A USE OF GALANTAMINE FOR THE TREATMENT OF ALZHEIMER'S DISEASE; TARGETING THE UNDERLYING CAUSE OF THE DISEASE

Abstract: Galantamine has be used in the treatment of a number of chronic diseases. Galantamine has been found to be safe and effective in the treatment of Alzheimer's disease. The therapeutic drugs, including galantamine, that have been used to date for the treatment of Alzheimer's disease were thought to provide only symptomatic relief. It has now been shown that galantamine can be used for the treatment of the underlying cause of the disease.

Description: A USE OF GALANTAMINE FOR THE TREATMENT OF ALZHEIMER'S DISEASE; TARGETING THE UNDERLYING CAUSE OF THE DISEASE The present invention relates to the use of an effective amount of galantamine for the production of a medicament for the treatment of Alzheimer's disease, wherein said treatment provides both symptomatic relief and also treats the underlying cause of the disease. BACKGROUND OF THE INVENTION Galantamine is known to be a reversible cholinesterase inhibitor that can be isolated from a number of different plant sources, including daffodil bulbs. Galantamine interacts competitively with the enzyme, acetylcholinesterase, and demonstrates a 10 to 50 fold selectivity for acetyl vs. butyryl cholinesterase. Galantamine has been used for the treatment of a number of chronic diseases, where lifelong treatment may be necessary. For example Galantamine has been shown to be effective in the treatment of Alzheimer's Disease (United States Patent 4,663,318). The etiology of neuronal degeneration and associated cognitive impairment in Alzheimer's disease is not fully understood. However, three consistent neuropathological hallmarks have been identified: amyloid-rich senile plaques, tau-positive neurofibrillary tangles, and neuronal cell death. Methods of treating Alzheimer's disease include the use of therapeutic drugs for symptomatic relief of the cognitive symptoms of the disease. US Patent 5,962,535 acknowledged the shortcomings of the prior treatments and proposed the use of a pharmaceutical composition for treating or preventing Alzheimer's disease which comprises idebenone in combination with a compound having acetylcholinesterase inhibitory activity. According to this prior art, this combination of compounds produced clinical benefits not seen in previous treatments. Thus, there is a need for other therapeutic drugs for treating, preventing and inhibiting the progression of Alzheimer's disease by targeting the underlying cause of the disease. SUMMARY OF THE INVENTION Thus, according to the present invention there is provided a use of galantamine for the production of a medicament for treating, preventing and inhibiting the progression of Alzheimer's disease by targeting the underlying cause of the disease. BRIEF DESCRIPTION OF THE DRAWINGS These and other features of the invention will become more apparent from the following description in which reference is made to the appended drawings wherein: FIGURE 1 shows the mean change (±SE) in ADAS-cog/11 from baseline to the end of the treatment period to the end of the washout period. FIGURE 2 shows the prior art results with donepezil hydrocliloride in a similar study. DESCRIPTION OF PREFERRED EMBODIMENT The present invention relates to the use of an effective amount of galantamine for the production of a medicament for treating, preventing and inhibiting the progression of Alzheimer's disease by targeting the underlying cause of the disease. Galantamine, a tertiary alkaloid, has been isolated from the bulbs of the Caucasian snowdrops Galantωms woronowi (Proskurnina, N. F. and Yakoleva, A. P. 1952, Alkaloids of Galanth s woronowi. II. Isolation of a new alkaloid. (In Russian.) Zh.Obschchei Khim. (J. Gen. Chem.) 22, 1899-1902). It has also been isolated from the common snowdrop Galanthus nivalis (Boit, 1954). Galantamine is a well-known acetylcholinesterase inhibitor which is active at nicotinic receptor sites but not at muscarinic receptor sites. It is capable of passing the blood-brain barrier in humans, and presents no severe side effects in therapeutically effective dosages. Galantamine has been used extensively as a curare reversal agent in anaesthetic practice in Eastern bloc countries (cf. review by Paskow, 1986) and also experimentally in the West (cf. Bretagne and Valetta, 1965: Wislicki, 1967; Consanitis. 1971). Galantamine has been marketed by the company Waldheim (Sanochemia Gruppe) as Nivalin™ in Germany and Austria since the 1970s for indications such as facial neuralgia. In the present invention when we refer to galantamine we include within this term galantamine itself, derivatives and salts thereof, such as halides, for example galantamine hydrobromide. For the purposes of the present invention galantamine and derivates and salts thereof may be formulated according to convention methods of pharmacy, together where appropriate with one or more pharmaceutically acceptable carriers, excipients or diluents, as is known in the art. Such formulations can take the form of tablets, capsules, solutions, or lozenges, pessaries, creams, suppositories or transdermal formulations, depending on the route of administration. According to the present invention, it has been found that galantamine, for example galantamine hydrobromide, acts on the cholinergic system in two ways - by modulating the release of acetylcholine nicotinic receptors and inhibiting acetylcholinesterase. Galantamine hydrobromide is thought to increase the release of acetylcholine through a mechanism called allosteric modulation of the nicotinic receptors. Although not wanting to be bound to any particular theory, it is thought that galantamine hydrobromide binds to a site on the presynaptic nicotinic receptor, that is distinct from the acetylcholine- binding site, and evokes a change in the shape of the receptor. This triggers the opening of ion channels in the presynaptic membrane, thus maldng cholinergic neurons more excitable. This results in an increased release of acetylcholine, which can then further stimulate the presynaptic nicotinic receptors to mediate the release of more acetylcholine. Such modulation is self-regulating, which produces overstimulation. The increased production of acetylcholine competitively inhibits the enzyme responsible for its breakdown, acetylcholinesterase. In addition to increasing the amount of acetylcholine released, stimulation of presynaptic nicotinic receptors also increases the release of other neurotransmitters (such as glutamate) thought to play important roles in cognitive function. In the present invention, the impact of drug withdrawal was used as an indication of the impact of the drug on cognitive function. The expectation was that patients treated with galantamine, and then withdrawn from the drug would return to levels of cognitive function similar to those documented in the placebo group. As is shown below, prior art studies have demonstrated that following the withdrawal of a cholinesterase inhibitor, in the treatment of Alzheimer's disease, the symptomatic improvement diminished rapidly as a function of the pharmacokinetic elimination of the inhibitor. However, according to the present invention it was found that patients treated with galantamine enjoyed some sustained benefit, even after being removed from the drug. According to the present invention, a safe and effective amount of galantamine can be used for treating, preventing and inhibiting the progression of Alzheimer's disease by targeting the underlying cause of the disease. Precise dosage rates and regimes can be determined empirically by the medical practitioner, depending on individual circumstances. For example, if the compound is delivered orally, a daily dose of from about 1 mg to about 100 mg is effective. In a further example the compound can be delivered at about 5 mg to about 50 mg per day. In yet a further example the compound can be delivered at about 16 mg to about 32 mg per day. Precise daily dosages can be selected from 16 mg, 18 mg, 24 mg or 32 mg per day. It is preferred that the daily dosage be divided into two or three equal dosages. It has been found that the tolerability or safety of the drug can be improved if the patient is introduced to the drug slowly over a number of weeks. In one embodiment of the present invention the patient is introduced to galantamine slowly from about 2 weeks to about 10 weeks, wherein the dose is increased over this period. In one embodiment of the present invention the patient received a dose of about 8 mg/day for about 1 week, followed by a dose of about 16 mg/day for about 1 week, followed by a maintenance dose of about 24 mg/day thereafter. In one embodiment of the present invention the patient received a dose of about 8 mg day for about 1 week, followed by a dose of about 16 mg/day for about 1 week, followed by a dose of about 24 mg day for about 1 week, followed by a maintenance dose of about 32 mg/day thereafter. In one embodiment of the present invention the patient received a dose of about 8 mg day for from about 2 weeks to about 4 weeks, followed by a dose of about 16 mg/day for from about 2 weeks to about 4 weeks, followed by a maintenance dose of about 24 mg/day thereafter. In one example of this embodiment the patient received a dose of about 8 mg/day for about 4 weeks, followed by a dose of about 16 mg/day for about 4 weeks, followed by a maintenance dose of about 24 mg/day thereafter. In a further embodiment of the present invention the patient received a dose of about 8 mg/day for from about 2 weeks to about 4 weeks, followed by a maintenance dose of about 16 mg/day thereafter. In one example of this embodiment the patient received a dose of about 8 mg/day for about 4 weeks, followed by a maintenance dose of about 16 mg/day thereafter. The present invention is illustrated by the following example, which is not to be construed as limiting. EXAMPLES A six -week randomized withdrawal study compared withdrawal from a three month treatment with galantamine, to continued treatment with 24 mg or 32 mg galantamine (given in two equal doses), or continued treatment with a placebo. Patients who received placebo in the earlier study continued to receive placebo (PLA PLA). Patients who received galantamine in the earlier study were randomized into one of two groups. The withdrawal group (GAL/PLA) were removed from the galantamine treatment and received placebo for 6 weeks. The other group (GAL/GAL) continued to receive the same dose of galantamine, 12 mg or 16 mg bid (twice daily). Saftey was assessed by ECG, periodic physical examination, laboratory tests and reports of adverse events. The Alzheimer's Disease Assessment Scale (ADAS) ADAS-cognitive scale (ADAS-cog) was used to evaluate efficacy during treatment (Rosen, W.G. et al., Amer. J. Psychiatry, 141: 1356- 1364, 1984). All patients were monitored throughout the study, with follow-up and cognitive evaluation at six weeks after the start of the withdrawal study. The primary efficacy endpoints were the change from baseline ADAS-cog/11. The ADAS consists of two parts — a cognitive subscale and a behavioral subscale. The behavioral subscale was not be used in this study. The cognitive subscale, the ADAS— cog-11 comprises the following 11 items, with a score ranging from 0 to 70: Word Recall (0 to 10) Word Recognition memory tests (0 to 12) Object and Finger Naming (0 to 5) Commands (0 to 5) Constructional Praxis (0 to 5) Ideational Praxis (0 to 5) Orientation (0 to 8) Remembering Test Instructions (0 to 5) Spoken language Ability (0 to 5) Comprehension of Spoken language (0 to 5) and Word Finding Difficulty (0 to 5). To reduce variability due to circadian fluctuations in cognitive status the ADAS was done always at the same time of the day, preferably before noon. The ADAS-cog/13 was used as a secondary variable. The ADAS-cog/13 subscale consisted of the 11 items in the ADAS-cog/11 subscale plus two new items, which were added to provide more information regarding the patient's status. This secondary variable, with a score ranging from 0 to 85 contains the additional two items: Concentration and Distraction (0 to 5) and Delayed Word Recall (0 to 10). Additional secondary variables included the ADAS-cog/10 and ADAS-cog/mem tests. The items in the ADAS-cog/10 analysis are: Object and Finger Naming (0 to 5) Commands (0 to 5) Constructional Praxis (0 to 5) Ideational Praxis (0 to 5) Orientation (0 to 8) Remembering Test Instructions (0 to 5) Spoken language Ability (0 to 5) Comprehension of Spoken language (0 to 5) Word Finding Difficulty (0 to 5) and Concentration and Distraction (0 to 5). The memory ADAS cognitive subscale is the sum of the following three items (score range 0 to 32): Word Recall (0 to 10) Word Recognition memory tests (0 to 12) and Delayed Word Recall (0 to 10). The MMSE is a very brief test of cognitive functions including orientation to time and place, instantaneous recall, short-term memory, and ability to perform serial subtractions or reverse spelling, constructional capacities and the use of language. The MMSE score was derived from the sum of the points assigned to each completed task. A total possible score is 30. The MMSE was performed at visit l(screening). Descriptive statistics for all patients were provided for demographic variables and baseline characteristics (obtained at baseline visit before the administration of galantamine). Similar summaries were provided for the three treatment groups (PLA/PLA, GAL/PLA, GAL/GAL). The comparability between treatment groups at baseline was evaluated with respect to demographic and baseline variables. A two-way analysis of variance (ANOVA) model with factors for treatment group, investigator, and their interaction term (when appropriate) was used for continuous variables. The Van Elteren test controlling for investigator was used for the between-treatment group comparison of ordinal categorical variables. For nominal categorical variables, the Cochran-Mantel-Haenszel test for general association controlling for investigator was used. The results for medical and surgical history updates since the beginning of randomized withdrawal phase were summarized by the number and percent of abnormality of each system. No formal statistical comparison was done. Concomitant and psychotropic medications used were summarized by the number and percentage of patients presenting per treatment. The primary efficacy parameter was the total score of the 11 cognitive items from the original ADAS cognitive subscale (ADAS-cog/11). The secondary efficacy parameters were ADAS cluster scores ADAS-cog/13, ADAS-cog/10, and ADAS-cog/mem, as well as the percentage of responders. All efficacy data were summarized and compared to the initial visit (the end of the initial treatment phase) to evaluate the changes that occurred during the 6 weeks of withdrawal. The entire efficacy profile from the beginning of the preceding study to the end of this withdrawal trial was also evaluated by methods for analyzing continuous repeated measures. The primary efficacy comparisons were made between the GAL/PLA group regardless of galantamine dose, and the PLA/PLA group, unless specified otherwise. Within-group comparisons for changes from the initial visit and changes from baseline were performed using the paired t-test or Wilcoxon signed rank test depending on the distribution of the data. For the continuous data, changes from the initial visit were compared among two treatment groups (PLA/PLA, GAL PLA). An analysis of covariance model (ANCOVA) with treatment, investigator, and their interaction (if found to be significant at p=0.1 significance level) as factors and the initial value as covariate was used. Following ANCOVA, pairwise comparisons were subsequently performed by Fisher's least significant difference procedure. If parametric methods were deemed inappropriate, that is, if the data did not follow a normal distribution, nonparametric methods such as two-way ANOVA on ranked data or Van Elteren test controlling for investigator were used. For ordinal categorical variables, the Van Elteren test controlling for investigator was used for the between-treatment group comparison. For the nominal data, the Cochran- Mantel-Haenszel test for general association controlling for investigator was used. All analyses indicated in the protocol were conducted as above. However, for continuous data, a one-way ANOVA with treatment as factor was applied at all time points instead of the ANCOVA model as described in the protocol. The center effect was not included in the ANOVA model due to the small center sizes in this trial. The longitudinal analysis using a mixed model approach was not performed since the GAL/PLA group changed treatment in this trial, a simple mixed effect model would not address this issue. The safety of the drug was also monitored throughout the study. All patients who had taken at least one dose of trial medication in this withdrawal trial were included in the safety summary. For these patients, the entire safety profile from the beginning of the preceding study to the end of this withdrawal trial (last day trial medication was taken plus 3 days) was also summarized. Serious adverse events were recorded up to 30 days after the last day of trial medication. The type and incidence of adverse events that patients experienced during the preceding trial and this withdrawal trial were summarized by treatment group. Separate tabulations were prepared for severity of treatment emergent adverse events, drug-related adverse events, serious adverse events, and other significant adverse events, such as those leading to the patient's discontinuation from treatment. For the clinical laboratory data, descriptive statistics and pre-versus within- and post- treatment cross-tabulations (with classes for below, within and above the normal range of the central laboratory, Covance Central Laboratory Services, Inc., Indianapolis, Indiana) were generated for all tests performed. In addition, potentially clinically important values were tabulated for all biochemistry tests and for all urine parameters. The parameters were assessed before (reference or baseline value), during or after treatment. Criteria limits for potentially clinically important values for most biochemical tests were as defined by Lippert and Lehmann (SI Units in Medicine. Baltimore-Munich; Urban & Schwarzenberg; 1978). For enzymes, the lower criteria limit is defined as zero, and the upper criteria limit as twice the upper limit of normal. This study was conducted on a total of 118 patients that had completed an earlier study, receiving a placebo, 24 mg/day or 32 mg/day of galantamine for three months. The placebo group, 47 patients, continued receiving the placebo. The galantamine group were divided into two groups. One group, 39 patients, were given a placebo in this withdrawal test, whereas the other group, 32 patients, continued receiving the dose of galantamine, 24mg/day or 32 mg/day, given in the earlier completed study. Ninety four percent of the patients completed the trail. Table 1 summarizes the demographics and baseline characteristics (from intake into the initial study) for all patients participating in this trial. Slightly more women (59%) than men (41%) participated in the trial. The majority (91 %) of patients were white, with an average age of 75 years and an average weight of 69 kg. These factors were well balanced across treatment groups, and no statistically significant differences were found among the three treatment groups. Table 1. Demographic and baseline disease characteristics for all patients The primary analysis was performed on ADAS data collected at Week 6 (traditional observed case) and compared to ADAS data collected at initial visit (primary) and baseline visit (secondary). Patients missing data for Week 6 were not included in the analysis. The primary comparison was between the PLA PLA group and the GAL PLA group in change from initial visit at Week 6. Five patients, 1 in the PLA/PLA group, 3 in the GAL/PLA group, and 1 in the GAIJGAL group, did not have any ADAS data collected at the initial visit. Eight patients, 5 in the PLA/PLA group, 1 in the GAIJPLA group, and 2 in the GAIJGAL group, did not have ADAS data collected at Week 6. In a traditional LOCF (last observation carried forward) analysis, available ADAS scores from the initial visit for these patients were used for the Week 6 visit. These results did not differ from results obtained in the traditional observed case analysis. ADAS-cog/11 (Alzheimer's Disease Assessment Scale - Cognitive Subscale) was the total score of 11 cognitive items on the ADAS. The total score ranges from 0-70, with a higher score indicating a worsening of cognitive function. ADAS-cog/11 score was calculated only when all 11 items were available. Missing ADAS-cog/11 scores were not replaced or imputed due to the low missing rate. The primary analysis was the change from initial visit versus Week 6. These data are summarized in Table2. Table 2. ADAS-cog/11 mean scores and change from initial visit for observed case data At the beginning of this trial, initial mean ADAS-cog/11 scores were slightly higher for patients who had been receiving galantamine as compared to patients who had been receiving placebo. At the end of the 6-week withdrawal period, patients in the placebo group through both treatment and withdrawal (PLA/PLA) had slightly higher mean ADAS scores compared to scores at the initial visit, indicating a decline in cognitive function. Patients in the galantamine group through both treatment and withdrawal group (GAIJGAL) had slightly lower mean ADAS scores, thus maintaining a trend towards improved cognitive function. Patients in the group that had received galantamine during treatment and who were withdrawn to placebo in this trial (GAIJPLA), had improved while on active treatment, and declined upon withdrawal of medication. Upon entry into the initial study, baseline ADAS-cog/11 scores were slightly higher for the GAIJPLA and GAL/GAL groups as compared to PLA PLA, but were not statistically significantly different between groups (p=0.491). These data, along with mean change from baseline, are shown in Table 3. Table 3. ADAS-cog/11 mean scores and change from baseline visit for observed case data a: Patients with ADAS-cog/11 score at initial visit (start of this trial) Patients in the PLA/PLA group, who received placebo throughout both trials, ended the withdrawal phase (Week 6) with slightly higher mean ADAScog/11 scores, indicating gradual deterioration of mental function. Patients in the GAL/GAL group, who received galantamine throughout both trials, ended the withdrawal phase (Week 6) with slightly lower mean ADAScog/11 scores, demonstrating a sustained symptomatic effect. Patients in the GAL/PLA group, who had received galantamine for 3 months and then were withdrawn from active treatment, had returned to near original baseline values after 6 weeks without galantamine. The mean change in ADAS-cog/11 scores and standard errors are displayed in Figure 1. In addition to ADAS-cog/11 score, three cluster scores were identified and analyzed as secondary efficacy parameters. Table 4 presents means and mean change from initial visit (beginning of this trial) for ADAS cluster scores at Week 6. Table 4. Mean score and change from initial visit for ADAS cluster scores at Week 6 Table 5 presents the means and mean change from baseline (beginning of the initial study) for ADAS cluster scores at Week 6. Table 5. Mean score and change from baseline for ADAS cluster scores at Week 6 Table 6 shows the mean changes from initial visit on ADAS individual item scores at Week 6. In general, no change from initial visit was seen in all of the groups. Table 6. Mean change from initial visit for individual ADAS item scores at Week 6: observed case Four definitions for ADAS-cog/11 response were used to summarize ADAS-cog/11 response data. Responder (0) was defined for those patients with no change or better (≥points improvement) on ADAS-cog/11 score. Similarly, responder (4) was for ≥4 points improvement, responder (7) for >7 points improvement and responder (10) for >10 points improvement. The percentages are based on total number of patients who had an evaluation at the specific visit. The response data, from initial visit, at Week 6 shows that about 61% of PLA/PLA patients had no change or were improved in ADAS-cog/11 score, as compared to 47% in the GAIJPLA group and 55% in the GAIJGAL group. The use of higher cutoff points demonstrate that patients who received galantamine were higher responders than patients who only received placebo. Only fifteen percent of PLA/PLA group patients had ≥4 points improvement in ADAS-cog/11 score at Week 6, as compared to 19% in the GAIJPLA group and 28% in the GAL/GAL group. Five percent of PLA/PLA group patients had >7 points improvement in ADAS-cog/11 score at Week 6, as compared to 6% in the GAIJPLA group and 14% in the GAL/GAL group. Only patients in the GAL/GAL group had any responders (7%) with >10 points improvement. In summary, response data for patients withdrawn from galantamine to placebo were intermediate between patients who remained on placebo and patients who remained on galantamine, for all four cutoff points. At the initial visit of this withdrawal trial, patients treated with galantamine for 3 months in a preceding double blind, flexible dose trial tended to have improved cognitive function (as measured by a reduction in ADAS-cog/11 score from baseline) compared to patients who had received placebo. At the final Week 6 visit of this withdrawal trial, ADAS-cog/11 scores for patients in the GAIJPLA group, who had received galantamine for 3 months, then were withdrawn and placed on placebo for 6 weeks, were back to approximately the level of the original double-blind baseline. Patients in the PLA/PLA group, who had received placebo during both the original treatment period and the withdrawal period, had ADAS-cog/11 scores that continued to increase, indicating a worsening in cognitive function. Patients in the GAIJGAL group, who had received galantamine during both the original treatment and the withdrawal period, had ADAS-cog/11 scores that continued to decrease, indicating an improvement in cognitive function. All adverse side effects were monitored throughout the 6 week withdrawal period. Serious side effects were few in this 6-week trial, and occurred with similar frequency across the treatment groups. None were considered to be related to trail medication. There were no adverse events reported that could be related to central or peripheral reduction in cholinergic tone after sudden withdrawal of galantamine (detail results nt shown). As noted above the results of the present invention contrast the results available in the prior art in a study using another cholinesterase inhibitor, donepezil hydrochloride. In the prior art study patients received either 5mg/day or 10 mg/day for a treatment period of 24 weeks, followed by a 6 week placebo washout period. At the end of the 24 week treatment period statistically significant improvements from baseline were demonstrated. However after removal from the drug, the treatment group was indistinguishable from the group that received only placebo for the 30 week period. These results are shown in Figure 2 and demonstrate that donepezil hydrochloride does not treat the underlying cause of the disease. All scientific publications and patent documents are incorporated herein by reference. The present invention has been described with regard to preferred embodiments. However, it will be obvious to persons skilled in the art that a number of variations and modifications can be made without departing from the scope of the invention as described in the following claims.

Claims: Claims 1. Use of an effective amount of galantamine or a pharmaceutically acceptable salt thereof for the production of a medicament for treating, preventing and inhibiting the progression of Alzheimer's disease by targeting the underlying cause of the disease. 2. The use of claim 1 wherein the galantamine is administered from about 1 mg to about 100 mg per day. 3. The use of claim 2 wherein the galantamine is administered from about 5 mg to about 50 mg per day. 4. The use of claim 3 wherein the galantamine is administered from about 16 mg to about 32 mg per day. 5. The use of claim 4 wherein the galantamine is administered at a dosage of from about 24 rag per day, wherein said dosage is reached after a titration of a dose of about 8 mg/day for about 1 week, followed by a dose of about 16 mg/day for about 1 week, followed by a daily dosage of about 24 mg/day thereafter. 6. The use of claim 4 wherein the galantamine is administered at a dosage of about 32 mg per day, wherein said dosage is reached after a titration of a dose of about 8 mg/day for about 1 week, followed by a dose of about 16 mg/day for about 1 week, followed by a dose of about 24 mg/day for about 1 week, followed by a daily dosage of 32 mg/day thereafter. 7. The use of claim 4 wherein the galantamine is administered at a dosage of from about 16 mg to about 24 mg of galantamine, wherein said dosage is reached after a titration of from about 2 to about 10 weeks with the initial dose at about 8 mg increasing to a final dose of from about 16 mg to about 24 mg. 8. The use of claim 7 wherein the galantamine is administered at a dosage of about 24 mg/day, wherein said dosage is reached after a titration of a dose of about 8 mg/day for from about 2 weeks to about 4 weeks, followed by a dose of about 16 mg/day for from about 2 weeks to about 4 weeks, followed by the daily dosage of about 24 mg/day thereafter. 9. The use of claim 7 wherein the galantamine is administered at a dosage of about 24 mg/day, wherein said dosage is reached after a titration of a dose of about 8 mg/day for about 4 weeks, followed by a dose of about 16 mg/day for about 4 weeks, followed by the daily dosage of about 24 mg/day thereafter. 10. The use of claim 4 wherein the galantamine is administered at a dosage about 16 mg/day, wherein said dosage is reached after a titration of a dose of about 8 mg/day for from about 2 weeks to about 4 weeks, followed by the daily dosage of about 16 mg/day thereafter. 11. The use of claim 10 wherein the galantamine is administered at a dosage of about 16 mg/day, wherein said dosage is reached after a titration of a dose of about 8 mg/day for about 4 weeks, followed by the daily dosage of about 16 mg/day thereafter.

Inventors: PARYS WIM LOUIS JULIEN, PONTECORVO MICHAEL, PARYS, WIM, LOUIS, JULIEN, PONTECORVO, MICHAEL
Applicants: JANSSEN PHARMACEUTICA NV, PARYS WIM LOUIS JULIEN, PONTECORVO MICHAEL, JANSSEN PHARMACEUTICA N.V., PARYS, WIM, LOUIS, JULIEN, PONTECORVO, MICHAEL
Application year: 2001
Main classification: A61K31
IPC codes: A61K31, A61P25