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

Bacterial Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05226923
• Other study ID #: KSP-1007-101
• Status: Completed
• Phase: Phase 1
• Start date: January 12, 2022
• Est. completion date: October 1, 2022

Study information

• Verified date: October 2022
• Source: Sumitovant Biopharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: October 1, 2022
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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 ß-lactams or ß-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

Related Conditions & MeSH terms

• Bacterial Infections
• Infections

Intervention

Drug:
• KSP-1007
Single and multiple doses, intravenous administration

Other:
• Placebo:0.9% sodium chloride
Single and multiple doses, intravenous administration

Drug:
• Meropenem
Multiple doses, intravenous administration

Locations

Country	Name	City	State
United States	PRA Health Sciences	Lenexa	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Sumitovant Biopharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events assessed by subject .	Incidence of adverse events	up to Day 14
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	ECG QTcF interval	Change from baseline QTcF interval	24 hours after start of dosing