3 November 2010
Sensidose AB in Uppsala has developed a system for
individual dosing of drugs in tablet form. The system includes an
electronic dosing device for drugs given in the form of microtablets,
and functions for the registration of symptoms. Two clinical Phase I
studies have been carried out, demonstrating that the concept of
dividing up a standard tablet into several microtablets works well
clinically. In addition to the fact that the microtablets enable a
personalized dosing in tablet form, the studies also show that the
system enables a more steady clinical effect compared to today’s
standard tablets. The studies concern drugs for the treatment of
Parkinson’s disease.
Today there are only standard doses for tablet treatment of many diseases, therefore individual dosing with tablets is generally not possible. Sensidose’s system is based on the use of microtablets, each containing just a very small dose of the drug. By calculating a patient specific number of these microtablets, the dose can be adjusted and fine-tuned individually for each patient. With the aid of Sensidose’s electronic dose automate the patient can simply dose exactly the specific individual amount of the drug that is optimal for the disease situation. In addition, a number of functions in the dose automate facilitate the patient’s handling of the tablets, e.g. an alarm reminding the patient to take the tablets, a function for registration of tablets taken and changes in dose, and an electronic diary for registration of symptoms and treatment effect. Information from the dosing device is transferred to the computer system of the patient’s physician. The microtablets are supplied in disposable cassettes for approximately one weeks’ consumption.
The first application of Sensidose’s system is a drug for the treatment of Parkinson’s disease. Indication areas that may later become interesting include the treatment of chronic pain, epilepsy in children, diabetes type II, cardiovascular diseases and cancer. Levodose® is a new dosage form of an approved drug used for the treatment of Parkinson’s disease. The active ingredient of the drug is levodopa, a substance that is transformed to dopamine in the brain. It is naturally occurring in small amounts in all humans. In order for levodopa not to be metabolized too quickly, the drugs also contain a so-called metabolization inhibitor. The inhibitor used in the microtablet is carbidopa. Two clinical Phase I studies have now been carried out where Levodose® was compared with approved registered drugs.
Study 1
The first study is a so-called bioequivalence study, where the aim was to compare Sensidose’s own product, Levodose® microtablets, with the same total dose of an existing drug product. This is a procedure that is common in the registration of generic drugs.
The aim of a bioequivalence study is to show that there is no significant difference in terms of absorption, distribution, metabolism or excretion of the active substance, what is also called pharmacokinetics. The drugs are given as single doses on one occasion, usually to healthy volunteers, under standardized conditions.
At predetermined points in time blood samples are drawn for analysis. In order for the substances to be considered bioequivalent, the speed as well as the degree of drug absorption must be the same. If the tested product is bioequivalent with an already registered product, you can in principle apply for marketing approval of the new product.
The product that is closest to Levodose® is Sinemet®, which contains the same active substances, levodopa and carbidopa. Sinemet® is, however, only available in standard doses that are considerably higher than the contents of a Levodose® microtablet, which contains only 5 mg levodopa and 1.25 mg carbidopa.
18 subjects were included in the study, where a comparison was made between Levodose® given in the form of 20 microtablets, for a total of 100 mg, and Sinemet® in the form one 100 mg tablet. The results showed that the two drugs performed identically in terms of absorption in the body, and thus were bioequivalent. Both drugs gave measurable concentrations already after approximately 10 minutes and maximum concentration after approximately half an hour. After approximately 1.5 hours half of the levodopa had been eliminated from the bloodstream. The study was led by the Department of Clinical Pharmacology, Karolinska University Hospital, Huddinge, Sweden.
Study 2
The rapid metabolism of levodopa is a problem for patients with Parkinson’s disease. In order to function normally they need to have a constant and individually adjusted plasma level of the drug. In this way a steady synthesis and availability of dopamine in the brain, with stable motor and psychomotor function is achieved. The drug Stalevo® contains levodopa and carbidopa, but also an inhibitor of the COMT enzyme and is considered to be the preparation in tablet form that best enables the desired steady supply of levodopa.
In the recently completed clinical study Levodose® was compared with Stalevo®. The aim was to demonstrate that repeated dosage with Levodose® can achieve a plasma concentration that is at least as steady during the day as with Stalevo®. Both drugs were given to 10 healthy volunteers, who were all administered 300 mg levodopa through the respective drug during a day. Levodose® was administered as follows: An initial 75 mg dose was given in the morning. Five 45 mg doses were then given at fixed intervals. Stalevo® was given as three 100 mg tablets every six hours, starting in the morning. Blood was sampled throughout the day. It was of special interest to register the maximum and minimum plasma concentrations of each drug. The results showed that Levodose® gave more steady concentrations than Stalevo®, i.e. Stalevo® gave both the lowest and the highest plasma concentrations during the day. Levodose® also gave a considerably faster absorption of levodopa, with shorter time to maximum plasma concentration, compared to Stalevo®. The study was led by the Department of Clinical Pharmacology, Karolinska University Hospital, Huddinge, Sweden.
Registration application in preparation
Sensidose believes that Levodose® will clearly be an interesting alternative to Stalevo® and the use of COMT inhibitors, and also an alternative to other so-called multi pharmacy regimens that are prescribed to most patients with Parkinson’s disease. There are several advantages with monotherapy, in this case personalized medication with levodopa alone. In addition to the possibility to achieve a more steady therapeutic effect, the absence of side effects from other substances should be a major advantage. Furthermore, the symptom registration made possible by the dose automat should result in improved collaboration between patient and physician, and optimized pharmacotherapy.
“The system from Sensidose meets major medical needs. Up to 90 percent of the three million patients in the world who suffer from Parkinson’s disease can benefit or benefit greatly from the product. The results from the clinical studies and the company’s assessment indicate that Levodose® has the potential to become an import drug for the treatment of Parkinson’s disease. The microtablets enable the exact dosing of the amount of drug that is adapted to the disease situation of the patient,” says Sten Magnus Aquilonius, professor emeritus at the Department of Neuroscience, Neurology at Uppsala University and board member of Sensidose.
”We continue to prepare a registration application for Levodose®. The majority of the factual basis is in place and we have started to compile the documentation, so we expect to file the registration application next year. It should be noted that the patent situation for the product is very good, says Sören Nygren, CEO of Sensidose.
Sensidose own all patents/application and patents are approved in the US and Europe, and other countries. According to Forskarpatent AB the patent situation is strong and there are no competing patents.
Further Information
