Brus
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Spain,
2023-12-09 18:45
(85 d 08:17 ago)

Posting: # 23790
Views: 792
 

 Single-dose study in patients [Design Issues]

Dear All,

When you need to perform the study in patients due to tolerability/safety reasons, How do you perform the washout period in patients? (Between periods and before period 1 to avoid pre-dose concentrations in both periods).

Thank you so much

Best regards,
Helmut
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Vienna, Austria,
2023-12-10 10:43
(84 d 16:19 ago)

@ Brus
Posting: # 23791
Views: 646
 

 Single-dose study in patients

Hi Brus,

❝ When you need to perform the study in patients due to tolerability/safety reasons, How do you perform the washout period in patients? (Between periods and before period 1 to avoid pre-dose concentrations in both periods).


A SD crossover is only possible for drugs in patients with a stable disease (e.g., theophylline in asthmatics). Otherwise, you have to opt for a parallel design.
  • Get PK data from the literature. Don’t use the average half life, be conservative (example).
  • Plan the study (first dose after the patients’ usual treatment, washout) with ≥ 5 × t½. If that’s longer than the common dosing interval → SD not possible.
  • Simulate concentrations (in Phoenix / Win­Non­lin’s ‘nonparametric superpostion’ module or even a spreadsheet) with your dose & regimen. If you would get pre-dose concentrations > 5% of Cmax in a substantial number of subjects → SD not possible.
  • If a SD study is not possible, you have to perform the study in steady state. Sorry.

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dshah
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India/United Kingdom,
2023-12-11 11:44
(83 d 15:18 ago)

@ Brus
Posting: # 23792
Views: 711
 

 Single-dose study in patients

Hi Brus!

❝ When you need to perform the study in patients due to tolerability/safety reasons, How do you perform the washout period in patients? (Between periods and before period 1 to avoid pre-dose concentrations in both periods).


Generally the patient study is required to be performed for stabilized patient. How can treatment be discontinued in patient?

Regards,
Divyen
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