A Study of the Safety and Efficacy of Posaconazole Versus Voriconazole for the Treatment of Invasive Aspergillosis (MK-5592-069)

NCT01782131 | Completed Phase 3 Results DMC

• 3 other identifiers: P062005592-0692011-003938-14
• Study Type: interventional
• Target: 585
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of posaconazole (POS) versus voriconazole (VOR) in the treatment of adults and adolescents with invasive aspergillosis (IA). The primary hypothesis is that the all-cause mortality through Day 42 in the POS treatment group is non-inferior to that in the VOR treatment group.

Conditions

Fungal Infections; Invasive Pulmonary Aspergillosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Died Through Day 42 in the Intention to Treat Population

  The percentage of participants who died with posaconazole (POS) compared to voriconazole (VOR) in the first line treatment of invasive aspergillosis (IA) in the Intention to Treat (ITT) population through Day 42 was assessed.

  Up to ~42 days

Secondary Outcomes (15)

• Percentage of Participants Who Died Through Day 42 in the Full Analysis Set Population

  Up to ~42 days

• Percentage of Participants Who Died Through Day 84 in the ITT Population

  Up to ~84 days

• Percentage of Participants Who Died Through Day 84 in the FAS Population

  Up to ~ 84 days

• Percentage of Participants Achieving Global Clinical Response at Week 12 in the FAS Population

  Up to 12 weeks (± 4 weeks)

• Percentage of Participants Achieving Global Clinical Response at Week 6 in the FAS Population

  Up to 6 weeks (± 2 weeks)

Study Arms (2)

Posaconazole (POS)

EXPERIMENTAL

Participants received 300 mg posaconazole (POS) intravenous (IV) twice per day (BID) on Day 1, and then received 300 mg POS IV plus placebo IV once per day (QD) starting on Day 2 until clinically stable when participants transitioned to oral POS tablets plus oral placebo tablets QD for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.

Drug: Posaconazole; Drug: Placebo

Voriconazole

ACTIVE COMPARATOR

Participants received 6 mg/kg voriconazole (VOR) IV twice per day (BID) on Day 1, and then received 4 mg/kg VOR IV BID on Day 2 until clinically stable when participants transitioned to oral therapy with VOR capsules or VOR placebo capsules BID for up to 12 weeks of treatment. Most participants were expected to initiate treatment with IV therapy and transition to oral therapy as clinically indicated, with some participants initiating treatment with oral therapy, per clinical judgment.

Drug: Voriconazole; Drug: Placebo

Interventions

Posaconazole DRUG

POS IV: Day 1: 300 mg BID Day 2-84: 300 mg QD POS oral: Day 1: 300 mg BID Day 2-84: 300 mg QD

Also known as: SCH 056592, MK-5592, Noxafil®

Posaconazole (POS)

Voriconazole DRUG

VOR IV: Day 1: 6 mg/kg per body weight administered BID Day 2-84: 4 mg/kg per body weight administered BID VOR oral: Day 1: 300 mg BID Day 2-84: 200 mg BID

Also known as: VFEND®

Voriconazole

Placebo DRUG

Matching placebo received for Posaconazole (IV and oral) or Voriconazole (oral)

Posaconazole (POS); Voriconazole

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Weight \>40 kg (88 lb) and ≤150 kg (330 lb); if between 13 and 14 years of age must weigh \>= 50 kg (110 lb)
• If with possible IA at time of randomization must be willing or be in process of an ongoing diagnostic work up which is anticipated to result in a mycological diagnosis of proven or probable IA postrandomization.
• Must have a central line (e.g., central venous catheter, peripherally-inserted central catheter, etc.) in place or planned to be in place prior to beginning IV study therapy. If without central catheter access, must be clinically stable and able to receive oral study therapy.
• Acute IA defined as duration of clinical syndrome of \<30 days.
• Must be willing to adhere to dosing, study visit schedule, and mandatory procedures as outlined in the protocol. The participant must be willing to continue on study therapy for up to 12 weeks and remain in the study through the 1-month follow-up visit.
• The participant must have the ability to transition to oral study therapy during the course of the study.
• Female participants of child-bearing potential must be using a medically accepted method of birth control before beginning study-drug treatment and agree to continue its use for 30 days after stopping study medication
• Is not taking prohibited antifungal prophylaxis or treatment

You may not qualify if:

• Chronic (\>1 month duration) IA, relapsed/recurrent IA, or refractory IA which has not responded to antifungal therapy.
• Has pulmonary sarcoidosis, aspergilloma, or allergic bronchopulmonary aspergillosis (ABPA).
• Known mixed invasive mold fungal infection including Zygomycetes, and/or a known invasive Aspergillus fungal infection in which either study drug may not be considered active.
• Receipt of any systemic (oral, intravenous, or inhaled) antifungal therapy for this infection episode for 4 or more consecutive days (\>= 96 hours) immediately before randomization.
• Developed the current episode of IA infection during receipt of \>13 days of antifungal prophylaxis with an agent considered to be a mold-active antifungal agent.
• Receipt of posaconazole or voriconazole as empirical treatment for this infection for 4 days (96 hours) or more within the 15 days immediately before randomization.
• Has condition that, in the opinion of the investigator, may interfere with optimal participation in the study.
• Known hypersensitivity or other serious adverse reaction to any azole antifungal therapy or to any other ingredient of the study medication used.
• Females who are pregnant, intend to become pregnant, or are nursing at the time of randomization.
• Known history of Torsade de Pointes, unstable cardiac arrhythmia or proarrhythmic conditions, or a history of recent myocardial infarction within 90 days of study entry.
• Has significant liver dysfunction
• Hepatic cirrhosis or a Child-Pugh score of C (severe hepatic impairment) at the time of randomization.
• Severe renal insufficiency (estimated creatinine clearance \<20 mL/min) or on hemodialysis at the time of randomization or likely to require dialysis during the study.
• Known hereditary problem of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• Acute symptomatic pancreatitis within 6 months of study entry or a diagnosis of chronic pancreatitis at the time of randomization.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (2)

• Maertens JA, Rahav G, Lee DG, Haider S, Ramirez-Sanchez IC, Klimko N, Ponce-de-Leon A, Han S, Wrishko R, Winchell GA, Grandhi A, Waskin H; study investigators. Pharmacokinetic and Exposure Response Analysis of the Double-Blind Randomized Study of Posaconazole and Voriconazole for Treatment of Invasive Aspergillosis. Clin Drug Investig. 2023 Sep;43(9):681-690. doi: 10.1007/s40261-023-01282-7. Epub 2023 Sep 7.

  PMID: 37676612 RESULT

• Maertens JA, Rahav G, Lee DG, Ponce-de-Leon A, Ramirez Sanchez IC, Klimko N, Sonet A, Haider S, Diego Velez J, Raad I, Koh LP, Karthaus M, Zhou J, Ben-Ami R, Motyl MR, Han S, Grandhi A, Waskin H; study investigators. Posaconazole versus voriconazole for primary treatment of invasive aspergillosis: a phase 3, randomised, controlled, non-inferiority trial. Lancet. 2021 Feb 6;397(10273):499-509. doi: 10.1016/S0140-6736(21)00219-1.

  PMID: 33549194 DERIVED

MeSH Terms

Conditions

Mycoses; Invasive Pulmonary Aspergillosis

Interventions

posaconazole; Voriconazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Pulmonary Aspergillosis; Aspergillosis; Invasive Fungal Infections; Lung Diseases, Fungal; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 1, 2013
• Study Start: September 25, 2013
• Primary Completion: July 10, 2019
• Study Completion: September 10, 2019
• Last Updated: January 18, 2024
• Results First Posted: August 21, 2020

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share