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

NCT04178577 | Completed Phase 1 FDA Drug

• 1 other identifier: SPR994-102
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

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.

Conditions

Renal Impairment

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Apparent total body clearance (CL/F).

  72 hours post dose

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

  72 hours post dose

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

  72 hours post dose

• Apparent steadystate volume of distribution (Vss/F).

  72 hours post dose

• Maximum plasma concentration (Cmax).

  72 hours post dose

• Time to the maximum plasma concentration (Tmax).

  72 hours post dose

• Terminal elimination half-life (t1/2).

  72 hours post dose

Secondary Outcomes (11)

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

  14 days post last dose

• Significant changes from baseline in clinical laboratory values.

  14 days post last dose

• Significant changes from baseline in physical examination.

  14 days post last dose

• Significant changes from baseline in vitals signs.

  14 days post last dose

• Significant changes from baseline in ECG

  14 days post last dose

Other Outcomes (2)

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

  72 hours post dose

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

  72 hours post dose

Study Arms (1)

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

EXPERIMENTAL

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

Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

Interventions

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) DRUG

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

Also known as: TBPM-PI-HBr, SPR994

Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Spero Therapeutics: lead

Study Sites (2)

Medical Facility

Miami, Florida, 33136, United States

Location

Medical Facility

Orlando, Florida, 32809, United States

Location

Related Publications (1)

• 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.

  PMID: 35420493 DERIVED

MeSH Terms

Conditions

Renal Insufficiency; Kidney Diseases

Interventions

tebipenem

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• David Melnick, M.D.

  Spero Therapeutics Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: November 26, 2019
• Study Start: December 6, 2019
• Primary Completion: September 6, 2020
• Study Completion: September 11, 2020
• Last Updated: November 27, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)