TABLE 1 

Summary of nonclinical and clinical in vivo study design following oral administration of MMB

SpeciesNo. of Animals and Subjects 
and SexDoseDose RegimenPurpose and Time Points
Single-dose mass-balance study in healthy subjectsHuman6 M200 mg total (100 μCi total)Single dosePK of radioactivity in blood and plasma, mass balance, excreta, metabolite identification
Blood and plasma: predose, 0.25, 0.50, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h
Urine: predose (−12 to 0), 0–4, 4–8, 8–12, 12–24, 24–36, 36–48, 48–72, 72–96, and 96–120 h
Feces: predose (−24 to 0), 0–24, 24–48, 48–72, 72–96, and 96–120 h
Cross-species comparison of MMB and metabolite plasma steady-state exposure after repeat dosesRata6 M and 6 F20 mg/kgRepeat dose: QD for 90 daysPlasma PK on day 91: predose, 1.5, 3, 6, 9, 24 h
Doga6 M and 6 F60 mg/kgRepeat dose: QD for 90 daysPlasma PK on day 91: predose, 1.5, 3, 6, 9, 24 h
Human9 M and 9F300 mgRepeat dose: QD for 28 daysPlasma PK on day 28: predose, 0.50, 1, 2, 3, 4, 8, and 24 h
Pharmacokinetics of MMB and M21 following oral coadministration to ratsRata3 M5/25 mg/kgbSingle dosePlasma PK: predose, 0.25, 0.50, 1, 2, 4, 6, 8, 12, 24 h
  • F, female; M, male; QD, once daily.

  • a Strain: Sprague Dawley rat; beagle dog.

  • b Coadministration of MMB and M21 at 5 and 25 mg/kg, respectively.