Study to Evaluate Daptomycin Given During Dialysis and After Dialysis

• ClinicalTrials.gov Identifier: NCT00882557
• Recruitment Status: Completed
• First Posted: April 16, 2009
• Results First Posted: October 25, 2011
• Last Update Posted: February 6, 2018
• Sponsor: Cubist Pharmaceuticals LLC
• Information provided by (Responsible Party): Cubist Pharmaceuticals LLC

Study Description

Brief Summary:

The purpose of this study is to determine whether daptomycin at a higher dose given during the last 30 minutes of a dialysis session is equal to a lower dose of daptomycin given after a dialysis session.

Condition or disease	Intervention/treatment	Phase
End-stage Renal Disease; Renal Failure Chronic Requiring Hemodialysis	Drug: daptomycin	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Randomized, Crossover-design Study to Evaluate the Pharmacokinetics and Safety of Daptomycin Administered at 9 mg/kg During and 6 mg/kg After Hemodialysis
• Actual Study Start Date: April 29, 2009
• Actual Primary Completion Date: July 17, 2009
• Actual Study Completion Date: July 17, 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: A; 9 mg/kg of daptomycin administered during the last 30 minutes of a hemodialysis session.	Drug: daptomycin; intradialytic: 9 mg/kg during the last 30 minutes of dialysis; Other Name: Cubicin
Experimental: B; Post dialysis dosing	Drug: daptomycin; 6 mg/kg administered after a hemodialysis session; Other Name: Cubicin

Outcome Measures

Primary Outcome Measures :

1. Evaluation of Area Under the Curve From Time 0 to Infinity [ Time Frame: Within 30 minutes prior to the start of the infusion, mid-infusion, and end of the infusion; at 1, 2, 4, 6, 9, 24, and 48 hours after the end of the infusion; and just prior to the next hemodialysis session (i.e., 68 hours post-infusion) ]
   Area under the plasma concentration versus time curve from time 0 to infinity for daptomycin doses

Secondary Outcome Measures :

1. Treatment-emergent Adverse Events [ Time Frame: Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15). ]
   Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests.

Other Outcome Measures:

1. Maximum Plasma Concentration [ Time Frame: Within 30 minutes prior to the start of the infusion, mid-infusion, and end of the infusion; at 1, 2, 4, 6, 9, 24, and 48 hours after the end of the infusion; and just prior to the next hemodialysis session (i.e., 68 hours post-infusion) ]
   Maximum plasma concentration over the entire sampling phase directly obtained from the experimental plasma concentration time data, without interpolation.
2. Time to Maximum Concentration [ Time Frame: Up to 68 hours post dose ]
   Sampling time at which maximum plasma concentration occurred, obtained directly from the experimental plasma concentration time data, without interpolation.
3. Half-life [ Time Frame: Up to 68 hours post dose ]
   Apparent terminal half-life.
4. Clearance of Daptomycin [ Time Frame: Up to 68 hours post dose ]
   Plasma clearance is dose (µg) divided by area under the concentration versus time curve from time 0 to last quantifiable concentration time.
5. Volume of Distribution [ Time Frame: Up to 68 hours post dose ]
   Volume of distribution at steady state (mL) calculated as the product of clearance and mean residence time.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Written informed consent prior to any study-related procedure not part of normal medical care;
• Male or female ≥ 18 years of age;
• If female of childbearing potential; willing to practice reliable birth control measures during study treatment and for at least 28 days after study completion, not lactating or pregnant, and has a documented negative pregnancy test result within 24 hours prior to study medication administration;
• End-stage renal disease on stable (for at least 2 weeks) hemodialysis regimen, three times weekly using high-flux membranes;
• Functioning hemodialysis access (for example, graft or fistula);
• Considered to be in appropriate health for study entry by the Investigator (for example, no acute, debilitating medical problems) and appropriate candidate for completing study treatment;
• If taking concomitant medications, subject must be on a relatively stable dose for at least two weeks prior to study drug administration.

Exclusion Criteria:

• Received an investigational drug (including experimental biologic agents) within 30 days of study drug administration;
• Has received any dose of daptomycin within 7 days prior to study drug administration;
• Known to be allergic or intolerant to daptomycin;
• Evidence of active ongoing infection;
• Known human immunodeficiency virus (HIV) infection with CD4 count ≤ 200 cells/mm3;
• Active illicit drug use or alcohol abuse;
• Myocardial infarction within last 6 months;
• Subject with a history of muscular disease (for example, polymyositis, muscular dystrophy);
• Subject with a history of neurological disease (for example, Guillain Barré, multiple sclerosis), except stroke > 6 months prior to study entry;
• Intramuscular injection within 7 days of study drug administration;
• Body mass index (BMI) ≤ 18.5 or ≥ 40 kg/m2 (BMI = weight [kg]/height [m2]);
• WBC ≥ 12, 000 cells/mm3 or ≤ 2500 cells/ mm3;
• Neutropenic subject with absolute neutrophil count ≤ 500 cells/mm3;
• Baseline CPK values ≥ 3X ULN (upper limit of normal);
• Alanine aminotransferase (ALT) > 5XULN;
• Aspartate aminotransferase (AST) > 5XULN;
• Hemoglobin ≤ 9 gm/dL;
• Is considered unlikely to comply with study procedures or to return for scheduled post-treatment evaluations;
• History of rhabdomyolysis.

Contacts and Locations

Locations

United States, California

West Coast Clinical Trials

Cypress, California, United States, 90630

United States, Minnesota

DaVita Clinical Research

Minneapolis, Minnesota, United States, 55404

Sponsors and Collaborators

Cubist Pharmaceuticals LLC

Investigators

• Study Director: Alistair Wheeler, MD, MFPM; Cubist Pharmaceuticals LLC

More Information

• Responsible Party: Cubist Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT00882557
• Other Study ID Numbers: 3009-027; DAP-RENID-08-06 ( Other Identifier: Cubist Study Number )
• First Posted: April 16, 2009
• Results First Posted: October 25, 2011
• Last Update Posted: February 6, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

Keywords provided by Cubist Pharmaceuticals LLC:

End-stage renal disease; hemodialysis; chronic renal failure

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency; Urologic Diseases; Renal Insufficiency, Chronic; Daptomycin; Anti-Bacterial Agents; Anti-Infective Agents