Febrile NeutropeniaPhase 4NCT01401010
Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients
A Phase 4 study testing Doripenem in people with Febrile Neutropenia, run by Gary E. Stein, Pharm.D. at 1 site in United States.
Trial summary
Primary: To determine the serum pharmacokinetics (PK) of doripenem in febrile neutropenic patients. Secondary: Monte Carlo Simulations Tested Against Various Gram-negative Isolates and Reported as Probability of Target Attainment (40% Time (fT)> minimum inhibitory concentration (MIC)) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Febrile Neutropenia
- What is being tested?
- Doripenem
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2010to Feb 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult neutropenic (< 500 cells) patients who are febrile
Who cannot join
- Patients with Creatinine Clearance < 30 ml/min or allergy to carbapenems will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients With Possible Bacterial Infection
Primary: To determine the serum pharmacokinetics (PK) of doripenem in febrile neutropenic patients.
Secondary: Monte Carlo Simulations Tested Against Various Gram-negative Isolates and Reported as Probability of Target Attainment (40% Time (fT)> minimum inhibitory concentration (MIC))
Read the detailed description
Background: Doripenem is a group 2 carbapenem with enhanced in vitro activity against Gram-negative bacteria including Pseudomonas aeruginosa. Currently, there is a paucity of pharmacokinetic/pharmacodynamic data on doripenem in patients with febrile neutropenia.
Objectives: To conduct a pharmacokinetic and safety evaluation of two doses of doripenem in febrile neutropenic patients and provide probability estimates of attaining effective drug exposure against common Gram-negative pathogens.
Methods: We obtained multiple blood samples from 12 adult patients with febrile neutropenia who were receiving either 500 mg or 1000 mg of doripenem IV over 4-hours every 8 hours. Following at least 2 doses, serum concentrations were measured in each subject at 1, 4, 6 and 8 hours after initiation of a dose by a validated HPLC assay. The derived pharmacokinetic (PK) parameters from these serum levels were utilized to perform a 5000 patient Monte Carlo simulation against bacteria with minimal inhibitory concentrations (MICs) of 0.008 to 64 mg/L to determine probability estimates of time of free drug concentration > MIC (fT>MIC).
Results: The mean PK parameters in these patients were a volume of distribution (Vd) of 43.9L, an elimination rate constant (k) of 0.37 hr -1, a total clearance (Cl) of 14.4 L/h, and an area under the concentration-time curve (AUC) of 57.6 mg∙h/L. An optimal probability of target attainment (40% fT>MIC) of 90% was obtained against bacteria with MICs ≤ 2.0 and ≤ 4.0 mg/L with 500 mg and 1000 mg doses, respectively. Adverse events associated with doripenem were not observed in these patients.
Conclusions: The findings from this analysis of doripenem suggest that higher doses as well as prolonged infusions may be necessary to optimally treat selected Gram-negative bacteria (eg. Pseudomonas aeruginosa) in patients with febrile neutropenia
- Conditions
- Febrile Neutropenia
- Being tested
- Doripenem
- Keywords
- neutropenia, doripenem
- Medical subject headings
- Febrile Neutropenia, Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoripenemDrug
Also called Doribac
500 mg every 8 hours
doripenemDrug
Also called Doribac
1000 mg every 8 hours
| Study group | Role | What they receive |
|---|---|---|
| Doripenem 500 mg | Active comparator | pharmacokinetics/pharmacodynamics Receives: Drug: Doripenem |
| Doripenem 1000 mg | Active comparator | pharmacokinetics/pharmacodynamics Receives: Drug: doripenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean (SD) Doripenem Pharmacokinetic Volume of Distribution Parameter in Febrile Neutropenic Patients
To determine the serum pharmacokinetic volume of distribution of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Measured: 1, 4, 6, 8 hours after at least two doses of drug
Mean (SD) Doripenem Pharmacokinetic (PK) Elimination Rate Constant Parameter in Febrile Neutropenic Patients
To determine the serum pharmacokinetic elimination rate constant of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Measured: 1, 4, 6, 8 hours after at least two doses of drug
Mean (SD) Doripenem Pharmacokinetic (PK) Half Life Parameter in Febrile Neutropenic Patients
To determine the serum pharmacokinetic half life of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Measured: 1, 4, 6, 8 hours after at least two doses of drug
Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Febrile Neutropenic Patients
To determine the serum pharmacokinetic clearance of drug of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Measured: 1, 4, 6, 8 hours after at least two doses of drug
Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Febrile Neutropenic Patients
To determine the serum pharmacokinetic area under serum curve of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Measured: 1, 4, 6, 8 hours after at least two doses of drug
Secondary outcomes (1)
Monte Carlo Simulations Tested Against Various Gram-negative Isolates and Reported as Probability of Target Attainment (40% Time (fT) > Minimum Inhibitory Concentrations (MIC))
Following determination of pharmacokinetic (PK) parameters from patients with febrile neutropenia, Monte Carlo simulations were then conducted to determine time of serum concentrations above the MIC (40% of the time) against Gram-negative isolates.
These Gram-negative isolates had a range of minimum inhibitory concentrations (MIC) to Doripenem.
Measured: 1, 4, 6, 8 hours after an infusion of doripenem to determine the PK parameters
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2011 (estimated)
- Study startAug 2010
- Primary completionFeb 2012
- Study completionFeb 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Febrile NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gary E. Stein, Pharm.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gary E. Stein, Pharm.D., Michigan State University
- Investigators
- Gary Stein, PharmD, Principal investigator, Michigan State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01401010
- Sponsor's protocol ID
- DORIBAC4006a
- Status last verified
- Oct 2015
- First submitted
- 14 Jul 2011
- Last updated
- 14 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients With Possible Bacterial Infection
- ClinicalTrials.gov ID
- NCT01401010
- Acronym / sponsor ID
- DORIBAC4006a
- Conditions
- Febrile Neutropenia
- Keywords
- neutropenia, doripenem
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Gary E. Stein, Pharm.D.University, hospital or other
- Study start
- Aug 2010
- Primary completion
- Feb 2012 (actual)
- Study completion
- Feb 2012 (actual)
- First posted
- 25 Jul 2011 (estimated)
- Results
- Posted 5 Jun 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary: To determine the serum pharmacokinetics (PK) of doripenem in febrile neutropenic patients.
Secondary: Monte Carlo Simulations Tested Against Various Gram-negative Isolates and Reported as Probability of Target Attainment (40% Time (fT)> minimum inhibitory concentration (MIC))
Detailed description
Background: Doripenem is a group 2 carbapenem with enhanced in vitro activity against Gram-negative bacteria including Pseudomonas aeruginosa. Currently, there is a paucity of pharmacokinetic/pharmacodynamic data on doripenem in patients with febrile neutropenia.
Objectives: To conduct a pharmacokinetic and safety evaluation of two doses of doripenem in febrile neutropenic patients and provide probability estimates of attaining effective drug exposure against common Gram-negative pathogens.
Methods: We obtained multiple blood samples from 12 adult patients with febrile neutropenia who were receiving either 500 mg or 1000 mg of doripenem IV over 4-hours every 8 hours. Following at least 2 doses, serum concentrations were measured in each subject at 1, 4, 6 and 8 hours after initiation of a dose by a validated HPLC assay. The derived pharmacokinetic (PK) parameters from these serum levels were utilized to perform a 5000 patient Monte Carlo simulation against bacteria with minimal inhibitory concentrations (MICs) of 0.008 to 64 mg/L to determine probability estimates of time of free drug concentration > MIC (fT>MIC).
Results: The mean PK parameters in these patients were a volume of distribution (Vd) of 43.9L, an elimination rate constant (k) of 0.37 hr -1, a total clearance (Cl) of 14.4 L/h, and an area under the concentration-time curve (AUC) of 57.6 mg∙h/L. An optimal probability of target attainment (40% fT>MIC) of 90% was obtained against bacteria with MICs ≤ 2.0 and ≤ 4.0 mg/L with 500 mg and 1000 mg doses, respectively. Adverse events associated with doripenem were not observed in these patients.
Conclusions: The findings from this analysis of doripenem suggest that higher doses as well as prolonged infusions may be necessary to optimally treat selected Gram-negative bacteria (eg. Pseudomonas aeruginosa) in patients with febrile neutropenia
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Doripenem 500 mg | Active comparator | Drug: Doripenempharmacokinetics/pharmacodynamics |
| Doripenem 1000 mg | Active comparator | Drug: doripenempharmacokinetics/pharmacodynamics |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- adult neutropenic (< 500 cells) patients who are febrile
Key exclusion criteria (1 listed)
- Patients with Creatinine Clearance < 30 ml/min or allergy to carbapenems will be excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DoripenemAlso: Doribac500 mg every 8 hours | Drug | Doripenem 500 mg |
| doripenemAlso: Doribac1000 mg every 8 hours | Drug | Doripenem 1000 mg |
Primary outcome
Mean (SD) Doripenem Pharmacokinetic Volume of Distribution Parameter in Febrile Neutropenic Patients
Time frame: 1, 4, 6, 8 hours after at least two doses of drug
To determine the serum pharmacokinetic volume of distribution of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Mean (SD) Doripenem Pharmacokinetic (PK) Elimination Rate Constant Parameter in Febrile Neutropenic Patients
Time frame: 1, 4, 6, 8 hours after at least two doses of drug
To determine the serum pharmacokinetic elimination rate constant of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Mean (SD) Doripenem Pharmacokinetic (PK) Half Life Parameter in Febrile Neutropenic Patients
Time frame: 1, 4, 6, 8 hours after at least two doses of drug
To determine the serum pharmacokinetic half life of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Mean (SD) Doripenem Pharmacokinetic (PK) Clearance of Drug Parameter in Febrile Neutropenic Patients
Time frame: 1, 4, 6, 8 hours after at least two doses of drug
To determine the serum pharmacokinetic clearance of drug of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
Mean (SD) Doripenem Pharmacokinetic (PK) Area Under Serum Curve (mg*h/L) Parameter in Febrile Neutropenic Patients
Time frame: 1, 4, 6, 8 hours after at least two doses of drug
To determine the serum pharmacokinetic area under serum curve of doripenem in febrile neutropenic patients with pneumonia. We obtained blood at 1, 4, 6, 8 hours after at least two doses of doripenem and measured these levels (mg/L)by HPLC assay.
1 secondary outcome
Monte Carlo Simulations Tested Against Various Gram-negative Isolates and Reported as Probability of Target Attainment (40% Time (fT) > Minimum Inhibitory Concentrations (MIC))
Time frame: 1, 4, 6, 8 hours after an infusion of doripenem to determine the PK parameters
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Stein, PharmD principal investigator
Michigan State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doripenem in people with Febrile Neutropenia, run by Gary E. Stein, Pharm.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean (SD) Doripenem Pharmacokinetic Volume of Distribution Parameter in Febrile Neutropenic Patients (time frame: 1, 4, 6, 8 hours after at least two doses of drug). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2015.