (standardized breakfast) on Day 1 with washout period of at least 7 days between consecutive drug intakes. |
| Treatment C | EXPERIMENTAL | Single-dose co-administration of 800 mg darunavir and 150 mg cobicistat as single agents (under fed condition - standardized breakfast). |
| Treatment D | EXPERIMENTAL | Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - standardized breakfast). |
| Treatment E | EXPERIMENTAL | Single-dose co-administration of the fixed dose combination darunavir/cobicistat 800/150-mg (under fasted condition). |
| Treatment F | EXPERIMENTAL | Single-dose co-administration of the fixed dose combination darunavir/cobicistat (800/150-mg) (under fed condition - high-fat breakfast). |
| Name | Type | Description |
|---|---|---|
| Darunavir | DRUG | Darunavir (DRV): type = exact number, unit = mg, number = 800, form = tablet, route = oral use |
| Ritonavir | DRUG | ritonavir (rtv): type = exact number, unit = mg, number = 100, form = tablet, route = oral use |
| Etravirine | DRUG | 200 mg (1\*200 mg/2\*100 mg) tablets twice daily up to 12 weeks postpartum. |
| Rilpivirine | DRUG | One 25 mg tablet once daily up to 12 weeks postpartum. |
| Darunavir/Cobicistat (FDC) | DRUG | Fixed dose combination (FDC) tablet of TMC114 (darunavir) 800 mg and cobicistat 150 mg once daily up to 12 weeks postpartum. |
| darunavir (DRV, TMC114) | DRUG | 800 mg qd (2 x 400 mg tablet) + 2 NRTI for 144 weeks |
| Darunavir(DRV) | DRUG | Oral administration of tablet DRV 800 mg (2 tablets of 400 mg) once daily at the same time, within 30 minutes after food for 48 weeks |
| 2 nucleoside reverse transcriptase inhibitors (NRTIs) | DRUG | 2 NRTIs will be administered as per the package inserts. |
| Cobicistat | DRUG | Participant will receive a single dose of Cobicistat tablets orally as per assigned treatment sequence. |
| Darunavir/Cobicistat FDC | DRUG | Participants will receive a single dose of darunavir and cobicistat FDC tablets orally as per assigned treatment sequence. |
| Darunavir (DRV) | DRUG | Darunavir 800 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/TAF(10mg). |
| Cobicistat (COBI) | DRUG | Cobicistat 150 milligram (mg) will be taken orally in FDC together with DRV(800mg)/FTC(200mg)/TAF(10mg). |
| Emtricitabine (FTC) | DRUG | Emtricitabine 200 milligram (mg) will be taken orally in FDC together with COBI(150mg)/DRV(800mg)/TAF(10mg). |
| Tenofovir Alafenamide (TAF) | DRUG | Tenofovir Alafenamide 10 milligram (mg) will be taken orally in FDC together with COBI(150mg)/FTC(200mg)/DRV(800mg). |
Inclusion Criteria: * HIV-1 infection * receiving HAART for at least 48 weeks * Have at least 2 documented plasma HIV-1 RNA \<50 copies/mL, and no HIV-1 RNA \>=50 copies/mL in the 48 weeks prior to the screening * Be taking the same antiretroviral (ARV) combination for at least 8 weeks before scree...
Darunavir is used for the treatment of Human Immunodeficiency Virus (HIV), including HIV-1 infections. It is being studied in pregnant women with HIV and HIV infections, as well as in healthy participants for pharmacokinetic and bioequivalence studies. The drug is in clinical development for these infectious disease indications.
Darunavir is developed by Johnson & Johnson, a company traded under the ticker JNJ. The drug is a small molecule being investigated for the treatment of HIV and HIV-1 infections.
Darunavir is in Phase 3 clinical development for HIV and HIV infections. It is an investigational drug and has not been reported as FDA approved. The Phase 3 trial is completed, and the drug is also being studied in earlier phase trials.
Darunavir has completed clinical trials including NCT00855335, a Phase 3 study in HIV-1 infected pregnant women, and NCT01619527, a Phase 1 bioequivalence study in healthy participants. Other completed trials include NCT02984852 and NCT04718805, both Phase 1 studies in healthy adults.
Darunavir is a small molecule that targets HIV protease, an enzyme essential for viral replication. By inhibiting this enzyme, the drug prevents the virus from maturing and producing infectious particles, thereby reducing viral load in patients with HIV.
Darunavir is also known by the brand name Prezista. It is being studied in combination with other antiretroviral agents such as cobicistat and ritonavir for the treatment of HIV-1 infection.