Posaconazole (MK-5592) Intravenous and Oral in Children With Invasive Aspergillosis (IA) (MK-5592-104)
- Conditions
- Invasive Aspergillosis
- Interventions
- Registration Number
- NCT04218851
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
This study will evaluate the safety, efficacy, and pharmacokinetics of posaconazole (POS) intravenous (IV) and oral formulations in pediatric participants 2 to \<18 years of age with invasive aspergillosis (IA).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- Has a diagnosis of possible, probable, or proven IA per modified 2008/2020 European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) disease definitions
- Has one or more of pre-defined risks as per modified 2008 EORTC/MSG disease definitions
- Has a central line (e.g., central venous catheter, peripherally-inserted central catheter) in place or planned to be in place prior to beginning IV study treatment.
- Has clinical symptoms consistent with an acute episode of IA, defined as duration of clinical syndrome of <30 days.
- Participants weigh at least 10 kg, and may be of any race/ethnicity.
- During the intervention period and for at least 30 days after the last dose of study treatment, males agree to be abstinent from heterosexual intercourse or use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).
- Female is not pregnant or breastfeeding, and is not a woman of child bearing potential (WOCBP) or is a WOCBP using a highly effective contraceptive method. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
- Has chronic (≥30 days' duration) IA, relapsed/recurrent IA, or refractory IA that has not responded to prior antifungal treatment.
- Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis
- Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study treatment used.
- Has any known history of torsade de pointes, unstable cardiac arrhythmia or proarrhythmic conditions, a history of recent myocardial infarction, congenital or acquired QT prolongation, or cardiomyopathy in the context of cardiac failure within 90 days of time of first dose of study treatment.
- Has known hereditary fructose intolerance.
- Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
- Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.
- Is on artificial ventilation at the time of first dose of study treatment.
- Has received any treatment prohibited by the protocol.
- Has enrolled previously in the current study and been discontinued.
- Is not expected, in the opinion of the investigator, to survive for at least 1 month after the initiation of study treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Posaconazole Posaconazole IV On Day 1 participants receive 2 administrations of posaconazole (POS) 6 mg/kg body weight by intravenous (IV) infusion. On Days 2 through 7, participants receive POS 6 mg/kg body weight once daily by IV infusion. Beginning at Day 8 up to Day 84, participants may transition to receiving an oral formulation, or they may remain on the IV formulation. Posaconazole Posaconazole PFS On Day 1 participants receive 2 administrations of posaconazole (POS) 6 mg/kg body weight by intravenous (IV) infusion. On Days 2 through 7, participants receive POS 6 mg/kg body weight once daily by IV infusion. Beginning at Day 8 up to Day 84, participants may transition to receiving an oral formulation, or they may remain on the IV formulation. Posaconazole Posaconazole tablet On Day 1 participants receive 2 administrations of posaconazole (POS) 6 mg/kg body weight by intravenous (IV) infusion. On Days 2 through 7, participants receive POS 6 mg/kg body weight once daily by IV infusion. Beginning at Day 8 up to Day 84, participants may transition to receiving an oral formulation, or they may remain on the IV formulation.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experience One or More Treatment-related Adverse Events (AEs) Up to 14 days after treatment (up to Day 102) An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Treatment-related AEs were determined by the investigator to be related to the drug. The 95% confidence interval (CI) was based on the exact binomial method by Clopper- Pearson.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 6 Up to week 6 A global clinical response is assessed by the investigator as favorable if the participant is alive and has a complete response (CR) or partial response (PR). CR is defined as survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease, resolution of radiological lesion(s), and documented clearance of infected sites that are accessible to repeated sampling. PR is defined as survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease, improvement of radiological lesion(s), and evidence of clearance of infected sites that are accessible to repeated sampling.
Percentage of Participants Who Have a Favorable Global Clinical Response Through Week 12 Up to Week 12 A global clinical response is assessed by the investigator as favorable if the participant is alive and has a complete response (CR) or partial response (PR). CR is defined as survival within the prespecified period of observation, resolution of all attributable symptoms and signs of disease, resolution of radiological lesion(s), and documented clearance of infected sites that are accessible to repeated sampling. PR is defined as survival within the prespecified period of observation, improvement in attributable symptoms and signs of disease, improvement of radiological lesion(s), and evidence of clearance of infected sites that are accessible to repeated sampling.
Percentage of Participants Who Have a Relapse of Invasive Aspergillosis (IA) at Any Point After Achieving Favorable Global Clinical Response Up to 28 days post-treatment (up to Day 116) In participants who achieved favorable global clinical response, relapse of IA is defined as the re-emergence of clinical, radiographic, or other relevant abnormalities indicating IA.
Average Plasma Concentration (Cavg) of POS by Age Cohorts Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady state Cavg was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Cavg parameter values (1 for IV dosing, 1 for oral dosing).
Minimum Plasma Concentration (Cmin) of POS by Age Cohorts Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady state Cmin was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Cmin parameter values (1 for IV dosing, 1 for oral dosing).
Maximum Plasma Concentration (Cmax) of POS by Age Cohorts Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady state Cmax was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Cmax parameter values (1 for IV dosing, 1 for oral dosing).
Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Age Cohorts Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady state AUCtau was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 AUCtau parameter values (1 for IV dosing, 1 for oral dosing).
Time to Reach Cmax (Tmax) of POS by Age Cohorts Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady state Tmax was determined by population PK analysis of plasma concentrations obtained pre-dose up to Week 12 for each of Cohorts 1 and 2, as well as the pooled Cohorts 1 and 2. Some participants had 2 Tmax parameter values (1 for IV dosing, 1 for oral dosing).
Average Plasma Concentration (Cavg) of POS by Formulation Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady-state Cavg was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N \> 2.
Minimum Plasma Concentration (Cmin) of POS by Formulation Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady-state Cmin was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N \> 2.
Maximum Plasma Concentration (Cmax) of POS by Formulation Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady-state Cmax was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N \> 2.
Percentage of Participants With Different Categories of Palatability After Last Day of Treatment With the POS PFS Formulation Last day of PFS treatment (Day 85) Palatability was categorized on the last day (Day 85) on PFS based on responses by participants to a palatability questionnaire. Per protocol participants were pooled into a single treatment group Palatability categories for taste are as follows: Very good; Good; Very bad; Neither good nor bad.
Area Under the Concentration Time Curve Over the Dosing Interval (AUCtau) of POS by Formulation Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady-state AUCtau was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N \> 2.
Time to Reach Cmax (Tmax) of POS by Formulation Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 Steady-state Tmax was determined by population PK analysis from plasma concentration obtained pre-dose up to Week 12 for each of the POS formulations: IV, PFS and tablet. Some participants may have received more than 1 formulation, and results were only reported when N \> 2.
Percentage of Participants With Different Categories of Palatability After First Day of Treatment With the POS PFS Formulation First day of PFS treatment (Day 8) Palatability was categorized on the first day (Day 8) on PFS based on responses by participants to a palatability questionnaire. Per protocol participants were pooled into a single treatment group. Palatability categories for taste are as follows: Very good; Good; Very bad; Neither good nor bad.
Trial Locations
- Locations (29)
Chaim Sheba Medical Center ( Site 1126)
🇮🇱Ramat Gan, Israel
Azienda Ospedaliera Universitaria Integrata ( Site 1151)
🇮🇹Verona, Italy
Heim Pal Orszagos Gyermekgyogyaszati Intezet ( Site 1103)
🇭🇺Budapest, Hungary
Ospedale Regina Margherita ( Site 1150)
🇮🇹Torino, Italy
Rambam Medical Center ( Site 1125)
🇮🇱Haifa, Israel
Children's Hospital of Orange County ( Site 1409)
🇺🇸Orange, California, United States
Del-pesti Centrumkorhaz Orszagos Hematologiai es Infektologiai Intezet ( Site 1102)
🇭🇺Budapest, Hungary
Washington University ( Site 1403)
🇺🇸Saint Louis, Missouri, United States
UZ Leuven ( Site 1001)
🇧🇪Leuven, Vlaams-Brabant, Belgium
General Hospital of Thessaloniki "Ippokrateio" ( Site 1050)
🇬🇷Thessaloniki, Greece
The Catholic University of Korea. Seoul St. Mary s Hospital ( Site 1325)
🇰🇷Seoul, Korea, Republic of
Hadassah Ein Karem Hebrew University Medical Center ( Site 1127)
🇮🇱Jerusalem, Israel
Seoul National University Hospital ( Site 1326)
🇰🇷Seoul, Korea, Republic of
Sourasky Medical Center ( Site 1128)
🇮🇱Tel Aviv, Israel
Dmitry Rogachev National Research Center ( Site 1275)
🇷🇺Moscow, Moskva, Russian Federation
Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 1402)
🇺🇸Chicago, Illinois, United States
Rady Children's Hospital-San Diego ( Site 1401)
🇺🇸San Diego, California, United States
UCL St Luc ( Site 1000)
🇧🇪Brussels, Bruxelles-Capitale, Region De, Belgium
University General Hospital of Thessaloniki "AHEPA" ( Site 1053)
🇬🇷Thessaloniki, Kentriki Makedonia, Greece
Institute of Invasive Mycosis ( Site 1282)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"-Infectologia ( Site 1204)
🇲🇽Monterrey, Nuevo Leon, Mexico
Athens Childrens Hospital Aglaia Kyriakou ( Site 1052)
🇬🇷Athens, Attiki, Greece
Instituto Nacional de Pediatria ( Site 1200)
🇲🇽Mexico City, Mexico
Hospital Nacional Edgardo Rebagliati Martins ( Site 1250)
🇵🇪Lima, Peru
Almazov National Medical Research Centre ( Site 1284)
🇷🇺Saint Petersburg, Leningradskaya Oblast, Russian Federation
Instituto Nacional de Enfermedades Neoplásicas ( Site 1251)
🇵🇪Lima, Peru
BAZ Megyei Korhaz. Klinikai Onkologia es Sugarterapias Centrum ( Site 1101)
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
UZ Gent ( Site 1002)
🇧🇪Gent, Oost-Vlaanderen, Belgium
Institute of Child Hematology and Transpl n.a.R.M.Gorbacheva ( Site 1281)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation