Study of Daptomycin Safety and Efficacy for Complicated Skin and Skin Structure Infections (cSSSI) and Bacteremia in Renal Impairment

NCT01104662 | Terminated Phase 4 Results

• 2 other identifiers: 3009-022DAP-RENSE-08-05
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 10

Brief Summary

This is a multicenter, randomized, evaluator-blinded, comparator-controlled study. Participants were to be randomized (1:1) to daptomycin or comparator, stratified by degree of renal impairment (creatinine clearance \[CLcr\] 30 - 50 milliliters per minute \[mL/min\] \[moderate impairment\] and \<30 mL/min \[severe impairment\]) and by type of infection (bacteremia and complicated skin and skin structure infections \[cSSSI\]) to create 4 cohorts defined as follows:

• Cohort 1: Bacteremia and CLcr \<30 mL/min
• Cohort 2: Bacteremia and CLcr 30 - 50 mL/min
• Cohort 3: cSSSI and CLcr \<30 mL/min
• Cohort 4: cSSSI and CLcr 30 - 50 mL/min Participants will be treated and evaluated for safety and microbiological and clinical efficacy in accordance with their type of infection and degree of renal impairment. Peak and trough samples will be collected to assess exposure to daptomycin for participants on Day 1 and following the 5th dose.

Conditions

Complicated Skin and Skin Structure Infections; S. Aureus Bacteremia; Renal Impairment

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations Through End of Therapy/Early Termination (EOT/ET)

  The number of participants with CPK elevations of \>500 units per liter (U/L) above baseline at any time from Day 1 through the EOT/ET visit are presented.

  Baseline through EOT/ET

Secondary Outcomes (1)

• Overall Therapeutic Outcome at Test of Cure (TOC)/Safety Visit

  Baseline through TOC/Safety Visit

Study Arms (8)

Daptomycin, Bacteremia, Severe Renal Impairment

EXPERIMENTAL

Cohort 1. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with Creatinine Clearance (CLcr) below 30 milliliters per minute (mL/min) and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 14 to 42 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 14 to 42 days based on disease resolution or Investigator discretion.

Drug: Daptomycin

Vancomycin or SSP, Bacteremia, Severe Renal Impairment

ACTIVE COMPARATOR

Cohort 1. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by Methicillin-Susceptible Staphylococcus Aureus (MSSA) could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered intravenously (IV) until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.

Drug: Vancomycin; Drug: Semi-Synthetic Penicillin

Daptomycin, Bacteremia, Moderate Renal Impairment

EXPERIMENTAL

Cohort 2. Daptomycin was given intravenously 6 milligrams per kilogram (mg/kg) per administration. For bacteremia participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 14 to 42 days based on disease resolution or Investigator discretion.

Drug: Daptomycin

Vancomycin or SSP , Bacteremia, Moderate Renal Impairment

ACTIVE COMPARATOR

Cohort 2. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered IV until end of antibiotic therapy for bacteremia or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.

Drug: Vancomycin; Drug: Semi-Synthetic Penicillin

Daptomycin, cSSSI, Severe Renal Impairment

EXPERIMENTAL

Cohort 3. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr below 30 mL/min and currently receiving hemodialysis, daptomycin was administered immediately following each hemodialysis session (3 per week) for 7 to 14 days based on disease resolution or Investigator discretion. For participants not receiving dialysis, daptomycin was administered every 48 hours for 7 to 14 days based on disease resolution or Investigator discretion.

Drug: Daptomycin

Vancomycin or SSP , cSSSI, Severe Renal Impairment

ACTIVE COMPARATOR

Cohort 3. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.

Drug: Vancomycin; Drug: Semi-Synthetic Penicillin

Daptomycin, cSSSI, Moderate Renal Impairment

EXPERIMENTAL

Cohort 4. Daptomycin was given intravenously 4 milligrams per kilogram (mg/kg) per administration. For cSSSI participants with CLcr values between 30 and 50 mL/min not receiving dialysis, daptomycin was administered every 24 hours for 7 to 14 days based on disease resolution or Investigator discretion.

Drug: Daptomycin

Vancomycin or SSP , cSSSI, Moderate Renal Impairment

ACTIVE COMPARATOR

Cohort 4. Participants randomized to the comparator therapy group received vancomycin or penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin). Investigators were allowed to select an agent based on local availability and normal treatment practices. Participants randomized to comparator subsequently found to have an infection caused by MSSA could have switched from vancomycin to penicillinase-resistant penicillin (nafcillin, oxacillin, or cloxacillin) at the Investigator's discretion. All treatments were dosed per Investigator's discretion and were administered IV until end of antibiotic therapy for cSSSI or until hospital discharge, whichever occurred first. Investigators treated participants according to their usual decision-making and discretion.

Drug: Vancomycin; Drug: Semi-Synthetic Penicillin

Interventions

Vancomycin DRUG

Vancomycin or SSP , Bacteremia, Moderate Renal Impairment; Vancomycin or SSP , cSSSI, Moderate Renal Impairment; Vancomycin or SSP , cSSSI, Severe Renal Impairment; Vancomycin or SSP, Bacteremia, Severe Renal Impairment

Daptomycin DRUG

Also known as: Cubicin

Daptomycin, Bacteremia, Moderate Renal Impairment; Daptomycin, Bacteremia, Severe Renal Impairment; Daptomycin, cSSSI, Moderate Renal Impairment; Daptomycin, cSSSI, Severe Renal Impairment

Semi-Synthetic Penicillin DRUG

Also known as: SSP, nafcillin, oxacillin, cloxacillin

Vancomycin or SSP , Bacteremia, Moderate Renal Impairment; Vancomycin or SSP , cSSSI, Moderate Renal Impairment; Vancomycin or SSP , cSSSI, Severe Renal Impairment; Vancomycin or SSP, Bacteremia, Severe Renal Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Male or female ≥18 years of age
• Diagnosis of cSSSI or Staphylococcus aureus (S. aureus) bacteremia
• Renal impairment of CLcr of 30 - 50 mL/min or CLcr \<30 mL/min per Cockcroft-Gault equation using actual body weight
• Functioning hemodialysis access and on stable regimen for those receiving dialysis
• In appropriate health for the study with no acute or chronic illnesses that could adversely impact safety or ability to complete the study
• Presence of a wound infection, major abscess, severe carbunculosis, infected ulcers, dialysis access site infection, or other type of infection in presence of complicating factor
• At least 3 of the following symptoms, signs, or laboratory values of a skin infection: elevated temperature; elevated white blood cell (WBC) count; pain; tenderness; swelling; erythema greater than 1 centimeter (cm) beyond wound edge; induration; pus formation
• Evidence of a Gram-positive infecting pathogen as indicated by positive Gram stain or culture obtained within 96 hours prior to study drug administration
• Infection of sufficient severity to require parenteral antimicrobial therapy
• Documented S. aureus bacteremia defined as at least one positive blood culture for S. aureus obtained within 96 hours prior to the first dose of study medication

You may not qualify if:

• Pregnant or lactating females, or unwilling to practice barrier methods of birth control
• Received an investigational drug (including experimental biologic agents) within 30 days of study entry
• Unable to discontinue use of HMG-CoA reductase inhibitor therapy while on study
• Known allergy or intolerance to daptomycin, penicillin, or vancomycin
• Active intravenous (IV) drug abuse
• Confirmed or suspected osteomyelitis, septic arthritis, meningitis, epidural abscess, intra-abdominal infection, pneumonia, or infective endocarditis
• Required use of non-study systemic antibacterial agent with activity against target pathogen
• History of muscular disease
• Neurological disease except stroke \>6 months prior to study entry
• Intramuscular injection within 7 days of study drug administration
• Moribund clinical condition (high likelihood of death during next 3 days)
• Shock or hypotension (supine systolic blood pressure \<80 millimeters of mercury \[mmHg\])
• Body mass index (BMI) \<18 or \>40 kilograms per meter squared (kg/m\^2) \[BMI = weight (kg)/height (m\^2)\]
• Known human immunodeficiency virus (HIV) infection with CD4 count ≤200 cells/millimeter (mm)\^3
• Neutropenic participants with an absolute neutrophil count ≤500 cells/mm\^3

Sponsors & Collaborators

• Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (10)

Unknown Facility

Azusa, California, United States

Location

Unknown Facility

Los Angeles, California, United States

Location

Unknown Facility

Torrance, California, United States

Location

Unknown Facility

Washington D.C., District of Columbia, United States

Location

Unknown Facility

Decatur, Georgia, United States

Location

Unknown Facility

Somers Point, New Jersey, United States

Location

Unknown Facility

Winston-Salem, North Carolina, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

West Reading, Pennsylvania, United States

Location

Unknown Facility

Mission, Texas, United States

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

Vancomycin; Daptomycin; Nafcillin; Oxacillin; Cloxacillin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Vice President, Clinical Research
• Organization: Cubist Pharmaceuticals, Inc.

1.781.860.8660

Study Officials

• Ellie Hershberger, Pharm.D.

  Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2010
• First Posted: April 15, 2010
• Study Start: April 19, 2010
• Primary Completion: June 12, 2012
• Study Completion: June 12, 2012
• Last Updated: September 5, 2018
• Results First Posted: May 13, 2015

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

US (10)