DFA-02 in Patients Undergoing Colorectal Surgery

NCT01496352 | Completed Phase 1 Results DMC

• 1 other identifier: DFA-02-CD-002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

This is a randomized, double-blind, placebo controlled, safety, tolerability, and pharmacokinetic dose escalation Phase II study of DFA-02 in patients undergoing colorectal surgery to evaluate the safety, tolerability and pharmacokinetics of DFA-02.

Conditions

Surgical Site Infection

Keywords

Surgical site infection; Colorectal surgery

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Adverse Events, Laboratory, Physical Examination Changes

  Safety and tolerability measured by number of patients with adverse events or changes in laboratory or physical examination findings from baseline (DFA-02 application during surgery on Day 1) to 30 days after surgery.

  Baseline up to Day 30

• Area Under Curve (AUC)

  Area under the curve (AUC) of plasma gentamicin and vancomycin levels using sparse sampling from baseline (DFA-02 application during surgery on Day 1) to 4 days after surgery

  1, 6, 24, 48 96 hours post-dose

Secondary Outcomes (4)

• Maximal Plasma Concentration (Cmax)

  1, 6, 24, 48, 96 hours post-dose

• Renal Function

  Baseline up to Day 14

• Antibiotic Resistance

  Baseline up to Day 5

• Incidence of Surgical Site Infection

  Up to 30 Days After Surgery

Study Arms (2)

DFA-02

EXPERIMENTAL

Progressive cohorts of 10 subjects (8 active, 2 placebo) receiving 10, 20 , 30 or 40 mL of DFA-02 or matching placebo.

Drug: DFA-02

DFA-02 placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

DFA-02 DRUG

Modified release product containing gentamicin and vancomycin for application at the conclusion of surgery after closure of the fascia and prior to skin closure

DFA-02

Placebo DRUG

DFA-02 placebo

DFA-02 placebo

Eligibility Criteria

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

You may qualify if:

• Males and females 18 years of age or older;
• If female, the patient must be:
• postmenopausal (if amenorrheic for \< 1 year, postmenopausal status must be confirmed by an elevated follicle stimulating hormone \[FSH\] level \> 30 mIU/mL; if amenorrheic for \> 1 year, FSH level not required);
• surgically sterilized (does not have a uterus or has had bilateral tubal ligation); or
• if of child-bearing potential, she must have a negative serum pregnancy test on entry in the study, and agree to use adequate birth control during the study and for 30 days after the administration of study agent. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD);
• BMI 25-40, inclusive;
• Scheduled to undergo nonemergent colorectal surgery involving a laparotomy incision of 7 cm or greater (hand-assisted laparoscopic surgery is allowed). List of eligible procedures: left, right or transverse colectomy, segmental/sleeve left colon resection, total abdominal colectomy with ileorectal anastomosis, total abdominal colectomy with ileostomy, total abdominal proctocolectomy, low anterior resection, sigmoid resection, non-emergent Hartmann's procedure, colotomy with polypectomy distal to hepatic flexure, colostomy takedown through laparotomy (not peristomal) incision, ileo-pouch anal anastomosis, abdominal perineal resection of the rectum;
• Willing and able to give informed consent;
• Available for evaluation from baseline until final evaluation at 30 days post surgery.

You may not qualify if:

• Known history of hypersensitivity to gentamicin or vancomycin, other aminoglycoside antibiotics or the excipients of the study products (soy bean products or sesame oil);
• Emergency surgery (urgent surgery is allowed if informed consent is obtained and the study procedures can be performed);
• Significant concomitant surgical procedure (Note: concomitant appendectomy, cholecystectomy, oophorectomy, and liver biopsy/wedge resection are allowed);
• Prior laparotomy within the last 60 days of this planned procedure;
• Planned second laparotomy or colorectal surgical procedure (e.g. colostomy or ileostomy takedown) within 30 days of this planned first procedure;
• Expectation that a surgical drain will be placed;
• Preoperative sepsis, severe sepsis, or septic shock;
• Abdominal wall infection/surgical site infection from previous laparotomy/laparoscopy or for any reason;
• Active systemic infection or systemic (oral or intravenous) antibiotic therapy within the 1 week prior to the date of surgery other than specified preoperative antimicrobial prophylaxis (Note: single dose antibiotic therapy for dental or other minor procedures is allowed as is the use of oral non-absorbable antibiotics for preoperative bowel decontamination);
• Requirement for gentamicin or vancomycin preoperative antimicrobial prophylaxis (Note: systemic antibiotic therapy within 72 hours after surgery with gentamicin or vancomycin must be avoided and any systemic antibiotic therapy during that time should be discussed with the Coordinating Center PI or Medical Monitor);
• Requirement for concomitant use or use during the 30 days prior to Day 1 of any prescription or OTC drug that would interfere with the study or place the patient at undue risk. Concurrent systemic or topical use of other potentially neurotoxic, nephrotoxic, and/or ototoxic drugs, such as gentamicin, cisplatin, cephaloridine, kanamycin, amikacin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, ethacrynic acid, furosemide, and viomycin, should be avoided;
• Preoperative evaluation suggests an intra-abdominal process that might preclude full closure of the skin;
• Ongoing treatment (e.g. chemotherapy, radiation) for non-colorectal cancer;
• History of significant drug or alcohol abuse within the past year;
• Serum Creatinine \> 1.3 mg/dL

Sponsors & Collaborators

• Dr. Reddy's Laboratories Limited: lead
• Duke Clinical Research Institute: collaborator

Study Sites (5)

Unknown Facility

Florence, Alabama, United States

Location

Unknown Facility

Tampa, Florida, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Bellaire, Texas, United States

Location

Unknown Facility

Temple, Texas, United States

Location

Related Publications (1)

• Bennett-Guerrero E, Minkowitz HS, Segura-Vasi AM, Marcet JE, White JA, Corey GR, Allenby KS. A randomized, double-blind, placebo controlled safety, tolerability, and pharmacokinetic dose escalation study of a gentamicin vancomycin gel in patients undergoing colorectal surgery. Perioper Med (Lond). 2016 Jun 16;5:17. doi: 10.1186/s13741-016-0043-2. eCollection 2016.

  PMID: 27313846 DERIVED

MeSH Terms

Conditions

Surgical Wound Infection

Condition Hierarchy (Ancestors)

Wound Infection; Infections; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Protocol specified cohorts of 10, 20, 30 or 40 mL to be placed after closure of the fascia and prior to skin closure. Experience with 20 and 30 mL dose levels showed that even largest patients would not accommodate 40 mL so that arm was not done.

Results Point of Contact

• Title: Kent Allenby, MD, VP, Drug Development
• Organization: Dr. Reddy's Laboratories, Inc.

kallenby@drreddys.com

609-375-9855

Study Officials

• Kent Allenby, MD

  Dr. Reddy's Laboratories

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2011
• First Posted: December 21, 2011
• Study Start: February 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: June 1, 2013
• Last Updated: September 1, 2014
• Results First Posted: September 1, 2014

Record last verified: 2014-08

Locations

US (5)