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Post by otherottawaguy on Apr 21, 2015 15:14:55 GMT -5
Horm Metab Res. 2003 May;35(5):319-23. Pilot study with technosphere/PTH(1-34)--a new approach for effective pulmonary delivery of parathyroid hormone (1-34). Pfützner A1, Flacke F, Pohl R, Linkie D, Engelbach M, Woods R, Forst T, Beyer J, Steiner SS.
Author information 1MannKind Biopharmaceuticals, 1 Casper Street, Danbury, CT, USA. AndreasP@IKFE.de
Abstract Sequential subcutaneous PTH injection therapy (repeated 14 days of PTH administration and a subsequent treatment pause for a few weeks) is known to increase bone mineral density in patients with osteopenic disorders. Alternative methods of drug delivery may be beneficial in increasing compliance. A pilot study was performed in 10 healthy volunteers (4 female/6-male, age: 25.6 +/- 3.5 years, BMI: 22.3 +/- 2.4 kg/m 2, mean +/- SD) to assess the pharmacokinetic profiles of 1600 IU of PTH(1 - 34) using the pulmonary Technosphere drug delivery system in comparison to a subcutaneous injection of 400 IU. The treatments were administered in the morning after an overnight fast and blood samples for measurement of PTH(1 - 34), PTH(1 - 84), and calcium and calcitonin were taken over a period of 6 hours. Both injection and pulmonary application of PTH(1 - 34) were well tolerated. After pulmonary administration of Technosphere/PTH(1 - 34), PTH(1 - 34) appeared in the serum with a faster concentration increase (T max: pulmonary 10 +/- 5 min vs. subcutaneous 28 +/- 8 min, p < 0.001) and with higher maximal concentrations (C max : pulmonary 309 +/- 215 pmol/l vs. subcutaneous 102 +/- 45 pmol/l, p < 0.05) as compared to the subcutaneous injection. The relative bioavailability of pulmonary Technosphere/PTH(1 - 34) was calculated to be 48 %. No differences were seen between pulmonary and subcutaneous application with regard to the PTH(1 - 84), calcitonin and calcium concentrations. In conclusion, pulmonary application of Technosphere/PTH(1 - 34) appears to be an effective and thus attractive candidate for PTH substitution therapy in osteoporosis and other conditions leading to a decrease in bone mineral density.
www.ncbi.nlm.nih.gov/pubmed/12916003
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Post by otherottawaguy on Apr 21, 2015 15:17:48 GMT -5
Regul Pept. 2012 Nov 10;179(1-3):71-6. doi: 10.1016/j.regpep.2012.08.009. Epub 2012 Sep 4. Receptor-mediated inhibition of small bowel migrating complex by GLP-1 analog ROSE-010 delivered via pulmonary and systemic routes in the conscious rat. Hellström PM1, Smithson A, Stowell G, Greene S, Kenny E, Damico C, Leone-Bay A, Baughman R, Grant M, Richardson P. Author information 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Per.Hellstrom@medsci.uu.se Abstract BACKGROUND: ROSE-010, a Glucagon-Like Peptide-1 (GLP-1) analog, reduces gastrointestinal motility and relieves acute pain in patients with irritable bowel syndrome (IBS). The rat small bowel migrating myoelectric complex (MMC) is a reliable model of pharmacological effects on gastrointestinal motility. Accordingly, we investigated whether ROSE-010 works through GLP-1 receptors in gut musculature and its effectiveness when administered by pulmonary inhalation. MATERIALS AND METHODS: Rats were implanted with bipolar electrodes at 5, 15 and 25 cm distal to pylorus and myoelectric activity was recorded. First, intravenous or subcutaneous injections of ROSE-010 or GLP-1 (1, 10, 100 μg/kg) with or without the GLP-1 receptor blocker exendin(9-39)amide (300 μg/kg·h), were studied. Second, ROSE-010 (100, 200 μg/kg) Technosphere® powder was studied by inhalation. RESULTS: The baseline MMC cycle length was 17.5±0.8 min. GLP-1 and ROSE-010, administered intravenously or subcutaneously, significantly inhibited myoelectric activity and prolonged MMC cycling; 100 μg/kg completely inhibited spiking activity for 49.1±4.2 and 73.3±7.7 min, while the MMC cycle length increased to 131.1±11.4 and 149.3±15.5 min, respectively. Effects of both drugs were inhibited by exendin(9-39)amide. Insufflation of ROSE-010 (100, 200 μg/kg) powder formulation totally inhibited myoelectric spiking for 52.6±5.8 and 70.1±5.4 min, and increased MMC cycle length to 102.6±18.3 and 105.9±9.5 min, respectively. CONCLUSIONS: Pulmonary delivery of ROSE-010 inhibits gut motility through the GLP-1R similar to natural GLP-1. ROSE-010 causes receptor-mediated inhibition of MMC comparable to that of intravenous or subcutaneous administration. This suggests that ROSE-010 administered as a Technosphere® inhalation powder has potential in IBS pain management and treatment. Copyright © 2012 Elsevier B.V. All rights reserved. www.ncbi.nlm.nih.gov/pubmed/22960405
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Post by yossarian on Apr 24, 2015 14:57:38 GMT -5
Artificial Pancreas and AFREZZA From: dst.sagepub.com/content/early/2015/04/17/1932296815582061.abstract Clinical Results of an Automated Artificial Pancreas Using Technosphere Inhaled Insulin to Mimic First-Phase Insulin Secretion Howard Zisser, MD*,1,2 Eyal Dassau, PhD*,1,2,3 Justin J. Lee, PhD1,2 Rebecca A. Harvey, PhD1,2 Wendy Bevier, PhD1 Francis J. Doyle III, PhD1,2,3 1Sansum Diabetes Research Institute, Santa Barbara, CA, USA 2Department of Chemical Engineering, University of California, Santa Barbara, Santa Barbara, CA, USA 3Institute for Collaborative Biotechnologies, University of California, Santa Barbara, Santa Barbara, CA, USA Howard Zisser, MD, Sansum Diabetes Research Institute, Department of Chemical Engineering, University of California, 15 W Los Olivos St, Santa Barbara, CA 93105, USA. Email: hzisser@gmail.com ↵* Contributed equally to this study. Abstract Objective: The purpose of this study was to investigate whether or not adding a fixed preprandial dose of inhaled insulin to a fully automated closed loop artificial pancreas would improve the postprandial glucose control without adding an increased risk of hypoglycemia. Research Design and Methods: Nine subjects with T1DM were recruited for the study. The patients were on closed-loop control for 24 hours starting around 4:30 pm. Mixed meals (~50 g CHO) were given at 6:30 pm and 7:00 am the following day. For the treatment group each meal was preceded by the inhalation of one 10 U dose of Technosphere Insulin (TI). Subcutaneous insulin delivery was controlled by a zone model predictive control algorithm (zone-MPC). At 11:00 am, the patient exercised for 30 ± 5 minutes at 50% of predicted heart rate reserve. Results: The use of TI resulted in increasing the median percentage time in range (70-180 mg/dl, BG) during the 5-hour postprandial period by 21.6% (81.6% and 60% in the with/without TI cases, respectively, P = .06) and reducing the median postprandial glucose peak by 33 mg/dl (172 mg/dl and 205 mg/dl in the with and without TI cases, respectively, P = .004). The median percentage time in range 80-140 mg/dl during the entire study period was 67.5% as compared to percentage time in range without the use of TI of 55.2% (P = .03). Conclusions: Adding preprandial TI (See video supplement) to an automated closed-loop AP system resulted in superior postprandial control as demonstrated by lower postprandial glucose exposure without addition hypoglycemia.
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Post by mnkdfan on Apr 25, 2015 14:21:41 GMT -5
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Post by peppy on Aug 18, 2015 9:29:10 GMT -5
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Post by peppy on Aug 18, 2015 9:35:09 GMT -5
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
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Post by peppy on Aug 29, 2015 19:24:35 GMT -5
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Post by peppy on Sept 12, 2015 15:17:07 GMT -5
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Post by peppy on Sept 18, 2015 12:58:07 GMT -5
Reduced hypoglycaemia is observed with inhaled insulin versus subcutaneous insulin aspart in patients with type 1 diabetes mellitus Presentation Abstract Presentation Number: 932 Abstract: Background and aims: Technosphere Insulin Inhalation Powder (TI) is a dry powder formulation of regular human insulin adsorbed onto Technosphere microparticles for oral inhalation in patients with diabetes. We conducted a post hoc analysis of hypoglycaemia rates from a 24-week, phase 3 randomized study of prandial TI (N = 172) versus insulin aspart (IA; N = 167) added to basal insulin in patients with type 1 diabetes mellitus (T1DM). Materials and methods: Annualised hypoglycaemia event rates were determined in the overall study population, patients taking ≥ 1 postmeal supplemental dose (TI, n = 111; IA, n = 91), and patients not taking a supplemental dose (TI, n = 61; IA, n = 76). Hypoglycaemia rates during study weeks 0-12 (dose adjustment) and 12-24 (stable dosing) were assessed. Hypoglycaemia was defined as total (all events), confirmed (blood glucose < 49 mg/dL), nocturnal (0:00−6:00 AM), and severe (assistance required). Data were adjusted for baseline HbA1c level. Results: There was no significant difference in the mean number of supplemental doses taken between the TI and IA arms (34.1 vs 26.6, respectively; P = 0.1907). Significantly higher hypoglycaemia rates (events per patient/year) were seen for IA versus TI in the overall study population (total 81.1 vs 55.2; confirmed 15.0 vs 9.0; nocturnal 8.8 vs 5.9; and severe 0.9 vs 0.5; all P < 0.05) and patients taking ≥ 1 supplemental dose (total 96.3 vs 60.9; confirmed 18.6 vs 9.8; nocturnal 11.5 vs 6.5; and severe 1.1 vs 0.6; all P < 0.05). In patients not taking a supplemental dose, a significantly higher total hypoglycaemia rate was seen with IA versus TI (64.9 vs 46.0 events per patient/year; P = 0.0160). Within each arm there was a trend for higher total hypoglycaemia rates ≥ 1 hour after supplemental dosing (events per patient/year) in patients with a higher supplemental dose frequency (TI vs IA: 0.4 vs 0.4; 1.7 vs 2.2; and 4.9 vs 6.6 for patients receiving 1-5, 6-20, and 21-60 supplemental doses during the study); there was no significant difference between the TI and IA arms. In the overall study population, within both treatments arms there was a trend for a higher rate of all types of hypoglycaemia during weeks 0-12 (titration) versus 12-24 (stable dosing). In patients taking a supplemental dose, a similar trend was seen in the IA arm only. In patients not taking a supplemental dose, there was a trend for higher total, confirmed, and nocturnal hypoglycaemia rates during weeks 0-12 versus 12-24 for IA; and total, confirmed, and severe hypoglycaemia for TI. Conclusion: These data show that the more rapid onset and offset of action with TI versus IA was not associated with greater supplemental dosing. There was a consistently lower hypoglycaemia rate in patients with T1DM treated with TI versus IA, including those taking supplemental doses, and during dose adjustment and stable dosing. These data show that supplemental TI dosing does not result in an increased hypoglycaemia risk.
Supported By: Study funding MannKind Corp/Sanofi US Inc. Editorial support Sanofi US Inc
Clinical Trial Registration Number: NCT01445951 www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=62f1f0fc-7ded-4303-8d04-025ecec18c70&cKey=aab6329e-6e01-4be3-ae8f-ef644b4fb662&mKey=2bb00804-c880-450c-a19d-6b47d880fc09
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Post by peppy on Sept 20, 2015 7:21:05 GMT -5
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Post by mssciguy on Sept 29, 2015 9:28:28 GMT -5
did web search for "afrezza clamp study results" , filter to past hour, for some reason a couple recent (but older) papers came up,, here is one (morale booster): dst.sagepub.com/content/8/6/1071.shortAfrezza Inhaled Insulin (free access!!!) The Fastest-Acting FDA-Approved Insulin on the Market Has Favorable Properties David C. Klonoff, MD1 1Mills-Peninsula Health Services, San Mateo, CA, USA I don't know why google populates google scholar results at the very top of the page even though I asked for past hour... need to retrain on google search and so many other things or find a better search engine. Anyone know of one?
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Post by mssciguy on Sept 29, 2015 10:26:37 GMT -5
cool. Search result for Afrezza in French www.exalead.com/search/web/results/?q=afrezza+language%3Afr&Here is one hit, translated from French (just for fun) ziaranisima.skyrock.com/INHALED INSULIN, A REAL REVOLUTION FOR DIABETIC MILLION! WASHINGTON - The FDA, the drug regulatory body in the United States, authorized the marketing end of June 2014 the Afrezza, a drug based on human insulin inhaled form. It's simply a revolution for millions of diabetics worldwide. The Afrezza should be available in the US market in 2015. This is a form of rapid-acting insulin and used at the beginning of each meal. In the US, an estimated 25.8 million people suffer from diabetes, that is to say around 8.3% of the population. In the world 371 million people have diabetes and 90 million diabetics must perform a daily injection of insulin. Hyperglycemia caused by diabetes can lead to serious complications like heart disease, blindness or nerve and kidney problems. Revolution in the treatment of diabetes The diabetes, whether type 1 diabetes or severe cases of type 2 diabetes, must now make insulin injections daily. Some patients bite up to 7 times a day, sometimes more. An important part of diabetes is hard to bear bites and that is why many patients do not take their medications properly. A side effect of injected insulin is hypoglycemia, characterized by unpleasant symptoms such as dizziness or dry mouth. This new drug Afrezza appears to enhance the risk of hypoglycemia by having a better regulation of sugar levels in the blood. One reason lies in its fast action, indeed this medication starts to effect 12 minutes after inhalation. Dr. Jean-Marc Guettier, Director of Endocrinology and Metabolism Division of FDA products, explained in a statement the FDA June 27, 2014: "Afrezza is a new treatment for diabetes patients who require insulin at the time of meal. " The Afrezza is against-indicated in some situations such as people who smoke or have chronic lung disease (eg. Asthma). In addition, this drug can not be substituted in a diabetic patient in need of insulin with long duration of action. The success of a talented man The Afrezza is marketed by the US laboratory MannKind based in Connecticut. The owner of this laboratory is a famous physicist, Mr. Mann, 88 years old. According to the scientist, the development of the drug cost him $ 2 billion and is the result of over 10 years working with his entire research team. He had already contributed to the development of insulin pumps in the 1980s. To receive the authorization on the market (AMM) by the FDA for Afrezza, MannKind company had to perform many studies, including clinical. More than 3,000 patients worldwide have tested this medication. So much for the type 1 diabetes than for type 2 diabetes, the results have proved positive and led to the end of June 2014 approval from the FDA. The marketing will have to wait a few months and is expected in the US in early 2015. We have not read the release date for Europe or Canada. The FDA conducts for any new drug postmarketing called studies (conducted after the placing on the market) and MannKind company must of course comply with this rule by delivering information to the FDA, including on the safety of drug, especially in children (pediatric), as well as the risk of tumorigenicity Afrezza in the lung, by performing a clinical study. A true revolution For some physicians, this new treatment is the greatest innovation of insulin based drugs since the introduction of insulin in the 1970s genetic, before that insulin was exclusively animal and sometimes led to allergies in some patients. In 2007 the US firm Pfizer had already marketed inhaled insulin Exubera under the name, but because of excessive side effects of insulin remains in large quantities in the bronchi, the FDA decided to withdraw the drug market. The Exubera contained insulin hexamer, which complicated its lung passage to the bloodstream. The Afrezza by against contains insulin monomers. The passage into the bloodstream seems therefore greatly facilitated. The future of diabetes treatment Researchers are working on a pancreas (the body which naturally releases insulin) and insulin artificial ingested forms (eg. Tablet), the proteinaceous structure of the insulin is destroyed by enzymes in the gastrointestinal intestinal and scientists must find techniques to allow its absorption. July 10, 2014. Xavier Gruffat (pharmacist). Sources: Press the FDA, Veja (Brazilian weekly magazine of reference).
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Post by mssciguy on Nov 5, 2015 6:49:15 GMT -5
Sneak preview of a positive result from pediatric study? (Sam Finta)
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Post by peppy on Nov 6, 2015 15:00:38 GMT -5
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Post by nuklerfizzacist on Nov 19, 2015 7:28:29 GMT -5
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