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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00811642 | Posaconazole Treatment of Invasive Fungal Infection (IFI) (P05551) | PHASE3 | COMPLETED | 63 | — | — | Nov 1, 2008 | Mar 1, 2010 | Apr 7, 2017 | - | — |
| NCT03336502 | Pharmacokinetics and Safety of Intravenous Posaconazole (MK-5592) in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-120) | PHASE1 | COMPLETED | 70 | — | — | Dec 20, 2017 | Nov 26, 2018 | Dec 19, 2019 | 7 | China |
| NCT02387983 | Pharmacokinetics and Safety of Oral Posaconazole (MK-5592)Tablets in Chinese Participants at High Risk for Invasive Fungal Infections (MK-5592-117) | PHASE1 | COMPLETED | 65 | — | — | May 6, 2015 | May 2, 2016 | Oct 9, 2018 | - | — |
| NCT01075984 | Pharmacokinetics, Safety, and Tolerability of Intravenous Posaconazole Solution Followed by Oral Posaconazole Suspension in Subjects at High Risk for Invasive Fungal Infections (P05520) | PHASE1 | COMPLETED | 279 | — | — | Feb 23, 2010 | Nov 20, 2012 | Nov 13, 2017 | - | — |
EVALUATION OF PARTICIPANTS' CLINICAL RESPONSE BASED ON CRITERIA: Complete Response: resolution of Invasive Fungal Infection (IFI) attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment. Partial Response: clinically significant improvement in IFI attributable symptoms, signs and laboratory or etiological abnormalities, if present at enrollment, of which, one still had not achieved complete recession. Stable disease: no progress in IFI attributable symptoms, if present at enrollment. Failure: deterioration in IFI attributable clinical symptoms.
Characterization of the pharmacokinetics (PK) parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Steady-state Cavg, where Cavg is defined as AUC0-24hr divided by the dosing interval. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.
Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Steady-state Cavg, where Cavg is defined as AUC0-24hr divided by the dosing interval. The percentage of participants with ssCavg ≥500 ng/mL are presented. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.
Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. AUC0-24 is defined as area under the plasma concentration-time curve from time 0 extrapolated to 24 hours. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.
Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Cmax is defined as the maximum concentration of POS in plasma. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.
Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Cmin is defined as the minimum concentration of POS in plasma. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.
Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. Tmax is defined as the time it takes to achieve maximum concentration of POS in plasma. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.
Characterization of the PK parameters of POS determined from plasma samples taken at steady-state after receiving IV administration of 300 mg POS twice a day (BID) on Day 1 and then 300 mg POS QD until at least Day 10. CL is defined as the time it takes for POS to be completely removed from the body's blood stream. Subgroup 1 - Serial PK, multiple same-day blood draw, performed specifically for determination of PK parameters of Cavg, AUC, Cmin, Cmax, Tmax and Total Body Clearance in addition to plasma trough determination. Subgroup 2 - Sparse PK, once a day blood draw, performed for plasma trough determination only.
Pre-dose plasma trough concentrations by study day between serial PK and Sparse PK - where serial PK is defined as multiple serial blood sampling of more than 6 timepoints; and sparse PK is defined as few blood samples taken and single or limited timepoints
The ssCavg was calculated in order to determine the percentage of participants achieving the pharmacokinetic (PK) target of ssCavg \>500 ng/mL on Day 8 when plasma drug levels had reached steady state.
The ssAUC0-24hr was calculated to determine the mean plasma drug concentration in the Intensive and Sparse PK subgroup from immediately after dosing to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation \[CV\]), where CV is calculated as (100 x standard deviation/arithmetic mean).
The ssCmax was calculated in order to determine the maximum post-dose plasma drug concentration in the Intensive and Sparse PK subgroup on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation \[CV\]), where CV is calculated as (100 x standard deviation/arithmetic mean).
The ssCmin was calculated in order to determine the lowest measurable drug concentration in the Intensive and Sparse PK subgroup up to 24 hours post-dose on Day 8. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation \[CV\]), where CV is calculated as (100 x standard deviation/arithmetic mean).
The ssTmax was calculated in order to determine the amount of time required to reach ssCmax in the Intensive and Sparse PK subgroup on Day 8.
The AUC0-24hr was calculated to determine the mean plasma drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation \[CV\]), where CV is calculated as (100 x standard deviation/arithmetic mean).
The Cmax was calculated to determine the maximum plasma drug concentration up to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation \[CV\]), where CV is calculated as (100 x standard deviation/arithmetic mean).
The Cmin was calculated in order to determine the lowest measurable drug concentration from immediately after dosing to 24 hours post-dose in the Immediate and Sparse PK subgroup on Day 1. Results data are presented as the arithmetic mean (% arithmetic coefficient of variation \[CV\]), where CV is calculated as (100 x standard deviation/arithmetic mean).
The Tmax was calculated in order to determine the time required to reach Cmax in the Immediate and Sparse PK subgroup on Day 1.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (24 hours).
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration.
Blood samples were collected from participants for the determination of plasma POS concentration. Cavg was calculated as steady state AUC / dosing interval (12 hours).
Blood samples were collected from participants for the determination of plasma POS concentration.
| Arm | Type | Description |
|---|---|---|
| Posaconazole | EXPERIMENTAL | Posaconazole 400 mg twice a day (BID) oral suspension for 12 weeks |
| POS IV 200 mg single dose (Cohort 0) | ACTIVE_COMPARATOR | POS 200 mg IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) |
| Dextrose 5% in water (Cohort 0) | PLACEBO_COMPARATOR | Placebo IV single dose infused over 1.5 hours on Day 1 followed 12 hours later by POS oral 400 mg, then by POS oral 400 mg BID on Days 2 through 6 and a single morning dose on Day 7 (Cohort 0) |
| POS IV 200 mg BID (Cohort 1) | EXPERIMENTAL | POS 200 mg IV infused over 1.5 hours BID on Day 1, followed by POS 200 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 1) |
| POS IV 300 mg BID (Cohort 2) | EXPERIMENTAL | POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 14, then by POS 400 mg oral BID through Day 28 (Cohort 2). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| POS IV 300 mg BID (Cohort 3) | EXPERIMENTAL | POS 300 mg IV infused over 1.5 hours BID on Day 1, followed by POS 300 mg IV once daily on Days 2 through 5, then by POS 200 mg oral TID or POS 400 mg oral BID through Day 28, or POS 200-300 mg IV once daily as required (Cohort 3). After Day 5, POS IV was administered continuously or intermittently, depending on oral tolerability. |
| Name | Type | Description |
|---|---|---|
| Posaconazole | DRUG | 400mg BID oral suspension for 12 weeks |
| Dextrose 5% in water | DRUG | - |
Inclusion Criteria: * Participants must be 18-70 years male or female * Identified or clinically diagnosed IFI participants or high risk population who are resistant to, or recurrent from, or intolerable to, or may suffer toxic reaction from standard antifungal treatment. * Sign informed consent fo...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| IQVIA Holdings Inc | IQV | 1 | PHASE3 | Olorofim, AmBisome |
| Merck & Co., Inc. | MRK | 1 | PHASE2 | Posaconazole /kg, Posaconazole PFS /kg |
| SCYNEXIS, Inc. | SCYX | 1 | — | Undisclosed |
| Innate Pharma SA Sponsored ADR | IPHA | 1 | — | Undisclosed |
| Gilead Sciences, Inc. | GILD | 1 | — | Undisclosed |