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

This study has been completed.
Sponsor:
Collaborator:
JSS Medical Research Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00550732
First received: October 29, 2007
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Mycoses
Drug: Posaconazole
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study on Treatment of Refractory Fungal Infections With Posaconazole. The "TIP" Study.

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percentage of Participants With Complete Response (CR) or Partial Response (PR) by 12 Weeks or End of Treatment [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Number of Participants With ≥50% Decrease in Lesion Size or Number [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With a CR or PR by 12 Weeks [ Time Frame: Up to 12 Weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With CR or PR by 4 Weeks and by 26 Weeks [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Infection-free Survival After the Last Dose of Study Drug [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Overall Survival at 3 Months [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    Total number of participant survivors was assessed at 3 months.

  • Number of Participants With Response to Posaconazole in Combination Therapy [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 40
Study Start Date: December 2007
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • SCH056592
  • Noxafil®

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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00550732     History of Changes
Other Study ID Numbers: P05090
Study First Received: October 29, 2007
Results First Received: September 11, 2013
Last Updated: June 2, 2014
Health Authority: Canada: Health Canada

Keywords provided by Merck Sharp & Dohme Corp.:
Triazoles

Additional relevant MeSH terms:
Mycoses
Posaconazole
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on July 24, 2014