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Post by Deleted on Aug 24, 2017 19:57:00 GMT -5
matt Do you know the difference between pharmacokinetics and pharmacodynamics and how to calculate the area under curves. If you did, you would see a tremendous difference between Afrezza and lispro. Just because a few data points coincide between the two products doesn't mean they are the same.
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Post by sayhey24 on Aug 24, 2017 20:05:17 GMT -5
Matt - what are the safety concerns you think they need to address? Use by kids with COPD and who smoke? I am not sure those kids will be included in the study.
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Post by nadathing on Aug 24, 2017 20:44:20 GMT -5
I seem to remember timetables of 3-6 months. With 6 months being on the long side... With the timetable that's listed many of the pediatric patients won't be "pediatric" when it finishes... I didn't see anything "suspicious" when giving it a read through. The only thing I can think of is they're expecting difficulties signing up patients. But there is 9 locations listed and they only expect 46 patients...weird. I have been in a few trials. Recruiting people for these trials is extremely difficult. You wouldn;t think it would be, but it is. Qualifying is not always easy and then sticking to the regiment can be really difficult.
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Post by thall on Aug 24, 2017 20:53:01 GMT -5
Makes absolutely no sense to me. Several have pointed out that the "Estimated Study Completion Date: January 2021" for what should be an easy phase 1 study seems pretty bizarre. Most of the secondary measures involving PK/PD take only one day. Then the primary outcome measures take only 6 weeks:
"•Number of patients with adverse events [ Time Frame: Baseline to week 6 ]
•Number of patients with hypoglycemic events"
The one requiring so much time is "Measurement of anti-insulin antibodies" which takes "up to 13 months." Was this Mannkind's or the FDA's idea? Nowhere have I seen much interest in anti-insulin antibodies in either kids or adults. Why include it, especially since it is what takes so long?
But if they insist on doing a trial that's going to take years to complete, where is A1c? That's the only thing that matters to insurers.
On top of all that, they have no RAA arm to compare to, so even if they get good numbers, they still won't be able to claim superiority to lispro.
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Post by mango on Aug 24, 2017 22:17:50 GMT -5
Makes absolutely no sense to me. Several have pointed out that the "Estimated Study Completion Date: January 2021" for what should be an easy phase 1 study seems pretty bizarre. Most of the secondary measures involving PK/PD take only one day. Then the primary outcome measures take only 6 weeks: "•Number of patients with adverse events [ Time Frame: Baseline to week 6 ] •Number of patients with hypoglycemic events" The one requiring so much time is "Measurement of anti-insulin antibodies" which takes "up to 13 months." Was this Mannkind's or the FDA's idea? Nowhere have I seen much interest in anti-insulin antibodies in either kids or adults. Why include it, especially since it is what takes so long? But if they insist on doing a trial that's going to take years to complete, where is A1c? That's the only thing that matters to insurers. On top of all that, they have no RAA arm to compare to, so even if they get good numbers, they still won't be able to claim superiority to lispro. Pay special close attention to this. Make sure you see the following: 1. Pediatric Phase 3 2. When Phase 3 begins 3. When phase 3 ends 4. Note that Phase 3 ID is the exact same as Phase 2 ID 5. Hopefully you will see it. 6. Also, there is no Phase 1 it has already been competed
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Post by agedhippie on Aug 24, 2017 22:59:05 GMT -5
Matt - what are the safety concerns you think they need to address? Use by kids with COPD and who smoke? I am not sure those kids will be included in the study. They need to see if there are safety issues specific to kids. Sometimes kids have different reactions to adults because they are still growing, or have incomplete immune systems.
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Post by scoy on Aug 24, 2017 23:18:10 GMT -5
Makes absolutely no sense to me. Several have pointed out that the "Estimated Study Completion Date: January 2021" for what should be an easy phase 1 study seems pretty bizarre. Most of the secondary measures involving PK/PD take only one day. Then the primary outcome measures take only 6 weeks: "•Number of patients with adverse events [ Time Frame: Baseline to week 6 ] •Number of patients with hypoglycemic events" The one requiring so much time is "Measurement of anti-insulin antibodies" which takes "up to 13 months." Was this Mannkind's or the FDA's idea? Nowhere have I seen much interest in anti-insulin antibodies in either kids or adults. Why include it, especially since it is what takes so long? But if they insist on doing a trial that's going to take years to complete, where is A1c? That's the only thing that matters to insurers. On top of all that, they have no RAA arm to compare to, so even if they get good numbers, they still won't be able to claim superiority to lispro. As you can see here: web.archive.org/web/20170408021411/https://clinicaltrials.gov/ct2/show/NCT02527265It used to say phase one with a completion date of August 2017. We've moved beyond phase one, and we're now in phase two. When I look at the pediatric trials for RAAs they often include testing for insulin antibodies. For example: www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DevelopmentResources/UCM401612.pdfAs far as the date goes, it'll finish when it finishes. If they're posting a date that's worst case, that they're certain they can meet, that's okay with me. It they posted an optimistic projection and they were one week late, all they naysayers would jump all over them.
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Post by itellthefuture777 on Aug 25, 2017 0:49:08 GMT -5
Significant reduction in hypo risk...
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Post by #NoMoreNeedles on Aug 25, 2017 3:44:18 GMT -5
Why not ask Mike directly via Twitter? He is very responsive! We will also learn a lot more when he starts presenting at investor conferences in the fall.
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Post by mango on Aug 25, 2017 5:23:58 GMT -5
Why not ask Mike directly via Twitter? He is very responsive! We will also learn a lot more when he starts presenting at investor conferences in the fall. Grasp a kettle top and shoot the breeze, please I think we need to look at the presentation s l i d e
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Post by #NoMoreNeedles on Aug 25, 2017 5:33:12 GMT -5
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Post by mnholdem on Aug 25, 2017 6:59:28 GMT -5
You shouldn't get too worked up about the estimated study completion date. This is a continuation and update of the trial started by Sanofi in 2015 and then later suspended.
The study history is available here: clinicaltrials.gov/archive/NCT02527265
The original Primary Outcomes measures (submitted Aug-2015)
- Number of patients with adverse events [ Time Frame: up to 1 week after last treatment ]
- Number of patients with hypoglycemic events [ Time Frame: up to 1 week after last treatment ]
The current Primary Outcomes measures (submitted Aug-2017)
- Number of patients with adverse events [ Time Frame: Baseline to week 6 ]
Number and percentage of patients with any TEAE, any serious TEAE, any severe TEAE, any TEAE leading to treatment discontinuation, or any TEAE leading to death (only if any occurred) will be summarized by age cohort.
(MnHoldem note: TEAE stands for "Treatment-Emergent Adverse Event")
- Number of patients with hypoglycemic events [ Time Frame: Baseline to week 6 ]
Hypoglycemia, defined as blood glucose <= 70 mg/dL or in absence of blood glucose, symptoms that are resolved by the administration of carbohydrates.
In addition, the current Secondary Outcome measures are similar to the original measures but with much more detail, laying out specific time points and specifying how they will be basing the titration rules: "Doses for each of 3 days' meals will be titrated based on the median SMBG (120 to 150 minutes post-dose)." Several SOs remain unchanged from the original trial plan.
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The original trial consisted of two parts - a PK/PD safety study that would take approximately 3-6 months (depending on speed of recruitment) followed by a continuation study of 52 weeks. The new trial timelines have been updated:
- The patients are expected to participate in the study for approximately 6 to 8 weeks from Screening to final follow-up visit.
- Patients who completed 4 weeks of Afrezza treatment and have shown to be safe and well controlled with Afrezza + basal insulin will have the option to continue the extension treatment up to 1 year.
The 52-week group will consist of those patients who demonstrated safety and control during the initial testing. They will be the group from which the bulk of the Primary and Secondary Outcomes data will be used to assess approval. It still surprises me that the FDA wanted patients as young as 4 years old to be included in this study but if this trial determines that some patients may be too young to safely administer Afrezza, the final outcome may be that the FDA will indicate that Afrezza may be used with a different age group such as 7 to 17 year olds. Many children currently use asthma inhalers effectively, so perhaps the ability of 4-6 year olds to effectively inhale Technosphere Insulin may be a non-issue.
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Post by promann on Aug 25, 2017 7:08:56 GMT -5
For the younger ages like 4 - 7 I would think the parents would supervise by loading the cartridge and giving instructions and times of use. Couldn't the FDA also stipulate that for children under a certain age use only with adult supervision. I don't think you can even leave a child alone at home under 10 years of age.
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Post by mango on Aug 25, 2017 7:17:37 GMT -5
For the younger ages like 4 - 7 I would think the parents would supervise by loading the cartridge and giving instructions and times of use. Couldn't the FDA also stipulate that for children under a certain age use only with adult supervision. I don't think you can even leave a child alone at home under 10 years of age. I was welding wielding a shotgun earlier than 10. mango grew up on a farm (and didn't learn how to spell)
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Post by sr71 on Aug 25, 2017 11:14:27 GMT -5
Yep, when soldering doesn't work, welding is the sure fix (:>
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