Pixie it is very heart breaking. Here is a comment in particular and a very insightful post "SW" put up on ymb following:
Comment from FDA Patient-Focused Meeting docket
FDA Questions
Topic 1: Disease Symptoms and Daily Impacts that Matter Most to Patients
1.Of all the symptoms that you experience because of your condition, which 1-3 symptoms have the most significant impact on your life? (Examples may include difficulty moving, pain, constipation, difficulty concentrating or remembering, daytime sleepiness, etc.
My ability to concentrate and articulate deteriorates throughout the day. When my wife gets home from work the difficulty is approaching the worse and we spend the rest of the evening with her asking me to clarify what I'm trying to say and/or to speak up. Even though she is patient with me it is embarrassing and I hesitate to try to talk. It's so difficult I don't want to try because it 'not worth it.
Difficulty concentrating is a significant problem. When my medications aren't effective I can feel when I've gone into an "Off" period. It is very difficult to complete any tasks or communicate with others. When they occur I am out of commission. It may take an hour to a day for me to get right. Until I get back "On" nothing gets done.
2.Are there specific activities that are important to you but that you cannot do at all or as fully as you would like because of your condition? (Examples of activities may include daily hygiene, feeding, dressing, etc.
Drive more than a few miles.
Care for my lawn. Sit out doors when it is warm ; walk
How do your symptoms affect your daily life on the best days?
My symptoms do not impact daily life on my best days.
On the worst days?
I become non functional
3.How has your ability to cope with symptoms changed over time?
It is getting more difficult as time passes. I can identify them being caused by Parkinson's Disease and rationally know why I'm experiencing them but at the same time the symptoms become more difficult to control.
Do your symptoms come and go? If so, do you know of anything that makes your symptoms better? Worse?
Yes my symptoms come and go. I can make them better by preventing myself from being exposed to stressors. Physical stressors as simple as trying to pull a few weeds on a hot summer morning. Emotional stressors such as seeing people confronting each other on TV.
As I experience the stressor I can feel my body y processing the experience.
5.What worries you most about your condition?
That it will progress to the point that I'm not able to care for myself but I don't have the ability to end my life sooner than it's natural course.
6.How has your condition affected your social interactions, including relationships with family and friends?
When I was diagnosed I tried to keep it a secret. Glad that I gave up that burden. My children are adults living outside of our home. They both know I have PD and are considerate of the need to make decisions. My wife is processing it too. Sometimes I feel she is being solicitous and treating me like a child. I know in my heart that's not her intention but I still feel it. My friends remain my friends. The problem is that they had a to make decisions about what activies we can enjoy that I could keep up with.
This man's daily struggle illuminates the importance of Trails B [or B minus A, for anyone familiar with enhancing how well Trails can serve as a measure of executive function by subtracting the effort and depressive influence of A from the overall measure of executive function by using B minus A] and the strength of the slower 6 month decline on 250mg. Imagine this HD patient being tested at various times throughout the day, and it should not be hard to realize that the Trails B will be sensitive to these daily variations (in fact, the more sensitive it is as a measure, the more it will be affected). Thus, even with the weight or noise introduced by the various levels of HD cognitive deficit, the group data was still able to show a remarkable (and statistical) change. Also, imagine what Trails B is -- a simple capacity to string together one something with the next or another something, and I hope you can see how much such capacity or incapacity disrupts one of the most (if not the most) significant functional aspects of living one's life, both cognitively and physically. In PHAROS, if I recall correctly, the top 'statistically' significant measures are physical measures of brain regions and other physical markers of HD, with the next bunch of measures "psychological/cognitive," including Trails B (at 15th), but it is performance on B that relates to what this patient is pointing out as one of the most devastating aspects of HD. If PBT2 can slow Trails B decline as it seems it might, it could well be a great help to patients with HD, perhaps especially in the early stages.
Here's a summary I wrote-
Very well said SW. A nice discussion about daily variability that can influence the statistical testing. Not sure if you saw this or not but it wasn't only observed in the Reach2HD trial but the same response was seen in the 2A trial with Alzheimer's patients -
Prana has conducted three Phase 2 trials with PBT2 to date in humans. First off, there were no safety issues encountered during the treatment in any of the three trials. Prana did a Phase 2A trial in an early AD population with 29 randomized to either the placebo or the group treated with 250 mg (another subgroup was treated with 50 mg). The patients treated with PBT2 250 mg had a dose-dependent (p=0023) and significant reduction in CSF Aβ₄₂ concentration compared with those treated with placebo (p=0.006). Meaning they saw a very significant reduction in CSFAB and the more of the medication they got the better they fared. Additionally, those in the 250 mg achieved a statistically significant improvement in the Trails Making Part B test after 12 weeks of treatment (p=0.009) which is a measure of executive function (i.e., how well you can organize your thoughts). The chances of this happening by chance are about 1:50 or 1:100.
Prana also conducted a Phase 2 trial in Huntington’s disease patients and patients were blindly randomized to either the placebo group (n=35), 100 mg dose (n=38) and the 250 mg dose (n=36). Again at the 12-week timeframe the patients treated with PBT2 250 mg had a dose-dependent and significant improvement in Trails Making Part B (p=0.009) and at 26 weeks (p=0.042). This measure is of highest importance in Huntington’s patients as communicated to the FDA in the 9/22/2015 patient-focused meeting. The chances of this happening by chance is
again about 1:100. Additionally, PBT2 was found to affect levels of soluble
mutant Htt in a small study of REACH2HD participants; the first drug to have
accomplished this in a human trial.
The chances of the Trails Making Part B testing repeating by chance in both trials (Phase 2A and REACH2HD) is about 1:400.
PBT Price at posting:
13.0¢ Sentiment: Buy Disclosure: Held
(20min delay)