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

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

Official Title
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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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference
* Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Open-Label, Randomized, Single-Dose, Semi-Replicate, 4-Period, Crossover
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: TBPM-PI-HBr (Reference - fasted)<br>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<br>* 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr.<br>|
| Experimental: B: TBPM-PI-HBr (Test - fasted)<br>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<br>* 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.<br>|
| Experimental: C: TBPM-PI-HBr (Test - fed)<br>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<br>* 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) |