Oral NONTOXIC Testosterone under review by FDA

MikeXL

Member
SAN DIEGO — A novel oral testosterone formulation (LPCN 1021, Lipocine), which was shown to be safe and effective at 13 weeks, continues to demonstrate similar results at 52 weeks, according to new data.
The formulation is currently under review at the US Food and Drug Administration (FDA).




Longer-term safety data are especially important because other testosterone pills in the United States have been "rarely" used because of liver toxicity, said Mohit Khera, MD, a urologist at the Baylor College of Medicine in Houston.


Dr Khera presented 52-week results from the phase 3 Study of Androgen Replacement (SOAR) here at the American Urological Association 2016 Annual Meeting.


"There is no liver toxicity because LPCN 1021 is absorbed by the lymphatic system," he told Medscape Medical News. "There's no liver toxicity at all," confirmed Tobias Köhler, MD, a urologist at Southern Illinois University in Springfield, who moderated the press conference at which Dr Khera spoke.
SOAR was a "well-done trial," said Dr Köhler. "The science is very good."


In the multicenter open-label trial of 315 hypogonadal men, 210 men were randomized to twice-daily oral LPCN 1021 at a starting dose of 225 mg and 105 men were randomized to testosterone gel 1.62%.
All men were 18 to 80 years of age and had testosterone levels below 300 ng/dL.


The LPCN 1021 dose could be titrated up if 24-hour average testosterone concentration remained below 300 ng/dL, and could be titrated down if maximum concentration was above 1500 ng/dL.
For this formulation of LPCN 1021, the FDA set average testosterone concentrations from 300 to 1140 ng/dL.


At week 13, the mean 24-hour average testosterone concentration was 446 ng/dL, consistent with nonoral testosterone replacement therapies, as previously reported by Medscape Medical News.
The new data show that those week 13 levels "were reliably maintained through 52 weeks."


Specifically, levels were reliably restored and maintained in the eugonadal range for approximately 87% of hypogonadal men over 52 weeks.


"The efficacy is on par with androgel," Dr Köhler noted. The levels are "excellent."
If the product is approved by the FDA, it will likely be well received by clinicians and patients. "This is the most convenient testosterone formulation we have," he said.




And now, for the first time, what is convenient has been shown to be safe, he added, echoing Dr Khera's comments about the hepatotoxicity of other oral testosterones available in the United States.

Gastrointestinal disorders are an adverse event of concern with oral therapy, said Dr Khera, but there was no significant difference in adverse events between the LPCN 1021 group and the testosterone gel group.

The most common drug-related adverse events over the 52 weeks for LPCN 1021 and testosterone gel were acne (2.9% vs 2.9%), headache (0.5% vs 3.8%), weight increase (2.4% vs 0.0%), hematocrit increase (1.9% vs 0.0%), liver enzyme level increase (1.4 % vs 0.0%), fatigue (0.5% vs 1.9%), and hypertension (0.5% vs 1.9%).

Lipid parameters (cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides) were comparable in the two treatment groups at week 52.

Changes in androgenic parameters from baseline to week 52 — such as hematocrit, hemoglobin, platelet, prothrombin, and prostate-specific antigen — were not significantly different between the two groups.

Dr Khera pointed out that LPCN 1021 must be taken with a meal that includes 15 g of fat, which is the amount in a sausage biscuit, half a cup of trail mix, or two pancakes.

Dr Khera reports financial ties to Lipocine, AbbVie, Endo Pharmaceuticals, and Repros.

American Urological Association (AUA) 2016 Annual Meeting: Abstract PD50-09. To be presented May 10, 2016.
 

PAUL-E

Member
Interesting but "average testosterone concentration was 446 ng/dL"
still has a long way to go IMHO
 

MikeXL

Member
Yes. I agree. However, if you look you will see that they say that dosages can be titrated up if below 300mg and titrated down if above 1500. So I would hope that if you had a good doctor, he or she would understand that he or she is treating the person. So the doc should be ok with upping the dosage until you are at a level at which you feel well. I am pleased to see that they SEEM to be telling docs you can go up to 1500. at least that is the way I see it.
 

Vince

Super Moderator
I don't believe we'll ever going to be using oral testosterone. Probably long-term would cause liver problems.
 

CSI007

Member
I would be more concerned with what this might do to the lymphatic system. i.e. cancer. This formulation would not even go into the liver so that is a moot point.
 

Vince

Super Moderator
Oral Agents Oral testosterone formulations are quickly absorbed by the liver and therefore require relatively large doses. Because of the risk of liver toxicity they are rarely prescribed. Do not waste your money or time using oral testosterone. Also, avoid over-the-counter supplements that claim to increase testosterone. Most do not increase testosterone for more than a few minutes and can also affect your liver and blood pressure. Oral testosterone also seems to cause larger decreases of the good cholesterol (HDL) than other forms of testosterone therapies. Chemically unbound testosterone, if taken orally, is immediately deactivated by the liver. Two chemically modified forms of testosterone are available that require several doses a day: methyl testosterone and testosterone undecanoate (not approved in the United States but popular in Canada). Methyl testosterone Methyl testosterone is one of the earliest available oral testosterones. Its chemical structure is the hormone testosterone with an added methyl group at the c-17 alpha position of the molecule to slow down its clearance by the liver. The use of oral c-17 alpha methylated testosterone causes toxicity to the liver and is not recommended for testosterone hormone therapy. Brand names around the world include “Metesto,” “Methitest,” “Testred,” “Oreton Methyl,” and “Android.” These products are responsible for many of the misconceptions that still exist about testosterone replacement due to their liver and lipid problems. The same information is applicable to fluroxymesterone, another oral formulation no longer used in the United States. Testosterone undecanoate Testosterone undecanoate is not a c-17 alpha alkylated hormone. Therefore it is considered a safer oral form of testosterone. It is designed to be absorbed through the small intestine into the lymphatic system, and has fewer negative effects on the liver. Brand names around the world for oral testosterone undecanoate include “Andriol,” “Androxon,” “Understor,” “Restandol,” and “Restinsol.” It is not available in the United States but widely used in Canada and some European countries. One disadvantage of orally administered undecanoate is that it is eliminated from the body very quickly, usually within three to four hours. Frequent administration is necessary—usually from three to six capsules a day, which makes it impractical for most men with busy lives. PERSONAL COMMENT: I've never used oral testosterones and I never will. Other formulations are so much more user-friendly.

Read more at: https://www.excelmale.com/forum/showthread.php?1487-Testosterone-Replacement-Treatment-Options
 

PAUL-E

Member
Yes. I agree. However, if you look you will see that they say that dosages can be titrated up if below 300mg and titrated down if above 1500. So I would hope that if you had a good doctor, he or she would understand that he or she is treating the person. So the doc should be ok with upping the dosage until you are at a level at which you feel well. I am pleased to see that they SEEM to be telling docs you can go up to 1500. at least that is the way I see it.

I agree but there might be more of an effect on system at higher doses
"The most common drug-related adverse events over the 52 weeks for LPCN 1021 and testosterone gel were acne (2.9% vs 2.9%), headache (0.5% vs 3.8%), weight increase (2.4% vs 0.0%), hematocrit increase (1.9% vs 0.0%), liver enzyme level increase (1.4 % vs 0.0%), fatigue (0.5% vs 1.9%), and hypertension (0.5% vs 1.9%). Lipid parameters (cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides) were comparable in the two treatment groups at week 52. Changes in androgenic parameters from baseline to week 52 — such as hematocrit, hemoglobin, platelet, prothrombin, and prostate-specific antigen — were not significantly different between the two groups."

If it was effective I would imagine underground labs adapting the delivery system for their oral products
 

MikeXL

Member
This does not go to the liver for the first pass. It is absorbed lymphatically. So, it should not affect the liver any more than shots. At least that's the theory
 

CSI007

Member
This does not go to the liver for the first pass. It is absorbed lymphatically. So, it should not affect the liver any more than shots. At least that's the theory

Exactly. That's why I made my post above. The whole point of this new pill is to avoid the liver entirely. Obviously everything that goes into our body eventually goes through the liver but this pill IS NOT metabolized by the liver which is why the older testosterone pills were causing the damage.

This really is a breakthrough if it actually does work as suggested.
 

PAUL-E

Member
Exactly. That's why I made my post above. The whole point of this new pill is to avoid the liver entirely. Obviously everything that goes into our body eventually goes through the liver but this pill IS NOT metabolized by the liver which is why the older testosterone pills were causing the damage.

This really is a breakthrough if it actually does work as suggested.
I hope it works but only time will tell.
 

Vince

Super Moderator
It does say oral, so I don't understand how it's absorbed by the lymphatic system or why?
 

CoastWatcher

Moderator
It does say oral, so I don't understand how it's absorbed by the lymphatic system or why?

A general overview of lymphatic, first-pass absorption.

Drug transport into the lymphatic vessels of the small intestine
The intestinal lymphatics—not the blood capillaries—are responsible for the transport of dietary lipids from the intestine back to the general (systemic) circulation. Drugs that are intrinsically lipophilic, or prodrugs that can be modified to be transiently lipophilic, are able to piggyback on this lipid absorption pathway, effectively achieving drug concentrations in the intestinal lymph 10 to 100 times higher than in the blood.
This unique drug absorption pathway has a number of highly significant benefits. Drug transport via the intestinal lymph circumvents first-pass metabolism in the liver, enhancing the oral bioavailability of drugs with high first-pass metabolism. The intestinal lymphatics channel drug absorption through the largest lymph node in the body, the mesenteric lymph node—a critical 'sensor' in determining whether the body launches an immune response. Drug delivery via the intestinal lymphatics has significant potential for the delivery of drugs, antigens and adjuvants that enhance or suppress immunity or tolerance.
 

Nelson Vergel

Founder, ExcelMale.com
This is an oral testosterone undecanoate similar to Andriol available in Canada but in a lipid matrix for better PK.

The study used 225 mg twice per day. This dose could be changed to 150 mg or 300 mg twice per day based on the target range of serum T of 300- 1100 ng/dl (average concentration). Half of patients required dose adjustment. At the end of the study, 51% had the same starting dose of 225 mg.

Here is a powerpoint presentation: http://files.shareholder.com/downlo...36/ENDO_oral_presentation_3-8-15_FINAL_v6.pdf


lipocine oral T.jpg
 
Last edited:

HarryCat

Member
Lipocine was not approved yesterday:

"SALT LAKE CITY, June 29, 2016 (GLOBE NEWSWIRE) -- Lipocine Inc. (NASDAQ:LPCN), a specialty pharmaceuticalcompany, today announced that it has received a Complete Response Letter ("CRL") from the United States Food and DrugAdministration ("FDA") regarding its New Drug Application ("NDA") for LPCN 1021, an oral testosterone product candidatefor testosterone replacement therapy ("TRT") in adult males for conditions associated with a deficiency or absence ofendogenous testosterone, also known as hypogonadism. A CRL is a communication from the FDA that informs companiesthat an application cannot be approved in its present form.The CRL identified deficiencies related to the dosing algorithm for the label. Specifically, the proposed titration scheme forclinical practice was significantly different from the titration scheme used in the Phase 3 trial leading to discordance intitration decisions between the Phase 3 trial and real-world clinical practice.The next step will be to request a meeting with the FDA to understand more fully the issues raised and to agree on a pathforward to achieve approval of LPCN 1021."We are evaluating the content of the CRL, including the FDA recommended actions to bring our NDA in a position forapproval, and will work closely with the FDA to determine the appropriate next steps for the NDA. We remain committed tobringing LPCN 1021 to patients who will benefit from its intended use," said Dr. Mahesh Patel, Chairman, President andCEO of Lipocine. "We continue to believe that LPCN 1021 has the potential to improve the ease of use compared to theavailable formulations, including topical gels and injections, and to overcome inadvertent testosterone transference risk tochildren and partners that exist with topical gels."
 

Nelson Vergel

Founder, ExcelMale.com
Thanks HarryCat

Lots of push back from the FDA. I am not impressed by the lack of regulatory knowledge of this company. The press release you posted shows how clueless they are.
 

Hopeful

New Member
Lipocine resubmits LPCN 1021

Old thread revived because Lipocine resubmits LPCN 1021 to FDA. Statement from Lipocine...

"Resubmission of this NDA as planned is an important milestone in bringing LPCN 1021 to patients," said Dr. Mahesh Patel, Chairman, President and Chief Executive Officer of Lipocine. "We believe the results from the recently completed DV study address the label-related deficiency identified by the FDA in the CRL. We consider LPCN 1021 to be a differentiated TRT option for treating hypogonadism in men. We anticipate a six-month review by the FDA with a projected PDUFA date in the first quarter of 2018 assuming the FDA acknowledges our submission is a complete response."
 

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