Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Adult Patients: ISENTRESS and ISENTRESS HD are human immunodeficiency virus integrase strand transfer inhibitors (HIV- FDA label
Also known as Raltegravir (ISENTRESS™), raltegravir potassium, Isentress, RAL, MK-0518, MK0518 (Raltegravir)
Raltegravir · 10 trials · 6 indications
Incidence of acute clinical renal graft rejection defined by 20% increase of serum creatinine, associated to histological features (Banff classification) 6 months after renal transplantation
Numbers of participants with HIV RNA copies \<50 copies/mL were summarized by race for each time point.
Numbers of participants with one or more adverse events were summarized by race.
Numbers of participants who discontinued due to an adverse event were summarized by race.
Percentage of participants who achieved HIV RNA \<400 copies/mL at Week 16
Percentage of participants who achieved HIV RNA \<400 copies/mL at Week 48
Percentage of participants who achieved HIV RNA \<400 copies/mL at Week 156
Percentage of participants who achieved HIV RNA \<400 Copies/mL at Week 240
Mean changes in alkaline phosphatase levels after 12 months treatment with combination antiretroviral therapy or placebo.
In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS Ultra Strength (US) 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid Maximum Strength (MS) taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected from pre-dose up to 24 hours post-dose, and analysis of variance (ANOVA) modeling was performed on natural log-transformed values to derive geometric least-squares means.
In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS US 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid MS taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected from pre-dose up to 24 hours post-dose, and ANOVA modeling was performed on natural log-transformed values to derive geometric least-squares means.
In Period 1 participants were treated with 1200 mg raltegravir alone; followed by Period 2 where participants were treated with 1200 mg raltegravir and three tablets of TUMS US 1000 taken orally concomitantly; followed by Period 3 where participants were treated with 1200 mg raltegravir and 12 hours later with 20 mL Leader Antacid MS taken orally; followed by Period 4 where participants were treated with 1200 mg raltegravir and 12 hours later with three tablets of TUMS US 1000 taken orally. The wait between Periods was a maximum of 7 days, during which participants were treated with 1200 mg raltegravir once daily. To determine the plasma concentration of raltegravir, blood samples were collected at 24 hours post-dose, and ANOVA modeling was performed on natural log-transformed values to derive geometric least-squares means.
Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.
Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir in order to determine the geometric mean area under the curve plasma concentration versus time.
Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration.
Blood was drawn 12 hours after dosing with raltegravir in order to determine the geometric mean plasma concentration.
Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean area under the curve plasma concentration versus time.
Blood was drawn at time 0, and at various intervals up to 12 hours after dosing with raltegravir, in order to determine the geometric mean maximum plasma concentration.
Participant blood samples were collected to measure the steady state plasma concentration of raltegravir 12 hours after administration alone or with a single dose of antacid. The primary hypothesis compared C12hrs of raltegravir when administered alone with C12hrs of raltegravir when coadministered with TUMS® or MINTOX®.
Participant blood samples were collected to measure the steady state plasma concentration of raltegravir 12 hours after administration alone or before or after a single dose of antacid. The secondary hypothesis compared C12hrs of raltegravir when administered alone with C12hrs of raltegravir when administered 2 hours before or after MINTOX®.
Participant blood samples were collected to measure the steady state AUC of raltegravir up to 12 hours after administration alone or with a single dose of antacid. The primary hypothesis compared AUC0-12hrs of raltegravir when administered alone with AUC0-12hrs of raltegravir when coadministered with TUMS® or MINTOX®.
Participant blood samples were collected to measure the steady state AUC of raltegravir up to 12 hours after administration alone or before or after a single dose of antacid. The secondary hypothesis compared AUC0-12hrs of raltegravir when administered alone with AUC0-12hrs of raltegravir when administered 2 hours before or after MINTOX®.
Participant blood samples were collected to measure the steady state maximum plasma concentration of raltegravir when administered alone or with a single dose of antacid. The primary hypothesis compared Cmax of raltegravir when administered alone with Cmax of raltegravir when coadministered with TUMS® or MINTOX®.
Participant blood samples were collected to measure the maximum steady state plasma concentration of raltegravir after administration alone or before or after a single dose of antiacid. The secondary hypothesis compared Cmax of raltegravir when administered alone with Cmax of raltegravir when administered 2 hours before or after MINTOX®.
Participant blood samples were collected to measure the time to achieve the maximum steady state plasma concentration of raltegravir when administered alone or with a single dose of antacid
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.
| Arm | Type | Description |
|---|---|---|
| HAART+Raltegravir 12 months (+/-) Maraviroc | EXPERIMENTAL | - |
| HAART | NO_INTERVENTION | - |
| Raltegravir | EXPERIMENTAL | Raltegravir associated to an antiretroviral regimen without ritonavir boosted antiprotease |
| 1 | EXPERIMENTAL | raltegravir |
| 2 | PLACEBO_COMPARATOR | Placebo |
| Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) & Raltegravir | EXPERIMENTAL | one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets |
| Placebo | PLACEBO_COMPARATOR | Identical tablets resembling one Emtricitabine 200mg and Tenofovir Disoproxil 300mg tablet two Raltegravir 600mg tablets |
| 001 | EXPERIMENTAL | TMC278 One 25 mg tablet once daily for 11 days (TrtA and C) |
| 002 | EXPERIMENTAL | Raltegravir One 400 mg tablet twice daily for 4 days (Trt B) and for 11 days (TrtC) |
| Raltegravir Pre- and 4 Period Sequence | EXPERIMENTAL | Starting five days prior to Period 1 participants will be treated with 1200 mg raltegravir, once daily for five days. In Period 1 participants will be treated with 1200 raltegravir alone; this is followed by Period 2 where participants will be treated with 1200 mg raltegravir and TUMS concomitantly; this is followed by Period 3 where participants will be treated with 1200 mg raltegravir and 12 hours later with Leader Antacid; followed by Period 4 where participants will be treated with 1200 mg raltegravir and 12 hours later with TUMS. The wait between Periods is 2-7 days. |
| Ralt→MAL4Ralt→Ralt4MAL→MAL6Ralt→Ralt6MAL | EXPERIMENTAL | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Raltegravir (Ralt) alone in Period 1, MAALOX (MAL) followed 4 hrs later by Ralt in Period 2, Ralt followed 4 hrs later by MAL in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
| MAL4Ralt→Ralt4MAL→Ralt→MAL6Ralt→Ralt6MAL | EXPERIMENTAL | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt followed 4 hrs later by MAL in Period 2, Ralt alone in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
| Ralt4MAL→Ralt→MAL4Ralt→MAL6Ralt→Ralt6MAL | EXPERIMENTAL | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, Ralt alone in Period 2, MAL followed 4 hrs later by Ralt in Period 3, MAL followed 6 hrs later by Ralt in Period 4, Ralt followed 6 hrs later by MAL in Period 5 |
| Ralt→Ralt4MAL→MAL4Ralt→Ralt6MAL→MAL6Ralt | EXPERIMENTAL | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt alone in Period 1, Ralt followed 4 hrs later by MAL in Period 2, MAL followed 4 hrs later by Ralt in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
| MAL4Ralt→Ralt→Ralt4MAL→Ralt6MAL→MAL6Ralt | EXPERIMENTAL | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: MAL followed 4 hrs later by Ralt in Period 1, Ralt alone in Period 2, Ralt followed 4 hrs later by MAL in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
| Ralt4MAL→MAL4Ralt→Ralt→Ralt6MAL→MAL6Ralt | EXPERIMENTAL | Part 1 was comprised of periods 1, 2 and 3; Part 2 was comprised of periods 4 and 5; with each study period separated by a washout period of at least 2 days. Part 1 was separated from Part 2 by a Pause. Each period had single oral dose treatments as follows: Ralt followed 4 hrs later by MAL in Period 1, MAL followed 4 hrs later by Ralt in Period 2, Ralt alone in Period 3, Ralt followed 6 hrs later by MAL in Period 4, MAL followed 6 hrs later by Ralt in Period 5 |
| RAL, TUMS+RAL, MINTOX+RAL, MINTOX Before RAL, MINTOX After RAL | EXPERIMENTAL | Participants received Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours After Raltegravir in treatment period 5. There was a 2-day washout between treatment periods. |
| TUMS+RAL, MINTOX+RAL, RAL, MINTOX Before RAL, MINTOX After RAL | EXPERIMENTAL | Participants received TUMS® + Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. |
| MINTOX+RAL, RAL, TUMS+RAL, MINTOX Before RAL, MINTOX After RAL | EXPERIMENTAL | Participants received MINTOX® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours before Raltegravir in treatment period 4, followed by MINTOX® 2 hours after Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. |
| RAL, MINTOX+RAL, TUMS+RAL, MINTOX After RAL, MINTOX Before RAL | EXPERIMENTAL | Participants received Raltegravir in treatment period 1, followed by MINTOX® + Raltegravir in treatment period 2, followed by TUMS® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. |
| TUMS+RAL, RAL, MINTOX+RAL, MINTOX After RAL, MINTOX Before RAL | EXPERIMENTAL | Participants received TUMS® + Raltegravir in treatment period 1, followed by Raltegravir in treatment period 2, followed by MINTOX® + Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. |
| MINTOX+RAL, TUMS+RAL, RAL, MINTOX After RAL, MINTOX Before RAL | EXPERIMENTAL | Participants received MINTOX® + Raltegravir in treatment period 1, followed by TUMS® + Raltegravir in treatment period 2, followed by Raltegravir in treatment period 3, followed by MINTOX® 2 hours after Raltegravir in treatment period 4, followed by MINTOX® 2 hours before Raltegravir in treatment period 5. There was a minimum 2-day washout between treatment periods. |
| Name | Type | Description |
|---|---|---|
| Isentress® | DRUG | P.O, 1 tablet containing 400 mg every 12 hours |
| Celsentri® | DRUG | p.o.: 1 tablet containing 150 mg morning and evening (due to combination with PI/r) or containing 300 mg if fosamprenavir/r is used as the PI (MA) |
| Raltegravir | DRUG | Introduction of Raltegravir 2 days after renal transplantation within an antiretroviral regimen without ritonavir boosted antiprotease |
| Comparator: raltegravir | DRUG | 400 mg tablets taken twice daily. Total treatment period is 48 weeks. |
| raltegravir potassium | DRUG | Raltegravir 400 mg twice daily (b.i.d.) by mouth (p.o.) with optimized background therapy. Treatment period of 48 weeks. |
| Comparator: placebo | DRUG | Placebo p.o. b.i.d. with optimized background therapy. Treatment period of 48 weeks. |
| Emtricitabine (FTC)/Tenofovir Disoproxil (TDF) | DRUG | Emtricitabine (FTC) 200 mg/Tenofovir Disoproxil (TDF) 300 mg by mouth once per day |
| Placebo Oral Capsule [CEBOCAP] | DRUG | Two capsules identical to Raltegravir and one capsule identical to Truvada with no active ingredients by mouth once per day |
| TMC278 | DRUG | One 25 mg tablet, once daily, for 11 days (TrtA and C) |
| Raltegravir 1200 mg | DRUG | Two tablets of 600 mg raltegravir administered orally, once daily, over 5 days of Pre-treatment, and once at the start of Periods 1-4. |
| TUMS | DRUG | Three tablets of TUMS Ultra Strength (US) 1000, taken orally, concomitantly with raltegravir in Period 2, and 12 hours after raltegravir in Period 4 |
| Leader Antacid | DRUG | 20 mL Leader Antacid Maximum Strength (MS) taken orally 12 hours after raltegravir, in Period 3 |
| Raltegravir (ISENTRESS™) | DRUG | Raltegravir 400 mg oral tablet once every 12 hours. Participants will continue with their other prescribed antiretroviral agents throughout the study. |
| MAALOX (MAL) | DRUG | MAL (or generic equivalent) 20 mL oral single dose on Day 1 |
| TUMS® Ultra Strength | DRUG | 3 tablets TUMS® Ultra Strength (US) 1000 mg Throughout the study, participants will continue to take raltegravir every 12 hours along with their other HIV medications. There will be a minimum of 2 days washout between treatment periods. On the day of co-dosing and intensive PK sampling, raltegravir will be dosed in the morning in a fasted state in all periods. |
| MINTOX® Maximum Strength | DRUG | 20 mL MINTOX® Maximum Strength (MS) Throughout the study, participants will continue to take raltegravir every 12 hours along with their other HIV medications. There will be a minimum of 2 days washout between treatment periods. On the day of co-dosing and intensive PK sampling, raltegravir will be dosed in the morning in a fasted state in all periods. |
Inclusion Criteria: * Male or female patients, aged over 18 years * HIV infection confirmed by Western Blot * Karnofsky score \> 80% * Treatment-experienced patients having received combined antiretroviral therapy including at least 2 RTI and 1 PI/r for at least 12 months with plasma viral load \<5...
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Raltegravir is a small molecule antiretroviral medicine developed by Merck & Company, Inc. (ticker MRK) for the treatment of HIV infection, including HIV-1 infection and human immunodeficiency virus. It has also been studied in primary biliary cholangitis. It is marketed under the brand name ISENTRESS.
Raltegravir is used to treat HIV infection, including HIV-1 infection and human immunodeficiency virus, as part of combination antiretroviral therapy. Merck has also studied it in primary biliary cholangitis, a liver condition, in a Phase 2 trial. Its HIV program includes Phase 3 development.
Raltegravir is made by Merck & Company, Inc., which trades under the ticker MRK. Merck is the developer of the drug, which is also known by the brand name ISENTRESS and as raltegravir potassium. The 1200 mg dose form is another name associated with the asset.
Raltegravir is in Phase 3 development for HIV infection according to its clinical program. It is an investigational and marketed antiretroviral small molecule. Across its registered studies, six trials are listed, of which five are completed and none are currently active.
Registered raltegravir trials include NCT03954327, a completed Phase 2 study of combination antiretroviral therapy for primary biliary cholangitis in Canada, and three completed Phase 1 pharmacokinetic studies in HIV-infected participants: NCT02473367, NCT01930045, and NCT01622673. These studies examined antacid effects on raltegravir pharmacokinetics.
Yes. Raltegravir is also known as ISENTRESS, its brand name, and as raltegravir potassium. The 1200 mg strength is another name used for the asset, and raltegravir appears as a comparator in some studies. All of these refer to the same Merck antiretroviral drug.