Ph1 Study of Valortim and Ciprofloxacin in Humans

This study has suspended participant recruitment.
(On partial hold for clinical investigation into AE and SAE reported.)
Sponsor:
Collaborators:
Medarex
Quintiles
Information provided by:
PharmAthene, Inc.
ClinicalTrials.gov Identifier:
NCT00964561
First received: August 22, 2009
Last updated: August 9, 2010
Last verified: August 2009
  Purpose

The purpose of this study is to evaluate the safety and tolerability of short-term dosing of IV ciprofloxacin when administered concomitantly with IV Valortim in healthy normal human subjects.


Condition Intervention Phase
Anthrax
Drug: Ciprofloxacin and Valortim
Drug: Placebo Antibiotic and Valortim
Other: Placebo Antibiotic and Placebo Valortim
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Phase I, Single Blind, Randomized, Placebo Controlled, Drug Interaction Study of Intravenous (IV) Valortim® and Intravenous (IV) Ciprofloxacin in Healthy, Normal Subjects

Resource links provided by NLM:


Further study details as provided by PharmAthene, Inc.:

Primary Outcome Measures:
  • Determination of changes from baseline for clinical laboratory tests and urinalysis, blood pressure, heart rate, respiratory rate, body temperature, physical examination and ECG [ Time Frame: 134 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluation of PK parameters for IV administration of ciprofloxacin when dosed concomitantly with Valortim [ Time Frame: 134 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 26
Study Start Date: August 2009
Estimated Study Completion Date: July 2010
Estimated Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ciprofloxacin and Valortim
First two subjects to receive treatment arm of Ciprofloxacin and Valortim. Total of sixteen volunteers to be randomized to receive Ciprofloxacin and Valortim.
Drug: Ciprofloxacin and Valortim
Days 1-3 400mg IV Ciprofloxacin BID over 60 minutes. Day 4 20mg/kg Valortim IV over 60 minutes.
Other Name: MDX-1303
Experimental: Placebo Antibiotic and Valortim
Randomized such that four subjects to receive Placebo Antibiotic and Valortim.
Drug: Placebo Antibiotic and Valortim
Days 1-3 20mg/kg IV Normal Saline BID over 60 minutes. Day 4 20mg/kg Valortim IV over 60 minutes.
Other Name: MDX-1303
Experimental: Placebo Antibiotic and Placebo Valortim
Randomized such that 4 subjects to receive Placebo Antibiotic and Placebo Valortim.
Other: Placebo Antibiotic and Placebo Valortim
Days 1-3 200mL IV Normal Saline for Placebo Antibiotic over 60 minutes. Day 4 200mL IV Normal Saline for Placebo Valortim over 60 minutes.
Other Name: Saline

Detailed Description:

Valortim (MDX-1303) is a fully human monoclonal antibody (hmAb) with a high affinity for B. anthracis protective antigen (PA). Valortim is designed to target PA, which is one of three plasmid-encoded proteins that together form the toxins released by B. anthracis. Individually, these proteins (protective antigen (PA), lethal factor (LF) and edema factor (EF)) are inactive. Toxic effects require the transport of LF and EF into the host cell, mediated by the activity of PA. Valortim binds to PA and interferes with the activity of the toxins. Based on both non-clinical and clinical data, Valortim may have utility for the pre- and post-exposure prophylaxis of individuals exposed to, or at risk of exposure to, B. anthracis and for the treatment of individuals displaying signs or symptoms of inhalational anthrax. Because the treatment of inhalational anthrax includes the use of antibiotics such as fluoroquinolones, it is necessary to demonstrate that there are no adverse interactions between newer therapeutic interventions and these medications. The purpose of this study is to assess the safety and pharmacokinetics of ciprofloxacin (a commonly used fluoroquinolone for both treatment and post-exposure prophylaxis of anthrax) and Valortim following co-administration, as well as the safety and tolerability of these medications when administered concomitantly. These data are intended to support the use of Valortim as a treatment for inhalational anthrax.

  Eligibility

Ages Eligible for Study:   18 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy Normal male or female subjects 18 to 59 years of age on Day -1 of the study
  2. Subject must have read, understood, and provided written informed consent after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures
  3. In the opinion of the Investigator, subjects should be in generally good health, based upon prestudy medical history, physical examination, ECG and laboratory tests
  4. Laboratory screening values (i.e., hematology, clinical chemistries and urinalysis tests) must be within study-defined ranges
  5. No detectable antibody to B. anthracis Protective Antigen (PA-IgG) as measured by ELISA testing at study Screening
  6. Women of childbearing potential may be enrolled if one of the following criteria applies:

    1. Must be using an effective form of contraception (e.g., oral contraceptives, vaginal ring, IUD, injected or implanted hormonal contraception, double barrier method of condom and spermicide, diaphragm with spermicide or sponge with spermicide) for at least one month prior to study entry, must have maintained a normal menstrual pattern for the three months prior to study entry and have a negative pregnancy test at the time of admission to the unit. Women must be willing to continue this contraception throughout the course of the study.
    2. Is sexually abstinent
    3. Is monogamous with a vasectomized partner (> 3 months prior)
    4. Is postmenopausal (i.e., no cycle for at least the previous 12 months, is of menopausal age (> 45 years) and has a negative urine pregnancy test prior to enrollment into the study and a negative serum pregnancy test on Day -1)
    5. Is surgically sterilized (confirmed by medical record review)
    6. Has had a total hysterectomy a minimum of 3 months prior to dosing on Day 1 (confirmed by medical record review)
  7. Sexually active male subjects may be enrolled if one of the following criteria applies:

    1. Has had a vasectomy (> 3 months prior to study entry, confirmed by medical record review)
    2. Using condoms and whose partner is using an acceptable form of contraception (IUD, oral contraceptives, birth control patch or vaginal ring, injectable or implanted contraceptives, or tubal ligation [surgical sterilization]) for the duration of the study
    3. Is sexually abstinent
  8. Female subjects must have a negative urine pregnancy test at study Screening and a negative serum pregnancy test on admission to the Phase I unit at Day -1
  9. Female subject who are using injectable, transdermal, vaginal ring, oral contraceptives, or an IUD must agree to also use a barrier method (i.e. male condom, female condom, diaphragm, cervical cap) for the duration of their participation in the study.
  10. Agreement to not receive any vaccinations from Day -1 through to 31 days post Valortim dosing. Vaccination against B. anthracis is prohibited during the study
  11. Body Mass Index (BMI) ≥ 19 and ≤ 30
  12. Abstinence from alcohol for 24 hours prior to study drug administration until discharge from the Phase I unit

Exclusion Criteria:

  1. Prior known or suspected exposure to B. anthracis
  2. Prior vaccination for B. anthracis
  3. Any participants in the original FTIH study of Valortim.
  4. History of drug or alcohol abuse i.e. having been treated either in an in-patient or out-patient facility within 12 months of study Screening
  5. Positive drug result and/or positive alcohol result at time of study Screening or at Day -1
  6. Smoke more than 10 cigarettes per day for the last 6 months
  7. Treatment with an investigational agent within 30 days or 5 half-lives (whichever is longer) of study Screening
  8. Use of systemic immunosuppressive agents within 12 months of study Screening. Individuals who have received prednisone or its equivalent in doses of less than 20 mg/day for 14 days or less, as long as it occurred more than 1 month prior to them entering the study and as long as there is no clinical or laboratory evidence of immunosuppression, may be considered for enrollment
  9. Use of NSAIDs within 24 hours prior to dosing
  10. History of asthma requiring any use of inhaled or oral medication within the previous 5 years
  11. History of renal impairment
  12. History of central nervous system reactivity to any quinolone
  13. Any factor known to increase the risk of tendinitis or tendon rupture when taking a fluoroquinolone, including age older than 59 years; organ transplantation; use of systemic steroids (see number 7)
  14. Clinically significant medical or psychiatric condition that, in the opinion of the Investigator, may impair study participation to include ongoing recent illness, new medications prescribed in the previous 6 weeks or use of immunosuppressive agents
  15. Electrocardiogram with evidence of clinically significant conduction abnormalities or active ischemia (as determined by the Principal Investigator) at the time of study screening
  16. Donation of one or more pints of blood 30 days prior to study Screening visit or donation prior to completion of Day 31 of the study
  17. Donation of plasma within 14 days prior to study Screening visit or donation prior to completion of Day 31 of the study
  18. Vaccinations within 30 days prior to Day -1 through to 31 days post Valortim dosing on Day 3
  19. Prior known serum positivity for human immunodeficiency virus (HIV) antibodies, hepatitis B (surface antigen) or hepatitis C as determined at study Screening
  20. Prior known allergy or allergic reaction to ciprofloxacin or any of the group of antibiotics known as quinolones
  21. Diagnosis of photosensitivity, including, but not limited to, a history of phototoxic and/or photoallergic reactions to medications
  22. Current treatment with, or use of, theophylline, methylxanthines, tizanidine, phenytoin, sulfonylurea glyburide, warfarin, probenecid, methotrexate, metoclopramide, corticosteroids and non-steroidal anti-inflammatory drugs
  23. History of seizures, excluding pediatric febrile seizures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00964561

Locations
United States, Kansas
Quintiles Phase I Services
Overland Park, Kansas, United States, 66211
Sponsors and Collaborators
PharmAthene, Inc.
Medarex
Quintiles
Investigators
Principal Investigator: Ralph A. Schutz, M.D. Quintiles
  More Information

Additional Information:
No publications provided

Responsible Party: Valerie Riddle, M.D., Vice President and Medical Director, PharmAthene, Inc.
ClinicalTrials.gov Identifier: NCT00964561     History of Changes
Other Study ID Numbers: #0036-08-05, NIAID #08-0053
Study First Received: August 22, 2009
Last Updated: August 9, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Anti-Bacterial Agents
Ciprofloxacin
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on October 16, 2014