Comparison of Candida Eradication and Serum Cidal Activity of Echinocandins

• Sponsor: Gary E. Stein, Pharm.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT00839540
• Collaborator: Astellas Pharma US, Inc. (Industry)
• Enrollment: 21
• Location: 1
• Arms: 3
• Duration (Months): 17
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this pharmacokinetic (PK) and pharmacodynamic (PD) study is:

To study the rate and duration of serum cidal activity of caspofungin (CFG) and micafungin (MFG) against Candida isolates from the subject and against Candida glabrata with varying degrees of caspofungin susceptibilities.

This investigation will provide clinicians information supporting the use of caspofungin and micafungin in situations where Candida strains may be a cause of infection.

Condition or Disease	Intervention/Treatment	Phase
Candidemia	Drug: micafungin; Drug: Micafungin; Drug: Caspofungin	Phase 4

Detailed Description

Methods:

Patients - Adult patients with presumptive candidemia. Patients with severe neutropenia (<500) APACHE II scores > 20, or significant liver disease will be excluded. All will give written informed consent (Pappas et al. CID. Oct 1, 2007).

Drugs - Patients will receive either CFG: 70 mg loading dose (LD) followed by 50 mg once daily (qd) (8 patients), MFG: 100 mg qd (8 patients) or MFG: 200 mg qd (8 patients). All agents will be given by slow IV infusion (MFG will be supplied by Astellas).

Sera - Blood samples will be collected at the end of the infusion (peak) and at 12 h and 24 h (trough) after the beginning of an infusion (day 3-4).

Each patients sera will be tested (MIC and cidal activity) against their own Candida isolate (if isolated). In addition, recent clinical isolates of C. glabrata will also be tested against patient sera (time-kill) to verify previous in vitro and animal PD studies (Cota. AAC. Nov. 2006; Wiederhold. AAC. May 2007).

Results:

• Patient outcome, including Candida eradication, will be documented for each patient by repeat culture.

• Serum concentrations (lab to be determined) and PK analysis of each echinocandin will be determined for each patient.

• Serum cidal titers will be measured against each of the Candida isolates for each agent at each time period. Median and geometric mean Peak and duration of cidal activity will then be determined and compared.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of Candida Eradication and Serum Cidal Activity of Echinocandins in Patients With Presumptive Candidemia
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: micafungin 100 Patients receive Micafungin 100 mg qd	Drug: micafungin; 100 mg qd by slow IV infusion for 24 h; Other Names: Micamine
Active Comparator: micafungin 200 Patients receive 200 mg Micafungin qd	Drug: Micafungin; 200 mg qd by slow IV infusion for 24 h; Other Names: Micamine
Active Comparator: Caspofungin Patients receive caspofungin 70 mg LD followed by 50 mg qd	Drug: Caspofungin; 70 mg LD followed by 50 mg qd by slow IV infusion for 24 h; Other Names: Cancidas

Outcome Measures

Primary Outcome Measures

1. Serum Cidal Activity as Tested Against Various Candida Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth) [Pre-treatment, 1.5 hour (h), 12 h and 24 h after receiving the drug]

   Serum cidal activity of serum collected at different timepoints from the patients will be tested against various Candida isolates and the ex-vivo effect reported as log inhibition (logrithmic measurement of the decrease in microbiological growth). These Candida isolates had a range of minimum inhibitory concentrations (MIC) to Caspofungin (C) and Micafungin (M).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adult patients with presumptive candidemia

Exclusion Criteria:

• Patients with severe neutropenia (<500)

• Patients with APACHE II scores > 20

• Patients with severe liver disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sparrow Hospital	Lansing	Michigan	United States	48912

Sponsors and Collaborators

• Gary E. Stein, Pharm.D.
• Astellas Pharma US, Inc.

Investigators

• Principal Investigator: Gary E Stein, Pharm.D., Michigan State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary E. Stein, Pharm.D., Professor of Medicine, Michigan State University
• ClinicalTrials.gov Identifier: NCT00839540
• Other Study ID Numbers: PA-07-004
• First Posted: Feb 9, 2009
• Last Update Posted: Feb 28, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Gary E. Stein, Pharm.D., Professor of Medicine, Michigan State University: candidemia; echinocandin; micafungin; caspofungin
• Additional relevant MeSH terms: Candidemia; Caspofungin; Micafungin

Study Results

Participant Flow

Recruitment Details	Subjects were inpatients (Sparrow Hospital) with probable fungal infections that required treatment with an antifungal; referral base was infectious disease consultations. The first subject was enrolled 12/24/08, with the last subject enrolled on 1/15/10.

Arm/Group Title	Micafungin (M) 100	Micafungin (M) 200	Caspofungin (C) 50
Arm/Group Description	Patients receive Micafungin (M) 100 mg once daily (qd)	Patients receive 200 mg Micafungin (M) once daily	Patients receive caspofungin 70 mg loading dose (LD) followed by 50 mg once daily (qd)
Period Title: Overall Study
STARTED	8	8	5
COMPLETED	8	8	5
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Micafungin (M) 100	Micafungin (M) 200	Caspofungin (C) 50	Total
Arm/Group Description	Patients receive Micafungin (M) 100 mg once daily (qd)	Patients receive 200 mg Micafungin (M) once daily	Patients receive caspofungin 70 mg loading dose (LD) followed by 50 mg once daily (qd)	Total of all reporting groups
Overall Participants	8	8	5	21
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 37.5%	4 50%	4 80%	11 52.4%
>=65 years	5 62.5%	4 50%	1 20%	10 47.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.62 (16.13282)	57.81 (17.38585)	44.0 (20.43282)	57.6 (18.65374)
Sex: Female, Male (Count of Participants)
Female	2 25%	5 62.5%	3 60%	10 47.6%
Male	6 75%	3 37.5%	2 40%	11 52.4%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	5 100%	21 100%

Outcome Measures

1. Primary Outcome

Title	Serum Cidal Activity as Tested Against Various Candida Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth)
Description	Serum cidal activity of serum collected at different timepoints from the patients will be tested against various Candida isolates and the ex-vivo effect reported as log inhibition (logrithmic measurement of the decrease in microbiological growth). These Candida isolates had a range of minimum inhibitory concentrations (MIC) to Caspofungin (C) and Micafungin (M).
Time Frame	Pre-treatment, 1.5 hour (h), 12 h and 24 h after receiving the drug

Outcome Measure Data

Analysis Population Description

Each subject received drug and had serum samples drawn at pre-treatment, 1.5h, 12h, and 24h after dosing.

Arm/Group Title	Log Inhibition of 50 mg/Day Caspofungin on Candida Spp.	Log Inhibition of 100 mg/Day Micafungin on Candida Spp.	Log Inhibition of 200 mg/Day Micafungin on Candida Spp.
Arm/Group Description	Measurement of the decrease in organism(Candida spp.) colony counts following exposure of serum containing Caspofungin based on 50 mg/day dosing, measured as Ex-vivo effect.	Measurement of the decrease in organism(Candida spp.) colony counts following exposure of serum containing Micafungin based on 100 mg/day dosing, measured as Ex-vivo effect.	Measurement of the decrease in organism(Candida spp.) colony counts following exposure of serum containing Micafungin based on 200 mg/day dosing, measured as Ex-vivo effect.
Measure Participants	5	8	8
Measure blood samples	10	19	19
C. albicans MIC: C, M 0.016 mg/L	3 (NA)	0.5	0
C. glabrata MIC: C, M 0.06 mg/L	3 (NA)	1.5	0.5
C. glabrata MIC: C, M 0.25 mg/L	0.5 (NA)	1	0.5
C. albicans 119 FKS mutant MIC:C 1, M 0.16 mg/L	0.5	0.5	1.5
C. albicans 90 FKS mutant MIC: C 1, M 0.25 mg/L	0	0.5	2
C. albicans A-15 FKS mutant MIC: C 2, M0.5 mg/L	0	0	0
C. glabrata MIC: C 2, M 0.5 mg/L	0	0	0
C. albicans 117 FKS mutant MIC: C 8, M 0.83 mg/L	0	0	0

Adverse Events

Arm/Group Title	Micafungin (M) 100		Micafungin (M) 200		Caspofungin (C) 50
Arm/Group Description	Patients receive Micafungin (M) 100 mg once daily (qd)		Patients receive 200 mg Micafungin (M) once daily		Patients receive caspofungin 70 mg loading dose (LD) followed by 50 mg once daily (qd)
All Cause Mortality
	Micafungin (M) 100		Micafungin (M) 200		Caspofungin (C) 50
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Micafungin (M) 100		Micafungin (M) 200		Caspofungin (C) 50
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		1/8 (12.5%)		0/5 (0%)
Cardiac disorders
Death	1/8 (12.5%)	1	1/8 (12.5%)	1	0/5 (0%)	0
Other (Not Including Serious) Adverse Events
	Micafungin (M) 100		Micafungin (M) 200		Caspofungin (C) 50
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/5 (0%)

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.