METHODS OF TREATING OBESITY IN RESPONDER AND NON-RESPONDER POPULATIONS
The disclosed embodiments relate to, dosing regimens for the administration of topiramate, optionally in combination with one or more sympathomimetic agents such as phentermine. The dosing regimens can, for example, limit the exposure of subjects to topiramate, identify subjects who are unlikely to obtain a benefit from treatment with escalating dosages of topiramate (with or without the sympathomimetic agent, such as phentermine), or both, thereby reducing or eliminating harmful or intolerable side effects in subjects who are unlikely to respond to treatment and maximizing the therapeutic benefits from treatment in subjects who do respond.
1 . A method of administering topiramate to a subject comprising
measuring the weight of a subject to obtain a initial subject weight;
administering a daily dose of about 23 mg of topiramate to the subject for about two weeks after measuring the weight of the subject;
administering a daily dose of about 46 mg of topiramate to the subject for about three months after the about two weeks of administering a daily dose of about 23 mg topiramate;
measuring the weight of the subject after the about three months of administering a daily dose of about 46 mg of topiramate to determine a first weight change of the subject from the initial subject weight; and wherein
if the weight of the subject has decreased by about 3% or more, maintaining administration of the daily dose of about 46 mg of topiramate; or wherein
if the weight of the subject has not decreased by about 3% or more, administering a daily dose of about 69 mg of topiramate.
2 . The method of claim 1 , wherein
administering a daily dose of about 69 mg of topiramate comprises administering the daily dose of about 69 mg of topiramate for about two weeks after determining the first weight change.
3 . The method of claim 2 , further comprising
administering a daily dose of about 92 mg of topiramate to the subject for about three months after the about two weeks of administering the daily dose of about 69 mg of topiramate.
4 . The method of claim 2 , further comprising
measuring the weight of a subject after the about three months of administering the 92 mg of topiramate to determine a second weight change of the subject from the initial subject weight; and wherein
if the weight of the subject has decreased by about 5% or more, maintaining administration of the daily dose of about 92 mg of topiramate; or wherein
if the weight of the subject has not decreased by about 5% or more, halting the administration of topiramate.
5 . The method of claim 1 , further comprising,
administering a daily dose of a sympathomimetic agent with the daily dose of about 23 mg of topiramate.
6 . The method of claim 5 , wherein the sympathomimetic agent is phentermine.
7 . The method of claim 6 , further comprising
administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate.
8 . The method of claim 7 , wherein administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate further comprises
administering a controlled release form of the about 23 mg of topiramate; and
administering an immediate release form of the about 3.75 mg of phentermine.
9 . The method of claim 8 , wherein
the controlled release form of the about 23 mg topiramate and the immediate release form of the about 3.75 mg of phentermine constitute a single dosage form.
10 . The method of claim 9 , wherein the single dosage form is a capsule comprising polymer coated beads or a bilayer tablet.
11 . The method of claim 1 , further comprising
administering a daily dose of a sympathomimetic agent with the daily dose of about 46 mg of topiramate.
12 . The method of claim 11 , wherein the sympathomimetic agent is phentermine.
13 . The method of claim 12 , further comprising administering a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate.
14 . The method of claim 13 , further comprising
administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate.
15 . The method of claim 14 , wherein
administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate further comprises administering a controlled release form of the about 23 mg of topiramate, and administering an immediate release form of the about 3.75 mg phentermine; and wherein
administering a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate further comprises administering a controlled release form of the about 46 mg topiramate; and administering an immediate release form of the about 7.5 mg of phentermine.
16 . The method of claim 15 , wherein
the controlled release form of the about 23 mg of topiramate and the immediate release form of the about 3.75 mg of phentermine constitute a single unit dosage form; and
the controlled release form of the about 46 mg of topiramate and the immediate release form of the about 7.5 mg of phentermine constitute a single unit dosage form.
17 . The method of claim 16 , wherein
the controlled release form of the about 23 mg topiramate is a polymer coated bead; and
the controlled release form of the about 46 mg of topiramate is a polymer coated bead.
18 . The method of claim 1 or 2 , further comprising
administering a daily dose of sympathomimetic agent with the daily dose of about 69 mg topiramate.
19 . The method of claim 18 , wherein the sympathomimetic agent is phentermine.
20 . The method of claim 19 , further comprising
administering a daily dose of about 11.25 mg of phentermine with the daily dose of about 69 mg of topiramate.
21 . The method of claim 20 , further comprising
administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate; and
administering a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate.
22 . The method of claim 21 , wherein
administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate further comprises
administering a controlled release form of the about 23 mg of topiramate, and
administering an immediate release form of the about 3.75 mg phentermine; and wherein administering a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate further comprises
administering a controlled release form of the about 46 mg of topiramate, and
administering an immediate release form of the about 7.5 mg of phentermine; and wherein administering a daily dose of about 11.25 mg of phentermine with the daily dose of about 69 mg of topiramate further comprises
administering a controlled release form of the about 69 mg of topiramate, and
administering an immediate release form of the about 11.25 mg phentermine.
23 . The method of claim 22 , wherein
the controlled release form of the about 23 mg of topiramate and the immediate release form of the about 3.75 mg of phentermine constitute a single unit dosage form;
the controlled release form of the about 46 mg of topiramate and the immediate release form of the about 7.5 mg of phentermine constitute a single unit dosage form; and
the controlled release form of the about 69 mg of topiramate and the immediate release form of the about 11.25 mg of phentermine constitute a single unit dosage form.
24 . The method of claim 23 , wherein
the controlled release form of the about 23 mg of topiramate is a polymer coated bead;
the controlled release form of the about 46 mg of topiramate is a polymer coated bead; and
the controlled release form of the about 69 mg of topiramate is a polymer coated bead.
25 . The method of claim 3 , further comprising
administering a daily dose of sympathomimetic agent with the daily dose of about 92 mg of topiramate.
26 . The method of claim 25 , wherein the sympathomimetic agent is phentermine.
27 . The method of claim 26 , further comprising
administering a daily dose of about 15 mg of phentermine with the daily dose of about 92 mg of topiramate.
28 . The method of claim 27 , further comprising
administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate;
administering a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate; and
administering a daily dose of about 11.25 mg of phentermine with the daily dose of about 69 mg of topiramate.
29 . The method of claim 28 , wherein
administering a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate further comprises
administering a controlled release dosage form of the about 23 mg of topiramate, and
administering an immediate release dosage form of the about 3.75 mg of phentermine; and wherein
administering a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate further comprises
administering a controlled release dosage form of the about 46 mg of topiramate, and
administering an immediate release dosage form of the about 7.5 mg of phentermine; and wherein
administering a daily dose of about 15 mg phentermine with the daily dose of about 92 mg topiramate further comprises
administering a controlled release form of the about 92 mg topiramate, and
administering an immediate release form of the about 15 mg phentermine.
30 . The method of claim 29 , wherein
the controlled release form of the about 23 mg topiramate and the immediate release form of the about 3.75 mg phentermine constitute a single unit dosage form;
the controlled release form of the about 46 mg topiramate and the immediate release form of the about 7.5 mg phentermine constitute a single unit dosage form;
the controlled release form of the about 69 mg topiramate and the immediate release form of the about 11.25 mg phentermine constitute a single unit dosage form; and
the controlled release form of the about 92 mg topiramate and the immediate release form of the about 15 mg phentermine constitute a single unit dosage form.
31 . The method of claim 30 , wherein
the controlled release form of the about 23 mg topiramate is a polymer coated bead;
the controlled release form of the about 46 mg topiramate is a polymer coated bead;
the controlled release form of the about 69 mg topiramate is a polymer coated bead; and
the controlled release form of the about 92 mg topiramate is a polymer coated bead.
32 . A method of administering topiramate to a subject who
has an initial body weight prior to taking topiramate;
has taken a daily dose of about 23 mg of topiramate for about two weeks; and
has taken a daily dose of about 46 mg of topiramate for about three months after the about two weeks of taking the about 23 mg of topiramate; and
has a body weight after the about three months of taking the daily dose of about 46 mg of topiramate that is about 97% or more of the initial body weight;
the method comprising administering to the subject a daily dose of about 69 mg of topiramate for about two weeks.
33 . The method of claim 32 , further comprising
administering to the subject a daily dose of about 92 mg of topiramate for about three months after the about two weeks of administering a daily dose of about 69 mg topiramate.
34 . The method of claim 32 or 33 , wherein the subject has taken a daily dose of a sympathomimetic agent with the daily dose of about 23 mg of topiramate.
35 . The method of claim 34 , wherein the sympathomimetic agent is phentermine.
36 . The method of claim 35 , wherein
the subject has taken a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate.
37 . The method of claim 36 , wherein
the about 3.75 mg of phentermine and the about 23 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
38 . The method of claim 37 , wherein
the single dosage form of about 3.75 mg of phentermine and about 23 mg of topiramate comprises a capsule comprising polymer coated beads or a bilayer tablet.
39 . The method of claim 32 or 33 , wherein
the subject has taken a daily dose of a sympathomimetic agent with the daily dose of about 46 mg of topiramate.
40 . The method of claim 39 , wherein the sympathomimetic agent is phentermine.
41 . The method of claim 40 , wherein
the subject has taken a daily dosage of about 7.5 mg phentermine with the daily dose of about 46 mg topiramate.
42 . The method of claim 41 , wherein
the daily dosage of about 7.5 mg phentermine and the daily dose of about 46 mg topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
43 . The method of claim 41 , wherein the single dosage form comprises a capsule comprising polymer coated beads or a bilayer tablet.
44 . The method of claim 32 or 33 , wherein
the subject has taken daily dose of a sympathomimetic agent with the daily dose of about 46 mg of topiramate.
45 . The method of claim 44 , wherein the sympathomimetic agent is phentermine.
46 . The method of claim 45 , wherein
the subject has taken a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate.
47 . The method of claim 46 , wherein
the about 7.5 mg of phentermine and the about 46 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
48 . The method of claim 47 , wherein
the single dosage form of about 7.5 mg of phentermine and about 46 mg of topiramate comprises a capsule comprising polymer coated beads or a bilayer tablet.
49 . The method of claim 32 or 33 , wherein
the subject has taken a daily dose of a sympathomimetic agent with the daily dose of about 69 mg of topiramate.
50 . The method of claim 49 , wherein the sympathomimetic agent is phentermine.
51 . The method of claim 50 , wherein
the subject has taken a daily dosage of about 11.25 mg of phentermine with the daily dose of about 69 mg of topiramate.
52 . The method of claim 51 , wherein
the daily dosage of about 11.25 mg of phentermine and the daily dose of about 69 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
53 . The method of claim 52 , wherein the single dosage form comprises a capsule comprising polymer coated beads or a bilayer tablet.
54 . The method of claim 33 , wherein
the subject has taken daily dose of a sympathomimetic agent with the daily dose of about 92 mg of topiramate.
55 . The method of claim 54 , wherein the sympathomimetic agent is phentermine.
56 . The method of claim 55 , wherein
the subject has taken a daily dose of about 15 mg of phentermine with the daily dose of about 46 mg of topiramate.
57 . The method of claim 56 , wherein
the about 15 mg of phentermine and the about 92 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
58 . The method of claim 57 , wherein
the single dosage form of about 15 mg of phentermine and about 92 mg of topiramate comprises a capsule comprising polymer coated beads or a bilayer tablet.
59 . A method of minimizing exposure to topiramate in a subject who
has an initial body weight prior to taking topiramate;
has taken a daily dose of about 23 mg of topiramate for about two weeks; and
has taken a daily dose of about 46 mg of topiramate for about three months after the about two weeks of taking the about 23 mg of topiramate; and
has a body weight after the about three months of taking the daily dose of about 46 mg of topiramate that is about 97% or more of the initial body weight;
the method comprising
halting administration of topiramate to the subject.
60 . The method of claim 59 , wherein
the subject has taken a daily dose of a sympathomimetic agent with the daily dose of about 23 mg of topiramate.
61 . The method of claim 60 , wherein the sympathomimetic agent is phentermine.
62 . The method of claim 61 , wherein
the subject has taken a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate.
62 . The method of claim 63 , wherein
the about 3.75 mg of phentermine and the about 23 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
63 . The method of claim 64 , wherein
the single dosage form of about 3.75 mg of phentermine and about 23 mg of topiramate comprises a capsule comprising polymer coated beads or a bilayer tablet.
64 . The method of claim 59 , wherein
the subject has taken a daily dose of a sympathomimetic agent with the daily dose of about 46 mg of topiramate.
65 . The method of claim 64 , wherein the sympathomimetic agent is phentermine.
66 . The method of claim 65 , wherein
the subject has taken a daily dosage of about 7.5 mg phentermine with the daily dose of about 46 mg topiramate.
67 . The method of claim 66 , wherein
the daily dosage of about 7.5 mg phentermine and the daily dose of about 46 mg topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
68 . The method of claim 67 , wherein the single dosage form comprises a polymer coated bead.
69 . The method of claim 59 , wherein
the subject has taken daily dose of a sympathomimetic agent with the daily dose of about 46 mg of topiramate.
70 . The method of claim 69 , wherein the sympathomimetic agent is phentermine.
71 . The method of claim 70 , wherein
the subject has taken a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate.
72 . The method of claim 71 , wherein
the about 7.5 mg of phentermine and the about 46 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
73 . The method of claim 72 , wherein
the single dosage form of about 7.5 mg of phentermine and about 46 mg of topiramate comprises a polymer coated bead.
74 . A method of minimizing exposure to topiramate in a subject who has an initial body weight prior to taking topiramate;
has taken a daily dose of about 23 mg of topiramate for about two weeks; and
has taken a daily dose of about 46 mg of topiramate for about three months after the about two weeks of taking the about 23 mg of topiramate;
has taken a daily dose of about 69 mg of topiramate for about two weeks after the about three months of taking a daily dose of about;
has taken a daily dose of about 92 mg of topiramate for about three months after the about two weeks of taking a daily dose of about 69 mg of topiramate; and
has a body weight after the about three months of taking a daily dose of 92 mg topiramate that is about 95% or more of the initial body weight;
the method comprising halting administration of topiramate to the subject.
75 . The method of claim 74 , wherein the sympathomimetic agent is phentermine.
76 . The method of claim 75 , wherein
the subject has taken a daily dose of about 3.75 mg of phentermine with the daily dose of about 23 mg of topiramate.
77 . The method of claim 76 , wherein
the about 3.75 mg of phentermine and the about 23 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
78 . The method of claim 77 , wherein
the single dosage form of about 3.75 mg of phentermine and about 23 mg of topiramate comprises a polymer coated bead.
79 . The method of claim 74 , wherein
the subject has taken a daily dose of a sympathomimetic agent with the daily dose of about 46 mg of topiramate.
80 . The method of claim 79 , wherein the sympathomimetic agent is phentermine.
81 . The method of claim 80 , wherein
the subject has taken a daily dosage of about 7.5 mg phentermine with the daily dose of about 46 mg topiramate.
82 . The method of claim 81 , wherein
the daily dosage of about 7.5 mg phentermine and the daily dose of about 46 mg topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
83 . The method of claim 81 , wherein the single dosage form comprises a polymer coated bead.
84 . The method of claim 74 , wherein
the subject has taken daily dose of a sympathomimetic agent with the daily dose of about 46 mg of topiramate.
85 . The method of claim 84 , wherein the sympathomimetic agent is phentermine.
86 . The method of claim 85 , wherein
the subject has taken a daily dose of about 7.5 mg of phentermine with the daily dose of about 46 mg of topiramate.
87 . The method of claim 86 , wherein
the about 7.5 mg of phentermine and the about 46 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
88 . The method of claim 87 , wherein
the single dosage form of about 7.5 mg of phentermine and about 46 mg of topiramate comprises a polymer coated bead.
89 . The method of claim 74 , wherein
the subject has taken a daily dose of a sympathomimetic agent with the daily dose of about 69 mg of topiramate.
90 . The method of claim 89 , wherein the sympathomimetic agent is phentermine.
91 . The method of claim 80 , wherein
the subject has taken a daily dosage of about 11.25 mg of phentermine with the daily dose of about 69 mg of topiramate.
92 . The method of claim 91 , wherein
the daily dosage of about 11.25 mg of phentermine and the daily dose of about 69 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
93 . The method of claim 92 , wherein the single dosage form comprises a polymer coated bead.
94 . The method of claim 93 , wherein
the subject has taken daily dose of a sympathomimetic agent with the daily dose of about 92 mg of topiramate.
95 . The method of claim 94 , wherein the sympathomimetic agent is phentermine.
96 . The method of claim 95 , wherein
the subject has taken a daily dose of about 15 mg of phentermine with the daily dose of about 46 mg of topiramate.
97 . The method of claim 96 , wherein
the about 15 mg of phentermine and the about 92 mg of topiramate constitute a single dosage form with an immediate release phentermine portion and a controlled release topiramate portion.
98 . The method of claim 97 , wherein
the single dosage form of about 15 mg of phentermine and about 92 mg of topiramate comprises a polymer coated bead.
99 . The method of claim 1 wherein the daily dose of about 46 mg of topiramate is maintained for at least 21 months after the about 3 months for a total of at least 2 years.
100 . The method of claim 16 wherein the daily dose of about 46 mg of topiramate and the daily dose of about 7.5 mg phentermine is maintained for at least 21 months after the about 3 months for a total of at least 2 years.
101 . A composition comprising:
(i) one or more sustained release topiramate beads, the sustained release topiramate beads consisting essentially of
about 1% (w/w) to about 5% (w/w) of a binder;
about 40% (w/w) to about 60% (w/w) of a filler;
about 25% (w/w) to about 50% (w/w) of an active agent, the active agent consisting of topiramate; and
a sustained release polymer coating; and either
(ii) one or more first phentermine beads, the first phentermine beads consisting essentially of
an inert core;
about 3% (w/w) to about 6% (w/w) phentermine on the inert core; and
about 2% to about 8% of a binder coated on the inert core; or
(iii) one or more second phentermine beads, the second phentermine beads consisting essentially of
an inert core;
about 6.5% (w/w) to about 13% (w/w) phentermine coated on the inert core; and
about 4% to about 15% of a binder coated on the inert core.
102 . The composition of claim 101 , further comprising a glidant.
103 . The composition of claim 102 , wherein the glidant is talc.
104 . The composition of any of claims 102 - 103 , comprising about 0.1% (w/w) to about 2% (w/w) of glidant.
105 . The composition of any of claims 102 - 104 , comprising about 0.5% (w/w) of glidant.
106 . The composition of any of any of claims 101 - 105 , wherein the sustained release polymer coating of the one or more sustained release polymer beads consists essentially of ethyl cellulose and polyvinylpyrrolidone.
107 . The composition of any of claim 106 , wherein the sustained release polymer coating of the one or more sustained release polymer beads comprises from about 2% (w/w) to about 10% (w/w) ethylcellulose.
108 . The composition of any of any of claims 106 - 107 , wherein the sustained release polymer coating of the one or more sustained release polymer beads comprises from about 5% (w/w) or about 5.5% (w/w) ethylcellulose.
109 . The composition of any of claims 106 - 108 , wherein the sustained release polymer coating of the one or more sustained release polymer beads comprises about 1% (w/w) to about 5% (w/w) polyvinylpyrrolidone.
110 . The composition of any of claims 106 - 109 , wherein the sustained release polymer coating of the one or more sustained release polymer beads comprises about 2.5% (w/w) polyvinypyrrolidone.
111 . The composition of any of claims 101 - 110 , wherein the binder in the one or more sustained release topiramate beads is methyl cellulose.
112 . The composition of any of claims 101 - 111 , wherein the binder in the one or more sustained release topiramate beads consists essentially of methyl cellulose.
113 . The composition of any of claims 101 - 112 , wherein the filler in the binder in the one or more sustained release topiramate beads is microcrystalline cellulose.
114 . The composition of any of claims 101 - 113 , wherein the the filler in the one or more sustained release topiramate beads consists essentially of microcrystalline cellulose.
115 . The composition of any of claims 101 - 114 , wherein inert core in the one or more first phentermine beads or the one or more second phentermine beads is a sugar sphere.
116 . The composition of any of claims 101 - 115 , wherein the binder in the one or more first phentermine beads or the one or more second phentermine beads is hydroxypropyl methylcellulose.
117 . The composition of any of claims 101 - 116 , comprising either:
about 3.75% (w.w) to about 5.85% (w/w) phentermine in the one or more first phentermine beads; or
about 7.5% (w/w) to about 11.75% (w/w) phentermine in the one or more second phentermine beads.
118 . The composition of any of claims 101 - 117 , comprising either:
about 4.67% (w/w) phentermine in the one or more first phentermine beads; or
about 9.33% (w/w) phentermine in the one or more second phentermine beads.
119 . The composition of any of claims 102 - 118 , wherein the glidant and the sustained release topiramate beads are present in a topiramate bead glidant blend.
120 . The composition of claim 119 , comprising about 80 mg to about 125 mg of the first phentermine beads and about 50 mg to about 79 mg of the topiramate bead glidant blend.
121 . The composition of any of claims 119 - 120 , comprising about 100 mg of the first phentermine beads and about 63 mg of the topiramate bead glidant blend.
122 . The composition of any of claims 119 - 121 , comprising about 23 mg of topiramate and about 3.75 mg of phentermine.
122 . The composition of claim 119 , comprising about 160 mg to about 250 mg of the first phentermine beads and about 100 mg to about 158 mg of the toiramate bead glidant blend.
123 . The composition of any of claim 119 or 122 , comprising about 200 mg of the first phentermine beads and about 126 mg of the topiramate bead glidant blend.
124 . The composition of any of claim 119 or 122 - 123 , comprising about 46 mg of topiramate and about 7.5 mg of phentermine.
125 . The composition of claim 119 , comprising about 120 mg to about 188 mg of the second phentermine beads and about 150 mg to about 235 mg of the topiramate bead glidant blend.
126 . The composition of any of claims claim 119 and 125 , comprising about 150 mg of the second phentermine beads and about 188 mg of the topiramate bead glidant blend.
127 . The composition of any of claims 119 and 125 - 126 , comprising about 69 mg of topiramate and about 11.25 mg of phentermine.
128 . The composition of claim 119 , comprising about 160 mg to about 250 mg of the second phentermine beads and about 200 mg to about 315 mg, such as about 251 mg, of the topiramate glidant blend.
129 . The composition of any of claim 119 or 128 , comprising about 200 mg of the second phentermine beads and about 250 mg of the topiramate bead glidant blend.
130 . A capsule comprising a capsule shell filled with the composition of any of claims 101 - 129 .
131 . A tablet comprising the composition of any of claims 101 - 123 .
132 . Use of a composition of any of claims 101 - 129 in a method of any of claims 1 - 100 .