U.S. patent application number 13/861099 was filed with the patent office on 2013-08-29 for method of providing pirfenidone therapy to a patient.
This patent application is currently assigned to INTERMUNE, INC.. The applicant listed for this patent is Intermune, Inc.. Invention is credited to Williamson Ziegler Bradford.
Application Number | 20130220871 13/861099 |
Document ID | / |
Family ID | 39259551 |
Filed Date | 2013-08-29 |
United States Patent
Application |
20130220871 |
Kind Code |
A1 |
Bradford; Williamson
Ziegler |
August 29, 2013 |
METHOD OF PROVIDING PIRFENIDONE THERAPY TO A PATIENT
Abstract
The invention relates to methods for decreasing adverse events
associated with pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone)
therapy. The invention discloses an optimized dose escalation
scheme that results in the patient having increased tolerance to
adverse events associated with the administration of pirfenidone.
The invention also discloses a starter pack that may be used in
conjunction with the dose escalation scheme.
Inventors: |
Bradford; Williamson Ziegler;
(Ross, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Intermune, Inc.; |
|
|
US |
|
|
Assignee: |
INTERMUNE, INC.
Brisbane
CA
|
Family ID: |
39259551 |
Appl. No.: |
13/861099 |
Filed: |
April 11, 2013 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12831944 |
Jul 7, 2010 |
8420674 |
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13861099 |
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11959338 |
Dec 18, 2007 |
7767700 |
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12831944 |
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60870593 |
Dec 18, 2006 |
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Current U.S.
Class: |
206/531 ;
206/538; 206/539; 514/345 |
Current CPC
Class: |
A61P 29/00 20180101;
A61K 31/4412 20130101; A61P 17/02 20180101; A61P 19/02 20180101;
A61K 31/4418 20130101; A61P 13/12 20180101; A61J 1/035 20130101;
A61P 11/00 20180101; A61J 1/03 20130101; A61P 13/08 20180101; A61P
37/00 20180101; A61P 43/00 20180101; A61P 1/16 20180101; A61J
2205/50 20130101 |
Class at
Publication: |
206/531 ;
514/345; 206/538; 206/539 |
International
Class: |
A61K 31/4412 20060101
A61K031/4412; A61J 1/03 20060101 A61J001/03 |
Claims
1. A method of providing pirfenidone therapy to a patient
comprising: providing a first daily dosage of pirfenidone to the
patient in a first amount for the duration of a first period of
time; providing a second daily dosage of pirfenidone to the patient
in a second amount for a second period of time; and providing a
third daily dosage of pirfenidone to the patient in a third amount
for a third period of time, wherein the first and second periods of
time total at least about 7 days.
2. The method according to claim 1, wherein the first amount is in
the range of about 400 mg/day to about 1,200 mg/day.
3. The method according to claim 2, wherein the first amount is in
the range of about 700 mg/day to about 900 mg/day.
4. The method according to claim 3, wherein the first amount is in
the range of about 780 mg/day to about 820 mg/day.
5. The method according to claim 4, wherein the first amount is
about 801 mg/day.
6. The method according to claim 1, wherein the second amount is in
the range of about 1,200 mg/day to about 2,000 mg/day.
7. The method according to claim 6, wherein the second amount is in
the range of about 1,500 mg/day to about 1,700 mg/day.
8. The method according to claim 7, wherein the second amount is in
the range of about 1,580 mg/day to about 1,620 mg/day.
9. The method according to claim 8, wherein the second amount is
about 1,602 mg/day.
10. The method according to claim 1, wherein the third amount is in
the range of about 2,000 mg/day to about 3,000 mg/day.
11. The method according to claim 10, wherein the third amount is
in the range of about 2,300 mg/day to about 2,400 mg/day.
12. The method according to claim 11, wherein the third amount is
in the range of about 2,380 mg/day to about 2,420 mg/day.
13. The method according to claim 12, wherein the third amount is
about 2,403 mg/day.
14. The method according to claim 1, wherein the first period of
time is in the range of about 3 days to about 10 days.
15. The method according to claim 14, wherein the first period of
time is about 7 days.
16. The method according to claim 1, wherein the second period of
time is in the range of about 3 days to about 10 days.
17. The method according to claim 16, wherein the second period of
time is about 7 days.
18. The method according to claim 1, wherein the third period of
time is at least one day.
19. The method according to claim 18, wherein the third period of
time is more than one day.
20. A method of providing pirfenidone therapy to a patient
comprising: providing a first daily dosage of pirfenidone to the
patient in an amount of 801 mg/day over the course of Day 1 to Day
7; providing a second daily dosage of pirfenidone to the patient in
an amount of 1602 mg/day over the course of Day 8 to Day 14; and
providing a third daily dosage of pirfenidone to the patient in an
amount of 2403 mg/day on the beginning of Day 15 and continuing
with the 2403 mg/day dosage on each day following Day 15.
21. The method according to claim 20, wherein the patient is
administered one capsule comprising 267-mg of pirfenidone three
times a day over the course of Day 1 to Day 7; wherein the patient
is administered two capsules comprising 267-mg of pirfenidone three
times a day over the course of Day 8 to Day 14; and wherein the
patient is administered three capsules comprising 267-mg of
pirfenidone three times a day on Day 15 and each day thereafter
where the therapy continues after Day 15.
22. A starter pack comprising: a first set of compartments each
having a first dosage amount of pirfenidone according to a first
daily or first sub-daily periodic dosage of pirfenidone;and at
least one additional set of compartments each having a dosage
amount of pirfenidone that is higher than the first dosage amount
of pirfenidone and is according to a higher daily or higher
sub-daily periodic dosage of pirfenidone.
23. The starter pack according to claim 22, wherein the starter
pack comprises a row for each Day that the first daily periodic
dosage is to be taken and for each Day that the higher daily
periodic dosage is to be taken and separate columns for each of the
first sub-daily periodic dosage to be taken and for each of the
higher sub-daily periodic dosage to be taken, and wherein the first
out of compartments are arranged within the rows and columns, and
wherein the at least one additional set of compartments is arranged
within the rows and columns.
24. The starter pack according to claim 23, wherein the first set
of compartments and the at least one additional set of compartments
each comprise three columns for each Day pirfenidone is to be
taken.
25. The starter pack according to claim 24, wherein the starter
pack comprises separate rows for Days 1, 2, 3, 4, 5, 6, 7, 8, 9,
10, 11, 12, 13, and 14.
26. The starter pack according to claim 25, wherein the first set
of compartments are for administering the first dosage amount of
pirfenidone for Days 1, 2, 3, 4, 5, 6, and 7, and each compartment
in the first set of compartments contains one pill of 267-mg
pirfenidone.
27. The starter pack according to claim 25, wherein the at least
one additional set of compartments comprises a second set of
compartments for administering a second dosage amount of
pirfenidone higher than the first dosage amount and for Days 8, 9,
10, 11, 12, 13, and 14, and each compartment in the second set of
compartments contains two pills of 267-mg pirfenidone.
28. The starter pack according to claim 27, wherein the starter
pack comprises separate rows for Days 15, 16, 17, 18, 19, 20, and
21.
29. The starter pack according to claim 28, wherein the at least
one additional set of compartments comprises a third set of
compartments for administering a third dosage amount of pirfenidone
higher than the second dosage amount and for Days 15, 16, 17, 18,
19, 20, and 21, and each compartment in the third set of
compartments contains three pills of 267-mg pirfenidone.
30. The starter pack according to claim 22, further comprising a
first panel having the first set of compartments and an additional
panel for each of the at least one additional set of compartments,
each of the first and additional panels containing an equal number
of compartments
31. The starter pack according to claim 22, wherein the
compartments are blisters.
32. The starter pack according to claim 22, wherein the starter
pack comprises at least two panels and at least one fold separating
the two panels, and wherein a first panel comprises dosage amount
for a first period of time and wherein a second panel comprises
dosage amounts for a second period of time.
33. The starter pack of claim 22, further comprising a casing for
holding several containers each container comprising a panel
bearing one of the first set of compartments or one of the at least
one additional set of compartments.
34. A starter pack comprising: an initial dosage amount, a second
dosage amount, and a third dosage amount of pirfenidone; and a
plurality of compartments that separate the initial, second, and
third dosage amounts according to a daily dosage of pirfenidone,
wherein the compartments are formed in columns and in rows; and the
compartments are arranged in such a manner that a user of the
starter pack is instructed to take the pirfenidone in accordance
with the method disclosed by claim 21.
35. A method for administering pirfenidone therapy to a patient,
comprising: administering a predetermined first daily dosage of
pirfenidone to the patient; and escalating the dosage administered
to the patient to a predetermined final daily dosage of
pirfenidone, wherein the time of escalation is measured from the
initial first dosage and is about 7 to about 20 days.
36. The method of claim 35, wherein the time of escalation is 13 or
14 days.
37. The method of claim 36, wherein the first dosage is about 801
mg/day.
38. The method of claim 37, wherein the final dosage is about 2,403
mg/day.
39. The method of claim 38, wherein each daily dosage is split into
three daily oral administrations.
40. A starter pack comprising: a first panel having a plurality of
compartments each providing a first daily dosage of pirfenidone for
a patient in a first amount for the duration of a first period of
time; a second panel having a plurality of compartments each
providing a second daily dosage of pirfenidone for the patient in a
second amount for a second period of time; and a third panel having
a plurality of compartments each providing a third daily dosage of
pirfenidone for the patient in a third amount for a third period of
time, wherein the first and second periods of time each total at
least about 7 days.
41. The starter pack according to claim 40, wherein the first daily
dosage is in the range of about 700 mg/day to about 900 mg/day.
42. The starter pack according to claim 40, wherein the second
daily dosage is in the range of about 1,500 mg/day to about 1,700
mg/day.
43. The starter pack according to claim 40, wherein the third daily
dosage is in the range of about 2,300 mg/day to about 2,400
mg/day.
44. The starter pack according to claim 40, wherein the first
period of time is in the range of about 3 days to about 10
days.
45. The starter pack according to claim 40, wherein the second
period of time is in the range of about 3 days to about 10
days.
46. The starter pack according to claim 40, wherein the third
period of time is more than one day.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional
Application Ser. No. 60/870,593, filed Dec. 18, 2006, the
disclosure of which is incorporated by reference in its
entirety.
BACKGROUND
[0002] 1. Field of the Invention
[0003] The invention relates to methods for decreasing adverse
events associated with pirfenidone
(5-methyl-1-phenyl-2-(1H)-pyridone) therapy.
[0004] 2. Description of the Related Art
[0005] Pirfenidone is small drug molecule whose chemical name is
5-methyl-1-phenyl-2-(1H)-pyridone. It is a non-peptide synthetic
molecule with a molecular weight of 185.23 Daltons. Its chemical
elements are expressed as C.sub.12H.sub.11NO, and its structure and
synthesis are known. Pirfenidone is manufactured commercially and
being evaluated clinically as a broad-spectrum anti-fibrotic drug.
Several pirfenidone Investigational New Drug Applications (INDs)
are currently on file with the U.S. Food and Drug Administration.
Phase II human investigations are ongoing or have recently been
completed for pulmonary fibrosis, renal glomerulosclerosis, and
liver cirrhosis. There have been other Phase II studies that used
pirfenidone to treat benign prostate hypertrophy, hypertrophic
scarring (keloids), and rheumatoid arthritis.
[0006] Pirfenidone is being investigated for therapeutic benefits
to patients suffering from fibrosis conditions such as
Hermansky-Pudlak Syndrome (HPS) associated pulmonary fibrosis and
idiopathic pulmonary fibrosis (IPF). Pirfenidone is also being
investigated for a pharmacologic ability to prevent or remove
excessive scar tissue found in fibrosis associated with injured
tissues including that of lungs, skin, joints, kidneys, prostate
glands, and livers. Published and unpublished basic and clinical
research suggests that pirfenidone may safely slow or inhibit the
progressive enlargement of fibrotic lesions, and prevent formation
of new fibrotic lesions following tissue injuries.
[0007] It is understood that one mechanism by which pirfenidone
exerts its therapeutic effects is modulating cytokine actions.
Pirfenidone is a potent inhibitor of fibrogenic cytokines and
TNF-.alpha.. It is well documented that pirfenidone inhibits
excessive biosynthesis or release of various fibrogenic cytokines
such as TGF-.beta.1, bFGF, PDGF, and EGF. Zhang Set al., Australian
and New England J Ophthalmology 26:S74-S76 (1998). Experimental
reports also show that pirfenidone blocks the synthesis and release
of excessive amounts of TNF-.alpha. from macrophages and other
cells. Cain et al., Int'l J Immunopharmacology 20:685-695
(1998).
[0008] As an investigational drug, pirfenidone is provided in
tablet and capsule forms principally for oral administration.
Various formulations have been tested and adopted in clinical
trials and other research and experiments. The most common adverse
reactions or events associated with pirfenidone therapy include
gastrointestinal upset, nausea, fatigue, somnolence, dizziness,
headache, and photosensitivity rash. Many of these effects can
interfere with everyday activities and quality of life. These
effects appear to be dose related. The adverse reactions associated
with pirfenidone therapy are exacerbated when pirfenidone is
administered at these higher doses.
[0009] Currently, adverse events following administration of
pirfenidone are alleviated by dose reduction or discontinuation of
pirfenidone. In a recent study, for adverse events rated Grade 2 or
worse, the dosage was reduced in a stepwise manner: from 9 tablets
having 200 mg of pirfenidone per day to 6 tablets having 200 mg of
pirfenidone per day and 6 tablets having 200 mg of pirfenidone per
day to 3 tablets having 200 mg of pirfenidone per day. Azuma, A. et
al., Am J Respir Crit Care Med 171:1040-47 (2005) ("Azuma study").
More specifically, if, after a period of 14 days of observation
with reduced dosage, the adverse event persisted or increased, the
dosage was further reduced by one more step--from6 tablets per day
to 3 tablets per day. If the adverse event persisted or increased
despite reducing the dosage to 3 tablets per day, the study
medication was discontinued.
[0010] The Azuma study discloses a dose-titration schedule for all
patients wherein patients received a 200-mg dose of pirfenidone
three times a day for the first two days; then a 400-mg dose of
pirfenidone three times a day for the following two days; and then
a maximum 600-mg dose of pirfenidone three times a day for the
remainder of treatment. Thus, the maximum dose obtained by the
Azuma study was only 1,800 mg/day of pirfenidone. Additionally, the
dose-titration schedule of the Azuma study reaches the full maximum
dosage of pirfenidone after only four days of treatment. There is
significant reason to believe that the Azuma dose escalation does
not optimally match the rate of dose escalation with the rate at
which a patient develops sufficient tolerance to reduce the
incidence of adverse events. Thus, there remains an unmet clinical
need for a method of administering higher doses of pirfenidone to a
patient in a manner that eliminates or minimizes adverse events,
such as nausea, vomiting, gastrointestinal upset, drowsiness,
dizziness, headache, somnolence, and other undesirable side
effects.
[0011] SUMMARY
[0012] The present invention overcomes the unmet clinical need by
providing an improved, optimized dose escalation scheme for the
administration of pirfenidone. The dose escalation scheme of the
present invention provides pirfenidone in an amount such that the
full maximum dosage is not reached for at least one week. In a
preferred embodiment, the full maximum dosage of pirfenidone is not
reached until about Day 15 of treatment. The method of the present
invention allows for a maximum dosage of 2,403 mg of pirfenidone
per day to be administered to a patient and also reduces the
incidence of adverse events associated with the administration of
pirfenidone by more accurately matching dose escalation with
tolerance development in the patient. Indeed, it has been observed
that even as the dosage escalates using the dosing escalation
scheme described herein, adverse events, such as somnolence,
decrease.
[0013] The present invention discloses a method of providing
pirfenidone therapy to a patient comprising providing an initial
daily dosage of pirfenidone to the patient in a first amount for
the duration of a first period of time; providing a second daily
dosage of pirfenidone to the patient in a second amount for a
second period of time; and providing a final daily dosage of
pirfenidone to the patient in a final amount for a final period of
time, wherein the first and second periods of time together total
at least about 7 days, more preferably about 8, 9, 10, 11 or 12
days, and most preferably about 13 or 14 days. In some embodiments,
the first and second periods can together total up to about 15 or
about 20 or 21 days.
[0014] In one embodiment, the first amount is about 801 mg/day; the
second amount is about 1,602 mg/day; and the third amount is about
2,403 mg/day. In another embodiment, the first period of time is
about 7 days; the second period of time is about 7 days; and the
third period of time is in the range of about 1 day up to an
unlimited number of days. In specific embodiments, the third period
of time lasts at least about 1 month, at least about 2 months, at
least about 3 months, at least about a year, at least about 18
months, at least about 2 years, or more than 2 years, at least
about 3 years, at least about 4 years, at least about 5 years, or
as long as therapy with pirfenidone is needed.
[0015] The present invention also discloses a starter pack
comprising dosage amounts of pirfenidone and compartments that
separate the dosage amounts according to a daily dosage of
pirfenidone. Advantageously, the compartments can be arranged in
columns and in rows, although other arrangements are also
contemplated.
[0016] In one exemplary embodiment, the starter pack comprises rows
designating Day numbers and separate columns for the number of
times a dosage of pirfenidone is taken each day. In one embodiment,
the starter pack may comprise separate rows for Days 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, and 14 with three separate columns for
three dosage amounts to be taken each day. In one embodiment, each
of the three compartments for Days 1, 2, 3, 4, 5, 6, and 7
separately contain one pill of 267-mg pirfenidone and each of the
three compartments for Days 8, 9, 10, 11, 12, 13, and 14 separately
contain two pills of 267-mg pirfenidone. In another embodiment,
each week of treatment may be designated on a separate panel. In
another embodiment, each panel contained within the starter pack
may be approximately the same size. In another embodiment, the
starter pack has compartments arranged such that a user of the
starter pack may administer the pirfenidone in accordance with the
dose escalation method taught by the present invention.
[0017] Also contemplated is use of pirfenidone in preparation of a
medicament for the treatment of a fibrosis condition comprising
administration of pirfenidone according to a dosing regimen as
disclosed herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 shows a structure of a portion of a starter pack for
the first week of treatment.
[0019] FIG. 2 shows a structure of a portion of a starter pack for
the second week of treatment.
[0020] FIG. 3 shows a structure of a portion of a starter pack for
the third week of treatment.
[0021] FIG. 4 shows a starter pack having multiple panels that are
folded.
[0022] FIG. 5 shows a starter pack having multiple panels in an
unfolded position.
[0023] FIG. 6 shows another structure of a portion of a starter
pack for the first week of treatment.
[0024] FIG. 7 shows another structure of a portion of a starter
pack for the second week of treatment.
[0025] FIG. 8 shows another structure of a portion of a starter
pack for the third week of treatment.
[0026] FIG. 9 shows a starter pack having a casing material holding
three different containers in such a manner that a user can easily
slide a container out of the casing material.
[0027] FIG. 10 shows a starter pack wherein a container is
partially pulled out from the casing material.
[0028] FIG. 11 shows a container comprising a panel having a
plurality of compartments for containing a dosage amount of
pirfenidone.
[0029] FIG. 12 shows a container wherein the panel has been pulled
outside of the container.
[0030] FIG. 13 shows a starter pack having a casing material
holding at least one circular panel containing pirfenidone.
[0031] FIG. 14 shows another structure of a portion of a circular
starter pack for the first week of treatment.
[0032] FIG. 15 shows another structure of a portion of a circular
starter pack for the second week of treatment.
[0033] FIG. 16 shows another structure of a portion of a circular
starter pack for the third week of treatment.
DETAILED DESCRIPTION
[0034] The present invention discloses a method of providing
pirfenidone therapy to a patient with an escalating dosage regimen
that mitigates adverse events associated with the use of
pirfenidone and, it is believed, better matches the development of
tolerance to potentially adverse effects of the drug with increases
in the dosage. In one embodiment of the present invention is a
method of providing pirfenidone therapy to a patient comprising
providing an initial daily dosage of pirfenidone to the patient in
a first amount for the duration of a first period of time;
providing a second daily dosage of pirfenidone to the patient in a
second amount for a second period of time; and providing a final
daily dosage of pirfenidone to the patient in a final amount for a
final period of time. The sum of the first and second periods of
time is preferably at least about 7 days, more preferably about 8,
9, 10, 11, or 12 days, and most preferably about 13 or 14 days. In
some embodiments, the first and second periods can together total
up to about 15 or about 20 or 21 days. Although it is also
contemplated that the first and second periods together can total
more than 21 days, and can (for example) be 22, 24, 26, or 30 days,
it is believed that the longer dose escalation periods are less
than optimal, due to the decrease in therapeutic benefit to the
patient resulting from the delay in administering the full
therapeutic dosage.
[0035] Although the present disclosure exemplifies dose escalation
regimens having three steps, it is also possible to have more steps
in the same amount of time, so that the dosage escalates in smaller
steps. Indeed, if desired, each dose can be incrementally larger
than the previous dose, or the dose can escalate every day, every
two days, or every three or four days, for example. Regardless of
the dose escalation step size, the use of an initial dose and an
ending dose in the amounts discussed below is particularly
preferred.
[0036] In one embodiment, the first amount is in the range of about
400 mg/day to about 1,200 g/day. In another embodiment, the first
amount is in the range of about 700 mg/day to about 900 mg/day. In
another embodiment, the first amount is in the range of about 780
mg/day to about 820 mg/day. In another embodiment, the first amount
is about 801 mg/day.
[0037] In one embodiment, the second amount is in the range of
about 1,200 mg/day to about 2,000 mg/day. In another embodiment,
the second amount is in the range of about 1,500 mg/day to about
1,700 mg/day. In another embodiment, the second amount is in the
range of about 1,580 mg/day to about 1,620 mg/day. In another
embodiment, the second amount is about 1,602 mg/day.
[0038] In one embodiment, the third amount is in the range of about
2,000 mg/day to about 3,000 mg/day. In another embodiment, the
third amount is in the range of about 2,300 mg/day to about 2,400
mg/day. In another embodiment, the third amount is in the range of
about 2,380 mg/day to about 2,420 mg/day. In another embodiment,
the third amount is about 2,403 mg/day.
[0039] In one embodiment, the first period of time is in the range
of about 3 days to about 10 days. In another embodiment, the first
period of time is about 6 to about 8 days. In another embodiment,
the first period of time is about 7 days.
[0040] In one embodiment, the second period of time is in the range
of about 3 days to about 10 days. In another embodiment, the second
period of time is about 6 to about 8 days. In another embodiment,
the second period of time is about 7 days.
[0041] In one embodiment, the final period of time is in the range
of about 1 day to an unlimited number of days. Preferably, the
final period of time will be however long the duration of treatment
with pirfenidone should last.
[0042] In one embodiment of the present invention is a method of
providing pirfenidone therapy to a patient comprising providing an
initial daily dosage of pirfenidone to the patient in an amount of
801 mg/day over the course of Day 1 to Day 7; providing a second
daily dosage of pirfenidone to the patient in an amount of 1602
mg/day over the course of Day 8 to Day 14; and providing a final
daily dosage of pirfenidone to the patient in an amount of 2403
mg/day on the beginning of Day 15 and continuing with the 2403
mg/day dosage on each day following Day 15.
[0043] In one embodiment, the patient is administered one capsule
(a sub-daily dosage) comprising 267-mg of pirfenidone three times a
day over the course of Day 1 to Day 7, to provide a daily dosage of
801 mg pirfenidone; then the patient is administered two capsules
(a sub-daily dosage) comprising 267-mg of pirfenidone three times a
day over the course of Day 8 to Day 14, to provide a daily dosage
of 1602 mg pirfenidone; and then the patient is administered three
capsules (a sub-daily dosage) comprising 267-mg of pirfenidone
three times a day on Day 15 and each day thereafter, to provide a
daily dosage of 2403 mg pirfenidone where the therapy continues
after Day 15.
[0044] In one embodiment, a dosage amount of pirfenidone is taken
with food. In another embodiment, the patient is instructed to
administer the dosage of pirfenidone with food.
[0045] In another embodiment of the present invention, there is
provided a starter pack comprising pirfenidone. Starter packs are a
relatively easy method for singulating, transporting, storing and
finally dispensing oral solid drugs. Such packs include, for
instance, a planar transparent piece of plastic provided with
"blisters" or convex protrusions configured in rows and columns.
Each of the blisters or convex protrusions is sized to receive a
singulated dosage amount of the particular oral solid drug being
dispensed.
[0046] Typically, at least one backing layer is fastened to a solid
receiving side of the blister pack. This layer is a low strength
retaining barrier. This low strength retaining layer stretches
across the backs of the blisters and retains the singulated oral
dosage amounts individually sealed within each of the blisters.
[0047] Dispensing of drugs from such blister packs is easy to
understand. The consumer presses down on a blister from the convex
side of the blister. Such pressure bears directly against the
singulated oral dosage amount contained in the blister. The
singulated oral solid drug is then forced through the low strength
retaining barrier. This low strength retaining barrier at least
partially tears and breaks away. During this partial breaking and
tearing away, the singulated oral dosage amount is partially--but
typically not totally--ejected from its individual blister.
Preferably, it is during this partial ejection that the oral solid
drug is grasped by the user and consumed as directed. The result is
a safe, sterile dispensing of the drug in desired single dosage
amounts from the blister pack.
[0048] The starter pack of the present invention may comprise
various dosage amounts of pirfenidone designated within blisters or
other individual compartments so that the patient will take the
proper dosage amount of the drug each day. The starter pack may
comprise many different forms. One embodiment of the starter pack
is shown in FIGS. 1-3. FIG. 1 shows a portion of a starter pack
comprising dosage amounts for the first week of therapy using
pirfenidone. The starter pack (10) for the first week of treatment
may comprise a panel (12) having a plurality of compartments (16)
for containing a dosage amount (18) of pirfenidone. The
compartments (16) may be arranged in column and row fashion as
illustrated, although other arrangements are also contemplated,
including having all of the compartments arranged in a line, or
having them arranged in a circular fashion. In an embodiment where
the starter pack comprises columns and rows, each daily dosage may
be represented in a singular row or a singular column.
[0049] FIG. 2 shows a portion of a starter pack comprising dosage
amounts for the second week of therapy using pirfenidone. The
starter pack (20) for the second week of treatment may comprise a
panel (22) having a plurality of compartments (26) for containing a
dosage amount (28) of pirfenidone. The compartments (26) for the
second week of treatment may be fashioned to hold a greater amount
of pirfenidone than the compartments (16) for the first week of
treatment. The dosage amount (28) of pirfenidone for the second
week may be greater than the dosage amount (18) of the first
week.
[0050] FIG. 3 shows a portion of a starter pack comprising dosage
amounts for the third week of therapy using pirfenidone. The
starter pack (30) for the third week of treatment may comprise a
panel (32) having a plurality of compartments (36) for containing a
dosage amount (38) of pirfenidone. The compartments (36) for the
third week of treatment may be fashioned to hold a greater amount
of pirfenidone than the compartments (26) for the second week of
treatment. The dosage amount (38) of pirfenidone for the third week
may be greater than the dosage amount (28) of the second week.
[0051] Although FIGS. 1-3 show a starter pack wherein a panel
represents one week of dosages, it is contemplated that a panel may
be constructed to comprise more or less compartments. For instance,
a panel may be constructed to hold dosage amounts for three days of
treatment. In another embodiment, a panel may be constructed to
hold dosage amounts for six days of treatment. In another
embodiment, a panel may be constructed to hold dosage amounts for
ten days of treatment. Any number of days and dosages in a single
panel are contemplated by the inventors. Preferably, the starter
pack may be designed so that the user administers pirfenidone
according to the dose escalation scheme of the present
invention.
[0052] In one embodiment, the starter pack comprises panels giving
dosage amounts of pirfenidone for the first week of treatment and
the second week of treatment. In another embodiment, the starter
pack further comprises a panel giving dosage amounts of pirfenidone
for the third week of treatment. In another embodiment, the starter
pack comprises a panel or an insert that gives instructions to a
patient for administering the proper dosage amount of
pirfenidone.
[0053] In one embodiment, the starter pack may comprise only dosage
amounts for the first week of treatment and the second week of
treatment. Preferably, such a starter pack may also comprise
instructions to the patient for administering the pirfenidone from
a bottle for therapy after dose escalation is completed. It is
contemplated that the user of the starter pack will continue
therapy with pirfenidone pills from a bottle after dose escalation
is completed.
[0054] The size of the starter pack and the panels that comprise
the starter pack may be typical of similar starter packs already
known. In a preferred embodiment, each panel within a starter pack
is approximately of similar size dimensions as the other panels of
the starter pack.
[0055] In some embodiments, the starter pack comprises a unitary
structure, wherein the unitary structure comprises more than one
panel and each panel may comprise dosage amounts for one week of
treatment. In some embodiments, the starter pack comprises a panel
that has printed instructions thereon. FIG. 4 shows a starter pack
(40) having multiple panels (42, 44, 46) that are folded. The
starter pack has at least one region (48) capable of folding so
that the separate panels (42, 44, 46) can be stacked upon one
another while the starter pack (40) maintains its unitary
structure. In some embodiments, the starter pack may comprise
panels (42, 44) having compartments for containing dosages of
pirfenidone. The dosages may be pushed through the low strength
retaining barrier at points (45) opposite the location of the
blisters.
[0056] FIG. 5 shows a fully unfolded starter pack (50) comprising
four panels (52, 54, 56, 58). The Week 1 panel (54) may have
compartments (54a) that comprise a dosage amount (54b) of
pirfenidone related to the first week of treatment. The Week 2
panel (56) may have compartments (56a) that comprise a dosage
amount (56b) of pirfenidone related to the second week of
treatment. Optionally, a panel for the dosage amounts of Week 3 may
be included. The Week 3 panel (58) may have compartments (58a) that
comprise a dosage amount (58b) of pirfenidone related to the third
week of usage. The other panel (52) may be left blank or provided
with instructions or any other type of indicia. In some
embodiments, the starter pack (50) may comprise an adhesive seal or
a sticker that holds the starter pack in folded form until the
adhesive seal or sticker is broken by a user. The starter pack may
comprise regions (55) capable of folding so that the separate
panels (52, 54, 56, 58) can be stacked upon one another while the
starter pack (50) maintains its unitary structure.
[0057] In one embodiment, one panel (54) may comprise compartments
(54a) giving the dosage amount (54b) for Days 1-7 of the dose
escalation scheme and the second panel (56) may comprise
compartments (56a) giving the dosage amount (56b) for Days 8-14 of
the dose escalation scheme. In another embodiment, an optional
third panel (58) may be further provided to comprise compartments
(58a) giving the dosage amount (58b) for Days 15-21 of the dose
escalation scheme.
[0058] FIG. 6 shows a portion of another starter pack comprising
dosage amounts for the first week of therapy using pirfenidone. The
starter pack (60) for the first week of treatment may comprise a
panel (62) having a plurality of compartments (66) for containing a
dosage amount (68) of pirfenidone. The compartments (66) may be
arranged in column and row fashion as illustrated, although other
arrangements are also contemplated, including having all of the
compartments arranged in a line, or having them arranged in a
circular fashion. Additionally, instructions may be provided on the
starter pack (60) indicating the proper day and time the dosage
amount (68) should be administered.
[0059] FIG. 7 shows a portion of another starter pack comprising
dosage amounts for the second week of therapy using pirfenidone.
The starter pack (70) for the second week of treatment may comprise
a panel (72) having a plurality of compartments (76) for containing
a dosage amount (78) of pirfenidone. The compartments (76) for the
second week of treatment may be fashioned to hold a greater amount
of pirfenidone than the compartments (66) for the first week of
treatment. The dosage amount (78) of pirfenidone for the second
week may be greater than the dosage amount (68) of the first week.
Additionally, instructions may be provided on the starter pack (70)
indicating the proper day and time the dosage amount (78) should be
administered.
[0060] FIG. 8 shows a portion of another starter pack comprising
dosage amounts for the third week of therapy using pirfenidone. The
starter pack (80) for the third week of treatment may comprise a
panel (82) having a plurality of compartments (86) for containing a
dosage amount (88) of pirfenidone. The compartments (86) for the
third week of treatment may be fashioned to hold a greater amount
of pirfenidone than the compartments (76) for the second week of
treatment. The dosage amount (88) of pirfenidone for the third week
may be greater than the dosage amount (78) of the second week.
Additionally, instructions may be provided on the starter pack (80)
indicating the proper day and time the dosage amount (88) should be
administered.
[0061] In some embodiments, the starter pack may comprise a casing
material that holds separate panels, wherein at least one panel
comprises a plurality of compartments for containing a dosage
amount of pirfenidone. In some embodiments, the panel may be
located within a container having flat outer surfaces so that the
container may easily be slid in and out of the casing material.
FIG. 9 shows a starter pack (90) having a casing material (98)
holding three different containers (92, 94, 96) in such a manner
that a user can easily slide a container out of the casing material
(98). In one embodiment, each container may comprise a panel that
comprises a plurality of compartments that hold a dosage amount of
pirfenidone. In some embodiments, the panels may further comprise
instructions or indicia so that a user can administer pirfenidone
according to the dose escalation scheme. In some embodiments, a
panel may be provided separately for providing indicia or
instructions on using the drug. In some embodiments, indicia or
instructions may be provided on one or more of the containers (92,
94, 96).
[0062] FIG. 10 shows a starter pack (100) comprising a casing
material (108) and at least one container (102). The container
(102) is partially pulled out from the casing material ( )8) and
may comprise a panel having a plurality of compartments for
containing a dosage amount of pirfenidone. For example, the
container (102) may comprise any of the panels shown in FIGS. 1-3
and FIGS. 6-8. Preferably, each panel will be approximately the
same size for easy and compact insertion into the casing material
(108).
[0063] FIG. 11 shows a container (110) comprising a panel (112)
having a plurality of compartments (116) for containing a dosage
amount (118) of pirfenidone. The panel (112) is partially pulled
out from the container (110) and can be slid in and out for easy
use. FIG. 12 shows a container (120) wherein the panel (122) having
a plurality of compartments (126) for containing a dosage amount
(128) of pirfenidone has been completely pulled from the container
(120). Instructions may be provided on a separate sheet (124)
within the container (120) in addition to the panel (122).
Alternatively, instructions or other indicia may be printed
directly on the container (120) or the panel (122).
[0064] One embodiment of the present invention is a starter pack
comprising dosage amounts of pirfenidone and compartments that
separate the dosage amounts according to a daily dosage of
pirfenidone. In one embodiment, the starter pack comprises a row
designating Day numbers and separate columns for the number of
times a dosage of pirfenidone is taken each day. In one embodiment,
the starter pack may comprise separate rows for Days 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, and 14 with three separate columns for
three dosage amounts to be taken each day. In one embodiment, each
of the three compartments for Days 1, 2, 3, 4, 5, 6, and 7
separately contain one pill of 267-mg pirfenidone and each of the
three compartments for Days 8, 9, 10, 11, 12, 13, and 14 separately
contain two pills of 267-mg pirfenidone. In another embodiment,
each week of treatment may be designated on a separate panel. In
another embodiment, each panel contained within the starter pack
may be approximately the same size. In another embodiment, the
starter pack has compartments arranged such that a user of the
starter pack will administer the pirfenidone in accordance with the
dose escalation method taught by the present invention.
[0065] In one embodiment, the starter pack further comprises
additional rows for Days 15, 16, 17, 18, 19, 20, and 21. In another
embodiment, each of the three compartments corresponding to Days
15, 16, 17, 18, 19, 20, and 21 separately contain three pills of
267-mg pirfenidone. The addition of the rows for Days 15, 16, 17,
18, 19, 20, and 21 is for the purpose of training the patient as to
the correct amount of dosage that will be needed after the starter
pack is finished and the patient begins taking pills from another
source, such as a pill bottle. By providing the starter pack with a
third week at the full dosage of pirfenidone, the patient will be
better accustomed to taking the 2,403 mg/day dosage from Day 15 and
each Day thereafter as required by the pirfenidone therapy method
of the present invention.
[0066] In another embodiment, the starter pack comprises a circular
form. FIG. 13 shows a container (130) comprising a base (138) that
holds at least one panel (132) having a plurality of compartments
(136) for containing a dosage amount of pirfenidone. The panel
(132) is circular in shape with compartments (136) extending in a
radial pattern from the center and wherein each radius designates
its own Day for treatment with pirfenidone. The dosages for AM,
noon, and PM may be separated in a manner shown in FIG. 13. The
container (130) also comprises a lid (139) so that at least one
panel (132) containing pirfenidone can be stored within the
container (130) and sealed.
[0067] FIG. 14 shows a portion of a starter pack comprising dosage
amounts for the first week of therapy using pirfenidone. The
starter pack (140) for the first week of treatment may comprise a
circular panel (142) having a plurality of compartments (146) for
containing a dosage amount (148) of pirfenidone. The compartments
(146) may be arranged so that they extend radially from the center
of the pane (142). The panel (142) may comprise indicia informing
the patient which dosage to administer at the appropriate time.
[0068] FIG. 15 shows a portion of a starter pack comprising dosage
amounts for the second week of therapy using pirfenidone. The
starter pack (110) for the second week of treatment may comprise a
circular panel (152) having a plurality of compartments (156) for
containing a dosage amount (118) of pirfenidone. The compartments
(156) may be arranged so that they extend radially from the center
or so that they fit within a panel. The panel (152) may comprise
indicia informing the patient which dosage to administer at the
appropriate time.
[0069] FIG. 16 shows a portion of a starter pack comprising dosage
amounts for the third week of therapy using pirfenidone. The panel
for the third week of therapy is optionally provided. The starter
pack (160) for the third week of treatment may comprise a circular
panel (162) having a plurality of compartments (166) for containing
a dosage amount (168) of pirfenidone. The compartments (146) may be
arranged so that they extend radially from the center of the pane
(162). The panel (162) may comprise indicia informing the patient
which dosage to administer at the appropriate time.
[0070] In another embodiment, the starter pack has compartments
arranged such that a user of the starter pack will administer the
pirfenidone in accordance with the dose escalation method taught by
the present invention. Of course, as an alternative to blister
packs, the doses can be contained in any other type of compartment,
such as plastic bags or other containers fastened together in book
form; plastic containers with snap-open lids arranged in a row or
other geometric pattern, or any of a wide variety of other
dosage-containing packages.
[0071] In one embodiment, a method for administering pirfenidone
therapy to a patient comprises initially administering a
predetermined starting dosage of pirfenidone to the patient and
escalating the dosage administered to the patient over a
predetermined time to a predetermined full dosage of pirfenidone.
In some embodiments, the predetermined time is measured from the
initial starting dosage and is between about 7 and 20 days. In some
embodiments, the predetermined time is 13 or 14 days. In some
embodiments, the starting dosage is about 801 mg/day. In some
embodiments, the full dosage is about 2,403 mg/day. In some
embodiments, the dosages are split into three daily oral
administrations.
[0072] The invention illustratively described herein suitably may
be practiced in the absence of any element or elements, limitation
or limitations which is not specifically disclosed herein. The
terms and expressions which have been employed are used as terms of
description and not of limitation, and there is no intention that
in the use of such terms and expressions indicates the exclusion of
equivalents of the features shown and described or portions
thereof. It is recognized that various modifications are possible
within the scope of the invention. Thus, it should be understood
that although the present invention has been specifically disclosed
by preferred embodiments and optional features, modification and
variation of the concepts herein disclosed may be resorted to by
those skilled in the art, and that such modifications and
variations are considered to be falling within the scope of the
invention.
* * * * *