Open-Label, Randomized, Parallel Group Study to Assess the Safety, Tolerability and PK of ETI-204 Alone and in Presence of Ciprofloxacin in Adult Volunteers

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Elusys Therapeutics
ClinicalTrials.gov Identifier:
NCT01952444
First received: September 20, 2013
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Inhalational Anthrax
Biological: ETI-204
Other: IV Ciprofloxacin
Other: Oral Ciprofloxacin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: An Open-Label, Randomized, Parallel Group Study to Assess the Safety, Tolerability and Pharmacokinetics of ETI-204 Alone and in the Presence of Ciprofloxacin in Adult Volunteers

Resource links provided by NLM:


Further study details as provided by Elusys Therapeutics:

Primary Outcome Measures:
  • Number of Adverse Events [ Time Frame: 71 Days ] [ Designated as safety issue: Yes ]
    Safety assessments will be assessed by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical assessments, infusion site assessments, and AEs


Secondary Outcome Measures:
  • Pharmacokinetics (PK) analysis [ Time Frame: 71 Days ] [ Designated as safety issue: No ]
    All PK parameters will be determined for a single Intravenous (IV) administration of ETI-204, a single IV dose of ciprofloxacin and oral ciprofloxacin at steady state.

  • Anti-ETI-204 Antibody [ Time Frame: 71 Days ] [ Designated as safety issue: No ]
    Immunogenicity measured by the percentage of subjects in each study arm with anti-ETI-204 antibody values greater than or equal to cutpoint at Day 1, 9, 43 and 71.


Estimated Enrollment: 40
Study Start Date: October 2013
Estimated Study Completion Date: May 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ETI-204
Intravenous (IV) single dose
Biological: ETI-204
Intravenous (IV)
Other: IV Ciprofloxacin Other: Oral Ciprofloxacin
Experimental: ETI-204 and IV Ciprofloxacin and Oral Ciprofloxacin
Intravenous (IV) ETI-204 and IV Ciprofloxacin and Oral Ciprofloxacin
Biological: ETI-204
Intravenous (IV)

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  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: NCT01952444

Locations
United States, Kansas
Quintiles
Overland Park, Kansas, United States, 66211
Sponsors and Collaborators
Elusys Therapeutics
Investigators
Principal Investigator: David Mathews, MD Quintiles
Principal Investigator: Jolene Berg, MD Davita Clinical Research
  More Information

No publications provided

Responsible Party: Elusys Therapeutics
ClinicalTrials.gov Identifier: NCT01952444     History of Changes
Other Study ID Numbers: AH110
Study First Received: September 20, 2013
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Anthrax
Bacillaceae Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Ciprofloxacin
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014