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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85283
      • Medical Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TBPM-PI-HBr Alone (Period 1); Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally alone.	Drug: Tebipenem pivoxil hydrobromide (TBPM-PI-HBr); Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.; Other Names: SPR994; TBPM-PI-HBr
Experimental: TBPM-PI-HBr and Antacid (Period 2); 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); Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.; Other Names: SPR994; 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); 20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL) oral suspension.
Experimental: TBPM-PI-HBr and Omeprazole (Period 3); 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); Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally.; Other Names: SPR994; TBPM-PI-HBr; Drug: Omeprazole; 40 mg (1 x 40 mg capsule) omeprazole administered QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Spero Therapeutics
• Investigators: Study Director: David Melnick, M.D., Spero Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): August 8, 2020
• Study Completion (Actual): August 21, 2020

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 27, 2020
• First Posted (Actual): April 30, 2020

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: September 2, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunologic Factors; Gastrointestinal Agents; Protective Agents; Dermatologic Agents; Adjuvants, Immunologic; Anti-Ulcer Agents; Proton Pump Inhibitors; Antioxidants; Antifoaming Agents; Emollients; Antacids; Simethicone; TEMPO; Magnesium Hydroxide; Omeprazole; Aluminum Hydroxide; Aluminum hydroxide, magnesium hydroxide, drug combination; Aluminum hydroxide, magnesium hydroxide, simethicone drug combination
• Other Study ID Numbers: SPR994-107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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