A Little Help With the AM-101 Phase 2 Study...

Hi Dr. Nagler, first off, thank you very much for keeping up with this board and providing your thoughts and opinions. its great to have you on here. I'm at 1 month with tinnitus now and I'm thinking very hard about going to get screened for the AM-101 trial. I've been keeping up with your comments and I understand you are not sold on the medication. I want to quickly run through just a couple of things from the phase 2 study with you and make sure I am understanding it right. Let me also say that I am a Nurse Anesthetist so I do feel comfortable with a lot of the medical jargon on here. In fact, I put patients to sleep for tympanotomies and intratympanic steroid injections all the time.

It seems like here on this board the "general concenusus" is that the AM-101 results thus far have been "underwhelming." Although it seems like 75% of the people on this board that have gotten the injections say that their tinnitus is better.

So let me get to the specific parts of the study. First off, with this statement it seems to imply that the study failed: "The global null hypothesis of no differences between treatment groups in the change of MML from baseline to Day 90 could not be rejected: least square means were 8.2, 7.9, and 7.9 dB (SL) for the placebo, low- and high-dose groups, respectively (p = 0.9919). The study thus failed to meet its primary efficacy end point."

But it then goes on to say this: "However, further analysis of descriptive statistics and ANCOVA models of the primary and coprimary end points with the prespecified covariates and subgroups revealed consistent differences between changes in MML and changes in tinnitus loudness and tinnitus annoyance."

I am taking the above to mean that although the specific measureable numbers needed to reject the null hypothesis were not met, but that there were statistical differences in treatment groups.

But here is the quote from the study I'd really like your opinion on: Improvement in TLQ from baseline to Day 90 of at least 50% was seen for 14% of patients in the placebo group compared with 42% of patients in the high-dose group. Approximately 57% of patients in the high-dose group rated their tinnitus severity at Day 90 compared with baseline as “much improved” or “very much improved,” compared with 39% and 34% of patients in the low-dose and placebo groups. Again, differences were more pronounced among unilateral cases (64% in the high-dose group versus 44% and 35% in the low-dose and placebo group) (Fig. 2)."

Is that not a significant improvement over placebo?

 

@aarondowns22 -

I read the full report, re-read it, and re-re-read it. Best I can tell - and I might be wrong here - the study showed no statistically significant effect over placebo in the basic study design. The investigators then took apart the data to see if something fell out outside the study design. Sort of like throwing a bunch of mud against a wall to see if anything stuck. And apparently it did. My feeling is that before coming to a conclusion one way or another, a formal study should be set up looking just at those parameters.

Your question is a good one, but it is way over my pay grade. I gave it my best shot, but I hope you will not hang your hat on my response.

Dr. Stephen Nagler