Invasive aspergillosis (IA) MedDRA version: 20.0 Level: LLT Classification code 10003488 Term: Aspergillosis System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Noxafil 100 mg gastro-resistant tablets
Pharmaceutical Form: Gastro-resistant tablet
INN or Proposed INN: Posaconazole
Current Sponsor code: MK-5592
Other descriptive name: POSACONAZOLE
C
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A participant will be eligible for inclusion in the study if the participant: 1. Has a diagnosis of possible, probable, or proven IA per modified 2008 EuropeanOrganization for Research and Treatment of Cancer/Mycoses Study Group(EORTC/MSG) disease definitions. 2. If enrolled with a possible or probable IA diagnosis, has one or more of the following risks as per modified 2008 EORTC/MSG disease definitions: - Recent history of neutropenia (3 weeks (average minimum dose of 0.3 mg/kg/day of prednisone equivalent). - Congenital or inherited severe immunodeficiency (including but not limited to chronic granulomatous disease or severe combined immunodeficiency). 3. If enrolled with a possible or probable IA diagnosis, meets mycologic and clinical criteria as per modified 2008 EORTC/MSG disease definitions: - Possible IA includes participants with clinical criteria, with the anticipation that further diagnostic workup is in progress and is anticipated to result in a diagnosis of probable IA. - Probable IA includes participants with clinical criteria, along with mycological criteria including serum or broncho-alveolar lavage (BAL) fluid, Aspergillus galactomannan antigen, or evidence of Aspergillus by histology or microscopy, or positive culture of a specimen taken by nonsterile sampling of an infected site. 4. If enrolled with a proven IA diagnosis, has demonstrated fungal elements (by cytology or microscopy) or positive culture for Aspergillus obtained by sterile sampling of diseased tissue as per modified 2008 EORTC/MSG disease definitions. 5. Has a central line (eg, central venous catheter, peripherally-inserted central catheter) in place or planned to be in place before beginning IV study treatment. 6. Has clinical symptoms consistent with an acute episode of IA, defined as duration of clinical syndrome of <30 days. 7. Is male or female, and =2 years of age and <18 years of age at the time of first dose of study treatment. Participants may be of any race/ethnicity. - Contraceptive use by males should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 8. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 30 days] after the last dose of study treatment: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a female of childbearing potential who is not currently pregnant. Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 9. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a female
Exclusion criteria
Exclusion criteria: The participant must be excluded from the study if the participant: 1. Has chronic (=30 days’ duration) IA, relapsed/recurrent IA, or refractory IA that has not responded to prior antifungal treatment. 2. Has cystic fibrosis, pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis. 3. Has a known hypersensitivity or other serious adverse reaction to any azole antifungal therapy, or to any other ingredient of the study treatment used. 4. 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. 5. Has a known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. 6. Is on artificial ventilation or receiving acute continuous positive airway pressure (CPAP)/bilevel positive airway pressure (BPAP) at the time of first dose of study treatment. 7. Has known or suspected Gilbert’s disease. 8. Has any condition that, in the opinion of the investigator, may interfere with optimal participation in the study. 9. A female of childbearing potential who has a positive urine pregnancy test within 72 hours before the first dose of study intervention or at any time during the study. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. Has received any treatment specifically listed in the Protocol within the specified timeframes before to the start of study treatment. 11. Has enrolled previously in the current study and been discontinued. 12. Has QTc prolongation (based on either Fridericia or Bazett’s correction) at screening >500 msec. 13. Has significant liver dysfunction (defined as total bilirubin >1.5 times ULN AND AST or ALT >3 times ULN with normal alkaline phosphatase) at screening. 14. Has calculated creatinine clearance <20 mL/min (Cockroft-Gault formula) or<20 mL/min/1.73m2 (modified Schwartz formula) at screening. 15. Is not expected, in the opinion of the investigator, to survive for at least 1 month after the initiation of study treatment. 16. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety of posaconazole (POS) intravenous (IV) and oral formulations overall;Secondary Objective: 1. To evaluate the efficacy of POS IV and oral formulations overall in participants with proven or probable invasive aspergillosis (IA) 2. To evaluate relapse in participants with proven or probable IA 3. To characterize the pharmacokinetics (PK) of POS overall and by formulation 4. To summarize the palatability of POS powder-for-suspension (PFS) formulation ;Primary end point(s): 1. Percentage of participants who experience one or more treatment-related adverse events (AEs);Timepoint(s) of evaluation of this end point: 1. Up to 14 days after treatment (up to Day 100) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Percentage of participants who have a favorable global clinical response 2. Percentage of participants who have a relapse of IA at any point after achieving favorable global clinical response 3. Average plasma concentration (Cavg) of POS 4. Minimum plasma concentration (Cmin) of POS 5. Maximum plasma concentration (Cmax) of POS 6. Area under the concentration-time curve (AUC) of POS 7. Time to reach Cmax (Tmax) of POS 8. Percentage of participants with different categories of palatability after treatment with the POS PFS formulation ;Timepoint(s) of evaluation of this end point: 1. Up to End of Trial (EOT) visit (up to Day 87) 2. Up to 28 days post-treatment (up to Day 114) 3. Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 4. Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 5. Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 6. Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 7. Pre-dose, Day 1, Weeks 1, 2, 4, 6, 9 and 12 8. Day 8 and Day 84 | — |
Countries
Belgium, Czech Republic, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Peru, Russian Federation, United States
Outcome results
None listed