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

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

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)

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Drug: KSP-1007; Other: Placebo:0.9% sodium chloride; Drug: Meropenem

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 Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events assessed by subject .	Incidence of adverse events	up to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration of KSP-1007	The plasma concentration of KSP-1007 will be measured over time, and the peak plasma concentration, or Cmax, of KSP-1007 will be determined	Up to 5 days after dosing
Plasma concentration of KSP-1007 versus time curve	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	Up to 5 days after dosing
Cumulative amount of KSP-1007 excreted in urine over time	Total amount of unchanged drug excreted in urine over a dosing interval	Up to 5 days after start of dosing
Renal clearance of KSP-1007 in urine over time	Renal clearance in urine. Urine was collected up to 5 days after dosing.	Up to 5 days after start of dosing
Peak plasma concentration of meropenem	The plasma concentration of meropenem will be measured over time, and the peak plasma concentration, or Cmax, of meropenem will be determined	Up to 5 days after start of dosing
Plasma concentration versus time curve of meropenem	The plasma concentration of meropenem will be measured over time and the area under the curve, or AUC, of meropenem will be determined	Up to 5 days after start of dosing
Cumulative amount of meropenem excreted in urine over time	Total amount of unchanged drug excreted in urine over a dosing interval.	Up to 5 days after start of dosing
Renal clearance of meropenem in urine over time	Renal clearance in urine. Urine was collected up to 5 days after dosing.	Up to 5 days after start of dosing
ECG QTcF interval	Change from baseline QTcF interval	24 hours after start of dosing

Collaborators and Investigators

• Sponsor: Sumitovant Biopharma, Inc.
• Investigators: Study Director: Hayes Dansky, M.D., Sumitovant Biopharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2022
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): October 1, 2022

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: February 3, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 26, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Bacterial Infections; Bacterial Infection; Bacterial; Bacterial Disease
• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Infections; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Meropenem
• Other Study ID Numbers: KSP-1007-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No