Healthy Participants
Conditions
Brief summary
The main purpose of the study is to characterize the systemic pharmacokinetic (PK) parameters (plasma, whole blood) of tebipenem (TBP) pharmacologically active moiety of tebipenem-pivoxil-hydrobromide (TBP-PI-HBr) and its urinary excretion at different dose levels in healthy participants. The study also aims to assess the plasma and urine PK parameters of SPR1349, a major metabolite of TBP.
Interventions
DRUGTBP-PI-HBr
TBP-PI-HBr film-coated immediate-release tablets
Sponsors
GlaxoSmithKline
Spero Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study involves 2 parts (A and B) and 3 cohorts (Cohort 1, 2 and 3) of which Cohort 2 has a crossover design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants who are healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and electrocardiogram (ECG). * Body weight considering body mass index (BMI) within the range of 18 to 32 kilogram per meter square (kg/m\^2), inclusive. * Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 55 years of age inclusive, at the time of signing the informed consent.
Exclusion criteria
* History or presence of/significant history of or current cardiovascular (CV), respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or study procedures or interfering with the interpretation of data. * Past or intended use of over-the-counter or prescription medication including herbal medications within 28 days prior to dosing, with the exception of supplemental vitamins, hormonal medications (contraceptives or hormone-replacement therapy), or occasional oral acetaminophen (not to exceeding 2 g total daily dose). * Current enrollment or past participation in another investigational/observational clinical study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within the last 30 days, or 5 half-lives whichever is longer. * Positive COVID-19 screening test using PCR or antigen assay at Day -1 * Donation of, or significant blood loss of, more than 500 mL of blood within 56 days prior to dosing. * Receipt of a blood transfusion within 1 year prior to enrollment or plasma donation within 7 days prior to dosing. * QTc \>450 msec. Note: Other inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part B: Fe of SPR1349 | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part A and B: Maximum Observed Concentration (Cmax) of TBP in Plasma and Blood | Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part A and B: Time to Cmax (Tmax) of TBP in Plasma and Blood | Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part A and B: Area Under the Concentration-Time Curve (AUC) Extrapolated to Infinity [AUC(0-inf)] of TBP in Plasma and Blood | Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part A and B: AUC From Time Zero to the Time of the Last Evaluable Concentration [AUC(0-t)] of TBP in Plasma and Blood | Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part A and B: Amount Excreted in Urine (Ae) of TBP | Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part A and B: Fraction of Dose Excreted in Urine (Fe) of TBP | Cohort 1: Pre-dose and at multiple timepoints post-dose up to Day 3; Cohort 2: Pre-dose and at multiple timepoints post-dose up to Day 5; Cohort 3: pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part B: AUC From Time Zero to 6 Hours Post-dose AUC(0-6) of TBP in Plasma and Blood | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part B: Ae of SPR1349 | Pre-dose and at multiple timepoints post-dose up to Day 7 |
Secondary
| Measure | Time frame |
|---|---|
| Part B: Cmax of SPR1349 in Plasma | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part B: AUC(0-inf) of SPR1349 in Plasma | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part B: AUC(0-t) of SPR1349 in Plasma | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part B: AUC(0-6) of SPR1349 in Plasma | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part B: Plasma AUC Ratio of SPR1349 to TBP | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Part B: Ae Ratio of SPR1349 to TBP | Pre-dose and at multiple timepoints post-dose up to Day 7 |
| Parts A and B: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Day 1 to Day 21 |
| Part B: Tmax of SPR1349 in Plasma | Pre-dose and at multiple timepoints post-dose up to Day 7 |
Countries
United States
Outcome results
None listed