Ph1 Study of Valortim and Ciprofloxacin in Humans
Information source: PharmAthene, Inc.
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Anthrax
Intervention: Ciprofloxacin and Valortim (Drug); Placebo Antibiotic and Valortim (Drug); Placebo Antibiotic and Placebo Valortim (Other)
Phase: Phase 1
Status: Suspended
Sponsored by: PharmAthene, Inc. Official(s) and/or principal investigator(s): Ralph A. Schutz, M.D., Principal Investigator, Affiliation: Quintiles
Summary
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.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
Primary outcome: Determination of changes from baseline for clinical laboratory tests and urinalysis, blood pressure, heart rate, respiratory rate, body temperature, physical examination and ECG
Secondary outcome: Evaluation of PK parameters for IV administration of ciprofloxacin when dosed concomitantly with Valortim
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
Minimum age: 18 Years.
Maximum age: 59 Years.
Gender(s): Both.
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
Locations and Contacts
Quintiles Phase I Services, Overland Park, Kansas 66211, United States
Additional Information
Go to this website for more information about this study.
Starting date: August 2009
Last updated: August 9, 2010
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