Study of the Safety and Pharmacokinetics of KSP-1007 Alone and Coadministered With Meropenem in Healthy Subjects

Sponsor

Sumitovant Biopharma, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05226923

Collaborator

(none)

128

Enrollment

Location

Arms

5.8

Anticipated Duration (Months)

22.1

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Bacterial Infections	Drug: KSP-1007 Other: Placebo:0.9% sodium chloride Drug: Meropenem	Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

128 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Other

Official Title:

A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of Single and Repeat Doses of KSP-1007 Alone and Coadministered With Meropenem in Healthy Subjects

Actual Study Start Date :

Jan 12, 2022

Anticipated Primary Completion Date :

Jul 7, 2022

Anticipated Study Completion Date :

Jul 7, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: KSP-1007 single ascending dose Single, ascending intravenous dose of KSP-1007	Drug: KSP-1007 Single and multiple doses, intravenous administration
Placebo Comparator: Placebo single dose Single dose of placebo (0.9% normal saline)	Other: Placebo:0.9% sodium chloride Single and multiple doses, intravenous administration
Experimental: KSP-1007 multiple ascending dose Multiple, ascending, intravenous doses of KSP-1007	Drug: KSP-1007 Single and multiple doses, intravenous administration
Placebo Comparator: Placebo multiple dose Multiple doses of placebo (0.9% saline)	Other: Placebo:0.9% sodium chloride Single and multiple doses, intravenous administration
Experimental: KSP-1007 multiple ascending dose + Meropenem multiple dose Multiple, ascending intravenous doses of KSP-1007 and multiple doses of meropenem (fixed dose)	Drug: KSP-1007 Single and multiple doses, intravenous administration Drug: Meropenem Multiple doses, intravenous administration
Placebo Comparator: Placebo + Meropenem multiple dose Multiple doses of placebo (0.9% normal saline) plus multiple doses of meropenem (fixed dose)	Other: Placebo:0.9% sodium chloride Single and multiple doses, intravenous administration Drug: Meropenem Multiple doses, intravenous administration

Outcome Measures

Primary Outcome Measures

Incidence of adverse events assessed by subject . [up to Day 14]
Incidence of adverse events

Secondary Outcome Measures

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
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.
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
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts 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