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The proposed study aims to assess the time above MIC (4 mg/mL), and the pharmacokinetics/pharmacodynamics and bioavailability of 1 g ceftriaxone administered by constant rate subcutaneous infusion over 2 hours compared with 1 g of ceftriaxone administered as a constant IV infusion over 0.5 hours. In addition, the study will compare the results obtained after 1 g ceftriaxone intravenous or subcutaneous administration with 2 g ceftriaxone administered subcutaneously
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IV ceftriaxone (0.5hr) 1 gm | Active Comparator | ceftriaxone for injection, (total dose = 1.0 g) administered IV over 30 minutes via infusion pump (Open Label) |
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| subcutaneous ceftriaxone, (2hr), 1 gm | Experimental | ceftriaxone for injection, (total dose = 1.0 g) administered subcutaneous over 2 hours (Blinded). |
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| subcutaneous ceftriaxone, (2 hr), 2 gm | Experimental | ceftriaxone for injection, (total dose = 2.0 g) administered subcutaneous over 2 hours (Blinded). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ceftriaxone | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration | Cmax, observed by inspection of individual study participant plasma concentration time plots. | 48 hours |
| Time of observed maximum plasma concentration | Tmax, obtained directly from the observed concentration-time data | 48 hours |
| Area under the plasma concentration-time curve | AUClast: AUC from time 0 to the last measureable non-zero concentration, calculated by a combination of linear and logarithmic trapezoidal methods | 48 hours |
| Area under the concentration time curve, extrapolated to infinity | AUCinf: Area under the concentration time curve from time 0 extrapolated to infinity, calculated as AUClast + Clast/λz | 48 hours |
| Terminal phase elimination rate constant | Terminal phase elimination rate constant, estimated by linear regression of logarithmically transformed concentration versus time data. | 48 hours |
| Terminal phase half life | Terminal phase half life, estimated using the equation [ln(2)/λz] | 48 hours |
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Inclusion Criteria:
An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.
Male and female subjects between 18 and 65 years of age inclusive.
Subjects must have body weight of 45.5 to 105 kg inclusive and body mass index (BMI) ≤34 kg/m2.
Females will be non-pregnant, non-lactating, and either post-menopausal for at least 1 year, surgically sterile (e.g., tubal ligation, hysterectomy) for at least 90 days, or agree, from the time of signing the informed consent or 14 days prior to Baseline until Follow-up, to use TWO (2) of the following forms of contraception: a IUD with spermicide, female condom with spermicide, contraceptive sponge with spermicide, an intravaginal system, diaphragm with spermicide, cervical cap with spermicide, a male sexual partner who agrees to use a male condom with spermicide, a sterile sexual partner, OR abstinence. For all females, a pregnancy test result must be negative at Screening and Baseline/Day 0
Males agree from the time of Baseline/Day 0 until Follow-up, to use TWO (2) forms of contraception: ONE must be a male condom with spermicide; the second may be ONE of the following: his female partner uses either an IUD with spermicide, female condom with spermicide, contraceptive sponge with spermicide, an intravaginal system, diaphragm with spermicide, cervical cap with spermicide, oral contraceptives; OR abstinence
Subject has normal (or abnormal and clinically insignificant) laboratory values at screening.
Subject is medically normal with no significant abnormal findings at the Baseline physical examination.
Subjects must have Baseline values of the following laboratory tests as specified:
Subject has the ability to understand the requirements of the study and is willing to comply with all study procedures.
Subject has not consumed and agrees to abstain from taking any vitamin or dietary supplements or non-prescription drugs (except as authorized by the Investigator and Medical Monitor) for 3 days prior to CRU admission through Follow-Up, with the exception of oral contraceptives.
Subject has not consumed and agrees to abstain from taking any prescription drugs (except as authorized by the Investigator and Medical Monitor) during the 14 days prior to CRU admission through Follow-Up.
Subject has not consumed and agrees to abstain from consuming grapefruit, grapefruit juice, or juices containing grapefruit, or Seville oranges during the 3 days prior to CRU admission through Follow-Up.
Subject agrees to abstain from using alcohol from 48 hours prior to Screening and CRU admission through CRU discharge for each period.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rene Myers, Ph.D. | scPharmaceuticals, Inc. | Study Director |
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| ID | Term |
|---|---|
| D002443 | Ceftriaxone |
| ID | Term |
|---|---|
| D002439 | Cefotaxime |
| D002505 | Cephacetrile |
| D002511 | Cephalosporins |
| D047090 | beta-Lactams |
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| D007769 |
| Lactams |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |