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

NCT04368585 | Completed Phase 1 FDA Drug

• 1 other identifier: SPR994-107
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (1)

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

  12 to 14 days after the last dose of study drug

Study Arms (3)

TBPM-PI-HBr Alone (Period 1)

EXPERIMENTAL

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

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

TBPM-PI-HBr and Antacid (Period 2)

EXPERIMENTAL

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); Drug: 20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL)

TBPM-PI-HBr and Omeprazole (Period 3)

EXPERIMENTAL

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); Drug: Omeprazole

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

TBPM-PI-HBr Alone (Period 1); TBPM-PI-HBr and Antacid (Period 2); TBPM-PI-HBr and Omeprazole (Period 3)

20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL) DRUG

20 mL aluminum hydroxide/magnesium hydroxide/simethicone (400 mg aluminum hydroxide/400 mg magnesium hydroxide/40 mg simethicone per 5 mL) oral suspension.

TBPM-PI-HBr and Antacid (Period 2)

Omeprazole DRUG

40 mg (1 x 40 mg capsule) omeprazole administered QD

TBPM-PI-HBr and Omeprazole (Period 3)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Spero Therapeutics: lead

Study Sites (1)

Medical Facility

Phoenix, Arizona, 85283, United States

Location

MeSH Terms

Interventions

tebipenem; Aluminum Hydroxide; Magnesium Hydroxide; Simethicone; Omeprazole

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes; Magnesium Compounds; Dimethylpolysiloxanes; Silicones; Siloxanes; Organosilicon Compounds; Organic Chemicals; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• David Melnick, M.D.

  Spero Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2020
• First Posted: April 30, 2020
• Study Start: July 1, 2020
• Primary Completion: August 8, 2020
• Study Completion: August 21, 2020
• Last Updated: September 4, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)