Bacterial Infections
Conditions
Keywords
Bacterial Disease, Bacterial Infection, Bacterial Infections, Bacterial, Healthy Volunteers
Brief summary
This study is a first-in-human, Phase 1, randomized, double- blind, four-part, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of single (Part 1) and repeat (Part 2) escalating intravenous doses of KSP-1007. Repeated escalating doses of KSP-1007 will be co-administered with meropenem (Part 3) and single, ascending doses of KSP-1007 will be administered alone in healthy Japanese subjects (Part 4)
Detailed description
Carbapenem-resistant Gram-negative bacteria are responsible for serious, life-threatening infections and are regarded as an urgent threat by the Centers for Disease Control and Prevention and the World Health Organizations. One principal mechanism of carbapenem resistance is bacterial production of carbapenemases, which reduce the effectiveness of meropenem and other carbapenem class antibiotics. Sumitovant Biopharma is developing a fixed combination of meropenem and KSP-1007 for the treatment of serious bacterial infections.
Interventions
DRUGMeropenem
Multiple doses, intravenous administration
DRUGKSP-1007
Single and multiple doses, intravenous administration
OTHERPlacebo:0.9% sodium chloride
Single and multiple doses, intravenous administration
Sponsors
Sumitovant Biopharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female subjects 18 to 55 years of age, inclusive * Females that engage in heterosexual activity must agree to use a highly selective birth control (BC) method (\< 1% failure rate per year) throughout the study, or have a documented reproductive status of non-childbearing based on medical history, or is postmenopausal * Males that engage in heterosexual activity that has the risk of pregnancy must agree to use effective BC and agree to not donate sperm during the study and for at least 90 days after the last dose of the study medication * Body mass index (BMI) 2: 18 kg/m2 and :s 32 kg/m2
Exclusion criteria
* History of Gilbert's Syndrome * History of severe allergic reactions to β-lactams or β-lactamase inhibitors or a history allergic reactions to multiple medications. * Pregnant female, determined by positive serum or urine human chorionic gonadotropin pregnancy test at Screening, or prior to dosing * Lactating female * Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at Screening) of \> 499 mL within 56 days prior to Day 1 * Participation in a study with an investigational drug or device study with last dose of investigational drug within 30 days (90 days if the study involved a biologic, cellular, or vaccine product) or 5 half-lives, whichever is longer, before study treatment administration * Subjects with abnormal hepatic and/or renal function, that could interfere with the metabolism, and/or excretion of the study treatments * Abnormal blood pressure, either low (defined as \< 90 mmHg systolic and/ or \< 45 mmHg diastolic) or high (defined as \> 140 mmHg systolic and/ or \> 90 mmHg diastolic) at Screening * Positive serology for hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV at Screening. Subjects who test positive for hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) also will be ineligible. Evidence of prior HBV vaccination (positive hepatitis B surface antibody \[HBsAb)) is not exclusionary. * Subjects unable to abstain from alcohol for 48 hours prior to admission through to completion of the Follow-up visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events assessed by subject . | up to Day 14 | Incidence of adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of KSP-1007 versus time curve | Up to 5 days after dosing | The plasma concentration of KSP-1007 will be measured over time and the area under the curve, or AUC, of KSP-1007 will be determined |
| Cumulative amount of KSP-1007 excreted in urine over time | Up to 5 days after start of dosing | Total amount of unchanged drug excreted in urine over a dosing interval |
| Renal clearance of KSP-1007 in urine over time | Up to 5 days after start of dosing | Renal clearance in urine. Urine was collected up to 5 days after dosing. |
| Plasma concentration versus time curve of meropenem | Up to 5 days after start of dosing | The plasma concentration of meropenem will be measured over time and the area under the curve, or AUC, of meropenem will be determined |
| Peak plasma concentration of KSP-1007 | Up to 5 days after dosing | The plasma concentration of KSP-1007 will be measured over time, and the peak plasma concentration, or Cmax, of KSP-1007 will be determined |
| Cumulative amount of meropenem excreted in urine over time | Up to 5 days after start of dosing | Total amount of unchanged drug excreted in urine over a dosing interval. |
| Renal clearance of meropenem in urine over time | Up to 5 days after start of dosing | Renal clearance in urine. Urine was collected up to 5 days after dosing. |
| ECG QTcF interval | 24 hours after start of dosing | Change from baseline QTcF interval |
| Peak plasma concentration of meropenem | Up to 5 days after start of dosing | The plasma concentration of meropenem will be measured over time, and the peak plasma concentration, or Cmax, of meropenem will be determined |
Countries
United States
Outcome results
None listed