Back to results

Phase 1 Study of PK and Safety of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Subjects With Various Degrees Of Renal Function

Primary Purpose

Renal Impairment

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

About this trial

This is an interventional other trial for Renal Impairment focused on measuring End State Renal Disease (ESRD), Renal Insufficiency, Renal Impairment, Renal Disease, Hemodialysis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Key Inclusion Criteria:

Adult males or females, 18 years of age or older.
BMI ≥ 18.5 and ≤ 39.9 (kg/m2) and weight between 50.0 and 130.0 kg
Medically healthy without clinically significant abnormalities (Healthy Volunteers) or medically stable without clinically significant acute or chronic illness (Subjects with Renal Disease).
Non-smoker for at least 1 month prior to screening for the study.
Ability and willingness to abstain from alcohol, caffeine, xanthinecontaining beverages or food.

Key Exclusion Criteria:

Any clinically significant medical history or abnormal findings upon physical examination, or clinical laboratory tests, not specifically excluded in other criteria below that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
Electrocardiogram (ECG) with QTcF interval duration equal or greater than 500 msec
Hemoglobin (HB), hematocrit (HCT), white blood cell count (WBC), or platelet count less than the lower limit of normal range of the reference laboratory (Cohort 1). HB < 8.5 gm/dL, WBC ≤ 3,000 cells/μL or platelet count ≤ 100,000 cells/μL (Cohorts 2-5).
Results of biochemistry tests for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin greater than 1.5 X the upper limit of normal (ULN) for the reference laboratory.
Recent history of known or suspected Clostridium difficile infection.
History of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic academia).
History of chronic liver disease, cirrhosis, or biliary disease.
History of seizure disorder except childhood history of febrile seizures.
Positive urine drug/alcohol testing.
Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibodies.
History of substance abuse or alcohol abuse.
Use of antacids within 24 hours prior to study drug administration.
Known history of clinically significant hypersensitivity reaction or anaphylaxis to any medication.

Sites / Locations

Medical Facility
Medical Facility

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

Arm Description

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.

Outcomes

Primary Outcome Measures

Apparent total body clearance (CL/F).

Area under the curve from time zero to the last quantifiable sample (AUC0-last).

Area under the curve extrapolated to infinity (AUC0-∞).

Apparent steadystate volume of distribution (Vss/F).

Maximum plasma concentration (Cmax).

Time to the maximum plasma concentration (Tmax).

Terminal elimination half-life (t1/2).

Secondary Outcome Measures

Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.

AEs will be categorized by system organ class (SOC) and AE preferred term (PT).

Significant changes from baseline in clinical laboratory values.

All laboratory data will be summarized by cohort, and at each scheduled time-point using descriptive statistics (n, mean, SD, median, minimum, and maximum). E.g. of laboratory values: hematology, biochemistry, coagulation and urinalysis

Significant changes from baseline in physical examination.

Changes in baseline in physical examination findings (Normal, Abnormal NCS, Abnormal CS) will be summarized using counts and percentages by cohort, and will also be listed individually for each scheduled time-point. Physical examination will include: HEENT; cardiovascular, respiratory, gastrointestinal, dermatological, musculoskeletal, nervous systems, lymph nodes and general appearance. Additional body systems may be evaluated at the Investigator's discretion.

Significant changes from baseline in vitals signs.

Vital sign values and changes from baseline at each scheduled time-point will be summarized by cohort for the Safety Analysis Population using descriptive statistics (n, mean, SD, median, minimum, and maximum). Vitals signs will include: systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.

Significant changes from baseline in ECG

Overall evaluation of safety ECGs will be summarized by cohort, using frequency counts and percentage of subjects as normal or abnormal, and the relevance of the abnormality will be summarized by CS or NCS. ECG parameters will include: heart rate, RR interval, PR interval, QRS, QT and QTcF

Renal clearance (CLR)

Fraction of drug excreted in the urine expressed as a percentage of the TBPM-PI-HBr dose administered (Ae%).

Amount of drug excreted in the urine through 24 hours (Ae0-24), through 48 hours (Ae0-48) and through 72 hours (Ae0-72) for Cohorts 1-4.

For subjects on dialysis, estimated hemodialysis clearance (CLHD) will be assessed.

For subjects on dialysis, the extraction ratio (ER) will be assessed.

For subjects on dialysis, the amount of the dose removed by hemodialysis (XHD) will be assessed.

Full Information

NCT ID

NCT04178577

First Posted

November 14, 2019

Last Updated

November 24, 2020

Sponsor

Spero Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT04178577

Brief Title

Phase 1 Study of PK and Safety of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Subjects With Various Degrees Of Renal Function

Official Title

A Phase 1, Open-Label Study to Assess the Pharmacokinetics and Safety of Orally Administered Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Subjects With Various Degrees of Renal Function

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Completed

Study Start Date

December 6, 2019 (Actual)

Primary Completion Date

September 6, 2020 (Actual)

Study Completion Date

September 11, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Spero Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Evaluation of the pharmacokinetics (PK) of TBPM-PI-HBr in subjects with normal renal function, subjects with various degrees of renal insufficiency, and subjects with end-stage renal disease (ESRD) receiving hemodialysis (HD) therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Impairment

Keywords

End State Renal Disease (ESRD), Renal Insufficiency, Renal Impairment, Renal Disease, Hemodialysis

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

Arm Type

Experimental

Arm Description

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.

Intervention Type

Drug

Intervention Name(s)

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

Other Intervention Name(s)

TBPM-PI-HBr, SPR994

Intervention Description

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.

Primary Outcome Measure Information:

Title

Apparent total body clearance (CL/F).

Time Frame

72 hours post dose

Title

Area under the curve from time zero to the last quantifiable sample (AUC0-last).

Time Frame

72 hours post dose

Title

Area under the curve extrapolated to infinity (AUC0-∞).

Time Frame

72 hours post dose

Title

Apparent steadystate volume of distribution (Vss/F).

Time Frame

72 hours post dose

Title

Maximum plasma concentration (Cmax).

Time Frame

72 hours post dose

Title

Time to the maximum plasma concentration (Tmax).

Time Frame

72 hours post dose

Title

Terminal elimination half-life (t1/2).

Time Frame

72 hours post dose

Secondary Outcome Measure Information:

Title

Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.

Description

AEs will be categorized by system organ class (SOC) and AE preferred term (PT).

Time Frame

14 days post last dose

Title

Significant changes from baseline in clinical laboratory values.

Description

Time Frame

14 days post last dose

Title

Significant changes from baseline in physical examination.

Description

Time Frame

14 days post last dose

Title

Significant changes from baseline in vitals signs.

Description

Time Frame

14 days post last dose

Title

Significant changes from baseline in ECG

Description

Time Frame

14 days post last dose

Title

Renal clearance (CLR)

Time Frame

72 hours post dose

Title

Fraction of drug excreted in the urine expressed as a percentage of the TBPM-PI-HBr dose administered (Ae%).

Time Frame

72 hours post dose

Title

Amount of drug excreted in the urine through 24 hours (Ae0-24), through 48 hours (Ae0-48) and through 72 hours (Ae0-72) for Cohorts 1-4.

Time Frame

72 hours post dose

Title

For subjects on dialysis, estimated hemodialysis clearance (CLHD) will be assessed.

Time Frame

Up to 1 day post dose - between start and end of hemodialysis.

Title

For subjects on dialysis, the extraction ratio (ER) will be assessed.

Time Frame

Up to 1 day post dose - between start and end of hemodialysis.

Title

For subjects on dialysis, the amount of the dose removed by hemodialysis (XHD) will be assessed.

Time Frame

Up to 1 day post dose - between start and end of hemodialysis.

Other Pre-specified Outcome Measures:

Title

For subject in Cohort 1, cumulative amount of TBPM metabolite excreted in urine.

Time Frame

72 hours post dose

Title

For subjects in Cohort 1, cumulative urinary excretion of TBPM and TBPM metabolite as a % of dose administered.

Time Frame

72 hours post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Adult males or females, 18 years of age or older. BMI ≥ 18.5 and ≤ 39.9 (kg/m2) and weight between 50.0 and 130.0 kg Medically healthy without clinically significant abnormalities (Healthy Volunteers) or medically stable without clinically significant acute or chronic illness (Subjects with Renal Disease). Non-smoker for at least 1 month prior to screening for the study. Ability and willingness to abstain from alcohol, caffeine, xanthinecontaining beverages or food. Key Exclusion Criteria: Any clinically significant medical history or abnormal findings upon physical examination, or clinical laboratory tests, not specifically excluded in other criteria below that, in the opinion of the Investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. Electrocardiogram (ECG) with QTcF interval duration equal or greater than 500 msec Hemoglobin (HB), hematocrit (HCT), white blood cell count (WBC), or platelet count less than the lower limit of normal range of the reference laboratory (Cohort 1). HB < 8.5 gm/dL, WBC ≤ 3,000 cells/μL or platelet count ≤ 100,000 cells/μL (Cohorts 2-5). Results of biochemistry tests for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin greater than 1.5 X the upper limit of normal (ULN) for the reference laboratory. Recent history of known or suspected Clostridium difficile infection. History of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic academia). History of chronic liver disease, cirrhosis, or biliary disease. History of seizure disorder except childhood history of febrile seizures. Positive urine drug/alcohol testing. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C (HCV) antibodies. History of substance abuse or alcohol abuse. Use of antacids within 24 hours prior to study drug administration. Known history of clinically significant hypersensitivity reaction or anaphylaxis to any medication.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David Melnick, M.D.

Organizational Affiliation

Spero Therapeutics Inc

Official's Role

Study Director

Facility Information:

Facility Name

Medical Facility

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Medical Facility

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35420493

Citation

Patel G, Rodvold KA, Gupta VK, Bruss J, Gasink L, Bajraktari F, Lei Y, Jain A, Srivastava P, Talley AK. Pharmacokinetics of Oral Tebipenem Pivoxil Hydrobromide in Subjects with Various Degrees of Renal Impairment. Antimicrob Agents Chemother. 2022 May 17;66(5):e0240721. doi: 10.1128/aac.02407-21. Epub 2022 Apr 14.

Results Reference

derived

Learn more about this trial

Phase 1 Study of PK and Safety of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Subjects With Various Degrees Of Renal Function

We'll reach out to this number within 24 hrs