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2010-07-07 07:27

Posting: # 5597
Views: 8,707

 Donepezil SR 23 mg Tablets BE study [Study Per­for­mance]

Dear all,

We are planning to conduct a bioequivalence study on Donepezil SR 23 mg tablets in comparision with 10 mg IR tablets for US regulatory. We would like to know whether this study is feasible to be conducted in healthy population or in patients?
If the study need to be conducted in patients, what is the severity of the diseased condition (mild/moderate/severe) to be selected?

With Regards,


2010-07-17 07:23

@ madhavaraob
Posting: # 5647
Views: 7,881

 Donepezil SR 23 mg Tablets BE study

Dear Mr.Madhav,

FDA recommends to conduct Single dose, two way cross over (both Fasting and Fed studies) in males and non-pregnant females general population for Donepezil. Hence, you can conduct the bioequivalence study in healthy volunteers not in patients with Alzheimer's Disease.

Dr.S.Gunasakaran, MD

Dr.S.Gunasakaran, MD
Vice President-Clinical Research & Medical Affairs
AZIDUS Clinical Research Organization. Linkedin Profile
Global Moderator – ClinicalResearchForum

2010-07-22 09:06

@ drgunasakaran1
Posting: # 5661
Views: 7,534

 Donepezil SR 23 mg Tablets BE study

Dear Members,

Thank You very much Dr.Gunasakaran for your reply. I still had a doubt regarding the use of antiemetic for Donepezil as it was clearly reported that it causes severe nausea and vomiting. I would like you suggest a proper Antiemetic in order to avoid emesis and subject withdrawal in the conduct of Bioequivalence study.
Is it approriate to choose Ondansetron (a substrate of CYP 3A4) as an antiemetic in BA/BE study of Donepezil (which is also a substrate of CYP 3A4) in order to avoid emesis? It would be highly appreciated if u share any literature study conducted on donepezil using antiemetic.

Thanking You in ancipation
Awaiting Your Reply.


2010-07-22 10:09

@ madhavaraob
Posting: # 5662
Views: 7,490

 Donepezil SR 23 mg Tablets BE study

Dear MadhavRaoB,

one suggestion: ███████.

KR, Pavidus

Edit: Deleted information considered proprietary by Pavidus’ employer (2010-12-08). [Helmut]

2010-07-23 05:18

@ Pavidus
Posting: # 5663
Views: 7,603

 Donepezil SR 23 mg Tablets BE study

Dear Mr. Kr. Pavidus/Members,
Thank You very much for suggesting the use of ███████. But, I would be very much pleased if you can provide me any literature data on this? i.e., Are there any associated drug interactions with such a combination? In order to proceed with further studies, is it really necessary the use of an antiemetic in BA/BE study of donepezil SR vs IR tablets. If so, Can anyone provide me the literature data on such studies?

With regard to the previous conversation on the use of ███████ as antiemetic to avoid Nausea and vomiting upon donepezil administration, I still had a doubt regarding the choice of antiemetic.
Literature data reveal that ███████ or promethazine can be used to avoid nausea and vomiting assosiated with rivastigmine as rivastigmine is metabolised by sulfate conjugation. Hence less prone to drug interactions. But Donepezil is metabolised by CYP 2D6 (minor), CYP 3A4 and CYP 1A2, hence making it a tedious job in choosing the right antiemetic. Is it appropriate to use ███████ prior to donepezil to prevent nausea and vomiting? Are there any studies reported using such a combination? Orelse Can anyone suggest me the safest antiemetic that can be administered to decrease the subject dropout rate?

Awaiting your reply.

Thanking You in anticipation

Edit: Later post merged to this one. You can edit your posts within 24 hours; no need to open a new one. [Helmut]

Edit: Deleted information considered proprietary by Pavidus’ employer (2010-12-08). [Helmut]

2010-07-26 14:34

@ drgunasakaran1
Posting: # 5680
Views: 7,639

 Donepezil SR 23 mg Tablets BE study

Dear Members,

I need a clarifiction regarding Donepezil SR study. There was a high dropout rate (due to vomiting in pilot studies) observed with Donepezil SR 23mg formulation when dosed in healthy subjects. Recently Pfizer which got approval from FDA for Donepezil SR 23 mg submitted Phase III efficacy results in Alzheimers patients. I would be very much pleased if someone provide me any information on the feasibility of the study in India/USA. Can anyone provide me any data regarding the instituitions/CROs conducting such trials.

Thanking You in anticipation.

Awaiting your reply.

Vienna, Austria,
2010-07-26 15:01

@ chaitanyag
Posting: # 5681
Views: 7,405


Dear Chaitanya and all!

» Can anyone provide me any data regarding the instituitions/CROs conducting such trials

I activated the contact-function in your profile. Other members can send you messages by means of a webform (your e-mail address is not unveiled). No commercial posts directly in the forum, please.

Helmut Schütz 

The quality of responses received is directly proportional to the quality of the question asked. ☼
Science Quotes
Dr. Solanki

2010-08-07 10:28
(edited by Dr. Solanki on 2010-08-07 11:30)

@ chaitanyag
Posting: # 5739
Views: 7,732

 Donepezil SR 23 mg Tablets BE study

Dear Chaitanya,

» We being a CRO in India have been exploring the possibility of conducting a BE study of the formulation both in pts and healthy human volunteers (HHVs) for a requested US submission.

Certain points to be noted as under:
  1. There is no specific draft guidance, yet available from the OGD, FDA. Controlled correspondence for the purpose might take 7-8 months time to know their views!!

  2. The 10 mg IR formulation requires to be tested in HHVs both under fasted & fed states as per the available guidance.

  3. Very limited avaiability of elderly pts fulfilling the eligibility criteria, readiness to sustain the required blood loss, probable dropouts due to vomiting, ethical concerns, etc. are found as hindrances for a multi-dose, steady-state (SS), two-way cross-over BE study in pts.

  4. Upon reviewing the literature, regulatiory guidance on modified ER formulations and BE studies, it appears that a single-dose, two-way, cross-over study in HHVs (if permissible in view of safety profile of the molecule) is expectd to give more reliable results as against a multi-dose, SS one in pt population. Moreover, the molecule has linear P/Ks. This also favours the single dose P/K assessment ruling out the compulsion for undertaking a multi-dose, SS study even from regulatoy point of view.

  5. Drug like quetiapine reported to cause serious cardiac arrhythmias, noticeable giddiness, nausea, vomiting, etc. is also allowed upto 200 mg ER to study in HHVs as a single-dose, two-way, cross-over study. BE reports are accepted without asking for a separate SS study or patient based P/K evaluation (BE). It is only when the strength exceeds (raising safety concerns), i.e. 400 mg ER requires participation by patients only as per the current thinking of OGD and the resultant modified guidance draft.

  6. According to me, reading with the PIL of RLD, the tolerability profile of donepezil 23 mg ER should permit us to do two single-dose, two-way, cross-over BE studies both under fasted and fed states in HHVs to suffice the regulatory requirements.

  7. Since the pilot studies have already reported considerable dropouts due to vomiting, study should be performed under cover of any suitable anti-emetic like ondansetron, dimenhydrinate, etc. having no interaction with the compound.

Pls feel free to share your views.

With best regards,

Dr. Solanki
Dr. Solanki

2010-08-12 11:30

@ Dr. Solanki
Posting: # 5772
Views: 7,163

 Donepezil SR 23 mg Tablets BE study

Dear Members,

Further to my last communication, I am expecting some comments/views from members on the subject. I also thought of a major risk of aspiration bronchopneumonia if the fed study is performed as multi-dose, steady-state in elderly pts. Most eligible pts for the study would be above 60.

Hence, it is even better to opt for the required fasted & fed studies in HHVs
under an apropriately chosen antiemetic. Ondansetron, dimenhyrinate, meclizine, promethazine, etc. have shown no interaction upon reviewing the litt.

Comments from other members pls.. including special request to Helmut.


Dr. Solanki
MD (Pharmacology)
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