Bioequivalence Study Comparing Two Tablet Formulations of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Healthy Adult Subjects

An Open-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, Crossover, Bioequivalence Study Comparing Two Tablet Formulations of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Healthy Adult Subjects

A bioequivalence and food-effect study comparing two tablet formulations of tebipenem pivoxil hydrobromide (TBPM-PI-HBr) in healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference; Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Medical facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, adult, male or female, 18 to 55 years of age
• Continuous non-smoker.
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs.
• Has suitable venous access for repeated blood sampling.
• A female of childbearing potential must agree to abstain from sexual activity that could lead to pregnancy.
• A female of non-childbearing potential.
• Understands the study procedures in the informed consent form (ICF), and be willing and able to comply with the protocol.

Exclusion Criteria:

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected to have during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease.
• History of any illness that might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• History of significant allergic disease requiring treatment.
• History or presence of alcoholism or drug abuse.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds.
• History of known genetic metabolism anomaly associated with carnitine deficiency.
• Female subjects with a positive pregnancy test or who are lactating.
• Positive urine drug or alcohol results.
• Positive results for human immunodeficiency virus (HIV 1 and 2), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
• QTcF interval is > 460 msec (males) or > 470 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at the screening visit.
• Estimated creatinine clearance < 80 mL/min at the screening visit.
• Unable to refrain from or anticipates the use of any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A: TBPM-PI-HBr (Reference - fasted); 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference; 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr.
Experimental: B: TBPM-PI-HBr (Test - fasted); 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions.	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test; 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.
Experimental: C: TBPM-PI-HBr (Test - fed); 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fed conditions.	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test; 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the curve extrapolated to infinity (AUC0-∞).	24h (Day 2) post dose (Arms: A, B, C)
Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t).	24h (Day 2) post dose (Arms: A, B, C)
Maximum plasma concentration (Cmax).	24h (Day 2) post dose (Arms: A, B, C)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the maximum plasma concentration (Tmax).		24h (Day 2) post dose (Arms: A, B, C)
Terminal elimination half-life (t½).		24h (Day 2) post dose (Arms: A, B, C)
Apparent total body clearance (CL/F)		24h (Day 2) post dose (Arms: A, B, C)
Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F).		24h (Day 2) post dose (Arms: A, B, C)
Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.	ECG, Clinical Laboratories, Vitals Signs and Physical Exams will be used as a safety measure to detect any AEs.	12 to 14 days after the last dose of study drug
Area under the curve extrapolated to infinity (AUC0-∞).	TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.	24h (Day 2) post dose (Arms: B, C)
Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t) (AUC0-t).	TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.	24h (Day 2) post dose (Arms: B, C)
Maximum plasma concentration (Cmax).	TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.	24h (Day 2) post dose (Arms: B, C)
Time to the maximum plasma concentration (Tmax).	TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.	24h (Day 2) post dose (Arms: B, C)
Terminal elimination half-life (t½).	TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.	24h (Day 2) post dose (Arms: B, C)
Apparent total body clearance (CL/F)	TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.	24h (Day 2) post dose (Arms: B, C)
Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F).	TPBM PK parameters following administration of the TBPM-PI-HBr Test tablet under fasted and fed conditions.	24h (Day 2) post dose (Arms: B, C)

Collaborators and Investigators

• Sponsor: Spero Therapeutics
• Investigators: Study Director: David Melnick, Spero Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Actual): July 11, 2020
• Study Completion (Actual): July 29, 2020

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): August 12, 2020
• Last Update Submitted That Met QC Criteria: August 10, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: SPR994-105

Drug and device information, study documents

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