Replies to post #169031 on Anavex Life Sciences Corp (AVXL)

[imho]

So the first part of the trial will probably be open label so patients can be closely monitored for signs of side effects in an effort to determine MTD for Rett patients. The inter-patient variability and the age related variability in drug clearance are probably why the FDA is requiring the 15 patient study first.

Thanks F1ash. That seems right.

IMHO

[Amatuer17]

“ This study will be followed by a planned placebo-controlled safety and efficacy evaluation of ANAVEX®2-73 over a 3 month treatment period. “

Seems to me that the 3 month study will be a different study and not connected with it.

M with request for protocol for above study which he had talked about but FDA requested kind of safety by conducting shorter study.

IMO it is same as Phase 1, then evaluation of data, new design of next trial and submission of separate protocol.

Well 1 year is lost and one trial is added - 6-8 months also added to timeline. Right approach by fda and shows that the quick final results/approval of Rett that was expected is not on the cards.

[Doc328]

Pharmacokinetic and dose finding will be investigated in a total of 15 patients over a 7-week treatment period including ANAVEX®2- 73-specific genomic precision medicine biomarkers. All patients who participate in the study will be eligible to receive ANAVEX®2-73 under a voluntary open label extension protocol. This study will be followed by a planned placebo-controlled safety and efficacy evaluation of ANAVEX®2-73 over a 3 month treatment period.

I think you are right. They will enroll 15 patients in the 1b dose finding study and follow this up with a larger placebo controlled randomized phase 2 (60-90 patients) based on results. They have not said what age range will be in the study but I assume they will need to have most if not all under age 15 (Neuren did one of their Rett studies with children ages 5-15)as older Rett teenagers and Rett adults could use existing PK/PD data.

They may have to do either weight based or body surface area based dosing as one size does not fit all in pediatrics. The average 5 year old is 43 inches and 43 pounds so has a BSA of about 0.8 m2 (meter squared) while the average 15 year old could be adult height with a range of weights from 100-200 pounds and BSA from 1.5 - 2.0 m2. So the 20-50 mg/day dose in AD would be anywhere from 10-33 mg/m2.

There are a couple ways they can do the ranges but I would expect 15 patients to be either 3 patients at 5 different doses or 5 patients x 3 different doses and they may or not do placebo as one of the doses (some 1b's do to get a truer estimate of AE's and some don't). They may randomly assign doses or do 3 at lowest, then next 3 at next higher dose, next 3 at next higher dose, etc. This allows skipping highest doses if tolerability issues arise and filling in with a mid-dose.

Phase 1's in healthy volunteers are not always listed on clinicaltrials.gov but phase 1 in the target population should be so we should be able to see the inc/exc and dose ranges.

Its good that they are giving out free drug after the study. This will improve recruitment as many parents would not want their child to get multiple blood draws for only 7 weeks of possible benefit.