Tesofensine - Weight Loss

  1. Cool Tesofensine - Weight Loss


    You guys heard of this? Seems to kill appetite like no other.

    I noticed there is a company selling it, and a guy repping it on another forum. Have not seen it brought up much here.

    Half life of 9 days...damnnn

    Tesofensine (NS2330) is a serotonin–noradrenaline–dopami ne reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity.[1] Tesofensine was originally developed by a Danish biotechnology company, NeuroSearch, who transferred the rights to Saniona in 2014.[2]

    As of 2015, tesofensine has been discontinued for the treatment of Alzheimer's and Parkinson's disease but is in Phase II clinical trials for obesity.[1]

    History:

    Tesofensine was originally investigated for the treatment of Alzheimer's disease and Parkinson's disease,[3] and was subsequently dropped from development for these applications after early trial results showed limited efficacy for treatment of these diseases.[4][5] However, weight loss was consistently reported as an adverse event in the original studies, especially in overweight or obese patients.[6] Therefore, it was decided to pursue development of tesofensine for the treatment of obesity.

    Tesofensine primarily acts as an appetite suppressant, but possibly also acts by increasing resting energy expenditure.[7] Phase 2 trials for the treatment of obesity have been successfully completed.

    Tesofensine has a long half-life of about 9 days (220 h)[3] "and is mainly metabolized by cytochrome P4503A4 (CYP3A4) to its desalkyl metabolite M1" NS2360.[8][9] NS2360 is the only metabolite detectable in human plasma.

    NS2330 is mainly metabolized by cytochrome P450 3A4 (CYP3A4) into .

    It has a longer half-life than tesofensine, i.e. approximately 16 days (374 h) in humans, and has an exposure of 31–34% of the parent compound at steady state. In vivo data indicate that NS2360 is responsible for approximately 6% of the activity of tesofensine. As in animals, the kidney appears to play only a minor role in the clearance of tesofensine in humans (about 15–20%).

    Phase 2b trial (TIPO-1) results reported in The Lancet[17] showed levels of weight loss over a 6-month period that were significantly greater than those achieved with any currently available drugs. Patients lost an average of 12.8 kg on the 1 mg dose, 11.3 kg on the 0.5 mg dose and 6.7 kg on the 0.25 mg dose, compared with a 2.2 kg loss in the placebo group.

    All participants were instructed to follow a diet with a 300 kcal deficit and to increase their physical activity gradually to 30–60 minutes of exercise per day. The placebo-subtracted mean weight losses were 4.5%, 9.2% and 10.6% in the 0.25 mg, 0.5 mg and 1 mg dose groups, respectively. This is approximately twice the weight loss produced by medications currently approved by the US Food and Drug Administration (FDA) for the treatment of obesity.

    NeuroSearch has also reported interim results[7] from a 48-week, open-label, extension trial (TIPO-4) in which 140 patients who completed the 24-week phase 2b trial (TIPO-1) were re-enrolled after an average of 3 months’ wash-out. All were initially treated with 0.5 mg tesofensine once daily but up-titration to 1.0 mg once daily was allowed in the first 24 weeks of the extension study. At this time point, all subjects were continued on the 0.5 mg dose for an additional 24 weeks. The 24-week interim results for those who were previously treated with tesofensine 0.5 mg in TIPO-1 showed a total mean weight loss of between 13 kg and 14 kg over 48 weeks of treatment. Furthermore, TIPO-4 confirmed the TIPO-1 results since those patients who were previously treated with placebo lost approximately 9 kg in the first 24 weeks of the TIPO-4 study.
    Source: Wikipedia


  2. Interesting find...
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  3. Actually found a guy logging this with GW somehwere else also. Going to keep and eye on it and see how that goes for him. Seems there have been some trials already done with it.

  4. Quote Originally Posted by EvanMan View Post
    Actually found a guy logging this with GW somehwere else also. Going to keep and eye on it and see how that goes for him. Seems there have been some trials already done with it.
    I would be curious if he develops ed or libido issues?
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  5. Interesting indeed!
    Life is fair it's your expectations that aren't.
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  6. Quote Originally Posted by hairygrandpa View Post
    Interesting indeed!
    Here is the guy who will try it!

    https://youtu.be/vYEXzx-TINc

  7. Quote Originally Posted by HIT4ME View Post
    Here is the guy who will try it!

    https://youtu.be/vYEXzx-TINc
    Life is fair it's your expectations that aren't.

  8. Ok so was doing some more reading on this. So one good thing is that there were human trials done and nothing crazy happened to anyone besides fat loss. Pretty amazing results compared to placebo group. I know we cant post links here but there are a few places selling it as research chem. Google will find it with the right word combination.

    Tesofensine...no, I did not miss a T there as the fourth letter...this is NOT a testosterone increasing drug. What is it then, why should you care? It is a weight loss drug. A VERY potent one. How potent? TWICE as powerful as the current prescription drugs on the market! But I have jumped to the end of the story already. Lets start at the beginning.

    Under development by NeuroSearch, a Danish pharmaceutical company, tesofensine is a serotonin-noradrenaline-dopamine reuptake inhibitor. It was originally in development for the treatment of neurological disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). It failed miserably at doing anything for PD and AD, but the scientists noticed that everyone who used Tesofensine lost weight - a LOT of weight. So they reclassified the drug and started trials all ove again. Yes, they had to start at the beginning again even though they alredy did some human trials, but that is because they changed the purpose of the drug.

    Trials on mice were done and they mice all lost weight, except those on the plecebo, they did not. They made mice fat using DIO. What is DIO? It literally stands for Diet Induced Obesity. They overfed the mice using a super high fat diet and, naturally, the mice became fat. They then used tesofensine on some of the mice and noticed they stopped eating as much as the other mice. They then injected the mice with something that made them feel hungry after being injected, to force them to eat as much as the other mice, and they went back up to the same weight as the other mice.

    What does this tell us? Tesofensine makes you lose weight because it makes you eat less food each time you eat and eat less often. We all know that the difference between your goes-insa and goes-outsa causes your weight to increase or decrease (more in than out, weight increases...more out than in, weight decreases). This can be done by decreasing the in, increasing the out, or a combination of the two.

    They then did human trials. Wait, what? HUMAN trials already? Yes. They were allowed to move quickly since they already used this stuff on humans before and no one got sick or died.

    They found that people said they felt satiated sooner while eating, and felt satiated longer after eating. There is a lot of science that goes on to explain how this most likely works, and you can find it in my source links at the end if you are so inclinded to read up on it.

    There is more to it than hunger control, though. The studies found that energy expendiature was increased as well; the basal metabolic rate went up. They know this because the mice became accustomed to the hunger control. In other words, some of the mice got used to feeling like they were not hungry and decided to increase the amount they ate anyway. But even when that happened, the subjects on tesofensine still remained at a lower weight than the plecebo group even though their food intake was back up to where it was before. This started at 14 weeks of use and continued forever. The interesting thing is that they did NOT see this in the human trials. Go figure, humans and mice are different.

    What about side effects? Great question. There are none. Well, not quite true, there is one. Heart rate increased by about 7bps at about 3 months of use but did not increase any more after that. It also had the same side effects as the plecebo had - dry mouth, headaches, etc. The stuff you read about on the back of every single over the counter drug you buy. So only a slight increase in heart rate, which is still just a small increase. This is amazing, considering the currently accepted precription drugs for weight loss have tons of side effects.

    161 (79%) participants completed a 24 week study. The mean weight loss produced by diet and placebo was 2.0% (SE 0.60). Tesofensine 0.25 mg, 0.5 mg, and 1.0 mg and diet induced a mean weight loss of 4.5% (0.87), 9.2% (0.91), and 10.6% (0.84), respectively, greater than diet and placebo (p<0.0001). After 24 weeks, tesofensine 0.25 mg and 0.5 mg showed no significant increases in systolic or diastolic blood pressure compared with placebo, whereas heart rate was increased by 7.4 beats per min in the tesofensine 0.5 mg group (p=0.0001).

    Tesofensine is ready for Phase III trials, which will test its use on unhealthy people, people on other drugs, verify previous results, etc. After that, it will appear on the market for consumption.


    I LOVE this stuff! I know you guys will to! Just make sure you only take it during a cut since it will decimate your appetite. It would be AMAZING to run in combination with GW50, which will boost your endurance.

  9. I'm interested as well. This could help a lot of people.
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  10. Yeah and I would probably take this rather than GW with the risk it carries. There is one research chem selling it and the guy is repping it like crazy across many boards. The only bad thing is I read some bad reviews on their company. Ive never bought from them and their prices are high. But when I saw this I got really excited considering how well it is working through human trials. Maybe some of the other more reputable research chem companies will pick it up when they catch wind of it?

  11. Quote Originally Posted by HIT4ME View Post
    Here is the guy who will try it!

    https://youtu.be/vYEXzx-TINc
    Lol

  12. Very interested in this.
    SEMPER FI!!

  13. Quote Originally Posted by EvanMan View Post
    Yeah and I would probably take this rather than GW with the risk it carries. There is one research chem selling it and the guy is repping it like crazy across many boards. The only bad thing is I read some bad reviews on their company. Ive never bought from them and their prices are high. But when I saw this I got really excited considering how well it is working through human trials. Maybe some of the other more reputable research chem companies will pick it up when they catch wind of it?
    @PRE
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  14. Quote Originally Posted by HIT4ME View Post
    Interesting find...
    x2 !!
    A-Minds HYPE-SLAYER! All posts & feedback are guaranteed to be unsolicited and legit
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  15. Mexico most overweight country in the world !


    Stage 3 trials started last August on overweight Mexicans. Had no idea they were the most obese in the world. Learn something everyday I guess.


    August 21, 2017 02:01 ET | Source: Saniona AB
    multilang-release
    PRESS RELEASE

    21 August 2017

    Saniona, a leading biotech company in the field of ion channels, today announces that Medix has recruited the first patients in the Phase 3 clinical study for tesofensine in Mexico. This trial in obese Mexican patients is expected to be completed within two years. This Phase 3 study will include a total of 372 patients at two sites in Mexico under the management of Medix.

    "The initiation of this Phase 3 study represents another crucial step in Saniona's history. Tesofensine has in previous studies provided a clinical significant and convincing weight loss in obese patients. Therefore, this study may lead to market approval of a novel and highly effective treatment in Mexico, where overweight and obesity represents a severe health problem," says Jørgen Drejer, CEO of Saniona.

    This randomized, double-blind, placebo-controlled, parallel-arm, Phase 3 clinical trial will include up to 372 ambulatory adult patients with obesity. The patients are randomized into three arms with 124 patients in each arm receiving either 0.25 mg tesofensine, 0.5 mg tesofensine or placebo tablets once daily for 24 weeks. The study starts with a 2-week run-in period where patients receive nutritional and exercise counselling. The first group of patients have started the run-in period and will be randomized in August.

    The primary endpoint is absolute and percent change in body weight over the treatment period. Secondary endpoints include proportions of patients achieving a weight loss of more than 5 and 10 percent respectively, metabolic including glycaemic endpoints, as well as quality of life, comprehensive tolerability and safety evaluation.

    In February 2016, Saniona entered a collaboration with Medix about the development and commercialization of tesofensine and Tesomet in Mexico and Argentina. Medix has exclusive rights to develop and commercialize tesofensine and Tesomet in the two countries. Medix will finance the studies and be responsible for the clinical development and regulatory filings. Medix will pay Saniona regulatory milestone payments and double-digit royalties on product sales in Mexico and Argentina. Saniona retains all rights to tesofensine and Tesomet in the rest of the world including the exclusive rights to use the clinical data developed by Medix.

    This information is information that Saniona (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 08:00 CET on 21 August 2017.

    About Saniona

    Saniona is a research and development company focused on drugs for diseases of the central nervous system, autoimmune diseases, metabolic diseases and treatment of pain. The company has a significant portfolio of potential drug candidates at preclinical and clinical stage. The research is focused on ion channels, which makes up a unique protein class that enables and controls the passage of charged ions across cell membranes. Saniona has ongoing collaboration agreements with Boehringer Ingelheim GmbH, Proximagen Ltd., Productos Medix, S.A de S.V and Luc Therapeutics Inc. Saniona is based in Copenhagen, Denmark, where it has a research center of high international standard. Saniona is listed at Nasdaq Stockholm Small Cap and has about 5,000 shareholders. The company's share is traded under the ticker SANION.

    About Productos Medix, S.A de S.V (Medix)

    Medix is a Mexican pharmaceutical company established in 1956. Medix is primarily focused on treatment of overweight and obesity. The company is the market leader for treatment of overweight and obesity in Mexico where it offers the most comprehensive product and service line. Medix's leading product for treatment of overweight and obesity is among the top ten pharmaceutical products in Mexico overall. Medix has earned several recognitions for its social responsibility through its participation in philanthropic programs for the benefit of the Mexican population and for its educational efforts involving thousands of doctors in Mexico. The company has subsidiaries in Argentina and certain other South American countries.

    About overweight and obesity in Mexico

    Mexico ranks the most obese country in the world. It is estimated that more than 70% of the 128 million Mexicans are overweight and that more than 30% are clinical obese. Since the 1990s, fat has become the principal source of energy in the Mexican diet and it is assumed that the consumption of highly processed food will continue increasing. Consequently, Mexico has seen the same kind of health issues that other countries with overweight populations have. Standardized mortality rates (SMR) for diabetes, acute myocardial infarction (AMI), and hypertension have increased dramatically. As of 2012, diabetes - associated with obesity - was the largest single killer in Mexico.

    Obesity is characterised by severe excess weight in the form of fat and is defined on the basis of a measure referred to as Body Mass Index (BMI). A BMI of more than 30 is referred to as clinical obesity, while a BMI of 25-30 expresses excess weight. Obesity is a serious clinical condition that involves a notably increased risk of cardiovascular diseases and the development of type 2 diabetes. According to the World Health Organization, obesity has reached epidemic proportions worldwide with more than one billion overweight adults of whom at least 300 million are clinically obese. Today, there is a strong medical need for more effective treatment options for obesity.

    About tesofensine

    Tesofensine, a monoamine uptake inhibitor, is focused on obesity. Tesofensine has been evaluated in Phase 1 and Phase 2 human clinical studies with the aim of investigating treatment potential with regards to obesity, Alzheimer's disease and Parkinson's disease. Tesofensine demonstrated strong weight reducing effects in Phase 2 clinical studies in obese patients. In general, tesofensine has been administered to more than 1,200 patients and is well tolerated.

    Mode of Action - Tesofensine potentiate dopamine

    Pathological overeating and obesity can be caused by decreased dopamine function in the reward centre of the brain. Dopamine transporter proteins are inhibited by tesofensine, so the dopamine receptors are stimulated for a longer period after activation and the brain's reward system is amplified. With a similar mechanism of action tesofensine also increases levels of two other monoamines, serotonin and noradrenaline.

    Each of these transmitters exert an important function on appetite and metabolism at different locations in the brain. Dopamine acts in the nucleus accumbens of the forebrain to modulate reward and the "pleasure"-feeling of food. The two other transmitters act in the hypothalamus to increase metabolism and reduce appetite.

    The unique efficacy of tesofensine in obesity may be explained by reversal of blunted dopamine response in obese patients. In obese individuals, the brain centre (striatum) controlling consummatory food reward dopamine receptors are reduced relative to lean individuals. It has been found that in the relevant brain region more than 70% of obese individuals have a blunted dopamine response to food intake.

    Clinical Programs - Tesofensine has produced superior weight loss data.

    The clinical Phase 2b trial (TIPO-1) reported in The Lancet showed levels of weight loss over a six-month period that were of high clinical relevance and highly competitive to other approaches. Patients lost an average of 12.8 kg on a 1 mg dose, 11.3 kg on a 0.5 mg dose and 6.7 kg on a 0.25 mg dose compared with a 2.2 kg loss in the placebo group. All participants were instructed to follow a diet with a 300 kcal deficit and to increase their physical activity gradually to 30-60 minutes of exercise per day. Of the patients receiving 0.5 mg daily, considered the relevant therapeutic dose, 87% of the patients (58% versus placebo) achieved more than 5% weight loss and 53% of the patients (46% versus placebo) achieved a weight loss of more than 10% after 6 months follow up.

    There has also been reported interim results from a 48-week, open-label extension trial (TIPO-4) in which 140 patients who completed the 24-week Phase 2b trial (TIPO-1) were re-enrolled after an average of three months' wash-out. All of them were then treated with 0.5 mg tesofensine once daily but up-titration to 1 mg once daily was allowed in the first 24 weeks of the extension study. The 24-week interim results for those who were previously treated with 0.5 mg tesofensine in TIPO-1 showed a total mean weight loss of between 13 kg and 14 kg over 48 weeks of treatment. Furthermore, TIPO-4 confirmed the TIPO-1 results since the patients who were previously treated with placebo lost approximately 9 kg in the first 24 weeks of the TIPO-4 study.

  16. Quote Originally Posted by EvanMan View Post
    Ok so was doing some more reading on this. So one good thing is that there were human trials done and nothing crazy happened to anyone besides fat loss. Pretty amazing results compared to placebo group. I know we cant post links here but there are a few places selling it as research chem. Google will find it with the right word combination.
    I’ve tried google 10 different ways and can’t find the RC site that has this.

  17. Interesting. I would love to know what the body composition changes were. Would a greater loss of fat occur comparative to muscle? I'm all for losing fat but not at the expense of my hard earned muscle.
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  18. Quote Originally Posted by DWeaver View Post
    I’ve tried google 10 different ways and can’t find the RC site that has this.
    MOD EDIT: Nope.

  19. Just keep looking. Cant tell sources here.

  20. I hope some more companies start selling it

  21. Quote Originally Posted by f4iguy View Post
    Interesting. I would love to know what the body composition changes were. Would a greater loss of fat occur comparative to muscle? I'm all for losing fat but not at the expense of my hard earned muscle.
    Supposedly it also works to increase metabolism on the study done with mice/rats. Its an interesting compound.

  22. This stuff a bust?
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