A Clinical Study of MK0991 (Caspofungin) in Japanese Patients With Deep-seated Candida or Aspergillus Infections (0991-062)(COMPLETED)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00717860
• Collaborator: (none)
• Enrollment: 121
• Arms: 2
• Duration (Months): 23

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and efficacy of MK0991 in patients with deep-seated mycoses.

Condition or Disease	Intervention/Treatment	Phase
Fungal Infection	Drug: caspofungin acetate; Drug: Comparator: Micafungin sodium	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 121 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Comparative Study of MK0991 (Caspofungin) Versus Micafungin in Adult Japanese Patients With Deep-seated Candida or Aspergillus Infections
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Caspofungin caspofungin acetate (MK0991)	Drug: caspofungin acetate; Caspofungin acetate (50 mg/day for participants with esophageal candidiasis and 50 mg/day for participants with invasive candidiasis or aspergillosis after a 70 mg loading dose on Day 1), once daily intravenously (IV) for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.
Active Comparator: Micafungin Micafungin sodium	Drug: Comparator: Micafungin sodium; Micafungin sodium 150 mg/day, once daily IV, for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Significant Drug-related Adverse Experience [1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis]

   A significant drug-related adverse experience was defined as a serious drug-related adverse experience or a drug-related adverse experience leading to study therapy discontinuation.

Secondary Outcome Measures

1. Number of Participants With a Specific Safety Finding [1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis]

   A specific safety finding was defined as a drug-related adverse experience, a serious drug-related adverse experience, or a drug-related adverse experience leading to study therapy discontinuation.

2. Number of Participants With Favorable Overall Response at the End of Study Therapy [1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis]

   Favorable overall response for each infection category of deep-seated fungal infections was based on the determination of the Independent Efficacy Assessment Committee.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Japanese Patients In Whom A Causative Fungus Is Detected Before Treatment With The Study Drug Or Patients With Strongly Suspected Deep-Seated Fungal Infection Due To Candida species (Spp.) Or Aspergillus Spp.

Exclusion Criteria:

• Patients With Mycoses Other Than Ones Due To Candida Spp. Or Aspergillus Spp.

• Patients Who Will Receive Other Systemic Antifungal Agents For The First Time In Screening Period.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT00717860
• Other Study ID Numbers: 0991-062; 2008_013
• First Posted: Jul 18, 2008
• Last Update Posted: Mar 23, 2017
• Last Verified: Feb 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Infections; Communicable Diseases; Mycoses; Aspergillosis; Caspofungin; Micafungin

Study Results

Participant Flow

Arm/Group Title	Caspofungin	Micafungin
Arm/Group Description	Caspofungin acetate (50 mg/day for participants with esophageal candidiasis and 50 mg/day for participants with invasive candidiasis or aspergillosis after a 70 mg loading dose on Day 1), once daily intravenously (IV) for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.	Micafungin sodium 150 mg/day, once daily IV for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.
Period Title: Overall Study
STARTED	61	60
COMPLETED	34	32
NOT COMPLETED	27	28

Baseline Characteristics

Arm/Group Title	Caspofungin	Micafungin	Total
Arm/Group Description	Caspofungin acetate (50 mg/day for participants with esophageal candidiasis and 50 mg/day for participants with invasive candidiasis or aspergillosis after a 70 mg loading dose on Day 1), once daily intravenously (IV) for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.	Micafungin sodium 150 mg/day, once daily IV for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.	Total of all reporting groups
Overall Participants	61	60	121
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.9 (11.2)	69.3 (9.0)	69.1 (10.1)
Sex: Female, Male (Count of Participants)
Female	11 18%	14 23.3%	25 20.7%
Male	50 82%	46 76.7%	96 79.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Significant Drug-related Adverse Experience
Description	A significant drug-related adverse experience was defined as a serious drug-related adverse experience or a drug-related adverse experience leading to study therapy discontinuation.
Time Frame	1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis

Outcome Measure Data

Analysis Population Description

All Participants as Treated (APaT) population.

Arm/Group Title	Caspofungin	Micafungin
Arm/Group Description	Caspofungin acetate (50 mg/day for participants with esophageal candidiasis and 50 mg/day for participants with invasive candidiasis or aspergillosis after a 70 mg loading dose on Day 1), once daily intravenously (IV) for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.	Micafungin sodium 150 mg/day, once daily IV for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.
Measure Participants	60	60
Number [Participants]	3 4.9%	6 10%

2. Secondary Outcome

Title	Number of Participants With a Specific Safety Finding
Description	A specific safety finding was defined as a drug-related adverse experience, a serious drug-related adverse experience, or a drug-related adverse experience leading to study therapy discontinuation.
Time Frame	1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis

Outcome Measure Data

Analysis Population Description

APaT population.

Arm/Group Title	Caspofungin	Micafungin
Arm/Group Description	Caspofungin acetate (50 mg/day for participants with esophageal candidiasis and 50 mg/day for participants with invasive candidiasis or aspergillosis after a 70 mg loading dose on Day 1), once daily intravenously (IV) for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.	Micafungin sodium 150 mg/day, once daily IV for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.
Measure Participants	60	60
Drug-related adverse experience	23 37.7%	25 41.7%
Serious drug-related adverse experience	0 0%	2 3.3%
Discontinued by drug-related adverse experience	3 4.9%	6 10%

3. Secondary Outcome

Title	Number of Participants With Favorable Overall Response at the End of Study Therapy
Description	Favorable overall response for each infection category of deep-seated fungal infections was based on the determination of the Independent Efficacy Assessment Committee.
Time Frame	1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS) population.

Arm/Group Title	Caspofungin	Micafungin
Arm/Group Description	Caspofungin acetate (50 mg/day for participants with esophageal candidiasis and 50 mg/day for participants with invasive candidiasis or aspergillosis after a 70 mg loading dose on Day 1), once daily intravenously (IV) for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.	Micafungin sodium 150 mg/day, once daily IV for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.
Measure Participants	44	41
Esophageal candidiasis (n=6, n=6)	6 9.8%	5 8.3%
Invasive candidiasis (n=3, n=1)	3 4.9%	1 1.7%
Aspergillosis (n=30, n=33)	14 23%	14 23.3%

Adverse Events

Arm/Group Title	Caspofungin		Micafungin
Arm/Group Description	Caspofungin acetate (50 mg/day for participants with esophageal candidiasis and 50 mg/day for participants with invasive candidiasis or aspergillosis after a 70 mg loading dose on Day 1), once daily intravenously (IV) for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.		Micafungin sodium 150 mg/day, once daily IV for 1-4 weeks for esophageal candidiasis, 2-8 weeks for invasive candidiasis, 2-12 weeks for aspergillosis.
All Cause Mortality
	Caspofungin		Micafungin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Caspofungin		Micafungin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/60 (20%)		14/60 (23.3%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/60 (1.7%)	1	0/60 (0%)	0
Endocrine disorders
Inappropriate antidiuretic hormone secretion	1/60 (1.7%)	1	0/60 (0%)	0
Gastrointestinal disorders
Ileus paralytic	1/60 (1.7%)	1	0/60 (0%)	0
General disorders
Death	0/60 (0%)	0	1/60 (1.7%)	1
Hepatobiliary disorders
Cholelithiasis	0/60 (0%)	0	1/60 (1.7%)	1
Infections and infestations
Bacteraemia	0/60 (0%)	0	1/60 (1.7%)	1
Bronchopulmonary aspergillosis	3/60 (5%)	3	2/60 (3.3%)	2
Infection	0/60 (0%)	0	1/60 (1.7%)	1
Pneumonia	3/60 (5%)	3	0/60 (0%)	0
Sepsis	2/60 (3.3%)	2	0/60 (0%)	0
Septic shock	1/60 (1.7%)	1	0/60 (0%)	0
Investigations
Alanine aminotransferase increased	0/60 (0%)	0	1/60 (1.7%)	1
Aspartate aminotransferase increased	0/60 (0%)	0	1/60 (1.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/60 (0%)	0	1/60 (1.7%)	1
Lung neoplasm malignant	0/60 (0%)	0	1/60 (1.7%)	1
Mesothelioma	0/60 (0%)	0	1/60 (1.7%)	1
Myelodysplastic syndrome	1/60 (1.7%)	1	0/60 (0%)	0
Peritoneal mesothelioma malignant advanced	1/60 (1.7%)	1	0/60 (0%)	0
Nervous system disorders
Cerebral infarction	0/60 (0%)	0	1/60 (1.7%)	1
Cerebrovascular disorder	0/60 (0%)	0	1/60 (1.7%)	1
Renal and urinary disorders
Renal failure acute	1/60 (1.7%)	1	1/60 (1.7%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/60 (0%)	0	1/60 (1.7%)	1
Haemoptysis	1/60 (1.7%)	1	0/60 (0%)	0
Interstitial lung disease	0/60 (0%)	0	1/60 (1.7%)	1
Pneumothorax	0/60 (0%)	0	1/60 (1.7%)	1
Skin and subcutaneous tissue disorders
Rash	0/60 (0%)	0	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Caspofungin		Micafungin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/60 (73.3%)		40/60 (66.7%)
Gastrointestinal disorders
Constipation	6/60 (10%)	7	5/60 (8.3%)	5
Diarrhoea	3/60 (5%)	3	7/60 (11.7%)	7
Nausea	5/60 (8.3%)	5	4/60 (6.7%)	5
Vomiting	4/60 (6.7%)	4	2/60 (3.3%)	3
General disorders
Injection site pain	4/60 (6.7%)	4	5/60 (8.3%)	7
Malaise	4/60 (6.7%)	6	4/60 (6.7%)	4
Oedema	4/60 (6.7%)	4	2/60 (3.3%)	2
Pyrexia	5/60 (8.3%)	5	4/60 (6.7%)	6
Infections and infestations
Nasopharyngitis	4/60 (6.7%)	4	5/60 (8.3%)	8
Pneumonia	5/60 (8.3%)	5	2/60 (3.3%)	2
Investigations
Alanine aminotransferase increased	6/60 (10%)	8	7/60 (11.7%)	7
Aspartate aminotransferase increased	9/60 (15%)	12	6/60 (10%)	7
Blood alkaline phosphatase increased	3/60 (5%)	3	9/60 (15%)	9
Blood glucose increased	7/60 (11.7%)	7	3/60 (5%)	3
Blood lactate dehydrogenase increased	4/60 (6.7%)	5	4/60 (6.7%)	4
Blood potassium decreased	6/60 (10%)	6	1/60 (1.7%)	1
Blood potassium increased	3/60 (5%)	3	5/60 (8.3%)	5
Blood pressure increased	3/60 (5%)	8	4/60 (6.7%)	4
C-reactive protein increased	5/60 (8.3%)	5	4/60 (6.7%)	4
Eosinophil count increased	3/60 (5%)	3	4/60 (6.7%)	4
Gamma-glutamyltransferase increased	3/60 (5%)	3	4/60 (6.7%)	4
Whtie blood cell count increased	2/60 (3.3%)	2	7/60 (11.7%)	7
Metabolism and nutrition disorders
Anorexia	4/60 (6.7%)	6	2/60 (3.3%)	2
Nervous system disorders
Headache	6/60 (10%)	7	5/60 (8.3%)	9
Psychiatric disorders
Insomnia	3/60 (5%)	3	4/60 (6.7%)	4
Skin and subcutaneous tissue disorders
Pruritus	2/60 (3.3%)	3	4/60 (6.7%)	5
Rash	5/60 (8.3%)	6	2/60 (3.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.