Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
TBPM-PI-HBr · 4 trials · 3 indications
Overall response is participants with combined clinical cure and microbiological eradication. Clinical cure is defined as complete resolution or significant improvement of signs and symptoms of cUTI or AP that were present at baseline and no new symptoms, such that no further antimicrobial therapy is warranted. Microbiological eradication is defined as reduction of baseline urine pathogen(s) to \<10\^3 colony forming unit/milliliter (CFU/mL) and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline.
An Adverse Event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation participant administered a pharmaceutical product, which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational/experimental) product, whether or not related to this product.
Plasma PK parameters will include the area under the curve (AUC) from time zero to the last quantifiable sample (AUC0-t), AUC from time zero to end of dosing interval (AUC0-8). The AUC0-8 values for ELF and AM will be determined. The ratios of the AUC0-8 of ELF to the AUC0-8 of plasma and the AUC0-8 of AM to the AUC0-8 of plasma will be calculated.
The primary PK outcome endpoints following oral administration of \[14C\]-TBPM-PI-HBr will be derived for TBPM in plasma (calculated from whole blood concentrations) based on the concentration-time profile
The primary PK outcome endpoints following oral administration of \[14C\]-TBPM-PI-HBr will be derived for total radioactivity in whole blood and plasma based on the total radioactivity concentration-time profile
Changes in the number of microorganisms identified in feces
Changes in the types of microorganisms identified in feces
| Arm | Type | Description |
|---|---|---|
| TBPM-PI-HBr 600 mg | EXPERIMENTAL | TBPM-PI-HBr 600 mg (300 mg×2 ) film-coated tablets, administered orally three times per day (every 8 hours \[q8h\] ± 0.5 h) plus a single dummy IV infusion over 30 minutes (min) once daily (every 24 hours \[q24h\] ± 0.5 h) up to Day 15; participants with moderate renal insufficiency (creatinine clearance \[CrCl\] \>30 to ≤50 mL/min) required TBPM-PI-HBr dosage adjustment to 300 mg (one tablet) q8h ± 0.5 h. |
| Ertapenem 1 g | ACTIVE_COMPARATOR | Ertapenem for IV injection, administered as a 1-gram IV infusion over 30 min once daily (q24h ± 0.5 h) plus dummy placebo tablets administered orally q8h (±0.5 h) up to Day 14; no dose adjustment of ertapenem was required for participants with renal insufficiency. |
| TBPM-PI-HBr | EXPERIMENTAL | Healthy subjects meeting eligibility criteria will receive a total of five doses of TBPM-PI-HBr 600 mg orally every 8 hours. |
| amoxicillin-clavulanate | ACTIVE_COMPARATOR | Healthy subjects meeting eligibility criteria will be sequentially randomized to receive either 500/125mg amoxicillin-clavulanate PO q8h (±1 hour) or 600mg TBPM-PI-HBr every 8 hours (PO q8h \[±1 hour\]) or for 10 days. |
| Name | Type | Description |
|---|---|---|
| TBPM-PI-HBr | DRUG | TBPM-PI-HBr tablets administered orally. |
| Ertapenem | DRUG | Antibiotic Therapy for cUTI. |
| Dummy Infusion | DRUG | Dummy intravenous infusion. |
| Dummy tablets | DRUG | Dummy tablets orally. |
| amoxicillin-clavulanate | DRUG | amoxicillin-clavulanate (1 × 500mg/125mg tablet) PO q8h \[±1 hour\] for 10 days |
Inclusion Criteria 1. Male and female participants at least 18 years of age. 2. Able to provide informed consent. 3. Able to ingest oral tablets for the anticipated treatment duration. If present at baseline, nausea and/or vomiting should have been mild or well-controlled with antiemetic therapy, i...
TBPM-PI-HBr is an investigational small molecule being studied for complicated urinary tract infection (cUTI) and acute pyelonephritis. It has completed a Phase 3 trial in these conditions, as well as Phase 1 trials in healthy volunteers to assess its effects on intestinal microbiota, absorption, metabolism, excretion, and intrapulmonary pharmacokinetics.
TBPM-PI-HBr is being developed by Spero Therapeutics, Inc., a biopharmaceutical company. Spero Therapeutics is publicly traded under the ticker symbol SPRO.
TBPM-PI-HBr is in Phase 3 clinical development for complicated urinary tract infection and acute pyelonephritis. A Phase 3 trial (NCT03788967) has been completed, along with three Phase 1 trials in healthy volunteers. The drug is investigational and not yet approved.
TBPM-PI-HBr has completed four clinical trials. The Phase 3 trial NCT03788967 evaluated its efficacy and safety versus ertapenem in 1372 participants with cUTI or acute pyelonephritis. Phase 1 trials include NCT04376554, NCT04625855, and NCT04710407, which studied its effects on gut microbiota, metabolism, and lung penetration in healthy volunteers.
Yes, TBPM-PI-HBr is the same as tebipenem pivoxil hydrobromide. The drug is also referred to by the code names SPR994 and SPR859 in clinical trial documentation. These names all refer to the same investigational oral carbapenem antibiotic.
TBPM-PI-HBr is an orally administered carbapenem antibiotic. It works by inhibiting bacterial cell wall synthesis, which leads to bacterial cell death. This mechanism makes it potentially effective against a range of gram-positive and gram-negative bacteria that cause complicated urinary tract infections.