Safety, Tolerability and PK of Intravenous (IV) ETI-204 Alone and in Presence of Ciprofloxacin in Adult Volunteers
Condition: Inhalational Anthrax
MeSH terms: Anthrax
Intervention: ETI-204; Ciprofloxacin
Intervention description: A single IV infusion of 16 mg/kg ETI-204 over 90 minutes on Day 1; A single IV Infusion of 400 mg Ciprofloxacin over 60 minutes immediately following the infusion of ETI-204 on Day 1, followed by oral Ciprofloxacin (750 mg every 12 hours) on Days 2-8, and a final oral dose on the morning of Day 9.
Intervention MeSH terms: Ciprofloxacin
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: monoclonal antibody, ETI-204, ciprofloxacin, safety, PK

Summary:

      Evaluate the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) ETI-204 alone
      and in the presence of IV and oral ciprofloxacin
    

Eligibility criteria:

        Inclusion Criteria:

          1. Females or males between 18 and 60 years of age

          2. All females, regardless of childbearing potential, must have a negative serum beta
             human chorionic gonadotropin (β-hCG) pregnancy test at Screening and Day -1

          3. Females of childbearing potential (i.e., not postmenopausal or surgically sterile)
             must agree to practice abstinence or to use a medically accepted method of
             contraception from the time of Screening through 30 days after the final study visit.
             Acceptable methods of contraception include diaphragm with spermicide; sponge with
             spermicide; condom with spermicide; or intrauterine device with condom or spermicide.
             The following contraceptive methods are acceptable only when used with a condom and
             spermicide: birth control pills, birth control patches, vaginal ring, hormone under
             the skin, or hormone injections

          4. Postmenopausal females, defined as females who have had amenorrhea for at least 12
             months either naturally or following cessation of all exogenous hormonal treatments,
             and have a follicle-stimulating hormone (FSH) level of > 40 mIU/mL at Screening

          5. Females who have undergone surgical sterilization, including hysterectomy, bilateral
             oophorectomy, bilateral salpingectomy, tubal ligation, or tubal essure ≥ 3 months
             prior to Screening. Tubal essure requires radiological confirmation of occlusion of
             the fallopian tubes. Subjects who cannot provide documentation may participate if they
             agree to follow the methods of contraception specified in Inclusion Criterion #3

          6. Males must agree to practice abstinence or use a condom with spermicide and refrain
             from sperm donation during the study and for 30 days after the final study visit. Note
             this does not apply to males who have undergone a vasectomy and can provide
             documentation of confirmatory sperm count 3 months post procedure.

          7. Provide written informed consent

          8. Willing to comply with study restrictions (see Section 4.5.3 for a complete list of
             study restrictions)

        Exclusion Criteria:

          1. Pregnant or lactating woman

          2. Clinically-significant comorbidity that would interfere with completion of the study
             procedures or objectives or compromise the subject's safety

          3. Supine systolic blood pressure (BP) ≥ 150 mmHg or ≤ 90 mmHg or diastolic BP ≥ 95 mmHg

          4. Use of H1 receptor antagonists (i.e. antihistamines) within 5 days prior to Day 1

          5. Evidence of drug or alcohol abuse as determined by the Investigator, within 6 months
             of Day 1

          6. Positive test result for drugs of abuse (with the exception of medically prescribed
             drugs) at Screening or on Day -1

          7. Positive test for alcohol at Screening or Day -1

          8. Treatment with an investigational agent within 30 days or five half-lives of the
             investigational agent at Day 1 (whichever is longer)-

          9. Congenital or acquired immunodeficiency syndrome

         10. Prior solid organ or bone marrow transplant

         11. Positive test for Hepatitis B (surface antigen), Hepatitis C, or human
             immunodeficiency virus (HIV) at Screening

         12. History of prior treatment for anthrax exposure or prior anthrax infection

         13. Prior immunization with any approved or investigational anthrax vaccine or prior
             treatment with an investigational anthrax treatment (i.e., ETI-204, raxibacumab, or
             anthrax immune globulin)

         14. Military personnel deployed in 1990 or after, unless the subject can provide
             documentation demonstrating they have not previously received any approved or
             investigational anthrax vaccine

         15. Therapeutic use of systemic steroids, immunosuppressive agents, anticoagulants, or
             anti-arrhythmics within 1 year prior to Day 1; a single short course (i.e., less than
             14 days) of systemic steroid therapy is allowed provided it concluded more than 6
             months prior to Day 1

         16. Donation or loss of > 500 mL of blood within 30 days or plasma within 7 days of Day 1

         17. Prior stroke, epilepsy, relapsing or degenerative CNS disease, or relapsing or
             degenerative ocular disease

         18. Myocardial infarction or acute coronary syndrome in the past 5 years, active angina
             pectoris, or heart failure (New York Heart Association scale > I)

         19. History of chronic liver disease

         20. Calculated creatinine clearance (CrCl) of < 30 mL/min using the Cockcroft-Gault
             equation (see Section 5.1)

         21. Any clinically significant abnormality, in the Investigator's opinion, on
             electrocardiogram (ECG) or clinical laboratory tests (hematology, clinical chemistry,
             or urinalysis) at Screening; out of range results may be repeated to confirm

         22. History of allergic or hypersensitivity reactions to other therapeutic antibodies or
             immunoglobulins

         23. History of any malignant neoplasm within the last 5 years, with the exception of
             adequately treated localized or in situ non-melanoma carcinoma of the skin (e.g. basal
             cell carcinoma) or the cervix

         24. Subjects who, in the opinion of the Investigator, are not suitable candidates for
             enrollment or who may not comply with the requirements of the study

        Exclusion Criteria Specific to the Use of Ciprofloxacin

          1. Hypersensitivity to any fluoroquinolone

          2. At increased risk of Clostridium. difficile (C. difficile) infection (e.g., prior
             systemic antibiotic therapy or in-hospital stay of greater than 2 nights over the past
             6 months, abdominal surgery within 3 months prior to Day 1, a chronic inflammatory
             bowel disease or prior C. difficile infection)

          3. Any medical condition that may require repeat courses of antibiotics, e.g., recurrent
             urinary tract or respiratory infections. A short course (i.e.≤ 10 days) of antibiotics
             within 6 months prior to Day 1 is not exclusionary.

          4. A history of any tendon rupture

          5. Subjects who smoke or have used tobacco or nicotine containing products within 3
             months of Day 1.

          6. Use of cation-containing drugs or food supplements within 2 days prior to Day 1

          7. Use of protheophylline, theophylline, methylxanthine, tizanidine, or other drugs
             metabolized via cytochrome P450 1A (CYP1A) within 30 days prior to Day 1

          8. Use of glyburide, cyclosporine, didanosine, methotrexate, or probenecid and
             medications that prolong the QT interval within 30 days prior to Day 1 or within 5
             half-lives of Day 1, whichever is longer

          9. Subjects at high risk for QT prolongation, including:

               1. Baseline prolongation of QTcF ≥ 500 msec

               2. Risk factors for Torsade de Pointes, including hypocalcemia, hypokalemia, sudden
                  death of unknown cause in a close family member (i.e. biological mother, father
                  or siblings), a near drowning episode, a family history of either Romano-Ward
                  syndrome or Jervell and Lange-Nielson syndrome

               3. The use of concomitant medications that prolong the QT interval within 30 days
                  prior to Day 1