Safety, Tolerability and PK of Intravenous (IV) ETI-204 Alone and in Presence of Ciprofloxacin in Adult Volunteers

• Status: Completed
• Trial end date: 2014-04-09
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Elusys Therapeutics
• Treatments: Ciprofloxacin

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