Pharmacokinetics and Safety of Tigecycline in the Treatment of Clostridium Difficile Associated Diarrhea (CDAD)

• Sponsor: Gary E. Stein, Pharm.D. (Other)
• Overall Status: Completed
• CT.gov ID: NCT01401023
• Collaborator: Pfizer (Industry)
• Enrollment: 10
• Locations: 2
• Arm: 1
• Duration (Months): 24
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a prospective, non-comparative, interventional, observational pilot study of the safety and pharmacokinetics of intravenous (IV) tigecycline in conjunction with standard oral therapy in patients with known mild to severe confirmed Clostridium difficile associated diarrhea (CDAD).

Condition or Disease	Intervention/Treatment	Phase
Diarrhea; Clostridium Difficile	Drug: Tigecycline	N/A

Detailed Description

The intervention is adding Tigecycline (standard doses) to standard oral therapy for CDAD. Patients will then be observed for clinical outcomes and relapse of CDAD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pharmacokinetics and Safety of Tigecycline in the Treatment of Clostridium Difficile Associated Diarrhea (CDAD)
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clostridium difficile Patient Open non-comparative trial	Drug: Tigecycline; : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 milligram loading dose followed by 50 milligrams every 12 hours) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.; Other Names: Tygacil

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics of Tigecycline Along With Standard Treatments for Clostridium Difficile [day 3 of treatment]

   Serum levels of tigecycline

2. Mean (SD) Minimun Inhibitory Concentration of Tigecycline of Clostridium Difficile Isolates [day 1 stool sample]

3. Mean (SD) Serum Tigecycline Concentration Level [day 3 of tigecycline therapy]

   Blood samples were obtained from each patient at the end of a dosing interval (trough concentration) on day 3 of tigecycline therapy. Serum concentrations were determined with the use of a validated high-performance liquid chromatography assay.

4. Mean (SD) Stool Tigecycline Concentration Level [day 3 of tigecycline therapy]

   Fecal samples were obtained from each patient at the end of a dosing interval (trough concentration) on day 3 of tigecycline therapy. Fecal concentrations were determined with the use of a validated high-performance liquid chromatography assay

5. Pharmacokinetics of Tigecycline Along With Standard Treatments for Clostridium Difficile [day 3 of treatment]

   Stool levels of tigecycline

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• non pregnant adults (≥18 years old) with a diagnosis of mild to severe CDAD (initial or recurrent) by positive C. difficile toxin assay along with clinical symptoms (watery stools, fever, abdominal pain). Patients will receive a minimum of 3 days of tigecycline.

Exclusion Criteria:

• pregnant patients

• allergy to tetracycline (or tigecycline) antibiotics or patients with life-threatening illness.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Michigan State University	East Lansing	Michigan	United States	48824
2	Sparrow Hosptial	Lansing	Michigan	United States	48912

Sponsors and Collaborators

• Gary E. Stein, Pharm.D.
• Pfizer

Investigators

• Principal Investigator: Gary Stein, PharmD, Michigan State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gary E. Stein, Pharm.D., Professor of Medicine and Pharmacology, Michigan State University
• ClinicalTrials.gov Identifier: NCT01401023
• Other Study ID Numbers: WS1481739
• First Posted: Jul 25, 2011
• Last Update Posted: Jul 10, 2018
• Last Verified: Jun 1, 2018

• Additional relevant MeSH terms: Clostridium Infections; Diarrhea; Tigecycline

Study Results

Participant Flow

Recruitment Details	Subjects were inpatients (Sparrow Hospital) with Clostridium difficile who were treated with tigecycline. Referral base was infectious disease consultations. The first patient was enrolled 11-23-2011 and the last 9-13-2012.

Arm/Group Title	Clostridium Difficile Patient
Arm/Group Description	Open non-comparative trial Tygacil : : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 mg LD followed by 50 mg Q12h) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.
Period Title: Overall Study
STARTED	10
COMPLETED	10
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	CDAD Patient
Arm/Group Description	Open non-comparative trial Tygacil : : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 mg LD followed by 50 mg Q12h) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.
Overall Participants	10
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	7 70%
>=65 years	3 30%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (16)
Sex: Female, Male (Count of Participants)
Female	4 40%
Male	6 60%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics of Tigecycline Along With Standard Treatments for Clostridium Difficile
Description	Serum levels of tigecycline
Time Frame	day 3 of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clostridium Difficile Patient
Arm/Group Description	Open non-comparative trial Tigecycline: : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 milligram loading dose followed by 50 milligrams every 12 hours) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.
Measure Participants	10
Mean (Standard Deviation) [milligrams/liter]	0.18 (0.14)

2. Primary Outcome

Title	Mean (SD) Minimun Inhibitory Concentration of Tigecycline of Clostridium Difficile Isolates
Time Frame	day 1 stool sample

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clostridium Difficile Patient
Arm/Group Description	Open non-comparative trial Tygacil : : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 mg LD followed by 50 mg Q12h) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.
Measure Participants	10
Mean (Standard Deviation) [milligram/liter]	0.15 (0.06)

3. Primary Outcome

Title	Mean (SD) Serum Tigecycline Concentration Level
Description	Blood samples were obtained from each patient at the end of a dosing interval (trough concentration) on day 3 of tigecycline therapy. Serum concentrations were determined with the use of a validated high-performance liquid chromatography assay.
Time Frame	day 3 of tigecycline therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clostridium Difficile Patient
Arm/Group Description	Open non-comparative trial Tygacil : : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 mg LD followed by 50 mg Q12h) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.
Measure Participants	10
Mean (Standard Deviation) [milligram/liter]	0.18 (0.14)

4. Primary Outcome

Title	Mean (SD) Stool Tigecycline Concentration Level
Description	Fecal samples were obtained from each patient at the end of a dosing interval (trough concentration) on day 3 of tigecycline therapy. Fecal concentrations were determined with the use of a validated high-performance liquid chromatography assay
Time Frame	day 3 of tigecycline therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clostridium Difficile Patient
Arm/Group Description	Open non-comparative trial Tygacil : : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 mg LD followed by 50 mg Q12h) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.
Measure Participants	10
Mean (Standard Deviation) [micrograms/gram]	17.8 (23.8)

5. Primary Outcome

Title	Pharmacokinetics of Tigecycline Along With Standard Treatments for Clostridium Difficile
Description	Stool levels of tigecycline
Time Frame	day 3 of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clostridium Difficile Patient
Arm/Group Description	Open non comparative trial
Measure Participants	10
Mean (Standard Deviation) [micrograms/gram]	17.8 (23.8)

Adverse Events

Arm/Group Title	CDAD Patient
Arm/Group Description	Open non-comparative trial Tygacil : : Standard treatment doses of oral antibiotics (vancomycin or metronidazole) for CDAD along with IV tigecycline (100 mg LD followed by 50 mg Q12h) will be given to patients during their hospitalization (usually 7-14 days). Patients well enough to go home will receive only oral therapy.
All Cause Mortality
	CDAD Patient
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	CDAD Patient
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Gastrointestinal disorders
Recurrence of Clostridium difficile infection	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	CDAD Patient
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Gastrointestinal disorders
Nausea	2/10 (20%)	2

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.