Pharma_88
☆    

India,
2024-05-15 07:37
(32 d 23:26 ago)

Posting: # 23996
Views: 1,550
 

 Single dose PK study on Patients [Design Issues]

Dear All,

Greetings!!

Would like to your feedback/opinion on conduction of Bioequivalence study (PK end point study) as a single dose administration for a product intended to use for ovarian cancer patients? as per USFDA guideline, its mentioned that steady state study is required. Clause from guideline is captured below.

When safety considerations suggest using patients who are already receiving a medication, often the only approach to establish BE without disrupting a patient’s ongoing treatment is in a steady state study. If a steady-state study is used, we recommend that applicants carry out appropriate dosage administration and sampling to demonstrate the attainment of steady state.


Regards,
Pharma_88

Regards,
Pharma_88
Ohlbe
★★★

France,
2024-05-15 11:39
(32 d 19:23 ago)

@ Pharma_88
Posting: # 23997
Views: 1,383
 

 Single dose PK study on Patients

Dear Pharma_88,

You are referring to a general FDA guidance, which gives general recommendations. Did they publish a product-specific guidance for your product ? It would overrule the general guidance.

The type of study to be performed depends on how the drug is normally used according to its labelling. For instance:
  • if the drug is to be taken continuously (e.g. a kinase inhibitor taken orally): you will indeed have to do a steady-state study;
  • if the drug is given only on Day 1 of each cycle: well, you're not going to give it every day till steady state, it would kill the patient. In such a case you would do a single-dose study. See e.g. the doxorubicin (liposomal) draft guidance.

Regards
Ohlbe
Pharma_88
☆    

India,
2024-05-17 12:06
(30 d 18:56 ago)

@ Ohlbe
Posting: # 23998
Views: 1,251
 

 Single dose PK study on Patients

Dear Ohlbe,

Thank you for responding. Drug is Olaparib and OGD recommends Two-way crossover Steady State PK study. One of our client wish to conduct single dose BE study as a conventional design without interrupting ongoing treatment of patient. Now whether its a feasible by taking appropriate measures of clinical safety?

Regards,
Pharma_88


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post #5! [Ohlbe]

Regards,
Pharma_88
Ohlbe
★★★

France,
2024-05-17 15:45
(30 d 15:18 ago)

@ Pharma_88
Posting: # 23999
Views: 1,241
 

 No, sorry

Dear Pharma_88,

Well, olaparib is to be taken every day, twice a day, and has a terminal half-life of 15 hours. How could you possibly do a single-dose BE in patients, without treatment interruption ? Even if you were to enrol patients requiring treatment and who have not started it yet, and do a 72-hour PK after their first dose: that would mean delaying the next doses, which would trigger some ethical concerns, and you would need to go for parallel design.

Regards
Ohlbe
Pharma_88
☆    

India,
2024-05-20 08:50
(27 d 22:12 ago)

@ Ohlbe
Posting: # 24002
Views: 1,196
 

 No, sorry

Dear Ohlbe,

Thank you for response. Could you please let me know how the parallel design will be planned?

As per my understanding...
Screening >> Stabilization Period (with the approved product) >> Randomization (T/R) >> EOS


Regards,
Pharma_88

Regards,
Pharma_88
Helmut
★★★
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Vienna, Austria,
2024-05-20 09:57
(27 d 21:05 ago)

@ Pharma_88
Posting: # 24004
Views: 1,204
 

 Deviating from a guidance

Hi Pharma_88,

if you want to deviate from a guidance, you have to initiate a Controlled Correspondence with the FDA’s OGD giving a justification. ‘Because my client wants it’ will not suffice.

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Pharma_88
☆    

India,
2024-05-21 10:32
(26 d 20:31 ago)

@ Helmut
Posting: # 24005
Views: 1,082
 

 Deviating from a guidance

Dear Helmut,

Thank you. Yes for For submission study, will definitely initiate CC with FDA. Since this is a pilot study where main objective is to assess the possibility of the single dose administration effect on pharmacokinetic as well as safety. So any possibility to conduct parallel design study? if yes, how it will be designed?

Regards,
Pharma_88
Ohlbe
★★★

France,
2024-05-21 14:41
(26 d 16:21 ago)

@ Pharma_88
Posting: # 24006
Views: 1,069
 

 No, sorry

Dear Pharma_88,

❝ Thank you for response. Could you please let me know how the parallel design will be planned?


No. I did mention parallel design, as this was the only option I could see with a single-dose administration rather than a steady-state study, but I would certainly not advise to do it. The FDA "recommends" a crossover steady-state study for good reasons.

Regards
Ohlbe
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