Inhalational Anthrax
Conditions
Keywords
monoclonal antibody, ETI-204, ciprofloxacin, safety, PK
Brief summary
Evaluate the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) ETI-204 alone and in the presence of IV and oral ciprofloxacin
Detailed description
An open-label, randomized, parallel group study of IV ETI-204 administered alone and in the presence of IV and oral ciprofloxacin in 40 adult volunteers. Subjects will be randomized to two groups of 20 subjects each in a 1:1 ratio. Group 1 will receive a single IV dose of ETI-204 16 mg/kg followed immediately at the end of the infusion by a single dose of IV ciprofloxacin (400 mg), followed by oral ciprofloxacin (750 mg) every 12 hours on Days 2-8 with the final oral dose on the morning of Day 9. Group 2 will receive IV ETI-204 (16 mg/kg) only. The total duration of the study for each subject will be approximately 100 days divided as follows:Screening: Days -28 to -2; In-Unit Phases: Days -1, 1 and 2 \[all subjects\]; Days 8, 9 and 10 \[Group 1 only\]; Out-of-Unit Visits: Day 9 \[Group 2 only\]; Day 16 (+/- 3 days); Day 29 (+/- 3 days); Day 43 (+/- 3 days); Final Visit: Day 71 (+/- 3 days). Following completion of a Screening visit subjects will arrive at the clinical research unit (CRU) on Day -1 following at least a 10-hour fast. On Day 1, subjects who qualify for entry into the study will be randomized to receive either ETI-204 plus IV and oral ciprofloxacin (Group 1) or ETI-204 only (Group 2) in a 1:1 ratio according to the randomization treatment assignment. On Day 1, all subjects will receive 50 mg oral diphenhydramine approximately 30 minutes prior to ETI-204 infusion. Subjects in Group 1 will receive IV ETI-204 16 mg/kg infused over 90 minutes, immediately followed by IV ciprofloxacin 400 mg infused over 60 minutes. Subjects in Group 2 will receive IV ETI-204 16 mg/kg infused over 90 minutes. All subjects will be discharged from the CRU on Day 2. On Days 2 through 8, subjects in Group 1 will receive oral ciprofloxacin (750 mg every 12 hours); the final dose will be received on the morning of Day 9. Oral ciprofloxacin dosing begins 24 hours after the initiation of the ciprofloxacin infusion on Day 1. Subjects in Group 1 will return to the CRU on Day 8 and will be discharged from the unit following completion of PK sampling on Day 10. Subjects in Group 2 will return to the unit for an out-patient visit on Day 9 but will not be re-admitted to the CRU for an overnight stay. All subjects will return to the CRU for out-patient visits on Days 16, 29, 43, and 71.
Interventions
BIOLOGICALETI-204
A single IV infusion of 16 mg/kg ETI-204 over 90 minutes on Day 1
DRUGCiprofloxacin
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.
Sponsors
Elusys Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Adverse Events | Up to 71 days or 101 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each group. | Safety was assessed for all subjects in the Safety Population by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical assessments, skin assessments, infusion site assessments, and adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last)) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Terminal Half-life (t1/2) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Maximum Observed Plasma Concentration of ETI-204 (Cmax) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Volume of Distribution (Vd) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Volume of Distribution at Steady State (Vss) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Number of Participants With Anti-ETI-204 Antibodies | On Day 1 at predose and on Days 9, 29, 43, and 71. | Serum anti-ETI-204 antibody titers were determined for all subjects in the Safety Population. Blood samples were collected and serum samples were assayed at an initial dilution of 1:10. Samples that were positive at the 1:10 dilution were serially diluted 1:2 and assayed until a negative result was attained. The titer of the most dilute sample yielding a positive result was recorded as the titer for that time point. Immunogenicity was measured by the number of participants in each study arm with anti-ETI-204 antibody values post-treatment ≥ 4-times higher than baseline at Day 8, 43 or 71, or if the titer was negative at baseline, the post-treatment sample(s) required a titer of at least 1:20 for it to be considered positive. |
| Systemic Clearance (CL) | On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71. | Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ETI-204 Participants received 16 mg/kg ETI-2041 by IV infusion over 90 minutes | 20 |
| ETI-204 + Ciprofloxacin Participants received 16 mg/kg ETI-204 by IV infusion over 90 minutes followed by IV infusion of 400 mg ciprofloxacin followed by oral ciprofloxacin (750 mg) every 12 hours on Days 2-8 and a final dose on the morning of Day 9 | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | ETI-204 | ETI-204 + Ciprofloxacin | Total |
|---|---|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 11.8 | 33 years STANDARD_DEVIATION 14 | 33 years STANDARD_DEVIATION 12.8 |
| BMI | 27.1 kg/m2 STANDARD_DEVIATION 4.8 | 26.2 kg/m2 STANDARD_DEVIATION 4.75 | 26.7 kg/m2 STANDARD_DEVIATION 4.74 |
| Body Weight | 78.4 kg STANDARD_DEVIATION 16.63 | 75.8 kg STANDARD_DEVIATION 18.26 | 77.1 kg STANDARD_DEVIATION 17.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 14 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 169.5 cm STANDARD_DEVIATION 7.29 | 169.4 cm STANDARD_DEVIATION 9.11 | 169.4 cm STANDARD_DEVIATION 8.15 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 14 Participants | 28 Participants |
| Region of Enrollment United States | 20 participants | 20 participants | 40 participants |
| Sex: Female, Male Female | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 14 / 20 | 13 / 20 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 |
Outcome results
Primary
Number of Participants Who Experienced Adverse Events
Safety was assessed for all subjects in the Safety Population by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical assessments, skin assessments, infusion site assessments, and adverse events (AEs).
Time frame: Up to 71 days or 101 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each group.
Population: All randomized subjects who received study drug were included in the Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETI-204 + Ciprofloxacin | Number of Participants Who Experienced Adverse Events | 14 Participants |
| ETI-204 | Number of Participants Who Experienced Adverse Events | 13 Participants |
Secondary
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: All subjects for whom Cmax, Tmax and AUC0-last were calculated minus 2 subjects (1 in the ETI-204 group and 1 in the ETI-204 + ciprofloxacin group) whose t1/2 values were \> than 50% of the total sample collection interval. AUC0-inf and AUC0-inf-based parameters were not reported for those subjects in accordance with the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETI-204 + Ciprofloxacin | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) | 4990 µg.day/mL | Standard Deviation 942 |
| ETI-204 | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf) | 4891 µg.day/mL | Standard Deviation 897 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last))
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: All subjects who received ETI-204 and had at least one valid PK parameter were included in the PK Population: Two subjects who received a partial dose of ETI-204 due to AEs and 1 who withdrew prematurely on Day 1 for personal reasons after the IV infusions of ETI-204 and ciprofloxacin were excluded from the ETI-204 + ciprofloxacin group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETI-204 + Ciprofloxacin | Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last)) | 4603 µg.day/mL | Standard Deviation 791 |
| ETI-204 | Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last)) | 4514 µg.day/mL | Standard Deviation 792 |
Secondary
Maximum Observed Plasma Concentration of ETI-204 (Cmax)
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: The Pharmacokinetic (PK) Population consisted of all subjects who received ETI-204 and had at least one valid PK parameter. Two subjects in the ETI-204 + ciprofloxacin group received partial doses of ETI-204 (discontinued study drug due to AEs) and were excluded from the PK Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETI-204 + Ciprofloxacin | Maximum Observed Plasma Concentration of ETI-204 (Cmax) | 397 µg/mL | Standard Deviation 63.7 |
| ETI-204 | Maximum Observed Plasma Concentration of ETI-204 (Cmax) | 402 µg/mL | Standard Deviation 91 |
Secondary
Number of Participants With Anti-ETI-204 Antibodies
Serum anti-ETI-204 antibody titers were determined for all subjects in the Safety Population. Blood samples were collected and serum samples were assayed at an initial dilution of 1:10. Samples that were positive at the 1:10 dilution were serially diluted 1:2 and assayed until a negative result was attained. The titer of the most dilute sample yielding a positive result was recorded as the titer for that time point. Immunogenicity was measured by the number of participants in each study arm with anti-ETI-204 antibody values post-treatment ≥ 4-times higher than baseline at Day 8, 43 or 71, or if the titer was negative at baseline, the post-treatment sample(s) required a titer of at least 1:20 for it to be considered positive.
Time frame: On Day 1 at predose and on Days 9, 29, 43, and 71.
Population: All subjects who received ETI-204 and were included in the Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ETI-204 + Ciprofloxacin | Number of Participants With Anti-ETI-204 Antibodies | 0 Participants |
| ETI-204 | Number of Participants With Anti-ETI-204 Antibodies | 1 Participants |
Secondary
Systemic Clearance (CL)
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: All subjects for whom Cmax, Tmax and AUC0-last were calculated minus 2 subjects (1 in the ETI-204 group and 1 in the ETI-204 + ciprofloxacin group) whose t1/2 values were \> than 50% of the total sample collection interval. AUC0-inf and AUC0-inf-based parameters were not reported for those subjects in accordance with the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETI-204 + Ciprofloxacin | Systemic Clearance (CL) | 0.247 Liters/day | Standard Deviation 0.0732 |
| ETI-204 | Systemic Clearance (CL) | 0.268 Liters/day | Standard Deviation 0.0583 |
Secondary
Terminal Half-life (t1/2)
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: All subjects for whom Cmax, Tmax and AUC0-last were calculated minus 2 subjects (1 in the ETI-204 group and 1 in the ETI-204 + ciprofloxacin group) whose t1/2 values were \> than 50% of the total sample collection interval. AUC0-inf and AUC0-inf-based parameters were not reported for those subjects in accordance with the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETI-204 + Ciprofloxacin | Terminal Half-life (t1/2) | 19.0 days | Standard Deviation 3 |
| ETI-204 | Terminal Half-life (t1/2) | 19.5 days | Standard Deviation 4.14 |
Secondary
Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax)
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: The PK Population consisted of all subjects who received ETI-204 and had at least one valid PK parameter. Two subjects in the ETI-204 + ciprofloxacin group received partial doses of ETI-204 (discontinued study drug due to AEs) and were excluded from the PK Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ETI-204 + Ciprofloxacin | Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | 0.104 days |
| ETI-204 | Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | 0.104 days |
Secondary
Volume of Distribution at Steady State (Vss)
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: All subjects for whom Cmax, Tmax and AUC0-last were calculated minus 2 subjects (1 in the ETI-204 group and 1 in the ETI-204 + ciprofloxacin group) whose t1/2 values were \> than 50% of the total sample collection interval. AUC0-inf and AUC0-inf-based parameters were not reported for those subjects in accordance with the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETI-204 + Ciprofloxacin | Volume of Distribution at Steady State (Vss) | 5.68 Liters | Standard Deviation 0.986 |
| ETI-204 | Volume of Distribution at Steady State (Vss) | 6.28 Liters | Standard Deviation 1.68 |
Secondary
Volume of Distribution (Vd)
Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.
Population: All subjects for whom Cmax, Tmax and AUC0-last were calculated minus 2 subjects (1 in the ETI-204 group and 1 in the ETI-204 + ciprofloxacin group) whose t1/2 values were \> than 50% of the total sample collection interval. AUC0-inf and AUC0-inf-based parameters were not reported for those subjects in accordance with the statistical analysis plan.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ETI-204 + Ciprofloxacin | Volume of Distribution (Vd) | 6.59 Liters | Standard Deviation 1.34 |
| ETI-204 | Volume of Distribution (Vd) | 7.57 Liters | Standard Deviation 2.58 |