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Atlas/Small molecules/Utebzi/First dose

Utebzi: how was the first human dose set?

tebipenem pivoxil · Penicillin-binding proteins
Check my plan vs. these
First-in-human starting dose
Not stated in public reviews
Why it's blank

The public FDA and EMA reviews of Utebzi don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.

How it's usually set for small molecules outside oncology

Find the highest dose with no adverse effects (NOAEL) in each animal species, convert it to a human equivalent dose, usually by body surface area, pick the most appropriate species, then divide by a safety factor (default 10) to get the maximum recommended starting dose.

“In general, one should consider using a safety factor of at least 10. The MRSD should be obtained by dividing the HED by the safety factor.”
✓ VerifiedFDA 2005: Estimating the Maximum Safe Starting Dose in Initial Clinical…, p. 7Source ↗
This product's starting point

NOAEL / key findings: Rat NOAEL 1000 mg/kg/day (28-day GLP) and 300 mg/kg/day (90-day); low-grade stomach and heart findings (FDA integrated review, p. 211)

Full method, every step sourced →

NOAEL / key findings
Rat NOAEL 1000 mg/kg/day (28-day GLP) and 300 mg/kg/day (90-day); low-grade stomach and heart findings
“Because of the low incidence, low severity and the absence of dose-dependency of findings in the stomach and heart, the NOAELs of the GLP 28-day study and non-GLP 14- and 28-day studies in rats are considered to be the high dose of 1000 mg/kg/day and the NOAEL of the non-GLP 90-day study in rats is considered to be 300 mg/kg/day”
✓ VerifiedFDA integrated review, p. 211Source ↗

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Ongentys

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Orgovyx

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Orladeyo

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Orlynvah

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Zepzelca

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Not stated in public reviews

Zokinvy

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Not stated in public reviews

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ganaxolone · GABA-A receptor (positive modulator)
Not stated in public reviews

Zulresso

brexanolone · GABA-A receptor (positive modulator)
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Zurzuvae

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Not stated in public reviews

Zycubo

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Summary across all 211 small molecules →