x Dose setting for a Phase I Clinical
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x Dose setting for a Phase I Clinical Study Suzanne M. Sensabaugh, MS, MBA smsensabaugh@hw-fda. com www. hw-fda. com 1
Suzanne Sensabaugh, MS, MBA Former FDA: Reviewer of hundreds of industry submissions. Committee member who drafted FDA Guidelines: Received numerous awards. Former industry: Drafted submissions for FDA review. Since 2009, assisted in the development of over 120 drugs. www. hw-fda. com 2
Dose setting for Phase I • Based on No Observed Adverse Effect Level (NOAEL) or Minimal Anticipated Biological Effect Level (MABEL) • FDA Guidance for Industry: Estimating the maximum safe starting dose in initial clinical trials for therapeutics in healthy adult volunteers, July 2005 www. hw-fda. com 3
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Conversion of Animal Doses to HED Based on Body Surface Area To Convert Animal Dose in mg/kg to HED in mg/kg, Human Child (20 kg) Mouse Hamster Rat Ferret Guinea pig Rabbit Dog Primates: Monkeys Marmoset Squirrel monkey Baboon Micro-pig Mini-pig Divide animal dose by ----12. 3 7. 4 6. 2 5. 3 4. 6 3. 1 1. 8 Multiply Animal Dose By 3. 1 6. 2 5. 3 1. 8 1. 4 1. 1 ----0. 08 0. 13 0. 16 0. 19 0. 22 0. 32 0. 54 0. 32 0. 16 0. 19 0. 54 0. 73 0. 95 www. hw-fda. com 5
MABEL • Determine No Observed Effect Level (NOEL) and lowest dose where pharmacological response was seen • Then apply a safety factor • A calculation based on microdosing is frequently used www. hw-fda. com 6
Any questions? smsensabaugh@hw-fda. com www. hw-fda. com 7