Study to Examine the Effect of Antacid and Omeprazole on the Single-Dose Pharmacokinetics of Tebipenem Pivoxil Hydrobromide (TBPM-PI-HBr) in Healthy Adult Subjects

Study Overview
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Brief Summary
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To assess the effect of a single dose of aluminum hydroxide/magnesium hydroxide/simethicone and omeprazole on the pharmacokinetics (PK) of TBPM, following a single dose of TBPM-PI-HBr in healthy adult subjects.

Official Title
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An Open-Label, 3-Period, Fixed-Sequence, Study to Examine the Effect of Aluminum Hydroxide/Magnesium Hydroxide/Simethicone and Omeprazole on the Single-Dose Pharmacokinetics 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)
* Drug: 20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL)
* Drug: Omeprazole


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy, adult, male or female, 18-55 years of age, inclusive, at the screening visit. Continuous non-smoker Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at the screening visit. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee. Key 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 in the opinion of the PI or designee. History of any illness that, in the opinion of the PI or designee, 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 within the past 2 years prior to the first dose. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (especially fluoroquinolone-, carbapenem-, penicillin-, and cephalosporin-antibiotics sensitivity). History of known genetic metabolism anomaly associated with carnitine deficiency (e.g., carnitine transporter defect, methylmalonic aciduria, propionic acidemia). History of cholecystectomy. Female subjects with a positive pregnancy test at the screening visit or first check-in or who are lactating. Positive urine drug or alcohol results at the screening visit or first check-in. Positive results at the screening visit for human immunodeficiency virus (HIV 1 and 2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).

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: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TBPM-PI-HBr Alone (Period 1)<br>Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally alone. | Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)<br>* Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.<br>* Other names: SPR994;|
| Experimental: TBPM-PI-HBr and Antacid (Period 2)<br>20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL) oral suspension will be coadministered with 600 mg (2 x 300 mg tablets) TBPM-PI-HBr at Hour 0 on Day 1. | Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)<br>* Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.<br>* Other names: SPR994;Drug: 20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL)<br>* 20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL) oral suspension.<br>|
| Experimental: TBPM-PI-HBr and Omeprazole (Period 3)<br>40 mg (1 x 40 mg capsule) omeprazole administered QD at Hour -2 on Days 1 through 5, with 600 mg (2 x 300 mg tablets) TBPM-PI-HBr administered at Hour 0 on Day 5. | Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr)<br>* Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.<br>* Other names: SPR994;Drug: Omeprazole<br>* 40 mg (1 x 40 mg capsule) omeprazole administered QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t). |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 
| Area under the curve extrapolated to infinity (AUC0-∞). |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 
| Percent of AUC0-inf extrapolated (AUC%extrap) |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 
| Maximum plasma concentration (Cmax). |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 
| Time to the maximum plasma concentration (Tmax). |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 
| Terminal elimination half-life (t½). |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 
| Apparent total body clearance (CL/F) |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 
| Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F). |  | Day 2 (Periods 1 and 2) and Day 6 (Period 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |