Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as TBPM-PI-HBr, Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference, Tebipenem pivoxil hydrobromide- Reference, TBP-PI-HBr, Tebipenem pivoxil hydrobromide (TBPM-PI-HBr), Tebipenem pivoxil hydrobromide, SPR994
Tebipenem HBr · 11 trials · 6 indications
Overall response includes combined clinical cure plus microbiological eradication. Clinical cure is defined as a complete resolution or significant improvement of signs and symptoms of cUTI or AP present at baseline and no new symptoms, such that no further antibacterial therapy is warranted, and participant is alive. Microbiological eradication (favorable microbiological response) is defined as a reduction of baseline uropathogens to \<10\^3 CFU/mL and negative repeated blood culture if blood culture was positive for uropathogen growth at baseline and participant is alive.
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
The incidence and severity of AEs
The type and frequency of medications used
Change from baseline to end of study visit
Change from baseline to end of study visit
Change from baseline to end of study visit
Change from baseline to end of study visit
Change from baseline to end of study visit
Change from baseline to end of study visit
Change from baseline to end of study visit
Change from baseline to end of study visit
| Arm | Type | Description |
|---|---|---|
| TBP-PI-HBr | EXPERIMENTAL | Participants received TBP-PI-HBr 600 milligrams (mg), two x 300mg film-coated tablets, orally (PO) and a dummy infusion intravenously (IV), every 6 hours (q6h) from Day 1 through Day 10. Participants with estimated baseline creatinine clearance (CrCl) greater than (\>) 30 millilitres per minute (mL/min) and less than or equal to (≤) 50 mL/min received TBP-PI-HBr 300 mg q6h. |
| Imipenem-cilastatin | ACTIVE_COMPARATOR | Participants received imipenem-cilastatin 500 mg, IV and matched dummy tablets, PO, q6h from Day 1 through Day 10. Dose adjustments for imipenem-cilastatin were made for participants with estimated baseline CrCl less than (\<) 90mL/min per approved imipenem-cilastatin package insert. Participants with baseline CrCl levels greater than or equal to (≥) 60 to \< 90 mL/min were administered imipenem-cilastatin, 400 mg IV q6h and participants with baseline CrCl levels \>30 to \<60 mL/min, were administered 300mg IV, q6h. |
| 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. |
| Part A: Cohort 1 | EXPERIMENTAL | Participants will receive TBP-PI-HBr, 900 milligrams (mg) tablets orally, as a single dose under fasted condition on Day 1. |
| Part A: Cohort 2 (Fasted/Fed) | EXPERIMENTAL | Participants will receive TBP-PI-HBr, 1200 mg, tablets, orally, as a single dose under fasted and fed conditions on Day 1 and Day 3, as per the assigned crossover sequence. |
| Part B: Cohort 3 | EXPERIMENTAL | Participants will receive TBP-PI-HBr, 600 mg, orally as a single dose on Day 1, followed by 9 doses every 6 hours from Day 3 through Day 5. (first and ninth dose will be given under fasted conditions). |
| TBP-PI-HBr 600 mg | EXPERIMENTAL | Healthy participants meeting eligibility criteria will receive a single oral dose of TBP-PI-HBr 600 mg tablets (2 x 300 mg) on Day 1 under fasted conditions. |
| 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. |
| TBPM-PI-HBr Alone (Period 1) | EXPERIMENTAL | Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally alone. |
| 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. |
| 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. |
| A: TBPM-PI-HBr (Reference - fasted) | EXPERIMENTAL | 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions. |
| B: TBPM-PI-HBr (Test - fasted) | EXPERIMENTAL | 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fasted conditions. |
| C: TBPM-PI-HBr (Test - fed) | EXPERIMENTAL | 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr administered at Hour 0 on Day 1, under fed conditions. |
| 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. |
| Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) | EXPERIMENTAL | Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally. |
| SPR994, FI, F2, F3, F4 Oral Tablets | EXPERIMENTAL | SPR994 is active against multidrug-resistant Gram-negative and Gram-positive pathogens that cause serious and life-threatening infections, including extended spectrum beta-lactamase (ESBL) producers as well as strains resistant to levofloxacin and trimethoprim/sulfamethoxazole. SPR994 is administered in tablet form orally. Up to five different time released formulations of SPR994 will be studied in this protocol at 100 mg, 300 mg, 600 mg and 900 mg dosages. SAD Cohorts: One dose (two for food effect cohort) MAD Cohorts: Twenty-seven (27) doses administered twice daily (BID) over a period of 14 days or forty doses administered three times daily (TID) over period of 14 days |
| Placebo Oral Tablet | PLACEBO_COMPARATOR | Placebo tablets (100, 300, and 600 mg) are pressed from a single placebo blend consisting of the same inactive ingredients; the active pharmaceutical ingredient (API) is replaced by Mannitol 200SD. SAD Cohorts: One dose (two for food effect cohort) MAD Cohorts: Twenty-seven (27) doses administered BID over a period of 14 days or forty doses administered TID over a period of 14 days |
| Optional Orapenem Open-Label Control | OTHER | A single, optional, open-label, control cohort that may enroll, in which all 8 subjects receive Orapenem. SAD Cohort: One dose under fasted conditions and one dose under fed conditions. |
| Name | Type | Description |
|---|---|---|
| TBP-PI-HBr | DRUG | TBP-PI-HBr film-coated immediate-release tablets. |
| Imipenem-cilastatin | DRUG | Sterile powder for reconstitution administered as IV. |
| Dummy Infusion | DRUG | 0.9% sodium chloride administered as IV infusion. |
| Dummy Tablets | DRUG | TBP-PI-HBr matching dummy tablets. |
| TBPM-PI-HBr | DRUG | TBPM-PI-HBr tablets administered orally. |
| Ertapenem | DRUG | Antibiotic Therapy for cUTI. |
| Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) | DRUG | Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) 600 mg single-dose given orally. |
| 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. |
| Omeprazole | DRUG | 40 mg (1 x 40 mg capsule) omeprazole administered QD |
| Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Reference | DRUG | 600 mg (2 x 300 mg tablets) clinical study drug product batch TBPM-PI-HBr. |
| Tebipenem pivoxil hydrobromide (TBPM-PI-HBr) - Test | DRUG | 600 mg (2 x 300 mg tablets) registration drug product batch TBPM-PI-HBr. |
| amoxicillin-clavulanate | DRUG | amoxicillin-clavulanate (1 × 500mg/125mg tablet) PO q8h \[±1 hour\] for 10 days |
| SPR994 | DRUG | SAD: Double-blind dosing will occur in all SAD Cohorts except for Cohort 12. In each cohort, six subjects will receive one of five different timed release formulations of SPR994 and 2 subjects will receive placebo. Subjects in SAD Cohorts 2, 3, 6, 16 and 17 will receive a single dose following a 10-h fast. Subjects in SAD Cohorts 1, 8-15 will receive one dose of SPR994 or placebo following a 10-h fast on Day 1 and a second dose following consumption of a standardized meal on Day 7. The dose escalation steps may be altered following review of the safety data of each cohort. MAD: Double-blind dosing will occur in all MAD Cohorts. Subjects will receive multiple doses of an optimal timed release formulation of SPR994 in MAD Cohort 4 (300 mg) and Cohort 5 (600 mg) or placebo for 14 consecutive days at either BID or TID dosing beginning on Day 1. |
| Placebo Oral Tablet | DRUG | Mannitol 200SD SAD: Two subjects in each cohort will receive matching placebo. MAD: Two participants in each cohort will receive matching placebo. |
| Orapenem® | DRUG | Tebipenem pivoxil granules |
Inclusion Criteria: 1. Have a diagnosis of cUTI or AP. 2. Have an adequate urine specimen for evaluation and culture obtained within 24 hours prior to randomization with evidence of pyuria that includes at least one of the following: 1. at least 10 white blood cells (WBCs) per high power field ...
Tebipenem HBr is an oral small-molecule antibiotic being developed by Spero Therapeutics for infectious disease indications, including complicated urinary tract infection. It is an investigational drug that has completed Phase 3 clinical testing.
Tebipenem HBr is being developed to treat complicated urinary tract infections, including acute pyelonephritis, and has also been studied in healthy participants and in people with renal impairment. It is an oral antibiotic intended for infections that are often treated with intravenous antibiotics.
Tebipenem HBr is developed by Spero Therapeutics, Inc., which trades under the ticker SPRO. Spero is the sponsor of the clinical program for the drug.
Tebipenem HBr has completed Phase 3 clinical development. Seven trials have been completed, including a Phase 3 study in complicated urinary tract infection or acute pyelonephritis, and no trials are currently active. It is an investigational drug and is not approved by the FDA.
Tebipenem HBr has been studied in completed trials including NCT06059846, a Phase 3 trial comparing oral TBP-PI-HBr to intravenous imipenem-cilastatin in complicated urinary tract infection or acute pyelonephritis, and Phase 1 trials NCT06727136, NCT05856747, and NCT04710407.
Yes, Tebipenem HBr is also known as SPR994, TBP-PI-HBr, and tebipenem pivoxil hydrobromide (TBPM-PI-HBr). These names refer to the same oral antibiotic candidate developed by Spero Therapeutics.