5.563"

5.563"
Vayacog®
DESCRIPTION
Vayacog® is an orally administered prescription medical food
for the clinical dietary management of certain lipid imbalances
associated with early memory impairment.
Each capsule contains Lipicogen™ 310 mg, providing:
Phosphatidylserine (PS) ............................................. 100 mg
Docosahexaenoic acid (DHA) .................................... 19.5 mg
Eicosapentaenoic acid (EPA) ...................................... 6.5 mg
CHEMICAL STRUCTURE*
O
O
O
O
O
O P
O
O-
CO2+NH3
CLINICAL EXPERIENCE
Vayacog® was evaluated in a randomized, double-blind,
placebo-controlled study of 15 weeks followed by an open label
extension of an additional 15 weeks. In the double-blind phase,
157 men and women (aged 50-90 years) with memory
complaints were randomly assigned to receive Vayacog® or
placebo (three capsules a day)[13]. During the open-label
extension, all participants consumed one capsule a day of
Vayacog®.
Cognitive performance was evaluated using Rey Auditory
Verbal Learning Test (Rey-AVLT) at baseline and endpoint
(week 15) of the double-blind phase and using a computerized
cognitive assessment tool at baseline (week 15) and endpoint
(week 30) of the open-label phase.
Safety assessment was evaluated by clinical laboratory
assessments including biochemical and hematological
parameters at baseline and endpoint (week 15) of the
double-blind phase and by adverse events recording, physical
examination and measurement of vital signs and weight at
baseline, week 7, and endpoint (week 15) of the double-blind
phase and at the end of the open-label extension (week 30).
* Schematic structure of one of the most abundant molecule
present in Vayacog®.
2.0
Mean change from baseline
(# words)
INGREDIENTS
Phosphatidylserine, Hypromellose, Maltodextrin, Silicon
Dioxide, Rosemary Extract (preservative), Mixed Tocopherols
(E306-E309), Ascorbyl Palmitate (E304), Titanium Dioxide
(color).
Rx Only
Capsules
Vayacog capsules contain soy and fish (e.g. herring, sprout,
blue whiting, anchovy).
®
Vayacog®
Sample
May contain shellfish.
Vayacog® capsules do not contain sugar, lactose, yeast or
gluten.
Rx Only
8.938"
• Mechanism of Action
Administration of phosphatidylserine (PS) enriched with omega
3 fatty acids was found to significantly increase DHA levels in
the brains of rats [1]. DHA brain and plasma levels are
suggested to be positively associated with cognitive
performance [2,3].
While the exact mechanism by which Vayacog® exerts its
effects is not fully understood, PS in the mammalian nervous
system, which is characterized by its substantial levels of
omega-3 fatty acids, has been implicated in numerous
membrane related functions, such as maintaining the integrity
of cell membranes, cell excitability and cell-to-cell recognition
and communication [4]. PS has been found to regulate key
proteins in neuronal membranes, including sodium/calcium
ATPase [5] and protein kinase C [6] which undertake crucial
functions in diverse signal transduction pathways. Similarly, PS
interacts with Raf-1 protein kinase to promote a cascade of
reactions that are believed to be involved in cell survival [7].
Additionally, PS has been found to influence neurotransmitter
activity, such as the release of acetylcholine, dopamine and
noradrenaline [8, 9] and to increase brain glucose levels.
• Absorption and Metabolism
Following dietary ingestion of phospholipids, pancreatic
digestive enzymes cleave specific fatty acids leading to the
formation of lysophospholipids that are absorbed by the
mucosal cells of the intestine and could be reacylated into
phospholipids [10]. The fatty acids released can be further used
for triglyceride synthesis. Because of the high activity of
decarboxylases in the mucosal cells, the majority of the PS is
converted into other phospholipids, primarily to
phosphatidylethanolamine [11]. The reacylated PS,
phosphatidylethanolamine and other phospholipids enter the
lymph and circulation, and are redistributed.
• Drug Interactions
PS can potentially interact with some anticholinergic and
cholinergic medications. It is recommended to consult with a
physician about Vayacog® interactions that may apply to
specific medical conditions.
• Toxicity
Vayacog®, similar to phosphatidylserine extracted from bovine
cortex (BC-PS), contains saturated and monounsaturated fatty
acids as well as DHA. The safety profile of BC-PS was
determined in several non-clinical studies. Repeat-dose safety
studies in rats and dogs show that oral administration of BC-PS
at doses up to 1000 mg/kg/day for up to 6 months was without
any significant adverse effects of toxicological concern [12].
The results of teratogenicity studies in rats at doses up to
200 mg/kg/day and in rabbits at doses up to 450 mg/kg/day
showed that oral administration of PS did not affect embryonic
and fetal development [12].
The mutagenic potential of BC-PS was investigated in several
cell types and revealed no significant findings. In a
micronucleus test, BC-PS was administered to mice at total
dosages of 30, 150 and 300 mg/kg in two equal doses separated
by 24-hours. The results of the study did not reveal any evidence
of mutagenic potential or bone marrow toxicity [12].
Rev. 8
Front
1.6
1.4
1.2
1.0
0.8
0.6
0.4
Placebo Vayacog®
Effect of Vayacog® (n=60) versus placebo (n=62) on
Rey-AVLT results following 15 weeks of administration
(per-protocol participants) during the double-blind phase.
Values are presented as mean change from baseline ±
standard error (SE). * p< 0.05 based on ANCOVA controlled for
Mini-Mental State Examination (MMSE) and baseline mean
score.
Immediate
Recall
Delayed
Recall
Total
Learning
8
3.0
Mean change from baseline
(# words)
Capsules
PHARMACOLOGY
Vayacog® is a prescription medical food used under medical
supervision.
1.8
7
2.5
6
2.0
5
4
1.5
3
1.0
2
0.5
1
0
0.0
Placebo
Vayacog®
Effect of Vayacog® (n=40) versus placebo (n=38) on
Rey-AVLT results following 15 weeks administration during
the double-blind phase, within a subgroup of participants
with relatively good cognitive status prior treatment. Subjects
were included in this selected subset upon fulfillment of two
out of the following criteria: I). A score in MMSE greater than
26. II) Baseline performance in the delayed recall trial above the
per-protocol mean (>7). III) Number of education years greater
than 12. Values are presented as mean change from baseline ±
SE. * p<0.05 and ** p<0.01 based on two-tailed T-test
comparison of the mean difference from baseline for
independent samples.
*
*
Mean score (pts.)
Vayacog
Sample
®
Immediate
Recall
Effect of Vayacog® on parameters of the computerized
cognitive assessment tool following 15 weeks administration
during the open-label phase (n=55, participants who
consumed placebo during the double-blind phase). Values are
presented as mean ± SE. * P < 0.05 based on paired two tailed
Student's t-test.
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Safety assessment
No significant differences were found in any of the tested
safety parameters between the study groups, or within each
group during the double-blind phase. At the end of the open
label phase, there was a reduction in resting diastolic blood
pressure and a slight weight gain among participants who
consumed Vayacog® for 30 weeks [14] (additional safety
information is detailed in the Adverse Events section).
PHYSICIAN SUPERVISION
Vayacog® is a medical food product dispensed by
prescription and must be used under physician supervision.
CONTRAINDICATIONS
Vayacog® is contraindicated in patients with known
hypersensitivity (e.g., anaphylactic reaction) to
Vayacog® or any of its components.
8.938"
Lipicogen™ is a proprietary composition containing
phosphatidylserine-omega 3, DHA enriched. Vayacog® and
Lipicogen™ are trademarks of Enzymotec Ltd.
US Patents No. 7,935,365, No. 7,968,112 and No. 5,965,413.
Distributed by: VAYA Pharma™ Inc.
REFERENCES
1. Vaisman, N. and D. Pelled, n-3 phosphatidylserine
attenuated scopolamine-induced amnesia in middle-aged
rats. Prog Neuropsychopharmacol Biol Psychiatry, 2009.
33(6): p. 952-9.
2. Soderberg, M., et al., Lipid composition in different regions
of the brain in Alzheimer's disease/senile dementia of
Alzheimer's type. J Neurochem, 1992. 59(5): p. 1646-53.
3. Conquer, J.A., et al., Fatty acid analysis of blood plasma of
patients with Alzheimer's disease, other types of dementia,
PRECAUTIONS
and cognitive impairment. Lipids, 2000. 35(12): p. 1305-12.
• Safety and effectiveness of Vayacog® in pediatric patients or
pregnant or lactating patients have not been established.
4. Mozzi, R., S. Buratta, and G. Goracci, Metabolism and
Therefore, Vayacog® is not recommended for these
functions of phosphatidylserine in mammalian brain.
populations.
Neurochem Res, 2003. 28(2): p. 195-214.
• Vayacog® should be used with caution in patients with known
hypersensitivity to soy and/or fish.
5. Wheeler, R.P.W., R. , ATPase activity of the sodium pump
needs of phosphatidylserine. Nature, 1970. 225(5231):
DRUG ABUSE
p. 449-450.
Vayacog® does not have any known drug abuse or withdrawal
effects.
6. Bittova, L., R.V. Stahelin, and W. Cho, Roles of ionic
residues of the C1 domain in protein kinase C-alpha
ADVERSE EVENTS
activation and the origin of phosphatidylserine specificity.
The adverse events of Vayacog® were evaluated in a randomized,
J Biol Chem, 2001. 276(6): p. 4218-26.
double blind, placebo-controlled study of 15 weeks followed by
an open label extension of additional 15 weeks [14] (additional
7. Vance, J.E., Phosphatidylserine and
information is detailed in the Clinical Experience section).
Phosphatidylethanolamine in Mammalian Cells: Two
Metabolically-related Aminophospholipids. ASBMB, 2008:
Adverse events reported during the course of the double-blind
p. 1-48.
phase: 10 participants from the Vayacog® group and 8
8. Pepeu, G., I.M. Pepeu, and L. Amaducci, A review of
participants from the placebo group were classified by the
phosphatidylserine pharmacological and clinical effects. Is
study physicians as suffering from treatment related, or
phosphatidylserine a drug for the ageing brain? Pharmacol
probably related, adverse events (16 and 11 adverse events,
Res, 1996. 33(2): p. 73-80.
respectively). There were no significant differences between
the study groups in the number of participants who reported an
9. Mazzari, S. and A. Battistella, Phosphatidylserine effects on
adverse event (P=0.637) or in the number of reported adverse
dopamine release from striatum synaptosomes. In:
events (P=0.472).
Multidisciplinary Approach to Brain Development
Elsevier/North Holland, Amsterdam 1980: p. 569-570.
Adverse events reported during the course of the open-label
extension: 3 participants reported 3 adverse events that were
classified by the study physicians as related or probably related 10. Tso, P., Intestinal lipid absorption. Physiology of the
Gastrointestinal Trac, ed. L.R. Johnson. Vol. 56. 1994, New
to the study treatment.
York: Raven Press.
Reported adverse events*
11. Wise, E.M., Jr. and D. Elwyn., Rates of reactions involved in
Open-label
phosphatide synthesis in liver and small intestine of intact
Study design
Double-blind phase
extension
rats. Journal of Biological Chemistry, 1965. 240:
Treatment Group Vayacog®
p. 1537-1548.
Placebo Vayacog®
[n=78]
[n=79]
[n=122]
Adverse event
12. Heywood, R., D.D. Cozens, and M. Richold, Toxicology of a
Gastrointestinal discomfort
13
2
1
PS preparation from bovine brain (BC-PS). Clinical Trials
Rash
1
0
0
Journal, 1987. 24: p. 25-32.
Increased appetite and weight
Strange general feeling
Headache
Dizziness
Mood swings
Weight loss
Tenesmus
Redness in the mouth
Pruritus
Sum
0
0
1
0
0
1
0
0
0
16 events in
10 participants
1
1
2
2
1
0
0
1
1
11 events in
8 participants
0
0
1
0
0
0
1
0
0
3 events in
3 participants
*Judged by the study physicians as related or probably related
to the study treatment
13. Vakhapova, V., et al., Phosphatidylserine containing
omega-3 fatty acids may improve memory abilities in
non-demented elderly with memory complaints: a
double-blind placebo-controlled trial. Dement Geriatr Cogn
Disord. 29(5): p. 467-74.
14. Vakhapova, V., et al., Safety of phosphatidylserine
containing omega-3 fatty acids in non-demented elderly: a
double-blind placebo-controlled trial followed by an
open-label extension. BMC Neurol. 11: p. 79.
Rev. 7/12
DOSAGE AND ADMINISTRATION
Usual dose is one capsule daily or as directed by a physician.
HOW SUPPLIED
Available as hard shell capsules. Commercial product is
supplied in bottles of 30 capsules.
Commercial Product
(30 capsules)
Use under medical/
75959-344-30* physician supervision.
Sample Product
Professional Samples
(Packet of 2 capsules) 75959-344-02* -Not for sale.
* VAYA Pharma™ does not represent these product codes to be
actual National Drug Codes (NDCs). NDC format codes are
product codes adjusted according to standard industry practice
to meet the formatting requirements of pharmacy and health
insurance computer systems.
STORAGE
Store at up to 77°F (25°C). Protect from light and moisture.
WARNING
Keep this product out of the reach of children.
Rev. 8
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