Clinical trial NCT04368585: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Spero Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-04-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


Eligibility criteria: 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).

Primary outcomes:
measure: Area under the concentration-time curve, from time 0 to the last observed non-zero concentration (t).
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
measure: Area under the curve extrapolated to infinity (AUC0-∞).
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
measure: Percent of AUC0-inf extrapolated (AUC%extrap)
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
measure: Maximum plasma concentration (Cmax).
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
measure: Time to the maximum plasma concentration (Tmax).
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
measure: Terminal elimination half-life (t½).
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
measure: Apparent total body clearance (CL/F)
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
measure: Apparent volume of distribution during the terminal elimination phase after oral (extravascular) administration (Vz/F).
timeFrame: Day 2 (Periods 1 and 2) and Day 6 (Period 3)
Secondary outcomes:
measure: Incidence of treatment-emergent AEs (including SAEs) categorized by severity and relationship to study drug.
timeFrame: 12 to 14 days after the last dose of study drug
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Medical Facility
state: Arizona
Study officials:
affiliation: Spero Therapeutics
name: David Melnick, M.D.
role: STUDY_DIRECTOR
References: