Afrezza® INHALE-1 Study in Pediatrics (INHALE-1)

[mango]

Jul 26, 2021 10:45:55 GMT -5 peppy said:

Jul 26, 2021 10:32:43 GMT -5 mango said:

It looks like the participants will be monitored via CGMs? I haven’t looked at the protocol closely, but if that’s the case, we will know the percentages of hypos they get from the RAAs and can thus show that it was an increase in frequency and duration of RAAs hypos that causes the often seen dramatic decline in A1c.

The HbA1c hypothesis is false and it’s time to put an end to using it for assessing glucose homeostasis and managing diabetes from it.

I AGREE WITH YOU,
however,
What are the chances the industry will throw away its greatest sales tool?

It is the gateway tool. One number and the patient can be reprimanded by the supreme white coat and be put into the system.
Makes commercial messages unnecessary.

Alpha-glucosidase inhibitors

These medications help your body break down starchy foods and table sugar. This effect lowers your blood sugar levels.

For the best results, you should take these drugs before meals. These drugs include:

acarbose (Precose)
miglitol (Glyset)
Biguanides

Biguanides decrease how much sugar your liver makes. They decrease how much sugar your intestines absorb, make your body more sensitive to insulin, and help your muscles absorb glucose.

The most common biguanide is metformin (Glucophage, Metformin Hydrochloride ER, Glumetza, Riomet, Fortamet).

Metformin can also be combined with other drugs for type 2 diabetes. It’s an ingredient in the following medications:

metformin-alogliptin (Kazano)
metformin-canagliflozin (Invokamet)
metformin-dapagliflozin (Xigduo XR)
metformin-empagliflozin (Synjardy)
metformin-glipizide
metformin-glyburide (Glucovance)
metformin-linagliptin (Jentadueto)
metformin-pioglitazone (Actoplus)
metformin-repaglinide (PrandiMet)
metformin-rosiglitazone (Avandamet)
metformin-saxagliptin (Kombiglyze XR)
metformin-sitagliptin (Janumet)
Dopamine agonist

Bromocriptine (Cycloset) is a dopamine agonist.

It’s not known exactly how this drug works to treat type 2 diabetes. It may affect rhythms in your body and prevent insulin resistance.

Dipeptidyl peptidase-4 (DPP-4) inhibitors

DPP-4 inhibitors help the body continue to make insulin. They work by reducing blood sugar without causing hypoglycemia (low blood sugar).

These drugs can also help the pancreas make more insulin. These drugs include:

alogliptin (Nesina)
alogliptin-metformin (Kazano)
alogliptin-pioglitazone (Oseni)
linagliptin (Tradjenta)
linagliptin-empagliflozin (Glyxambi)
linagliptin-metformin (Jentadueto)
saxagliptin (Onglyza)
saxagliptin-metformin (Kombiglyze XR)
sitagliptin (Januvia)
sitagliptin-metformin (Janumet and Janumet XR)
sitagliptin and simvastatin (Juvisync)
Glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists)

These drugs are similar to the natural hormone called incretin.

They increase B-cell growth and how much insulin your body uses. They decrease your appetite and how much glucagon your body uses. They also slow stomach emptying.

These are all important actions for people with diabetes.

For some people, atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease may predominate over their diabetes. In these cases, the American Diabetes Association (ADA) recommends certain GLP-1 receptor agonists as part of an antihyperglycemic treatment regimen.

These drugs include:

albiglutide (Tanzeum)
dulaglutide (Trulicity)
exenatide (Byetta)
exenatide extended-release (Bydureon)
liraglutide (Victoza)
semaglutide (Ozempic)
Meglitinides

These medications help your body release insulin. However, in some cases, they may lower your blood sugar too much.

These drugs aren’t for everyone. They include:

nateglinide (Starlix)
repaglinide (Prandin)
repaglinide-metformin (Prandimet)
Sodium-glucose transporter (SGLT) 2 inhibitors

Sodium-glucose transporter (SGLT) 2 inhibitors work by preventing the kidneys from holding on to glucose. Instead, your body gets rid of the glucose through your urine.

In cases where atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease predominate, the ADA recommends SGLT2 inhibitors as a possible treatment option.

dapagliflozin (Farxiga)
dapagliflozin-metformin (Xigduo XR)
canagliflozin (Invokana)
canagliflozin-metformin (Invokamet)
empagliflozin (Jardiance)
empagliflozin-linagliptin (Glyxambi)
empagliflozin-metformin (Synjardy)
ertugliflozin (Steglatro)
Sulfonylureas

These are among the oldest diabetes drugs still used today. They work by stimulating the pancreas with the help of beta cells. This causes your body to make more insulin.

These drugs include:

glimepiride (Amaryl)
glimepiride-pioglitazone (Duetact)
glimepiride-rosiglitazone (Avandaryl)
gliclazide
glipizide (Glucotrol)
glipizide-metformin (Metaglip)
glyburide (DiaBeta, Glynase, Micronase)
glyburide-metformin (Glucovance)
chlorpropamide (Diabinese)
tolazamide (Tolinase)
tolbutamide (Orinase, Tol-Tab)
Thiazolidinediones

Thiazolidinediones work by decreasing glucose in your liver. They also help your fat cells use insulin better.

These drugs come with an increased risk of heart disease. If your doctor gives you one of these drugs, they’ll watch your heart function during treatment.

Options include:

rosiglitazone (Avandia)
rosiglitazone-glimepiride (Avandaryl)
rosiglitazone-metformin (Amaryl M)
pioglitazone (Actos)
pioglitazone-alogliptin (Oseni)
pioglitazone-glimepiride (Duetact)
pioglitazone-metformin (Actoplus Met, Actoplus Met XR)

[agedhippie]

Jul 24, 2021 14:12:34 GMT -5 prcgorman2 said:

Matt, agedhippie, and at least one newly minted doctor, all provided good posts on importance of a well-designed “large trial”. Is this that trial? I wonder if we will be seeing another trial for adults. ...

This is far better. It's got a control arm, they are only altering one parameter (RAA vs. Afrezza), the numbers are good, the duration is good. This needs to be duplicated for adults as I have been saying all along. This is the sort of trial that can start to change the SoC. The rate of change is directly related to the population size of the trial, and to a lesser extent the outcome. A good outcome is a small group has less impact that a reasonable outcome in a large group.

[peppy]

Jul 26, 2021 11:55:31 GMT -5 agedhippie said:

Jul 24, 2021 14:12:34 GMT -5 prcgorman2 said:

Matt, agedhippie, and at least one newly minted doctor, all provided good posts on importance of a well-designed “large trial”. Is this that trial? I wonder if we will be seeing another trial for adults. ...

This is far better. It's got a control arm, they are only altering one parameter (RAA vs. Afrezza), the numbers are good, the duration is good. This needs to be duplicated for adults as I have been saying all along. This is the sort of trial that can start to change the SoC. The rate of change is directly related to the population size of the trial, and to a lesser extent the outcome. A good outcome is a small group has less impact that a reasonable outcome in a large group.

That is all that was altered in the time in range study.
The problem with the studies, is timing is everything.

The timing used is still the RAA SUBQ timing.
That slow leach into the vascular.



And then the follow up doses..... You can not dose afrezza for the slow leach. When Afrezza comes into the blood stream like a Hail Mary.



Hello agedhippie, here I am with the pictures and arrows.

Hey, Have you taken a long position in MND? 

[wsulylecoug]

Jul 24, 2021 18:26:03 GMT -5 sayhey24 said:

Jul 24, 2021 9:38:09 GMT -5 wsulylecoug said:

As long as participants aren’t handcuffed by protocols that ultimately favor RAA and allow flexibility in timing, amount and follow-ups as needed. I don’t associate FDA trials with flexibility but I’m trusting MC fought for the best design to benefit Afrezza users and the trial outcome. Past comments suggest the FDA was willing to work with MNKD but then again I wouldn’t expect too much bad-mouthing during the trial design process.

160 might not have been an option for TIR upper bound. I assume there was some back and forth for some trial details that required some give and take.

It’s been mentioned previously, but once the trial gets the green light, it appears the expectation is that recruitment will take a long time. Typically Clinicaltrials.gov also lists recruitment sites and maybe there aren’t very many. Participants also need to be using basal with mealtime MDI. Does that include pumps? If not, the recruiting pool shrinks again. At first glance it doesn’t seem like it should take long to fill but time will tell. Those dates can be adjusted on the website with a few clicks of a mouse.

The study says "RAA injection combined with a basal insulin".  If they are using a pump they are not using a basal. 

The 180 mg/dl is nearly an A1C of 8.  An A1c of 160 is still over 7, but its a lot better than an 8.  Now, the 180 is the safe historical number to target because of the fear of hypoglycemia.  The historical treatment approach is its much better to have the PWD'sBG high and have vascular degeneration which takes years than to have the PWD go low and get a severe hypo.   I too agree with this but a study like this needs to showcase afrezza's benefits.

Afrezza is a game changer and this study protocol is just not designed to bring out the best in afrezza.  The next time I see Mike I will probably give him my opinion.  I am sure he will have reasons like the FDA is comfortable with 180 and they may not have accepted 160.  He will also probably say the FDA is not yet ready to drop A1C as the primary outcome when evaluating diabetes meds.  He may also say going for 160 mg/dl may limit the number of moms who want to let their kids participate in this study if they are in the RAA arm.

As far as getting kids, Sports already had a great suggestion in another post about going to the diabetes summer camps.  

Thanks for info. I still have lots to learn about diabetes in general and wasn't sure how a pump could handle both basal and prandial insulin without having two different insulins or if it just boiled down to how much was injected at any one time. It doesn't seem to make sense to have a pump for just basal then do MDI for meals.

With regard to protocol, I would be very surprised if the FDA would approve a trial that allows Afrezza and RAA to be used with customized protocols to maximize each of their abilities to treat diabetes. Don't get me wrong, I would love to see that because I think the results would speak for themselves and be a real eye-opener for many. I trust that MC got the best trial he could within the parameters set by FDA. 

Having a presence at diabetes camps sounds like a fantastic idea with or without this impending trial. Let's not forget though (if my understanding of FDA trial enrollment is correct) enrollment is required through approved sites which aren't listed at this point. Hopefully there are 100's of sites participating! Maybe there would be a way to add sites based upon interest after the trial starts and if so, maybe this could be used an opportunistic educational tool to bring new endos on board. Or maybe Vdex can provide enrollment sites and substitute their own protocol for FDAs!?!? Just kidding...but kind of not. 

[agedhippie]

Jul 26, 2021 14:33:44 GMT -5 wsulylecoug said:

Thanks for info. I still have lots to learn about diabetes in general and wasn't sure how a pump could handle both basal and prandial insulin without having two different insulins or if it just boiled down to how much was injected at any one time. It doesn't seem to make sense to have a pump for just basal then do MDI for meals.

...
Let's not forget though (if my understanding of FDA trial enrollment is correct) enrollment is required through approved sites which aren't listed at this point. Hopefully there are 100's of sites participating! Maybe there would be a way to add sites based upon interest after the trial starts and if so, maybe this could be used an opportunistic educational tool to bring new endos on board. Or maybe Vdex can provide enrollment sites and substitute their own protocol for FDAs!?!? Just kidding...but kind of not. 

Pumps handle basal by steadily dripping RAA into your bloodstream. You have a basal profile of so many units per hour and this is typically set lower at night than during the day. Most, at this point probably all, pumps allow a temporary basal rate to be set when the regular rate is not perform as required. On the sensor driven systems the basal rate is adjusted on the fly to keep your levels in range.

Recruitment will take time because the population is required to have been on RAA insulin for the last six months (or three months if Type 2). I am curious about the Type 2 group as that's a relatively small pool to be fishing in for participants. The CGM restriction isn't going to help either as with kids if they are on a CGM they are probably also on a pump (using a pump would exclude them).

The outcome primary is HbA1c which is unsurprising. The secondary is the rate of hypos (under 70). There is a laundry list of others with TIR as one of them. These are things that the sponsor wants to be able to talk about as outcomes, but which are not the headline outcomes. For example TIR would allow a good outcome to be promoted, or explain why a headline outcome is better than it initially appears.

[sayhey24]

Jul 26, 2021 22:13:42 GMT -5 agedhippie said:

Jul 26, 2021 14:33:44 GMT -5 wsulylecoug said:

Thanks for info. I still have lots to learn about diabetes in general and wasn't sure how a pump could handle both basal and prandial insulin without having two different insulins or if it just boiled down to how much was injected at any one time. It doesn't seem to make sense to have a pump for just basal then do MDI for meals.

...
Let's not forget though (if my understanding of FDA trial enrollment is correct) enrollment is required through approved sites which aren't listed at this point. Hopefully there are 100's of sites participating! Maybe there would be a way to add sites based upon interest after the trial starts and if so, maybe this could be used an opportunistic educational tool to bring new endos on board. Or maybe Vdex can provide enrollment sites and substitute their own protocol for FDAs!?!? Just kidding...but kind of not. 

Pumps handle basal by steadily dripping RAA into your bloodstream. You have a basal profile of so many units per hour and this is typically set lower at night than during the day. Most, at this point probably all, pumps allow a temporary basal rate to be set when the regular rate is not perform as required. On the sensor driven systems the basal rate is adjusted on the fly to keep your levels in range.

Recruitment will take time because the population is required to have been on RAA insulin for the last six months (or three months if Type 2). I am curious about the Type 2 group as that's a relatively small pool to be fishing in for participants. The CGM restriction isn't going to help either as with kids if they are on a CGM they are probably also on a pump (using a pump would exclude them).

The outcome primary is HbA1c which is unsurprising. The secondary is the rate of hypos (under 70). There is a laundry list of others with TIR as one of them. These are things that the sponsor wants to be able to talk about as outcomes, but which are not the headline outcomes. For example TIR would allow a good outcome to be promoted, or explain why a headline outcome is better than it initially appears.

Aged - I don't think being on a CGM prior to this study is a requirement.  I think they are going to give the kids CGMs if they don't already have them.  I then think they are going to try and build on the Affinity-1 results seen by that one doctor at the Adcom who had his patients follow-up dose with the afrezza.  His results were so good the FDA accused him of cheating.

If they can do this they have a fighting chance of beating the RAA A1C.  The key is going to be how proactively they monitor the afrezza kids and make sure they are follow-up dosing.

[lennymnkd]

I’m sure Mikes has his ducks in a row with the CGM , MIKE AND THE COMPANY,has been waiting
For a long time for this opportunity ! All this second guessing means nothing. My money is with Mike
… literally…. Al spoke about this day years ago at the annual shareholder meetings…Im sure it’s been
Negotiated well! If that’s what you want to call it.

[peppy]

Jul 27, 2021 7:19:23 GMT -5 sayhey24 said:

Jul 26, 2021 22:13:42 GMT -5 agedhippie said:

Pumps handle basal by steadily dripping RAA into your bloodstream. You have a basal profile of so many units per hour and this is typically set lower at night than during the day. Most, at this point probably all, pumps allow a temporary basal rate to be set when the regular rate is not perform as required. On the sensor driven systems the basal rate is adjusted on the fly to keep your levels in range.

Recruitment will take time because the population is required to have been on RAA insulin for the last six months (or three months if Type 2). I am curious about the Type 2 group as that's a relatively small pool to be fishing in for participants. The CGM restriction isn't going to help either as with kids if they are on a CGM they are probably also on a pump (using a pump would exclude them).

The outcome primary is HbA1c which is unsurprising. The secondary is the rate of hypos (under 70). There is a laundry list of others with TIR as one of them. These are things that the sponsor wants to be able to talk about as outcomes, but which are not the headline outcomes. For example TIR would allow a good outcome to be promoted, or explain why a headline outcome is better than it initially appears.

Aged - I don't think being on a CGM prior to this study is a requirement.  I think they are going to give the kids CGMs if they don't already have them.  I then think they are going to try and build on the Affinity-1 results seen by that one doctor at the Adcom who had his patients follow-up dose with the afrezza.  His results were so good the FDA accused him of cheating.

If they can do this they have a fighting chance of beating the RAA A1C.  The key is going to be how proactively they monitor the afrezza kids and make sure they are follow-up dosing.

Inclusion Criteria:
Assent from the pediatric subject, as appropriate, and fully informed consent from the parent(s) or legal guardian, as required by both state and federal laws and the local Institutional Review Board (IRB);
Subjects ≥4 and <18 years of age;
Clinical diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) per the Investigator and have been using insulin for at least 6 months for T1DM, or at least 3 months for T2DM
Treatment with basal-bolus insulin therapy delivered by multiple daily injections for at least 2 weeks:
Acceptable bolus insulins are restricted to the RAAs insulin lispro or insulin aspart, including biosimilar products.
Basal insulins are restricted to 100-U/mL formulations of insulin glargine or insulin degludec, including biosimilar products.
HbA1c ≥7.0% and ≤11%
Average prandial dose of insulin ≥2 units per meal
Utilized continuous glucose monitor (CGM) for ≥70% of the time over a 14-day period preceding randomization.

[Clement]

Thanks, Pep!

Re: "Utilized continuous glucose monitor (CGM) for ≥70% of the time over a 14-day period preceding randomization."

That inclusion criterion implies that trial participants will use CGMs. But it seems to leave the door open for recruiting and providing CGMs a few weeks before randomization.

[agedhippie]

Jul 27, 2021 7:19:23 GMT -5 sayhey24 said:

Aged - I don't think being on a CGM prior to this study is a requirement.  I think they are going to give the kids CGMs if they don't already have them.  I then think they are going to try and build on the Affinity-1 results seen by that one doctor at the Adcom who had his patients follow-up dose with the afrezza.  His results were so good the FDA accused him of cheating.

If they can do this they have a fighting chance of beating the RAA A1C.  The key is going to be how proactively they monitor the afrezza kids and make sure they are follow-up dosing.

This is a six month trial with an optional six month extension for Afrezza. The monitoring will come down to the parents although there will be periodic check-ins so I wouldn't bet to heavily on consistent follow up dosing. However, everyone has been on MDI so they should be familiar with the concept of corrections.

[agedhippie]

Jul 27, 2021 8:10:45 GMT -5 Clement said:

Thanks, Pep!

Re: "Utilized continuous glucose monitor (CGM) for ≥70% of the time over a 14-day period preceding randomization."

That inclusion criterion implies that trial participants will use CGMs. But it seems to leave the door open for recruiting and providing CGMs a few weeks before randomization.

It's an inclusion criteria - if you don't meet it you are not going to be selected. They are looking for people who are used to using a CGM to manage their levels otherwise the selection criteria would have been for people prepared to use a CGM.

[peppy]

Jul 27, 2021 21:47:20 GMT -5 agedhippie said:

Jul 27, 2021 8:10:45 GMT -5 Clement said:

Thanks, Pep!

Re: "Utilized continuous glucose monitor (CGM) for ≥70% of the time over a 14-day period preceding randomization."

That inclusion criterion implies that trial participants will use CGMs. But it seems to leave the door open ,for recruiting and providing CGMs a few weeks before randomization.

It's an inclusion criteria - if you don't meet it you are not going to be selected. They are looking for people who are used to using a CGM to manage their levels otherwise the selection criteria would have been for people prepared to use a CGM.

This is 2021 correct?
These are adolescent and children correct?
They are looking for people used to using CGM's.

This is the USA. Many have employer health insurance.
Many people with children who develop type 1 have their child on a continuous glucose monitors.

agedhippie , times have changed. I have heard stories from people who found out they were diabetic in 1969. I was told the standard of care they received was, "here, is some insulin."
Was that you?
Molly's dad used to boil his needles.

[prcgorman2]

Jul 28, 2021 3:23:37 GMT -5 peppy said:

Jul 27, 2021 21:47:20 GMT -5 agedhippie said:

It's an inclusion criteria - if you don't meet it you are not going to be selected. They are looking for people who are used to using a CGM to manage their levels otherwise the selection criteria would have been for people prepared to use a CGM.

This is 2021 correct?
These are adolescent and children correct?
They are looking for people used to using CGM's.

This is the USA. Many have employer health insurance.
Many people with children who develop type 1 have their child on a continuous glucose monitors.

agedhippie , times have changed. I have heard stories from people who found out they were diabetic in 1969. I was told the standard of care they received was, "here, is some insulin."
Was that you?
Molly's dad used to boil his needles.

Ooh, good thread here.  I need to stay away from the Short Interest stuff.  I get too annoyed with the glowing admiration for shorts.

Anyway, great insightful post peppy!  It helps me appreciate how important it is to remember the history of treating diabetes to better understand the current context of Afrezza as an extremely important tool in the toolbox for Persons With Diabetes.

I’ve read that the first insulin treatments for PWDs was with dog insulin.  Later it was pig insulin.  Eli Lilly slaughtered millions of pigs in order to extract pig insulin.  These insulins would not have been ideal and it would be a nightmare to know how much insulin to give.  Eventually a “Time In Range” estimate became available which is an A1C test, which is a measurement of average blood glucose TIR over some period of months.  Not exactly a precise measurement.  I assume the use of urinating on paper strips or pricking fingers to make them bleed onto paper strips that changed color to estimate the level of blood glucose in order to estimate the amount of insulin that was needed came into use about the same time (or perhaps before).  In the digital age it’s become possible to more accurately measure blood glucose using equipment which could read the strips more effectively.  At some point, it became obvious that what was needed was low amounts of insulin available all the time for some PWDs and then increased amounts of insulin at mealtime so insulins that were slower (basal) and faster (prandial) were developed.  And, to improve information about blood glucose levels and how an individual’s body responds to eating and fasting and activity, Continuous Glucose Monitors (CGMs) were developed and continue to improve in capability and decrease in cost.

What this history highlights is the extreme importance of using the right amount of insulin for the right amount of requirements over the right amount of time.  The A in Afrezza was chosen because of the resemblance of Afrezza inhaled human insulin PK/PD profile as a close mimic of the healthy pancreatic reaction to a spike in blood sugar from a meal.  Blood sugar spikes, the pancreas excretes a dose of human insulin, the spike is stopped, and the blood sugar tails away, but much faster than is possible with conventional dosing using so-called Rapid Acting Analogue (RAA) insulins.  The point there is RAA does NOT mimic a healthy pancreas, but Afrezza does.  It makes me wonder how many T1  PWDs use all 3 insulins?  Basal for background, Afrezza for meal combined with a very low dose of RAA for a desired post-spike tail, especially if carb loading for activity, and with a CGM to warn if a follow-up (lower?) dose of Afrezza if necessary.

It’s all about having information and applying the right insulin for the known and anticipated need.  I know the PWDs tell us this all the time, but until you (Peppy) made the comment about the history of insulin, it didn’t click for me.  Fascinating and kind of terrifying all at the same time.  Thank God for Dr. Al Mann.

[Clement]

Jul 27, 2021 21:47:20 GMT -5 agedhippie said:

Jul 27, 2021 8:10:45 GMT -5 Clement said:

Thanks, Pep!

Re: "Utilized continuous glucose monitor (CGM) for ≥70% of the time over a 14-day period preceding randomization."

That inclusion criterion implies that trial participants will use CGMs. But it seems to leave the door open for recruiting and providing CGMs a few weeks before randomization.

It's an inclusion criteria - if you don't meet it you are not going to be selected. They are looking for people who are used to using a CGM to manage their levels otherwise the selection criteria would have been for people prepared to use a CGM.

Does randomization always happen at the moment of recruitment?

[wsulylecoug]

Jul 27, 2021 21:43:05 GMT -5 agedhippie said:

Jul 27, 2021 7:19:23 GMT -5 sayhey24 said:

Aged - I don't think being on a CGM prior to this study is a requirement.  I think they are going to give the kids CGMs if they don't already have them.  I then think they are going to try and build on the Affinity-1 results seen by that one doctor at the Adcom who had his patients follow-up dose with the afrezza.  His results were so good the FDA accused him of cheating.

If they can do this they have a fighting chance of beating the RAA A1C.  The key is going to be how proactively they monitor the afrezza kids and make sure they are follow-up dosing.

This is a six month trial with an optional six month extension for Afrezza. The monitoring will come down to the parents although there will be periodic check-ins so I wouldn't bet to heavily on consistent follow up dosing. However, everyone has been on MDI so they should be familiar with the concept of corrections.

Brief Summary:

INHALE-1 is a Phase 3, open-label, randomized clinical study evaluating the efficacy and safety of Afrezza in combination with a basal insulin (i.e., the Afrezza group) versus insulin aspart or insulin lispro in combination with a basal insulin (i.e., the RAA injection group) in pediatric subjects with type 1 or type 2 diabetes mellitus. Following 26 weeks of randomized treatment (i.e., Afrezza or RAA injection combined with a basal insulin), all subjects will enter a treatment extension where subjects will receive Afrezza until Week 52. The purpose of the treatment extension is to assess safety and efficacy with continued use of Afrezza.

It looks to me like everyone will go for a full 52 weeks with the RAA switching over at week 26. I think this will be a great trial within a trial.