Bioequivalence and Bioavailability Forum • Inclusion of Smokers

IID
☆

US,
2014-04-11 17:25
(3666 d 12:19 ago)

Posting: # 12814
Views: 3,213

Inclusion of Smokers [Design Issues]

What's US FDA current standing on inclusion of smokers in a BE Study? In this case the BE Study, parallel single dose will be for a long acting, highly variable intramuscular contraceptive. The sample size will 330 Healthy nonpregnant women. The sampling period will be 150 days. Recruitment for such large sample size will be difficult. Thus I would like to include smokers. Will this be acceptable to US FDA?

IID

Edit: Category changed. [Helmut]

Helmut
★★★

Vienna, Austria,
2014-04-11 18:37
(3666 d 11:07 ago)

@ IID
Posting: # 12815
Views: 2,694

Inclusion of Smokers

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Hi IID,

❝ What's US FDA current standing on inclusion of smokers in a BE Study?

Interesting question!

❝ […] parallel single dose will be for a long acting, highly variable intramuscular contraceptive. The sample size will 330 Healthy nonpregnant women. The sampling period will be 150 days. Recruitment for such large sample size will be difficult. Thus I would like to include smokers.

Some ideas:

FDA in their guidances prefers subjects from the general population. I don’t know what the % of smoking women in the US currently is…
AFAIK smoking affects only P450 1A1. If your drug is not a substrate of this CYP-subtype smoking status is not expected to influence PK at all.
If you opt for including smokers, try as best as you can to keep the smoker/nonsmoker-ratio in both treatment groups as similar as possible.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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jag009 ★★★ NJ, 2014-04-11 19:57 (3666 d 09:47 ago) @ Helmut Posting: # 12818 Views: 2,645	Inclusion of Smokers Post reply
	Hello guys and girls, ❝ ❝ What's US FDA current standing on inclusion of smokers in a BE Study? ❝ ❝ Interesting question! No issues (unless FDA specified/metabolite pathway issues). We submitted studies with smokers+non-smokers. I prefer non-smokers though but never did a study with only smokers (okay, except for a NDA study which we did for a smoking sessation drug). John

IID ☆ US, 2014-04-12 06:34 (3665 d 23:10 ago) @ jag009 Posting: # 12822 Views: 2,708	Inclusion of Smokers Post reply
	Thanks John IID 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! [Helmut]

IID ☆ US, 2014-04-12 06:36 (3665 d 23:08 ago) @ Helmut Posting: # 12823 Views: 2,615	Inclusion of Smokers Post reply
	Thanks Helmut. I appreciate. IID 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! [Helmut]

Helmut
★★★

Vienna, Austria,
2014-04-12 17:28
(3665 d 12:15 ago)

@ IID
Posting: # 12825
Views: 2,955

Subgroup analysis?

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Hi IID,

one more thought. The percentage of females aged ≥18 years who were cigarette smokers in 2012 (US data) is estimated with 15.8%.
I don’t know the base of your sample size estimate, but played around with assumptions. For a T/R-ratio 0.90, CV 45%, and target power 80% I got n=332 (80.2% power). The FDA does not expect subgroups to be powered to demonstrate BE, but if you would perform an analysis of the expected 271 non-smokers power will still be 72.8%. Not that bad.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes