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Two clinical Phase I studies have been carried out where Levodose® was compared with approved registered drugs.
Study 1
The first study was 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 rate 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.
A phase I investigation of bioavailability and pharmacokinetics (bioequivalence study) following single dosing of three formulations of levodopa with addition of a decarboxylase inhibitor in 18 healthy subjects was thus conducted during 2009. The clinical phase of the study was conducted at the Department of Clinical Pharmacology, C1:68, Huddinge, Karolinska University Hospital. The study was a single dose, open, randomized, three-way crossover, phase I study in healthy volunteers. Subjects were randomized to one of three treatment sequences. All subjects received three treatments, one with each dosage form, with a minimum of a 4 day washout between. The objective of the study was to compare the bioavailability of Levodose® (20 micro-tablets corresponding to a total dose of 100mg/25mg levodopa/carbidopa) with two reference products -Madopark® Quick (levodopa/benserazide 100/25) and Sinemet®, (levodopa/carbidopa 100/25 mg) and to determine their bioequivalence.
The outcome of the study was to full satisfaction and in accordance with the expectations of the company. The data obtained for both levodopa and carbidopa compared to Sinemet®were within the acceptance levels, i.e. Levodose® and Sinemet® are bioequivalent following single dosing. 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 results of study has been published in the journal Clinical Neuropharmacology, 30 April 2012 see www.ncbi.nlm.nih.gov/pubmed/22549097
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 a recently completed clinical study Levodose was compared with Stalevo®. The study was a multiple dose, open, randomized, two-way crossover, phase I study in healthy volunteers. Subject’s treatment orders was randomized. All subjects received two treatments, one with each dosage form, with a minimum of a 4 day washout between.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, C1:68, Huddinge, Karolinska University Hospital.
The results of study has been published in the journal Acta Neurol Scand. 2012 Jul 4. see
www.ncbi.nlm.nih.gov/pubmed?term=22762460
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