Nereus
tradipitant
Species
RatMouseDog
Longest study
26 wk
Genotox
Conducted Conducted
Carcinogenicity
Conducted Conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Rat and dog (plus 13-week mouse)
“Repeat-dose oral toxicity studies with tradipitant have been conducted in mice (13 weeks), rats (up to 6 months), and dogs (up to 3 months).”
Why that species
Not stated in public reviews
The reviews list the species but not why. For small molecules, ICH M3(R2) expects one rodent and one non-rodent species, chosen with in vitro metabolism, protein binding and exposure data compared with human.
“In vitro metabolic and plasma protein binding data for animals and humans and systemic exposure data (ICH S3A, Ref. 7) in the species used for repeated-dose toxicity studies generally should be evaluated before initiating human clinical trials.”
✓ VerifiedICH 2009: ICH M3(R2): Guidance on Nonclinical Safety Studies for the Conduct…, p. 11Source ↗
Surrogate molecule
No surrogate; the clinical compound was tested
“In a 6-month toxicity study in Fischer 344 rats, tradipitant was orally administered once daily at doses of 0 (vehicle), 15, 150, or 1500 mg/kg/day.”
Study lengthopen answer page →
Longest pivotal study
26 (6-month rat)
“Repeat-dose oral toxicity studies with tradipitant have been conducted in mice (13 weeks), rats (up to 6 months), and dogs (up to 3 months).”
Pivotal GLP studies
6-month Fischer rat, 3-month Han Wistar rat and 3-month dog studies
“repeat-dose toxicity studies in mice (13 weeks), Fisher rats (1, 3, and 6 months), Han Wistar rats (3 months), and dogs (1 and 3 months)”
Route in tox
Oral
“In a 6-month toxicity study in Fischer 344 rats, tradipitant was orally administered once daily at doses of 0 (vehicle), 15, 150, or 1500 mg/kg/day.”
Skipped studiesopen answer page →
Genotoxicity
Negative in Ames, in vitro human lymphocyte chromosomal aberration and mouse micronucleus assays
“Tradipitant was negative in a complete battery of genetic toxicity studies, including the Ames assay, an in vitro chromosomal aberration assay in human lymphocytes, and an in vivo micronucleus assay in mice.”
Carcinogenicity
26-week rasH2 mouse: no tumors; 2-year rat: dose-related thyroid follicular cell tumors at all doses
“In transgenic rasH2 mice orally administered tradipitant (15, 50, or 1500 mg/kg/day) for 26 weeks, there was no increase in tumors. In rats orally administered tradipitant (10, 30, or 150 mg/kg/day) for at least 104 weeks, a dose- related increase in the incidence of thyroid follicular cell tumors (adenomas or adenomas combined with carcinomas), correlating with the findings of thyroid masses and cysts, was observed at all tested doses”
Reproductive & developmental
Rat combined fertility/EFD: no effects on fertility, maternal health or embryo-fetal development up to 1000 mg/kg/day
“No effects on fertility, maternal health, or embryo-fetal development were observed in rats treated with tradipitant during the periods of mating and organogenesis at doses up to 1000 mg/kg/day (57-fold the maximum clinical dose, based on HED; 2.2-fold based on AUC).”
Safety pharmacology
No ECG effects in conscious dogs at single oral doses up to 800 mg/kg (157-fold clinical dose)
“In a cardiovascular safety pharmacology study in conscious male and female Beagle dogs, single oral doses of tradipitant up to 800 mg/kg had no significant effects on qualitative or quantitative ECG parameters (157-fold the maximum clinical dose of 170 mg, based on HED).”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Nereus 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.”
This product's starting point
NOAEL / key findings: Target organs liver and thyroid (FDA integrated review, p. 107)
NOAEL / key findings
Target organs liver and thyroid
“Repeat-dose oral toxicity studies with tradipitant have been conducted in mice (13 weeks), rats (up to 6 months), and dogs (up to 3 months). Target organs were identified as liver and thyroid.”
Risksopen answer page →
Immune & cytokine safety
Not stated in public reviews
Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.
Biodistribution & persistence
Excreted in milk of lactating rats
“Tradipitant was excreted in milk of lactating rats that received tradipitant at 100, 300, or 1000 mg/kg (2.3, 2.4, and 3.3 times the exposure to tradipitant at the MRHD) during pregnancy from gestation day 6 through lactation day 20.”
Modality-specific risk
Hepatotoxicity: liver injury risk from tradipitant and its major metabolites
“Based on the available nonclinical data, a risk for liver injury with tradipitant and its major metabolites has been identified.”