Sound Pharmaceuticals (SPI-5557 & SPI-1005)

Is this for noise induced tinnitus?

 

Yes I believe it is.

 

Thank you for clarifying, @FGG! That is actually a relief to me because I had a really bad reaction to NAC, and I was starting to worry that I’d have the same issue with ebselen. The thought of this drug helping in anyway is the only thing keeping me off the ledge. I can’t take years more of this extreme hyperacusis pain and isolation away from my family.

I’m sorry the IVs didn’t work for you. I would give the Glutathione IV a try, but considering my bad NAC reaction that’s probably not a good idea. I wonder if my bad NAC reaction was because of my metal fillings? Who knows.

 

I can't seem to find any data on the safety profile of SPI-1005 from phase 1. Is it available somewhere?

 

They reported no serious adverse effects but the details of the mild to moderate effects would be reported at a meeting "by the end of the year". This was in 2019. So maybe it wasn't a meeting that had a transcript or a webcast?

Sound Pharmaceuticals announces positive topline results from the SPI-1005 Phase 2b Meniere’s Disease clinical trial

This is just a hunch but since the drug can apparently act on the same calcium channel as Amlodipine, I imagine hypotension might be one of the possible adverse effects, especially to anyone already prone to it but maybe someone knows how to find the specifics.

 

So the claim for SPI-1005 is that it works by reducing inflammation? I can see how that potentially improves SNHL in Meniere's Disease patients, but how would it improve anything for someone with just ”regular” hearing loss/tinnitus? What would the mechanism be?

 

Sorry if this information has already been posted (although I did not find it on the forum).

A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania

Full article:
https://link.springer.com/article/10.1007/s00213-020-05654-1

These are the sentences of interest:

"Ebselen has been studied in several phase 3 trials in Japan as a neuroprotective treatment to limit the neurological deficits produced by acute stroke and in several phase 2 trials in the USA as a treatment for hearing loss and tinnitus disorders (Kil et al. 2017)."

"Our collaborators, Sound Pharmaceuticals Inc. (SPI), Seattle, USA, supplied ebselen (SPI-1005) and matching placebo and cross referenced four active indications (INDs) in the USA where SPI-1005 had been tested for 3–4 weeks in several hearing loss and tinnitus indications."


And the link that matters to us:

Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial

Summary

Background
Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial.

Methods
In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18–31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846.

Findings
Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these participants were excluded from the efficacy analysis. Mean TTS at 4 kHz was 1·32 dB (SE 0·91) in the 400 mg ebselen group compared with 4·07 dB (0·90) in the placebo group, representing a significant reduction of 68% (difference −2·75 dB, 95% CI −4·54 to −0·97; p=0·0025). Compared with placebo, TTS at 4 kHz was non-significantly reduced by 21% in the 200 mg ebselen group (3·23 dB [SE 0·91] vs 4·07 dB [0·90] in the placebo group; difference −0·84 dB, 95% CI −2·63 to 0·94; p=0·3542) and by 7% in the 600 mg ebselen group (3·81 dB [0·90] vs 4·07 dB [0·90] in the placebo group; difference −0·27, 95% CI −2·03 to 1·50; p=0·7659). Ebselen treatment was well tolerated across all doses and no significant differences were seen in any haematological, serum chemistry, or radiological assessments between the ebselen groups and the placebo group.

Interpretation
Treatment with ebselen was safe and effective at a dose of 400 mg twice daily in preventing a noise-induced TTS. These data lend support to a role of GPx1 activity in acute noise-induced hearing loss.

Full article:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31791-9/fulltext

 

Imagine this, SPI-1005 allows noxacusis sufferers to live a relatively normal life (with some compromises, just not the level of no life we have right now) on a high enough dose.

Yes I'm a dreamer. Fingers crossed.

 

That would be beyond amazing!

 

Are there any specific reasons that you would put your hope to this drug when it comes to noxacusis, compared to others that are currently in the pipeline?

 

It’s likely to be the first available to the public. That helps.

 

Read the thread.

 

How is your overall protocol working for you? Seeing any benefits?

 

I'm still experimenting and adding new supplements every week. I would say I have seen marginal benefits, but it's always difficult to know exactly whether it's down to any individual or combination of supplements or not. I felt the best I had felt until a couple of days ago, only for a friend to accidentally speak near my left ear and I've had another setback, so here we go again. I've added Tru Niagen (Nicotinamide Riboside) to the protocol and will be adding resveratrol soon as well when my microscale arrives. I believe these supplements to be the most promising from all the reading/research I've done, especially when combined with others such as Lion's Mane, so will report back in a month or two after I've taken them for an established period of time. You really need to give some of these supplements two months or so to get an idea as to whether they're helping you or not.

 

Weird one does anyone think this will help with misophonia?

 

Misophonia is discomfort from particular sounds, like crunching or chewing. Do you mean phonophobia, the irrational fear of sound? That's psychological, this aims to treat inflammation in the inner ear. Or are you actually asking if this can help with noxacusis? Anyway, I imagine that's something that would have to be treated through counseling only once and if the underlying hyperacusis damaged is fully repaired, otherwise the fear of noise causing pain is completely justified and not irrational.

The hope is that this can dull or completely remove noxacusis pain altogether if it is caused by inflammation. We'll find out once the drug is released.

 

Misophonia is thought to be a neurological condition, so no, it wouldn't treat misophonia.

 

I just want to see even one of these ear drugs out so we can start to get some form of relief. If even one drug gives relief from hyperacusis, tinnitus or even gives back a little hearing it'll be awesome. Really hoping SPI-1005 will be out by next year. I'm so tired of hyperacusis, spasms, and feeling like my entire face is on fire.

 

Are we sure SPI-1005 would cure noxacusis? Completely?

 

I don't think it should be regarded as a cure because ultimately it's not a drug that's actually aimed at repairing the cochlea. But there's probably a good amount of cochlear inflammation from noxacusis that would be well served by this drug.

 

No.

 

Still hoping it will also work for reactive tinnitus. Seriously, if this helps my tinnitus from fluctuating as wildly throughout the day, I'll be happy.

 

I hope that too. Just now I'm living a hell spike since morning after two weeks of "less" reactiveness. I thought it was going to calm down a bit but then here I am. Can't live forever with this.

 

Holy hell are the development timelines long... the last NIHL trial is from 2013/2014.

 

Is SPI-1005 an injection or a tablet that you consume?

When are they likely going to release SPI-1005?

 

It’s a tablet.

Pans if it passes it’s COVID-19 trial in April, probably soon after that COVID-19 is a high priority.

 

It's a consumable tablet. It's in numerous trials for different conditions. All are in various phases. The furthest is for Meniere's disease and that's entering Phase 3, but it could be out sooner because it's been proven effective against COVID-19 and the Phase 2 trial for that ends in April.

If I were to guess I would say it's going to be available either late next year or early 2022.

 

Fuck I’m glad it’s in tablet form. If it comes out in the United States will anyone be trying it for pain hyperacusis first or are you going to wait for an anecdote?

 

I’m an American and I’ll probably try to get it.

 

Let me know how it goes. Does anyone have links to both the Meniere’s and COVID-19 clinical trials for SPI-1005?