Micafungin Pharmacokinetics in Obese Patients (MICADO)

• ClinicalTrials.gov Identifier: NCT03102658
• Recruitment Status: Completed
• First Posted: April 6, 2017
• Last Update Posted: October 19, 2020
• Sponsor: Radboud University
• Collaborators: St. Antonius Hospital; Astellas Pharma Inc
• Information provided by (Responsible Party): Radboud University

Tracking Information

• First Submitted Date: January 5, 2017
• First Posted Date: April 6, 2017
• Last Update Posted Date: October 19, 2020
• Actual Study Start Date: January 2017
• Actual Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2017)

Micafungin concentration in plasma to examen the area under the plasma concentration versus time curve (AUC0-48) [ Time Frame: Up to 3 months ]

The exposure to micafungin in obese will be compared with that in non-obese subjects.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 30, 2017)

Long-term exposure to micafungin after repeated dose [ Time Frame: Up to 6 months ]

Predict long-term exposure (AUC0-tau) after repeated dosing by popPK modeling and simulation.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Micafungin Pharmacokinetics in Obese Patients
• Official Title: Micafungin (Mycamine®) Pharmacokinetics Given as a Single Intravenous Dose to Obese Patients (MICADO).

Brief Summary

Because micafungin is generally well tolerated and appears to have limited interaction with other drugs, it is a potential important agent in the treatment of invasive fungal infections. Although micafungin is approved for the treatment of invasive candidiasis, dosing guidelines for micafungin in (morbidly) obese patients are not available. Subsequently, the pharmacokinetic profile of micafungin (as well as other echinocandins) in this specific patient population is still largely unknown.

To build a valid pharmacokinetic model, obese patients with a BMI ≥ 40 undergoing endoscopic gastric bypass surgery will receive a single dose of 100 mg or 200mg micafungin (besides standard anti-bacterial prophylaxis) and samples for a pharmacokinetic curve will be taken. These PK-values can then be compared to the PK in a normal-weight group which will receive 100mg micafungin

• Detailed Description: Obese patients with a BMI ≥ 40 kg/m2 undergoing endoscopic gastric bypass surgery will receive a 100 mg or a 200mg dose of micafungin. A PK curve will be determined after administration at t=0.5, 0.95, 1.25, 1.5, 2, 4, 8, 12, 24, and (if feasible) 48 hours post infusion. Blood samples (4 mL) on PK days will be taken to obtain at least 2.0 mL of plasma.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Morbid Obesity

Intervention

Drug: Micafungin

Administration of study drug

Other Name: Mycamine

Study Arms

• Experimental: Obese subjects 100mg
  8 subjects with a BMI>40kg/m2 will receive 100mg Micafungin
  Intervention: Drug: Micafungin
• Active Comparator: Obese subjects 200mg
  8 subjects with a BMI>40kg/m2 will receive 200mg Micafungin
  Intervention: Drug: Micafungin
• Active Comparator: non-obese subjects
  8 non obese subjects with a BMI >18.5 and <25 kg/m2 will receive 100mg Micafungin
  Intervention: Drug: Micafungin

• Publications *: Wasmann RE, Smit C, Ter Heine R, Koele SE, van Dongen EPH, Wiezer RMJ, Burger DM, Knibbe CAJ, Brüggemann RJM. Pharmacokinetics and probability of target attainment for micafungin in normal-weight and morbidly obese adults. J Antimicrob Chemother. 2019 Apr 1;74(4):978-985. doi: 10.1093/jac/dky554.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 30, 2017): 24
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 2017
• Actual Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

1. Subjects BMI:

   • obese groups: subject must have a BMI > 40 kg/m2 at the time of inclusion,
   • non-obese group: subject must have a BMI ≥18.5 and < 25kg/m2 at the time of inclusion.
2. Subject is at least 18 of age on the day of screening and not older than 65 years of age on the day of dosing;
3. If a woman, is neither pregnant nor able to become pregnant and is not nursing an infant;

4. Subject is able and willing to sign the Informed Consent before screening evaluations.

   For the non-obese subjects the following additional exclusion criteria apply:

5. Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, hematology and urinalysis testing within 4 weeks prior to study drug administration. Results of biochemistry, hematology and urinalysis testing should be within the laboratory's reference ranges. If laboratory results are not within the reference ranges, the subject is included based on the investigator's judgment that the observed deviations are not clinically relevant. This should be clearly recorded;
6. Subject has a normal blood pressure and pulse rate, determined by the investigator;
7. Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to study drug administration.

Exclusion Criteria:

1. Documented history of sensitivity to medicinal products or excipients similar to those found in the micafungin preparation;
2. History of, or known abuse of drugs, alcohol or solvents (up until a maximum of three months before study drug administration);
3. Inability to understand the nature of the trial and the procedures required;

4. Use of medication that has known interaction with study drug as determined by the investigator up to 4 weeks prior to study drug administration.

   For the non-obese subjects the following additional exclusion criteria apply:

5. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs or clinical laboratory determinations;
6. Clinical relevant liver enzymes (alkaline phosphatase, alanine aminotransferase, aspartate transaminase) abnormalities at screening;
7. Donation of blood or plasma to a blood bank or in a clinical study (except a screening visit) within 4 weeks prior to study drug administration;
8. Blood transfusion within 8 weeks prior to study drug administration;
9. Inability to be venipunctured and/or tolerate venous access;
10. Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal disorders, hepatic disorders (Child-Pugh B or C), hormonal disorders (especially diabetes mellitus), coagulation disorders;
11. Any other sound medical, psychiatric and/or social reason as determined by the investigator.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT03102658
• Other Study ID Numbers: UMCN-AKF 16.02
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Radboud University
• Study Sponsor: Radboud University

Collaborators

• St. Antonius Hospital
• Astellas Pharma Inc

Investigators

• Principal Investigator: Roger Brüggemann, PharmD, PhD; Radboud University

• PRS Account: Radboud University
• Verification Date: September 2017