A Study to Examine the Efficacy and Safety of Posaconazole When Introduced Early in the Treatment of Refractory Fungal Infections (P05090 AM2) (TIP)

A Phase II Study on Treatment of Refractory Fungal Infections With Posaconazole. The "TIP" Study.

The purpose of this study is to evaluate the efficacy and safety of posaconazole in the early treatment of fungal infections in participants who are refractory to, intolerant to, or medically precluded from first-line monotherapy or first-line combination antifungal therapy.

Study Overview

• Status: Completed
• Conditions: Mycoses
• Intervention / Treatment: Drug: Posaconazole

Detailed Description

In the past two decades, invasive fungal infections (IFI) have become increasingly common among immunocompromised people, including solid-organ or hematopoietic stem-cell transplant recipients, those with HIV infection, those with hematological malignancies, and individuals on immunosuppressive drug regimens. There is a high rate of morbidity and mortality associated with IFI. Over the past decade, there has been an increase in resistance to commonly used antifungal agents and an epidemiological shift to more drug-resistant strains. This has demonstrated the need for the development of a new generation of azoles.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Proven or probable invasive fungal infection (IFI) including breakthrough infection while on antifungal treatment for at least 7 days.
• Refractory or intolerant to prior antifungal therapy, or medically unable to receive standard antifungal therapy.
• Age ≥13 years old.
• Expected to survive >1 month.
• Negative pregnancy test (serum or urine) at baseline for women of childbearing potential.

Exclusion Criteria:

• Serum bilirubin >10 times upper limit of normal (ULN).
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >10 times ULN.
• Documented allergy to azoles.
• Unable to take oral suspension medications or enteral feeding.
• Pregnant or breastfeeding.
• Participants who have received an investigational drug are allowed to be enrolled if the investigational drug was given 30 days prior to study registration, unless approved by the Sponsor.
• Requires surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Posaconazole; Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.	Drug: Posaconazole; Posaconazole oral suspension was administered as 400 mg twice daily (bis in die, BID) with food or 200 mg four times daily (quater in die, QID) without food for a minimum of 1 month.; Other Names: Noxafil®; SCH056592

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Complete Response (CR) or Partial Response (PR) by 12 Weeks or End of Treatment	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With ≥50% Decrease in Lesion Size or Number	Reduction in lesion size was analyzed by computed tomography (CT) scan. An imaging response was defined as >=50% reduction in lesion size for pulmonary and cerebral disease or >=50% reduction in the number of lesions for liver disease.	Up to 6 months
Percentage of Participants With a CR or PR by 12 Weeks	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.	Up to 12 Weeks
Percentage of Participants With CR or PR by 4 Weeks and by 26 Weeks	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.	Up to 26 weeks
Percentage of Participants With Infection-free Survival After the Last Dose of Study Drug	Infection-free survival was the proportion of evaluable participants included in the efficacy analysis who are infection-free and alive at 6 months post last dose visit. Infection-free is defined as the resolution of signs and symptoms of infection.	Up to 6 months
Overall Survival at 3 Months	Total number of participant survivors was assessed at 3 months.	3 months
Number of Participants With Response to Posaconazole in Combination Therapy	Complete Response was defined as resolution of all attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline. Partial Response was defined as clinically meaningful improvement in attributable clinical signs and symptoms and radiologic and mycologic abnormalities, if present at baseline.	Up to 6 months
Number of Participants Experiencing Adverse Events (AEs)	An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the study drug.	Up to 12 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: JSS Medical Research Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: October 29, 2007
• First Submitted That Met QC Criteria: October 29, 2007
• First Posted (Estimate): October 30, 2007

Study Record Updates

• Last Update Posted (Actual): April 7, 2017
• Last Update Submitted That Met QC Criteria: March 9, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Triazoles
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; 14-alpha Demethylase Inhibitors; Trypanocidal Agents; Posaconazole
• Other Study ID Numbers: P05090

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php