Sunosi
solriamfetol
Species
RatMouseDog
Longest study
52 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 3-month mouse)
“Pivotal repeat-dose toxicity studies have been performed in mice (up to 3 months), rats (up to 6 months with a 3-month recovery period) and dogs (up to 12 months with a 13 weeks recovery period).”
Why that species
Dog metabolism similar to human (limited hepatic metabolism, mostly renal excretion of parent); no unique human metabolite
“The in vivo metabolism profiles of solriamfetol are similar between dogs and humans, for which limited hepatic metabolism is observed and the majority of the drug is excreted unchanged in the urine.”
Surrogate molecule
No surrogate; the clinical compound was tested
“Rats: In a pivotal 6-month repeat-dose toxicity study with a 3-month recovery period, daily oral doses of 29, 253 and 505 (reduced to 379 at study day 93 because of overt toxicity) mg/kg solriamfetol produced”
Study lengthopen answer page →
Longest pivotal study
52 (12-month dog)
“Pivotal repeat-dose toxicity studies have been performed in mice (up to 3 months), rats (up to 6 months with a 3-month recovery period) and dogs (up to 12 months with a 13 weeks recovery period).”
Pivotal GLP studies
6-month rat and 12-month dog oral studies, plus 3-month mouse
“Pivotal repeat-dose toxicity studies have been performed in mice (up to 3 months), rats (up to 6 months with a 3-month recovery period) and dogs (up to 12 months with a 13 weeks recovery period).”
Route in tox
Oral
“Rats: In a pivotal 6-month repeat-dose toxicity study with a 3-month recovery period, daily oral doses of 29, 253 and 505 (reduced to 379 at study day 93 because of overt toxicity) mg/kg solriamfetol produced”
Skipped studiesopen answer page →
Genotoxicity
Negative in an adequate battery of genotoxicity assays
“Solriamfetol was non-genotoxic in an adequate battery of genotoxicity assays.”
Carcinogenicity
Rat and mouse oral studies: no tumors at up to ~3.5x (rat) and 9x (mouse) the MRHD by AUC
“Solriamfetol was not carcinogenic and did not induce tumors in rats or mice when administered orally at doses up to approximately 3.5- and 9- times the MRHD of 300 mg/day to rats and mice, respectively, based on AUC.”
Reproductive & developmental
Rat and rabbit EFD: maternal and fetal toxicity; teratogenic in rats at 9.5x and rabbits at >=2.5x MRHD
“In embryo-fetal developmental studies, oral administration of solriamfetol during organogenesis caused maternal and fetal toxicities in rats and rabbits at doses ≥ 2- and 2.5- times- and was teratogenic at doses 9.5- and ≥ 2.5- times, respectively, the MRHD”
Safety pharmacology
Cardiovascular, respiratory and CNS studies: no severe adverse effects at clinically relevant doses
“The safety pharmacology of solriamfetol was evaluated in the cardiovascular, respiratory, and CNS systems. No severe adverse effects were identified at the clinically relevant doses.”
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 Sunosi 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: Lung target organ in rats and dogs: alveolar macrophages and phospholipidosis-like inclusions without functional adversity (FDA pharmacology/toxicology review, p. 11)
NOAEL / key findings
Lung target organ in rats and dogs: alveolar macrophages and phospholipidosis-like inclusions without functional adversity
“In both rats and dogs, the target organ of the drug is the lung with elevated macrophages and phospholipidosis-like inclusion bodies (without functional adversity in the lung).”
Risksopen answer page →
Immune & cytokine safety
Dose-dependent changes in immune cell counts and immune organ weight/morphology, most prominent in rats
“Concerning the immune system, dose-dependent effects of solriamfetol on numbers of immune cells and morphology/weight of immune-system related organs (most prominent in rat studies) were observed.”
Biodistribution & persistence
Extensive distribution into pigmented and non-pigmented tissues, including brain
“After oral administration, solriamfetol was extensively distributed into pigmented and non-pigmented tissues, including the brain.”
Modality-specific risk
Stimulant-like CNS toxicity, the most prominent effect across species
“In nonclinical toxicology studies in the mouse, rat, dog, and rabbit, the most prominent drug-related effects of solriamfetol are observed in the CNS, most likely due to its stimulant-like pharmacology.”