- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04178577
Phase 1 Study of PK and Safety of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Subjects With Various Degrees Of Renal Function
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Florida
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Miami, Florida, United States, 33136
- Medical Facility
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Orlando, Florida, United States, 32809
- Medical Facility
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)
Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.
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Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Apparent total body clearance (CL/F).
Time Frame: 72 hours post dose
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72 hours post dose
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Area under the curve from time zero to the last quantifiable sample (AUC0-last).
Time Frame: 72 hours post dose
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72 hours post dose
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Area under the curve extrapolated to infinity (AUC0-∞).
Time Frame: 72 hours post dose
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72 hours post dose
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Apparent steadystate volume of distribution (Vss/F).
Time Frame: 72 hours post dose
|
72 hours post dose
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Maximum plasma concentration (Cmax).
Time Frame: 72 hours post dose
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72 hours post dose
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Time to the maximum plasma concentration (Tmax).
Time Frame: 72 hours post dose
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72 hours post dose
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Terminal elimination half-life (t1/2).
Time Frame: 72 hours post dose
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72 hours post dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.
Time Frame: 14 days post last dose
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AEs will be categorized by system organ class (SOC) and AE preferred term (PT).
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14 days post last dose
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Significant changes from baseline in clinical laboratory values.
Time Frame: 14 days post last dose
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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 |
14 days post last dose
|
Significant changes from baseline in physical examination.
Time Frame: 14 days post last dose
|
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. |
14 days post last dose
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Significant changes from baseline in vitals signs.
Time Frame: 14 days post last dose
|
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. |
14 days post last dose
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Significant changes from baseline in ECG
Time Frame: 14 days post last dose
|
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 |
14 days post last dose
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Renal clearance (CLR)
Time Frame: 72 hours post dose
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72 hours post dose
|
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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
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72 hours post dose
|
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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
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72 hours post dose
|
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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.
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Up to 1 day post dose - between start and end of hemodialysis.
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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.
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Up to 1 day post dose - between start and end of hemodialysis.
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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.
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Up to 1 day post dose - between start and end of hemodialysis.
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
For subject in Cohort 1, cumulative amount of TBPM metabolite excreted in urine.
Time Frame: 72 hours post dose
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72 hours post dose
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For subjects in Cohort 1, cumulative urinary excretion of TBPM and TBPM metabolite as a % of dose administered.
Time Frame: 72 hours post dose
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72 hours post dose
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: David Melnick, M.D., Spero Therapeutics Inc
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SPR994-102
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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