Thanks...I selected the examples below as some I thought would qualify as RWE. Just a guess.
Fig.8 Is a chart of Anavex 2-73 improving components of cogstate tasks.
ANAVEX 2-73 treatment demonstrates reduction in overall Hamilton Depression Rating Scale (HAM-D) after 31 weeks. Over 31 weeks of treatment, ANAVEX 2-73 was associated with a sustained benefit in psychomotor function, attention and working memory. The specificity and consistency of these benefits establsh that ANAVEX 2-73 sustains activation of attentionaJ and working memory functions with repeated dosing in Alzheimer's disease.
Table 3 and Fig.9 presents EEG/ERP data that ANAVEX 2-73 Rescues
Cognitive Effects on a Cellular Level on the subjects of the Phase 2a study.
ANAVEX 2-73 effect on synaptic networks and effect on cognition and behavior at daJy doses of 10mg-50mg is shown. ERP peak measures (P300) are shown. The P300 (P3) wave IB an event related potential (ERP) component elicited in the process of decision making. It Is considered to be an endogenous potential, as its occurrence inks not to the physical attributes of a stimulus, but to a person's reaction to it More specifically, the P300 is thought to reflect processes Involved in stimulus evaluation or categorization. ERP target detection task is a direct measure of attention, speed of brain, processing, and simple behavioral performance. Psychometric measures (Cogstate) cognitive measures: Detection: processing speed (psychomotor function),
Identification: reaction time (attention), One Bade working memory (cognition), One Card Learning: visual learning (visual memory), ISLT: verbal learning, ISLT-delay:
verbal memory. Psychometric measures (MMSE): cognitive measures.
Behavioral measures (ADCS-ADL): behavioral measures. Notably, Rg.9 shows that all tested areas exhibited i improvement at 5 weeks as compared with the starling baseline (hence, absent expected decline).
Oral daily doses of ANAVEX 2-73 ranging from 10mg to 50mg exhibit a converging and consistent response for all measurements (MMSE, ADCS-ADL, CogstHto, EEG/ERP) throughout 31 weeks (7 months) of ANAVEX 2-73 treatment Patient retention rate at week 31 was 84%. Treatment of ANAVEX 2-73 and related drugs demonstrates reduction in overall HAM-D score after 31 weeks, notably through reductions in insomnia, anxiety and agitation. Seventeen week data as well as 31 week data of all available patients derranstrate that ANAVEX 2-73 preserves average MMSE and ADCS-ADL scores across the entire patient group. In a dsease state where progression is invariable over time, a stable MMSE and ADCS-ADL score is considered a positive outcome. When the group is tentatively stratified into mild to moderate and MCI (mfld cognitive impaired) AD patients, no significant difference was observed within the MMSE or the ADCS-ADL score, respectiveiy. Likewise, when tentatively stratified between ANAVEX 2-73 alone and ANAVEX 2-73 PLUS donepezfl administration, no significant difference was observed within the MMSE or the ADCS-ADL score, respectiveiy. For cognitive assessment using the Cogstate test batteries, ANAVEX 2-73 continues to show benefits over baseline at 17 weeks and 31 weeks. ANAVEX 2-73 related improvement in psychomotor function, attention and working memory are preserved through 17 weeks and 31 weeks of treatment Repeated-measures ANOVA reveals that Cogstate values maintained the baseline values through week 31.
An additional benefit of the therapeutic regimen disclosed herein is the beneficial control of systolic blood pressure in AD subjects taking daily oral dosages of A2-73 of from about 10mg to about 50mg. Systolic blood pressure was monitored over the first 25 days of dosing. A1-41 and A19-144 are similarly useful therapeutics.
Table 3 shows that A2-73 therapy significantly reduced systolic blood pressure in hypertensive subjects with greater reduction for increasingly hypertensive subjects.
And further surprisingly, systolic blood pressure rose is subjects that exhibited high- normal systolic blood pressure.
EXAMPLE 1
Maintenance Insomnia Therapy
A 48 year old female presents as suffering from maintenance insomnia for one year. She Is started on oral A2-73 at 10 mg/day. Follow up at 30 days of dairy dosing reveals she is sleeping well. She is currently maintained on 10 mg of A2-73 and is sleeping weil.
EXAMPLE 2
Anxiety Therapy
A 51 year old female presents with anxiety of three years' duration. She is administered A2-73 at 20 mg oral per day every other day. Resolution of the anxiety is noted after two days of dosing. She is maintained on this dosing schedule for 60 days.
EXAMPLE 3
Agitation Theraov
The patient is a 29-y8r-o(d male exhibiting agitation. He is treated with 30 mg A2-73 oral daily for 30 days. Clinical evaluation reveals normal affect without agitation, depression, anxiety, or substance use. He Is currently maintained at that dosage and is not anxious.
EXAMPLE 4
Maintenance Insomnia Therapy
A 68 year old female presents with MCI and reports maintenance insomnia for one year. She is started on oral A 1-41 at 10 mg/day. Follow up at 30 days of dafly dosing reveals she is sleeping well. She is currently maintained on 10 mg of A1-41 and is sleeping well.
EXAMPLE 5
Anxiety Therapy
The patient is a 52 year old female with diagnosed AD and reported anxiety of three years' duration. She is administered ?1T-144 at 20 mg oral per day every day for 90 day8. Resolution of the anxiety is noted after two days of dosing. She is chronicaly maintained on this dosing schedule.
EXAMPLE 6
Maintenance Insomnia Therapy In MIC
A 66 year old male diagnosed with mild cognitive impairment presents as suffering from maintenance insomnia for one year. He is started on oral A2-73 at 50 mg/day. FoBow up at 30 days of daily dosing reveals he is sleeping well. Ho is currently maintained on 50 mg of A2-73 daily and is sleeping well.
EXAMPLE 7
Maintenance Insomnia Therapy in Alzheimer's Disease Related Insomnia and
Agitation
A 72 year old male diagnosed with Alzheimer's disease presents with
insomnia/WASO and agitation and a systolic blood pressure of 145 mm Hg. He is started on oral A2-73 at 30 mg/day. Follow up at 30 days of daily dosing reveals he is sleeping well through the night and not waking up repeatedly and Ms systolic BP is 129. He is also less agitated. His results on afl cognitive tests and HAM-D improve. He is currently maintained on 30 mg of A2-73 daily.
EXAMPLE 8
Maintenance Insomnia Therapy in Alzheimer's Disease Insomnia and
Agitation
A 72 year oid male diagnosed with Alzheimer's disease presents with
insomnia/WASO and agitation. He is started on oral A2-73 at 100 mg/day. Follow up at 30 days of daily dosing reveals he is sleeping well through the night and not waking up repeatedly. He is also less agitated, His results on all cognittve tests and HAM-D improve. He is currently maintained on 100 mg of A2-73 every other day.
EXAMPLE S
Maintenance Insomnia Therapy in Aizhflimer's Disease Related Insomnia and
Agitation
A 77 year oid male diagnosed with Alzheimer's disease presents with
insomnia/WASO and agitation. He is started on oral A19-144 at 50 mg/day. Foflow up at 30 days of daily dosing reveals he is sleeping well through the night and not waking up repeatedy. He is also less agitated. His resulte on all cognitive tests and HAM-D improve. He is currently maintained on 50 mg of A19-144 daily.
EXAMPLE 10
Malntenanca Insomnia Therapy in Alzheimer's Disease Related Insomnia and
Agitation
A 77 year old male diagnosed with Alzheimer's disease presents with
insomnia/WASO and agitation. He is started on oral A1-41 at 30 rnp/day. Foflow up at 60 days of daily dosing reveals he is sleeping well through the night and not waking up repeatedy. He is also less agitated. Hie results on all cognitive tests and HAM-D improve. He is currently maintained on 30 mg of A1 -41 daily.
The pharmacologicaly active compositions of this invention can be processed in accordance with conventional methods of Gaenlic pharmacy to produce medicinal agents for administration to subjects, e.g., mammals including humans.
The compositions of this irivention individually or in combination are employed in admixture with conventional exdpients, i.e., pharmaceutically acceptable organic or inorganic carrier substances suitable for parenteral, enteral {e.g., oral or inhalation) or topical application which do not deleterfously react with the active compositions.
Suitable pharmaceutical ty acceptable carriers include but are not limited to water, salt solutions, alcohols, gum arable vegetable oils, benzyl alcohols, polyethylene glycols, gelatin, caibotiydrates such as lactose, amylase or starch, magnesium stearate, talc, titanium dioxide, sKdc add, viscous paraffin, perfume oil, fatty acid esters, hydroxy methytcellulose, polyvinyl pyrroiidone, etc. The pharmaceutical preparations can be sterlHzed and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, flavoring and/or aromatic substances and the Ike which do not aeleteriously react with the active compositions. They can also be combined where desired with other active agents, e.g., vitamins.
In some embodiments of the present invention, dosage forms include instructions for the use of such compositions.
For parenteral application, particularly suitable are Injectable, sterile solutions, preferably oily or aqueous solutions, as wefl as suspensions, emulsions, or implants, including suppositories. Ampules, vials, and Injector cartridges are convenient unit
