Bioequivalence and Bioavailability Forum

Rajdoc ☆ India, 2014-03-11 13:08 (4488 d 11:18 ago) Posting: # 12590 Views: 5,002	Drowsiness [Regulatives / Guidelines] Post reply
	Hi all For most of the antipsychotics drowsiness is a common side effect, and some times it could be 100 %. what are the options we have when the drowsiness is 100 % in a study, Do we have to report individually???? Drowsiness is a side effect and extension of a pharmacodynamic effect so is it really necessary to report it as an AE

Helmut
★★★

Vienna, Austria,
2014-03-11 14:40
(4488 d 09:47 ago)

@ Rajdoc
Posting: # 12594
Views: 4,350

TEAE

Post reply

Hi Rajdoc,

❝ For most of the antipsychotics drowsiness is a common side effect, and some times it could be 100 %. what are the options we have when the drowsiness is 100 % in a study, Do we have to report individually????

Yes.

❝ Drowsiness is a side effect and extension of a pharmacodynamic effect so is it really necessary to report it as an AE

Again yes. I’m pretty sure your protocol contains even a section classifying AEs (see this post for an example). In your case the AE is well known – why do you think that it will not be necessary to report it?

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

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Rajdoc ☆ India, 2014-03-12 08:06 (4487 d 16:21 ago) @ Helmut Posting: # 12602 Views: 4,324	TEAE Post reply
	Hii My question is. Is drowsiness an unintended effect of anti psychotics????.... Could we really term the side effect as an adverse effect FDA itself states that the participant has to be in supine position for certain period for antipsychotics, we cannot expect the participant to be awake and alert in that position....

Ohlbe ★★★ France, 2014-03-12 15:17 (4487 d 09:09 ago) @ Rajdoc Posting: # 12606 Views: 4,249	TEAE Post reply
	Dear Rajdoc, If you are doing your study in patients, fine. If the study is on healthy volunteers, I would also consider this to be an adverse event. Expected for sure, but an adverse event nevertheless. — Regards Ohlbe

Helmut
★★★

Vienna, Austria,
2014-03-12 17:53
(4487 d 06:33 ago)

@ Rajdoc
Posting: # 12609
Views: 4,340

TEAE

Post reply

Hi Rajdoc,

❝ My question is. Is drowsiness an unintended effect of anti psychotics????....

❝ Could we really term the side effect as an adverse effect

Perseverated. You have to report all AEs, expected or not, drug-related or not. Once in our studies a volunteer was bitten by a dog in the washout period. Since he had to visit the next ambulance to get some stitches, it was even an SAE. Drug-related? No way. Reported? Sure.

I don’t understand why you are trying to navigate around reporting AEs, especially if they are clearly TEAEs like in your case.

❝ FDA itself states that the participant has to be in supine position for certain period for antipsychotics, we cannot expect the participant to be awake and alert in that position...

Are you trying to tell that subjects are drowsy not caused by the drug but by the fact that they are lying in bed?

Sometimes I watch TV in bed and I can assure you that I’m both awake and alert.
Sometimes in the office (in upright position) while reading posts in the forum only a quick shot of coffee can prevent me from falling into a deep slumber.

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

The quality of responses received is directly proportional to the quality of the question asked. 🚮
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ElMaestro
★★★

Denmark,
2014-03-12 18:17
(4487 d 06:10 ago)

@ Helmut
Posting: # 12610
Views: 4,207

TEAE

Post reply

Hi Hötzi,

❝ You have to report all AEs, expected or not, drug-related or not. Once in our studies a volunteer was bitten by a dog in the washout period. Since he had to visit the next ambulance to get some stitches, it was even an SAE. Drug-related? No way. Reported? Sure.

What if a volunteer eats a psychotropic drug and then bites a dog? Who can hold who legally responsible if the investigator considers this occurrence of aggression drug related? - What if the drug was T? What if it was R? Who must pay the vet's fee when the dog needs stitches?

—
Pass or fail!
ElMaestro

Helmut
★★★

Vienna, Austria,
2014-03-12 18:38
(4487 d 05:49 ago)

@ ElMaestro
Posting: # 12611
Views: 4,230

OT

Post reply

Hi ElMaestro,

❝ What if a volunteer eats a psychotropic drug and then bites a dog? Who can hold who legally responsible if the investigator considers this occurrence of aggression drug related? - What if the drug was T? What if it was R? Who must pay the vet's fee when the dog needs stitches?

You are raising very important points calling for thoughtful considerations! Reminds me of an e-mail conversation I had with one of our mutual friends.

Dear respectful Sir!
I started my two-stage study with reference A and a street-dog ate the remaining IMPs. In the meantime the innovator went bancrupt. Can I use another generic as a reference in the second part, and if yes, another – better – analytical method? Awaiting your highly esteemed reply.
Yours faithfully,
██████████████, MD, PhD, PharmD, MBA.
Dear ██████████████,
you should have an SOP in place to take care of such situations; this is a true deficiency in your Quality System. First of all you need to find this street dog and have it sign a consent form after informing it of the possible side effects of the drug. You will need an impartial witness such as the dog’s owner. As per DCGI recent recommendations you should take a video and audio recording of the consenting process. Make sure that the consent form is signed from before the dog ate the IP. In case of a female dog run a pregnancy test. You have to take measures to ensure that the same dog does not eat further IPs for the next 90 days, as per the exclusion period in your protocol. You also have to inform immediately the Ethics Committee, unless you had very thoughtfully planned for this possibility in your protocol. As per Schedule Y, DCGI only needs to be informed in case the study is on a new drug or a modified release formulation. For the remainder of the study, just run it as test versus test as per common practice.
Dear respectful Sir!
I will follow your suggestions and will include them in my updated SOPs.
██████████████, MD, PhD, et cetera.

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

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mittyri
★★

Russia,
2014-03-13 21:40
(4486 d 02:46 ago)

@ Helmut
Posting: # 12616
Views: 4,577

AE definition in BEQ study

Post reply

Hi Rajdoc, Helmut & All!

I'd like to discuss the problem of AEs in BEQ studies in this topic, if you please.

At this moment we haven't clear harmonization with clinical center about AE definitions in healthy volunteers.
The investigator insists that if the volunteer has no clinical signs (no complaints) - there's no AE.
I think this position is a little bit strange. For example, if control lab test indicates that WBC level is 3.6 and the volunteer has no complaints, Investigator concludes - NCS! No AE!
I think in this case AE should be reported. But where is a borderline??
OK, We have reference values for lab test. We can say that results exceeded the reference limits are AE. (e.g. Hb was changed from 170 g/l to 172 g/l - AE!)

What about ABP? 95/60? 110/59? Waiting for collapse?
What about HR? 59? 50? Waiting for Morgagni syndrome?

I've found a nice article from Michel Sibille et al. about AE definitions in healthy volunteers in phase 1. Is that applicable for BEQ study?
What is your experience in AE definitions? Please advise

—
Kind regards,
Mittyri

Helmut
★★★

Vienna, Austria,
2014-03-14 15:39
(4485 d 08:47 ago)

@ mittyri
Posting: # 12627
Views: 4,321

Great post!

Post reply

Hi Mittyri,

that’s a great post!

❝ The investigator insists that if the volunteer has no clinical signs (no complaints) - there's no AE.

❝ I think this position is a little bit strange. For example, if control lab test indicates that WBC level is 3.6 and the volunteer has no complaints, Investigator concludes - NCS! No AE!

❝ I think in this case AE should be reported.

Fully ACK. I’m not sure whether it is already an AE, but most protocols would require at least a follow-up lab exam.

❝ But where is a borderline??

Very good question. Invest the intellectual horsepower in the protocol. I think the PI does the reliability of the study’s procedures no good if he/she checks as many as possible lab deviations “NCS” and has the ambition to report as few as possible AEs. I’m always a little bit suspicious if I read a report with a very limited numbers of AEs. In many countries most people are habitual consumers of coffee/tea – which is prohibited in many studies. Caffeine-withdrawal leads to headaches in up to 30% of subjects… No AEs in the report? I doubt it.

❝ I've found a nice article from Michel Sibille et al. about AE definitions in healthy volunteers in phase 1.

Nice article. THX.

❝ Is that applicable for BEQ study?

With some adaptations it is a good starting point. However – unlike in FIM – the AE-profile is already known; this would allow to adapt the “warning levels”.

❝ What is your experience in AE definitions?

Case-by-case – mainly led by the SmPC of the reference product and the IMPD.

—
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

Drowsiness [Regulatives / Guidelines]

TEAE

TEAE

TEAE

TEAE

TEAE

OT

AE definition in BEQ study

Great post!