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Post by tchalaa on Apr 22, 2016 5:08:38 GMT -5
Study: Evaluate Safety of Technosphere® Insulin (TI) in Diabetic Subjects With Moderate Obstructive Pulmonary Disease
Purpose: Examine the effects of TI in combination with an anti-diabetic regimen including inhaled insulin versus anti-diabetic treatment without inhaled insulin on lung function & pulmonary safety Stand: This study has been terminated.
(Terminated upon recommendation of the Data Safety Monitoring Board (DSMB))
Sponsor: Sanofi Collaborator: Mannkind Corporation Information provided by (Responsible Party): Sanofi ClinicalTrials.gov Identifier: NCT00642616 First received: March 21, 2008
Last updated: February 12, 2016
Last verified: February 2016... source: clinicaltrials.gov/ct2/show/study/NCT00642616?term=NCT00642616&rank=1The DSMB should conclude each review with their recommendations to NIDCR as to whether the study should continue without change, be modified, or terminated. Recommendations regarding modification of the design and conduct of the study could include: Modifications of the study protocol based upon the review of the safety data; Suspension or early termination of the study or of one or more study arms because of serious concerns about subjects’ safety, inadequate performance or rate of enrollment; Suspension or early termination of the study or of one or more study arms because study objectives have been obtained according to pre-established statistical guidelines;...
source: www.nidcr.nih.gov/Research/ToolsforResearchers/Toolkit/DSMBGuidelines.htm
If you ask me this is one on the latest groundbreaking result to be presented because MNKD has the first right to present and control all future publication of this result. You don't go in front of your peers to present bad result, therefor the termination was done because study objectives were met.
"Restriction Description: MannKind has right to 1st joint multicenter publication. After 1st publication PI may publish data only if PI submits proposed publication to MNKD for review 60 days prior to publication date. MNKD may remove any confidential information. If a multicenter publication is not submitted 12 months after conclusion, abandonment, or termination of the Study at all sites, or if MNKD confirms there will be no multicenter Study publication, PI may publish the Study results subject to MNKD rights herein.
"
source: clinicaltrials.gov/ct2/show/results/NCT00642616?term=NCT00642616&rank=1
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Post by dooberxl on Apr 22, 2016 5:14:04 GMT -5
I feel this is just a small step towards a much bigger goal - stronger wording in support of using afrezza in future diabetic treatment guidelines. The more data we have regarding the efficacy and safety of afrezza, the more likely it'll get a stronger recommendation for use in step-wise treatment alogrithms. This study isn't even remotely groundbreaking on its own, but a useful (albeit small) part of a much larger sum of evidence.
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Post by tchalaa on Apr 22, 2016 5:27:19 GMT -5
I feel this is just a small step towards a much bigger goal - stronger wording in support of using afrezza in future diabetic treatment guidelines. The more data we have regarding the efficacy and safety of afrezza, the more likely it'll get a stronger recommendation for use in step-wise treatment alogrithms. This study isn't even remotely groundbreaking on its own, but a useful (albeit small) part of a much larger sum of evidence. here is the purpose of the study: Examine the effects of TI in combination with an anti-diabetic regimen including inhaled insulin versus anti-diabetic treatment without inhaled insulin on lung function & pulmonary safety - below is the Warning Label - IMPORTANT SAFETY INFORMATION FOR AFREZZA® (INSULIN HUMAN) INHALATION POWDER WARNING: RISK OF SUDDEN LUNG PROBLEMS (BRONCHOSPASM) IN PATIENTS WITH LONG-TERM (CHRONIC) LUNG DISEASE Sudden lung problems (acute bronchospasm) have been seen in patients with asthma and COPD (chronic obstructive pulmonary disease) using Afrezza®. Afrezza® is not to be used in patients with long-term lung disease such as asthma or COPD. |
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Post by dooberxl on Apr 22, 2016 6:23:46 GMT -5
I feel this is just a small step towards a much bigger goal - stronger wording in support of using afrezza in future diabetic treatment guidelines. The more data we have regarding the efficacy and safety of afrezza, the more likely it'll get a stronger recommendation for use in step-wise treatment alogrithms. This study isn't even remotely groundbreaking on its own, but a useful (albeit small) part of a much larger sum of evidence. here is the purpose of the study: Examine the effects of TI in combination with an anti-diabetic regimen including inhaled insulin versus anti-diabetic treatment without inhaled insulin on lung function & pulmonary safety - below is the Warning Label - IMPORTANT SAFETY INFORMATION FOR AFREZZA® (INSULIN HUMAN) INHALATION POWDER WARNING: RISK OF SUDDEN LUNG PROBLEMS (BRONCHOSPASM) IN PATIENTS WITH LONG-TERM (CHRONIC) LUNG DISEASE Sudden lung problems (acute bronchospasm) have been seen in patients with asthma and COPD (chronic obstructive pulmonary disease) using Afrezza®. Afrezza® is not to be used in patients with long-term lung disease such as asthma or COPD. Yes, your point being? This is not groundbreaking in my opinion. Groundbreaking evidence, in my opinion, would cause a significant change in the current clinical approach to the treatment of diabetes e.g. metformin being first line therapy assuming no contraindications exist to therapy. For example, if the ADA comes out tomorrow and includes afrezza as first line therapy plus metformin, then this is groundbreaking. Or, alternatively, a trial indicating superiority of afrezza over rapid/regular insulin - in which case, we as practitioners would have a moral obligation to utilize the superior therapy when the cost/benefit ratios make sense. This study likely found a non-statistically significant change in pulmonary function between patients on afrezza vs. oral therapies - further confirming results from the initial trials done leading up to FDA approval. Of course, I'd have to see the full publication of the study to say this definitively. |
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Post by tchalaa on Apr 22, 2016 6:47:59 GMT -5
dooberxl as a Practitioner, I believe you are already aware of this FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function source: www.fda.gov/Drugs/DrugSafety/ucm493244.htmA label change will be groundbreaking for Afrezza and Technosphere first and surely later on PWD
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Post by peppy on Apr 22, 2016 6:59:02 GMT -5
here is the purpose of the study: Examine the effects of TI in combination with an anti-diabetic regimen including inhaled insulin versus anti-diabetic treatment without inhaled insulin on lung function & pulmonary safety - below is the Warning Label - IMPORTANT SAFETY INFORMATION FOR AFREZZA® (INSULIN HUMAN) INHALATION POWDER WARNING: RISK OF SUDDEN LUNG PROBLEMS (BRONCHOSPASM) IN PATIENTS WITH LONG-TERM (CHRONIC) LUNG DISEASE Sudden lung problems (acute bronchospasm) have been seen in patients with asthma and COPD (chronic obstructive pulmonary disease) using Afrezza®. Afrezza® is not to be used in patients with long-term lung disease such as asthma or COPD. Yes, your point being? This is not groundbreaking in my opinion. Groundbreaking evidence, in my opinion, would cause a significant change in the current clinical approach to the treatment of diabetes e.g. metformin being first line therapy assuming no contraindications exist to therapy. For example, if the ADA comes out tomorrow and includes afrezza as first line therapy plus metformin, then this is groundbreaking. Or, alternatively, a trial indicating superiority of afrezza over rapid/regular insulin - in which case, we as practitioners would have a moral obligation to utilize the superior therapy when the cost/benefit ratios make sense. This study likely found a non-statistically significant change in pulmonary function between patients on afrezza vs. oral therapies - further confirming results from the initial trials done leading up to FDA approval. Of course, I'd have to see the full publication of the study to say this definitively. Reworded: all that needs to happen is the ADA adds fast acting insulin to first line therapy. www.idf.org/treatment-algorithm-people-type-2-diabetes insulin and fast acting insulin is on the list. 3rd and 4th line therapy.
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Post by dooberxl on Apr 22, 2016 7:04:00 GMT -5
Yes, your point being? This is not groundbreaking in my opinion. Groundbreaking evidence, in my opinion, would cause a significant change in the current clinical approach to the treatment of diabetes e.g. metformin being first line therapy assuming no contraindications exist to therapy. For example, if the ADA comes out tomorrow and includes afrezza as first line therapy plus metformin, then this is groundbreaking. Or, alternatively, a trial indicating superiority of afrezza over rapid/regular insulin - in which case, we as practitioners would have a moral obligation to utilize the superior therapy when the cost/benefit ratios make sense. This study likely found a non-statistically significant change in pulmonary function between patients on afrezza vs. oral therapies - further confirming results from the initial trials done leading up to FDA approval. Of course, I'd have to see the full publication of the study to say this definitively. Reworded: all that needs to happen is the ADA adds fast acting insulin to first line therapy. www.idf.org/treatment-algorithm-people-type-2-diabetes insulin and fast acting insulin is on the list. 3rd and 4th line therapy.
I was not writing as if I'm the actual editor for the ADA diabetic treatment guidelines, but rather to get a point across; however, thanks for arguing semantics. |
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Post by dooberxl on Apr 22, 2016 7:05:46 GMT -5
dooberxl as a Practitioner, I believe you are already aware of this FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function source: www.fda.gov/Drugs/DrugSafety/ucm493244.htmA label change will be groundbreaking for Afrezza and Technosphere first and surely later on PWD Yes I am aware. A colleague graciously emailed this out to us. Whats interesting is the new label change utilizes eGFR<30 as a cutoff instead of creatinine clearance. |
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Post by matt on Apr 22, 2016 7:16:37 GMT -5
While I think a label change would certainly help, I don't think I can agree with a change "sooner rather than later". This was an extremely small study, just 34 patients across four different arms, so an average of just 8.5 subjects per arm. That makes for some very weak statistical power and as a matter of pure mathematics the study cannot meet the FDA's criteria for a label change; that will take a much larger study. Note that the study was originally designed in 2008 and just terminated (for undisclosed reasons) in 2016. Nothing happens fast in pharma, especially when rolling back a safety measure is concerned.
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Post by dooberxl on Apr 22, 2016 7:20:17 GMT -5
While I think a label change would certainly help, I don't think I can agree with a change "sooner rather than later". This was an extremely small study, just 34 patients across four different arms, so an average of just 8.5 subjects per arm. That makes for some very weak statistical power and as a matter of pure mathematics the study cannot meet the FDA's criteria for a label change; that will take a much larger study. Note that the study was originally designed in 2008 and just terminated (for undisclosed reasons) in 2016. Nothing happens fast in pharma, especially when rolling back a safety measure is concerned. Given the likely small effect size and the small study population, I'd lean towards the fact that this study was underpowered simply from your summary matt. Agreed. |
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Post by peppy on Apr 22, 2016 7:20:46 GMT -5
I was not writing as if I'm the actual editor for the ADA diabetic treatment guidelines, but rather to get a point across; however, thanks for arguing semantics. I am the semantics queen. afrezza IS fast acting INSULIN. non inferior. we get this delivery system priced correctly, demand should make it fly off the shelf. Type 1's can demand. type 2's an uphill battle. Type 1's can not forget about the dis ease. type two's can ignore the kit and caboodle for a long time. Pep
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Post by yossarian on Apr 22, 2016 7:21:41 GMT -5
Why isn't anyone worried about "Terminated upon recommendation of the Data Safety Monitoring Board (DSMB)" Doesn't that suggest something showed up that suggested a danger to participants? Here is what the DSMB does - grants.nih.gov/grants/guide/notice-files/not98-084.html"It is the policy of the NIH that each Institute and Center (IC) should have a system for the appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the data for all NIH-supported or þconducted clinical trials. . . ." |
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Post by dooberxl on Apr 22, 2016 7:28:40 GMT -5
I was not writing as if I'm the actual editor for the ADA diabetic treatment guidelines, but rather to get a point across; however, thanks for arguing semantics. I am the semantics queen. afrezza IS fast acting INSULIN. non inferior. we get this delivery system priced correctly, demand should make it fly off the shelf. Type 1's can demand. type 2's an uphill battle. Type 1's can not forget about the dis ease. type two's can ignore the kit and caboodle for a long time. Pep
I wouldn't expect any less from a TA expert.  Your posts have made me a significant sum by the way. Much appreciated. Keep up the good work! |
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Post by dooberxl on Apr 22, 2016 7:38:19 GMT -5
Why isn't anyone worried about "Terminated upon recommendation of the Data Safety Monitoring Board (DSMB)" Doesn't that suggest something showed up that suggested a danger to participants? Here is what the DSMB does - grants.nih.gov/grants/guide/notice-files/not98-084.html"It is the policy of the NIH that each Institute and Center (IC) should have a system for the appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the data for all NIH-supported or þconducted clinical trials. . . ." Likely just confirmed bronchospasm in COPD patients using afrezza. Won't know until full results are published. |
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Post by peppy on Apr 22, 2016 7:53:18 GMT -5
Why isn't anyone worried about "Terminated upon recommendation of the Data Safety Monitoring Board (DSMB)" Doesn't that suggest something showed up that suggested a danger to participants? Here is what the DSMB does - grants.nih.gov/grants/guide/notice-files/not98-084.html"It is the policy of the NIH that each Institute and Center (IC) should have a system for the appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the data for all NIH-supported or þconducted clinical trials. . . ." My Guess is Sanofi terminated the study. The pediatric study was terminated. www.clinicaltrials.gov/ct2/show/NCT02527265?term=diabetes&lup_s=08/04/2015&lup_d=14&show_rss=Y&sel_rss=mod14
Regarding the studies and the up coming ADA presentations. The titration study was completed. The Clamp Study
Single Dose Clamp Study to Evaluate Concentration-time Profile and Metabolic Activity of 3 Dose Levels of Afrezza and 3 Dose Levels of Insulin Lispro in Patients With Type 1 Diabetes Mellitus
www.clinicaltrials.gov/ct2/show/NCT02470637 information on euglycaemic clamp technique
illingworthresearch.com/2012/07/20/glucose-clamping-in-clinical-trials/
Matt stated 4 presentations.
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Your posts have made me a significant sum by the way. Much appreciated. Keep up the good work!