Post-marketing Surveillance Study of Invasive Mycosis With Posaconazole (Study P04641)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00726609
• Collaborator: (none)
• Enrollment: 214
• Duration (Months): 30

Study Details

Study Description

Brief Summary

The purpose of this postmarketing surveillance study is to collect an extensive body of data in a large patient population in every day life to investigate the safety and efficacy of NOXAFIL® (posaconazole) in the treatment of invasive fungal disease.

Condition or Disease	Intervention/Treatment	Phase
Mycoses	Drug: Posaconazole

Detailed Description

Data regarding demographics, underlying disease, prior fungal infection, prior antifungal medication, invasive fungal infection signs & symptoms, concomitant medication, posaconazole use, tolerability, safety and therapy outcome will be collected on abstracted electronic Case Report Forms.

This surveillance study was originally limited to subjects receiving posaconazole as salvage antifungal therapy as indicated. A subgroup of subjects at risk for invasive fungal infection was included for prophylactic treatment following the enlargement of the marketing authorization for NOXAFIL® (posaconazole) during the course of the study. These participants only contributed data for the assessment of safety.

Study Design

• Study Type: Observational
• Actual Enrollment: 214 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: Post-marketing Surveillance (PMS) Management of Invasive Mycosis With Posaconazole
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Posaconazole (assigned by physician in normal practice) Treatment of invasive fungal infection. Prophylaxis of invasive fungal infection.	Drug: Posaconazole; The usual dose of NOXAFIL® is 400 mg twice daily (10 mL) at meals or with 240 mL of a food supplement. For patients unable to take meals or food supplements, NOXAFIL® is administered at a dose of 200 mg (5 mL) four times daily.; Other Names: SCH 56592 NOXAFIL®

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting Adverse Drug Reactions. [Before starting treatment with posaconazole, during treatment, and until 100 days after treatment.]

   The severity of an Adverse Drug Reaction is determined on the basis of the following definitions: Mild: The abnormality, symptom or event is noticed but well tolerated. Moderate: Symptoms impair normal activities and may require intervention. Severe: Clinical status is significantly impaired, normal activity is no longer possible, intervention is required.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Adult subjects with:

• Invasive aspergillosis refractory to, or intolerant of, amphotericin B or itraconazole,

• Fusariosis refractory to, or intolerant of, amphotericin B,

• Chromoblastomycosis and mycetoma refractory to, or intolerant of, itraconazole,

• Coccidiomycosis refractory to, or intolerant of, amphotericin B, itraconazole or fluconazole.

• Subjects receiving remission-induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) expected to result in prolonged neutropenia and who are at high risk for developing invasive fungal infections.

• Hematopoietic stem-cell transplant (HSCT) recipients who are undergoing high-dose immunosuppressive therapy for Graft-versus-host disease and who are at high risk for developing invasive fungal infections.

Exclusion Criteria:

• Comedication of the participant with ergotamine, dihydroergotamine, terfenadine, astemizole, cisapride, pimozide, halofantrine, or chinidine.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00726609
• Other Study ID Numbers: P04641
• First Posted: Aug 1, 2008
• Last Update Posted: Mar 5, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Mycoses; Invasive Fungal Infections; Posaconazole

Study Results

Participant Flow

Arm/Group Title	Posaconazole (Assigned by Physician in Normal Practice)
Arm/Group Description	Treatment of invasive fungal infection. Prophylaxis of invasive fungal infection.
Period Title: Overall Study
STARTED	214
COMPLETED	116
NOT COMPLETED	98

Baseline Characteristics

Arm/Group Title	Posaconazole (Assigned by Physician in Normal Practice)
Arm/Group Description	Treatment of invasive fungal infection. Prophylaxis of invasive fungal infection.
Overall Participants	214
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.6 (12.77)
Sex: Female, Male (Count of Participants)
Female	79 36.9%
Male	135 63.1%
Region of Enrollment (participants) [Number]
Germany	214 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Adverse Drug Reactions.
Description	The severity of an Adverse Drug Reaction is determined on the basis of the following definitions: Mild: The abnormality, symptom or event is noticed but well tolerated. Moderate: Symptoms impair normal activities and may require intervention. Severe: Clinical status is significantly impaired, normal activity is no longer possible, intervention is required.
Time Frame	Before starting treatment with posaconazole, during treatment, and until 100 days after treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Posaconazole (Assigned by Physician in Normal Practice)
Arm/Group Description	Treatment of invasive fungal infection. Prophylaxis of invasive fungal infection.
Measure Participants	214
All	52 24.3%
Mild	30 14%
Moderate	21 9.8%
Severe	1 0.5%

Adverse Events

Arm/Group Title	Posaconazole (Assigned by Physician in Normal Practice)
Arm/Group Description
All Cause Mortality
	Posaconazole (Assigned by Physician in Normal Practice)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Posaconazole (Assigned by Physician in Normal Practice)
	Affected / at Risk (%)	# Events
Total	33/214 (15.4%)
Blood and lymphatic system disorders
THROMBOTIC THROMBOCYTOPENIC PURPURA	1/214 (0.5%)	1
Cardiac disorders
ATRIOVENTRICULAR BLOCK COMPLETE	1/214 (0.5%)	1
Congenital, familial and genetic disorders
CYSTIC LYMPHANGIOMA	1/214 (0.5%)	1
Eye disorders
VISUAL ACUITY REDUCED	1/214 (0.5%)	1
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	1/214 (0.5%)	1
HAEMORRHOIDS	2/214 (0.9%)	2
SMALL INTESTINAL PERFORATION	1/214 (0.5%)	1
General disorders
CHEST PAIN	1/214 (0.5%)	1
DEATH	2/214 (0.9%)	2
DISEASE PROGRESSION	2/214 (0.9%)	2
GENERAL PHYSICAL HEALTH DETERIORATION	1/214 (0.5%)	1
INJECTION SITE THROMBOSIS	1/214 (0.5%)	1
MULTI-ORGAN FAILURE	2/214 (0.9%)	3
PYREXIA	1/214 (0.5%)	2
Hepatobiliary disorders
CHOLANGITIS	1/214 (0.5%)	1
CHOLECYSTITIS	2/214 (0.9%)	2
HEPATOTOXICITY	1/214 (0.5%)	1
Immune system disorders
ACUTE GRAFT VERSUS HOST DISEASE	1/214 (0.5%)	1
ACUTE GRAFT VERSUS HOST DISEASE IN INTESTINE	1/214 (0.5%)	1
ACUTE GRAFT VERSUS HOST DISEASE IN LIVER	1/214 (0.5%)	1
ANAPHYLACTIC REACTION	1/214 (0.5%)	1
Infections and infestations
ABSCESS LIMB	1/214 (0.5%)	1
ABSCESS SWEAT GLAND	1/214 (0.5%)	1
BRONCHOPNEUMONIA	1/214 (0.5%)	1
CYTOMEGALOVIRUS INFECTION	4/214 (1.9%)	4
ENTEROCOCCAL SEPSIS	1/214 (0.5%)	1
ESCHERICHIA SEPSIS	2/214 (0.9%)	3
INFECTION	2/214 (0.9%)	2
KLEBSIELLA SEPSIS	1/214 (0.5%)	1
OTITIS MEDIA BACTERIAL	1/214 (0.5%)	1
PNEUMONIA	2/214 (0.9%)	2
PSEUDOMONAL SEPSIS	1/214 (0.5%)	1
SEPSIS	2/214 (0.9%)	2
SEPTIC SHOCK	1/214 (0.5%)	1
SKIN INFECTION	2/214 (0.9%)	2
STAPHYLOCOCCAL SEPSIS	6/214 (2.8%)	10
STREPTOCOCCAL SEPSIS	2/214 (0.9%)	2
UROSEPSIS	1/214 (0.5%)	1
Injury, poisoning and procedural complications
SPLENIC RUPTURE	1/214 (0.5%)	1
SUBDURAL HAEMATOMA	1/214 (0.5%)	1
TRANSFUSION REACTION	1/214 (0.5%)	1
Investigations
BLOOD CREATININE INCREASED	1/214 (0.5%)	1
BLOOD CULTURE POSITIVE	1/214 (0.5%)	4
C-REACTIVE PROTEIN INCREASED	2/214 (0.9%)	2
HAEMOGLOBIN DECREASED	1/214 (0.5%)	1
HEPATIC ENZYME INCREASED	2/214 (0.9%)	2
RENAL FUNCTION TEST ABNORMAL	2/214 (0.9%)	2
Metabolism and nutrition disorders
DIABETES MELLITUS	1/214 (0.5%)	1
Musculoskeletal and connective tissue disorders
BACK PAIN	1/214 (0.5%)	1
FACET JOINT SYNDROME	1/214 (0.5%)	1
MYOPATHY	1/214 (0.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG ADENOCARCINOMA	1/214 (0.5%)	1
LYMPHOMA	1/214 (0.5%)	1
PROSTATIC ADENOMA	1/214 (0.5%)	1
Nervous system disorders
CRITICAL ILLNESS POLYNEUROPATHY	1/214 (0.5%)	1
ENCEPHALITIS	1/214 (0.5%)	1
TOXIC NEUROPATHY	1/214 (0.5%)	1
Psychiatric disorders
TRANSIENT PSYCHOSIS	1/214 (0.5%)	1
Renal and urinary disorders
ACUTE PRERENAL FAILURE	1/214 (0.5%)	1
RENAL FAILURE	1/214 (0.5%)	1
RENAL FAILURE ACUTE	1/214 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
LUNG INFILTRATION	3/214 (1.4%)	3
PULMONARY HAEMORRHAGE	1/214 (0.5%)	1
RESPIRATORY FAILURE	1/214 (0.5%)	1
Vascular disorders
SUBCLAVIAN VEIN THROMBOSIS	1/214 (0.5%)	1
THROMBOSIS	1/214 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Posaconazole (Assigned by Physician in Normal Practice)
	Affected / at Risk (%)	# Events
Total	49/214 (22.9%)
Gastrointestinal disorders
DIARRHOEA	19/214 (8.9%)	19
NAUSEA	12/214 (5.6%)	18
General disorders
PYREXIA	27/214 (12.6%)	34
Investigations
C-REACTIVE PROTEIN INCREASED	11/214 (5.1%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.