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`UNITED STATES PATENT AND TRADEMARK OFFICE
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`-----------------------------------------
`KVK-TECH, INC.,
` Petitioner,
` Case IPR 2018-00290
` v. Patent 8,846,100 B2
`SHIRE PLC,
` Patent Owner.
`-----------------------------------------
`KVK-TECH, INC.,
` Petitioner,
` Case IPR 2018-00293
` v. Patent 9,173,857
`SHIRE PLC,
` Patent Owner.
`-----------------------------------------
`
` DEPOSITION OF JAMES T. MCCRACKEN,
`M.D., the Witness herein, taken by Patent
`Owner, at the offices of Lucas & Mercanti,
`LLP, 30 Broad Street, New York, New York,
`on Wednesday, February 27, 2019, at 9:39
`a.m., before Debra Stevens, a Certified
`Realtime and Registered Professional
`Reporter and Notary Public within and for
`the State of New York.
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`SHIRE EX. 2082
`KVK v. SHIRE
`IPR2018-00290
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`-----------------------------------------
`KVK-TECH, INC.,
` Petitioner,
` Case IPR 2018-00290
` v. Patent 8,846,100 B2
`SHIRE PLC,
` Patent Owner.
`-----------------------------------------
`KVK-TECH, INC.,
` Petitioner,
` Case IPR 2018-00293
` v. Patent 9,173,857
`SHIRE PLC,
` Patent Owner.
`-----------------------------------------
`
` DEPOSITION OF JAMES T. MCCRACKEN,
`M.D., the Witness herein, taken by Patent
`Owner, at the offices of Lucas & Mercanti,
`LLP, 30 Broad Street, New York, New York,
`on Wednesday, February 27, 2019, at 9:39
`a.m., before Debra Stevens, a Certified
`Realtime and Registered Professional
`Reporter and Notary Public within and for
`the State of New York.
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`SHIRE EX. 2082
`KVK v. SHIRE
`IPR2018-00290
`
`
`
`Page 2
`
`A P P E A R A N C E S :
`LUCAS & MERCANTI, LLP
` Attorneys for Petitioner
`30 Broad Street
`New York, New York
` BY: DAVID J. GALLUZZO, ESQ.
` djg@lmiplaw.com
`
` STEVEN D. ROTH, ESQ.
` sroth@lmiplaw.com
`
`TROUTMAN SANDERS LLP
` Attorneys for Patent Owner
`875 Third Avenue
`New York, New York 10022
` BY: JOSEPH R. ROBINSON, ESQ.
` joseph.robinson@troutman.com
`
` TANYA LEAVY, Ph.D., Patent Agent
` tanya.leavy@troutman.com
`
`ALSO PRESENT:
` Thomas Divine, Videographer
` * * *
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`Page 3
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` E X A M I N A T I O N S
` Witness Page
` James T. McCracken, M.D.
` By Mr. Robinson 8
` By Mr. Galluzzo 209
` By Mr. Robinson 220
`
` E X H I B I T S
` McCracken
` Exhibits Description Page
` Exhibit 600 U.S. Patent 38
` Publication
` 20040059002, Couch
` Exhibit 601 Corrected Declaration 47
` of James McCracken,
` M.D.
` Exhibit 602 Brauer 1996, "Acute 53
` Tolerance" article
` Exhibit 603 McCracken 2003, 60
` "Analog Classroom
` Assessment.."
` Exhibit 604 Spencer Chapter 35 in 69
` "Current Diagnosis
` and Treatment
` Psychiatry"
` Exhibit 605 Kratochvil article, 73
` ADHD Treatment and
` Outcome
` (Continued)
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` E X H I B I T S
`McCracken
`Exhibits Description Page
` Exhibit 606 McGough article, 120
` "Pharmacokinetics of
` SLI381 Adderall XR,
` an Extended-Release
` Formulation of
` Adderall"
` Exhibit 607 Label for Adderall XR 135
` capsules
` Exhibit 608 Swanson article, 144
` "Acute tolerance to
` methylphenidate in
` the treatment of
` attention deficit
` hyperactivity
` disorder in children"
` Exhibit 609 James, "Double-Blind, 156
` Placebo-Controlled
` Study of Single-Dose
` Amphetamine
` Formulations in ADHD"
` Exhibit 610 2005 edition of the 157
` Physicians' Desk
` Reference
` Exhibit 611 Dexedrine label 158
` Exhibit 612 Blow-ups of 2005 175
` Physicians' Desk
` Reference
` Exhibit 613 American Academy of 175
` Pediatrics paper
`
` (Continued)
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` E X H I B I T S
` McCracken
` Exhibits Description Page
`
` Exhibit 614 Swanson 2009, 184
` "Psychopharmacology:
` Concepts and opinions
` about the use of
` stimulant
` medications"
` Exhibit 615 Patent 8,846,100 B2 188
` Exhibit 616 Patent 6,605,300 201
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`Page 6
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` THE VIDEOGRAPHER: Good morning.
` We are going on the record at
` 9:39 a.m. on February 27, 2019.
` Please note that the microphones are
` sensitive and may pick up whispering,
` private conversations and cellular
` interference. Please turn off all
` cell phones or place them away from
` the microphones as they can interfere
` with the deposition audio. Audio and
` video recording will continue to take
` place unless all parties agree to go
` off the record.
` This is media unit 1 of the
` video-recorded deposition of James
` McCracken, M.D., taken by counsel for
` the Patent Owner in the matter of
` KVK-Tech, Inc. versus Shire PLC, filed
` in the U.S. Patent and Trademark
` Office, Case Number -- excuse me --
` Case IPR 2018-00290, U.S. Patent
` Number 8,846,100.
` This deposition is being held at
` Lucas & Mercanti, located at 30 Broad
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`Page 7
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` Street, New York, New York. My name
` is Thomas Divine from the firm
` Veritext, New York, and I am the
` videographer. The court reporter is
` Debra Stevens, also with Veritext, New
` York.
` I am not authorized to
` administer an oath, I am not related
` to any party in this action, nor am I
` financially interested in the outcome.
` Counsel and all present in the
` room will now please state appearances
` and affiliations for the record. If
` there are any objections to
` proceeding, please state them at the
` time of your appearance, beginning
` with the noticing attorney.
` MR. ROBINSON: Joseph Robinson,
` from Troutman Sanders, representing
` Patent Owner. With me is Tanya Leavy,
` Ph.D., also representing Patent Owner.
` MR. GALLUZZO: David Galluzzo of
` Lucas & Mercanti, representing
` Petitioner KVK-Tech. With me I have
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`Page 8
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` Mr. Steven Roth.
` Whereupon,
` J A M E S T. M c C R A C K E N,
` having been first duly sworn/affirmed,
` was examined and testified as follows:
`EXAMINATION BY
`MR. ROBINSON:
` Q. Dr. McCracken, thank you for
`appearing today.
` MR. ROBINSON: Before we start,
` I would like to make an objection.
` This deposition was noticed for today,
` to start at 9:30, which it is. We
` have an agreement with former counsel
` that expert depositions will last 10
` hours. If present counsel has
` disavowed that agreement, we object to
` that, number one.
` Number two, present counsel said
` this deposition must stop at 5:30,
` hard stop, which would not even be
` seven hours of deposition. We object
` to that.
` Furthermore, we object to new
`
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`Page 9
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` J. McCracken, M.D.
` Exhibit 1059 as being an entirely new
` document. We reserve the right to
` cross-examine on that but we reserve
` our objections as well.
` MR. GALLUZZO: In response, it
` is Petitioner's position that the
` prior agreement with prior counsel was
` specific for those two witnesses that
` were being deposed, number one. It
` was not a global agreement for all
` expert witnesses or witnesses in this
` case.
` The 10 hours was not extended to
` us for Dr. Polli when we took
` Dr. Polli's deposition. And we did
` not know about this agreement until
` yesterday, the day before this
` deposition.
` MR. ROBINSON: We put no limit
` on Dr. Polli's deposition. We did not
` restrict you in any way. You were
` allowed to cross-examine as long as
` you wished. On top of that, just
` because you're new counsel does not
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`Page 10
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` J. McCracken, M.D.
` excuse you from familiarizing yourself
` with all the agreements we had with
` former counsel.
` MR. GALLUZZO: Our position is
` there were no former agreements. It
` was a series of emails that were
` specific for those two witnesses.
`BY MR. ROBINSON:
` Q. Dr. McCracken, could you give
`your name and address, please?
` A. James Thomas McCracken, M.D. My
`work address is UCLA, Semel Institute, 760
`Westwood Plaza, Los Angeles, California
`90024.
` Q. And that is where you would
`accept service?
` A. Yes.
` Q. You have a medical doctor
`degree. Is that correct?
` A. Yes, that's correct.
` Q. And you completed a residency in
`general psychiatry. Is that correct?
` A. Yes, correct.
` Q. And you completed a fellowship
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`Page 11
`
` J. McCracken, M.D.
`in child psychiatry. Is that correct?
` A. Yes.
` Q. And you have been board
`certified in general and child and
`adolescent psychiatry for 31 years. Is
`that correct?
` A. I believe the math adds up to
`that. My child psychiatry board was in
`1988.
` Q. And you have been an active
`clinician for over 30 years. Is that
`correct?
` A. Yes, correct.
` Q. And you have won awards in
`diagnosis, treatment and pharmacology. Is
`that correct?
` MR. GALLUZZO: Objection to form
` of the question.
` A. I have received awards for my
`research in ADHD and in a number of areas
`of research.
` Q. And you teach about ADHD. Is
`that correct?
` A. Yes, I do.
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`Page 12
`
` J. McCracken, M.D.
` Q. Have you participated in any
`studies funded in whole or in part by
`Shire?
` MR. GALLUZZO: Objection to form
` of the question.
` A. Yes, I have.
` Q. What was the first study funded
`by Shire in which you participated?
` A. I don't recall entirely, but one
`of the first was my participation in the
`multisite SPD 301 or Adderall XR analog
`classroom study, which was described in my
`2003 publication.
` Q. And when was the last study you
`participated in that was funded in whole
`or in part by Shire?
` A. I don't remember the actual
`year, but the last study involved,
`similarly, an analog classroom study of
`guanfacine for the treatment of ADHD in
`children and adolescents.
` Q. Was that study concluded more
`than 10 years ago?
` A. Yes, it was.
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`Page 13
`
` J. McCracken, M.D.
` Q. More than 15 years ago?
` A. More than 15? I don't recall.
`I could look that up if you wish.
` Q. It's fine.
` Why have you not participated in
`any studies funded in whole or in part by
`Shire in the last 10 years?
` MR. GALLUZZO: Objection to form
` of the question.
` A. I have focused my research in a
`somewhat different area, which has led me
`to pursue and receive the majority of my
`funding from the National Institute of
`Health.
` Q. Okay. So you don't do any
`research on ADHD in the last 10 years. Is
`that correct?
` MR. GALLUZZO: Objection --
` A. No, that is not correct.
` Q. How has the focus of your
`research changed in the last 10 years so
`that you no longer need funding from
`Shire?
` MR. GALLUZZO: Objection to form
`
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`Page 14
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` J. McCracken, M.D.
` of the question.
` A. Well, I never needed funding
`from Shire, but I have participated in
`research that I thought was interesting
`and potentially of significance.
` Q. How has the focus of your
`research changed in the last 10 years so
`that you no longer participate in studies
`funded by Shire?
` A. I have moved to looking at
`different aspects of the treatment of
`ADHD, including, you might say, looking
`beyond the effect of medications on simple
`behaviors or symptoms to examine the
`effects on actual cognitive performance,
`of medications given singly or in
`combination, and also to utilize other
`tools such as electroencephalogram as a
`means to understand the effects on brain
`function of different treatments for ADHD.
`These are topics that a drug company is
`not particularly interested in supporting,
`but the federal government is.
` Q. And why about 10 years ago did
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`Page 15
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` J. McCracken, M.D.
`you change the focus of your research?
` MR. GALLUZZO: Objection.
` Mischaracterizes the testimony.
` A. Well, around that time I came to
`the conclusion, right or wrong, that we
`had several reasonably effective
`medications for ADHD and other childhood
`psychiatric disorders, but we failed in
`being able to predict, at the level of the
`individual child, what would be their
`optimum treatment and how to best match
`their treatment to them in a manner that
`would lead them to show superior
`improvement and perhaps even change their
`long-term outcome.
` These are questions that I felt
`became more and more compelling for my
`research at that time with the advent of
`multiple stimulant preparations and
`non-stimulant alternatives.
` Q. In the last 10 years, have you
`turned down an opportunity to participate
`in a study funded in whole or in part by
`Shire?
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`Page 16
`
` J. McCracken, M.D.
` MR. GALLUZZO: Objection. Lacks
` foundation.
` A. I don't recall. I have
`definitely not sought as much
`pharmaceutical company funding during that
`time, as I have been quite busy with my
`federally funded research and other
`research that I felt was more compelling
`scientifically.
` Q. A few minutes ago you said that
`one of the reasons why you changed your
`focus of your research is that there were
`already several effective medications for
`the treatment of ADHD. What were those
`medications you were referencing?
` MR. GALLUZZO: Objection.
` Mischaracterizing testimony.
` A. There is a long list. There are
`two classes of stimulants with multiple
`delivery systems. I mentioned guanfacine,
`which, in its extended-release
`preparation, is FDA approved for children
`and teenagers.
` There is also atomoxetine,
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`Page 17
`
` J. McCracken, M.D.
`non-stimulant, approved for the treatment
`of ADHD in children and adults.
` So, there are multiple choices
`that practitioners have available that
`often can work quite well even despite
`individual differences, which are
`profound.
` Q. You mentioned guanfacine and
`atomoxetine. Any others?
` A. Well, those are the approved
`general classes at this time. Clonidine
`is similar to guanfacine, an alpha 2
`agonist that has recently been approved
`for ADHD in a new preparation.
` Q. So, the effective medications
`that you referenced a few minutes ago when
`you changed your focus of research
`included guanfacine, atomoxetine and
`clonidine. Anything else?
` A. I mentioned the two stimulant
`classes, the broad stimulant classes,
`methylphenidate-containing and
`amphetamine-containing preparations.
` Q. Anything else?
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`Page 18
`
` J. McCracken, M.D.
` A. Those are the ones that I
`consider to be best studied, safest, have
`FDA-approved formulations.
` Q. Another name for acute tolerance
`is tachyphylaxis. Correct?
` A. Correct.
` Q. Were you aware of reports before
`2003 that amphetamines were subject to
`acute tolerance?
` MR. GALLUZZO: Objection. Lacks
` foundation.
` A. No, I was not aware of acute
`tolerance being demonstrated for
`amphetamines at that time.
` Q. Were you aware of reports that
`amphetamines were subject to acute
`tolerance?
` MR. GALLUZZO: Objection to
` form.
` Q. Before 2003.
` MR. GALLUZZO: Same objection.
` A. There was not evidence in the
`literature, to my knowledge, as best as I
`can recall, prior to 2003, nor since.
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`Page 19
`
` J. McCracken, M.D.
` Q. Is there any difference between
`acute tolerance and chronic tolerance?
` MR. GALLUZZO: Objection to
` form.
` A. Yes.
` Q. What is that difference?
` A. Absolutely.
` Q. What is that difference?
` A. Well, acute tolerance refers to
`the relatively rapid development of
`diminished effect, be it subjective or
`biological, within an initial exposure,
`with classic examples being nicotine.
` Chronic tolerance relates to a
`different set of adaptive processes, and
`those are best exemplified by drugs of
`abuse, such as opioids. And as a
`consequence of the development of chronic
`tolerance, one sees withdrawal symptoms
`upon discontinuation of the agent, usually
`requiring weeks or months of high-dose
`exposure.
` Q. You said acute tolerance refers
`to the relatively rapid development of
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`diminished effect. Correct?
` A. Yes.
` Q. What is "relatively rapid"?
` MR. GALLUZZO: Objection to
` form.
` A. It depends wholly on the agent
`and that agent's unique pharmacokinetics.
`So it is difficult to make a general
`answer to the question because it depends
`so much on what agent is being referenced.
` Q. And you said that it depends
`wholly on the agent and that agent's
`unique pharmacokinetics. What do you mean
`by "unique pharmacokinetics"?
` A. It's the speed of its
`absorption, its clearance, accumulation.
`Standard pharmacokinetic properties.
` Q. And what is the relationship
`between acute tolerance and speed of a
`drug's absorption?
` MR. GALLUZZO: Objection to form
` of the question.
` A. Well, this is not the defining
`feature of what determines acute
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` J. McCracken, M.D.
`tolerance, but drugs with rapid absorption
`would tend to manifest -- if they did
`invoke acute tolerance, the evidence of
`such tolerance would be seen equally
`rapidly.
` Q. What is "rapid absorption"?
`What time period?
` MR. GALLUZZO: Objection to form
` of the question.
` A. It depends on what you are
`referring to. I mean, should I answer in
`relation to ADHD treatment, or what kind
`of context?
` Q. You can answer in relation to
`ADHD treatment. That would be fine.
` A. Well, with ADHD treatment, one
`hopes to achieve some initial benefit
`after not too long. Clinically speaking,
`preparations which have some demonstrable
`benefit within an hour or so are deemed
`satisfactory.
` Q. What is the relationship between
`acute tolerance and clearance of a drug?
` MR. GALLUZZO: Objection to
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` form.
` A. Well, that can influence the
`extent to which the effect, whether it is
`subjective or physiologic, is declining,
`at what pace.
` Q. What is the relationship between
`acute tolerance and accumulation of a
`drug?
` MR. GALLUZZO: Objection to
` form.
` A. Well, again, it depends on the
`agent. Not all drugs, in fact -- not all
`drugs manifest acute tolerance. In fact,
`a small number do, at least in clinical
`practice.
` Q. Does amphetamine accumulate in
`the blood over time?
` MR. GALLUZZO: Objection to
` form.
` A. I am not sure what you mean by
`"does amphetamine accumulate in the blood
`over time." It has -- it has a definable
`clearance, it has a definable time of
`maximum concentration and time of
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` J. McCracken, M.D.
`approximate elimination, half life.
` Q. Before I asked, "And what is the
`relationship between tolerance and speed
`of a drug's absorption," and you answered,
`"Well, this is not the defining feature of
`what determines acute tolerance."
` Is there a defining feature of
`what determines acute tolerance of a drug?
` MR. GALLUZZO: Objection.
` Mischaracterizes testimony.
` A. I would say the mechanism varies
`uniquely by each medication or compound.
` Q. Acute tolerance results in a
`decrease in effect of a drug, correct?
` MR. GALLUZZO: Objection. Lacks
` foundation.
` A. Well, I think acute tolerance
`would refer to the rapid loss of action,
`be it therapeutic benefit or -- depending
`on the drug, loss of subjective effect.
`More rapid than its actual clearance or
`binding.
` Q. In order for acute tolerance to
`be present, does the complete elimination
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` J. McCracken, M.D.
`of the effect on the drug need to be
`established?
` MR. GALLUZZO: Objection to
` form.
` A. I am sorry. Could you restate
`your question, please?
` Q. Sure.
` Acute tolerance need not result
`in complete elimination of an effect of a
`drug. Correct?
` MR. GALLUZZO: Objection to
` form.
` A. Well, the demonstration or the
`evidence for acute tolerance would, by
`definition, include a clinically
`meaningful loss of effect, more rapid than
`its simple clearance.
` Q. Acute tolerance can develop over
`hours. Correct?
` MR. GALLUZZO: Objection, lacks
` foundation.
` A. Are you asking in reference to a
`particular agent?
` Q. In general.
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` J. McCracken, M.D.
` A. It has been observed that
`rapidly, yes, for nicotine, for example.
` Q. Acute tolerance can develop over
`the course of a day. Correct?
` MR. GALLUZZO: Objection to form
` of the question.
` A. In theory, it can be observed
`within the course of a day, depending on
`the agent.
` Q. Can the decline in efficacy due
`to acute tolerance of a drug vary from
`time to time after administration of the
`drug?
` MR. GALLUZZO: Objection to form
` of the question.
` A. If I understand your question, I
`would think the acute tolerance effect
`would be fairly reproducible and
`identifiable or predictable if studied
`sufficiently.
` Q. My question really was, during
`the course of a day, could the declining
`in efficacy, the amount of the decline of
`efficacy vary?
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` MR. GALLUZZO: Objection to form
` of the question.
` A. If I am understanding your
`question, I would say no.
` Q. What is the basis for that
`response?
` A. Again, acute tolerance would
`refer to the rapid loss or clinically --
`the development of a clinically
`significant decline in efficacy, in a
`biologic index that is more rapid than a
`simple clearance of a medication or its
`active moieties.
` Q. So, there is no degree of
`decline that is clinically significant,
`either all or none? Is that what you are
`saying?
` MR. GALLUZZO: Objection.
` Mischaracterizes testimony.
` A. No, that is not what I said at
`all. I referred to clinically meaningful
`declines in effect, and that would be
`something observable and identified by
`most observers, by a significant drop in
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` J. McCracken, M.D.
`typical measures of efficacy that meets a
`usual standard of loss of the drug effect.
` Q. Are there varying degrees of
`clinically meaningful declines in effect?
` MR. GALLUZZO: Objection to
` form.
` A. Would you like me to respond
`with respect to ADHD treatment?
` Q. Let's try that.
` A. Actually, the metric for
`determining a clinically meaningful change
`have been written about for quite a long
`time, and most of those definitions are
`relatively consistent related to change on
`the order of 25 to 35 percent as
`clinically meaningful.
` Q. So would 50 percent be
`clinically meaningful?
` A. Of course.
` MR. GALLUZZO: Objection to
` form.
` Q. Would 60 percent?
` MR. GALLUZZO: Same objection.
` A. Even more meaningful.
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` J. McCracken, M.D.
` Q. Would 75 percent?
` MR. GALLUZZO: Same objection.
` A. Indeed.
` Q. And would 90 percent?
` MR. GALLUZZO: Same objection.
` A. Well, I want to be sure that you
`are referring to the rapid loss of
`clinical effect.
` Q. I am referring to the percentage
`that you gave. You said 25 to 35 percent.
` A. Yes. So by definition, anything
`above that would be considered by most
`experts as clinically significant.
` Q. What is acute tolerance of
`amphetamine due to?
` MR. GALLUZZO: Objection to the
` form of the question.
` Mischaracterizes testimony and lacks
` foundation.
` A. I don't believe acute tolerance
`exists with respect to amphetamines in
`their typical and approved prescription
`for the treatment of ADHD. I don't
`believe that's ever been established in
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` J. McCracken, M.D.
`the literature.
` Q. And what approved prescription
`treatment are you referencing?
` A. Primarily acute tolerance has
`been invoked with regards to stimulants,
`but most -- mostly with respect to
`methylphenidate-containing products, less
`so amphetamine.
` Q. Did you ever prescribe Adderall
`IR to be administered twice daily about
`four hours apart?
` A. Yes. I still prescribe that at
`times.
` Q. To whom do you prescribe that?
` A. Patients, big and small.
` Q. Why four hours apart?
` A. Well, the Adderall's effect
`varies. And I should say I am not rigid
`in the way that I would prescribe Adderall
`immediate release. I certainly don't
`restrict it to a simple four-hour kind of
`one size fits all. That's not at all the
`way that I practice medicine.
` But some may take it that often.
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` J. McCracken, M.D.
`Usually, in fact, I don't find it
`necessary for it to be given that
`frequently, so a schedule of separating by
`six hours, eight hours would be equally
`common in the manner that I would
`prescribe it.
` In my 2003 study, I actually
`showed that a single dose of Adderall
`10 milligrams in the morning manifested
`efficacy as late as 10 and a half hours.
`So, therefore, many people don't need even
`a twice-daily dose of immediate-release
`amphetamine, which flies in the face of
`any claim of acute tolerance, I would say.
` Q. So, it's your position that the
`data on Adderall IR in your 2003 article
`demonstrated that Adderall IR showed no
`clinically significant evidence of acute
`tolerance issues?
` A. That is my interpretation, yes.
` Q. Okay.
` A. I think other data supports that
`quite substantially.
` Q. And it is your position that the
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` J. McCracken, M.D.
`data on Adderall XR in your article,
`McCracken 2003, Exhibit 1037, demonstrated
`Adderall XR showed no clinically
`significant evidence of acute tolerance
`issues?
` MR. GALLUZZO: Objection, lacks
` foundation.
` A. Correct. I find no evidence
`from that study, especially when paired
`with the McGough, et al. 2003
`pharmacokinetic data from the same
`clinical trial, that there is any
`indication of acute tolerance. Rather,
`our data shows that efficacy is determined
`primarily by the amount of amphetamine
`concentration at any given moment across a
`12-hour period.
` Q. So, in your clinical use of
`Adderall XR, if a patient had any
`significant decline in efficacy beyond 12
`hours, you would usually manage that with
`a later-day dose of amphetamine IR. Is
`that correct?
` MR. GALLUZZO: Objection to form
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` J. McCracken, M.D.
` of the question.
` A. I am sorry. Can you repeat your
`question, please.
` Q. In your clinical use of Adderall
`XR, if a patient had any significant
`decline in efficacy beyond 12 hours, would
`you usually manage that with a later-day
`dose of amphetamine IR?
` MR. GALLUZZO: Same objection.
` A. I am not sure I completely
`understand your question, but I would say
`that in a significant proportion of
`patients, perhaps 25 percent or so of
`those that I prescribe Adderall XR to, I
`do prescribe a supplement or a booster of
`IR, simply because I know from my own
`research that the clearance of the
`medication can vary profoundly from
`individual to individual.
` Some individuals are going to
`clear so much amphetamine by eight hours
`that they will lose a substantial amount
`of the efficacy and hence need to have the
`plasma level restored.
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` J. McCracken, M.D.
` Q. What percent of your patients to
`whom you prescribe Adderall XR need a
`booster, as you termed it, later in the
`day?
` A. About 25 percent is a rough
`estimate.
` Q. And you give those patients
`Adderall IR later in the day. Is that
`correct?
` A. Yes.
` Q. Why don't you give them
`Dexedrine Spansules later in the day?
` MR. GALLUZZO: Objection to form
` of the question.
` A. Well, it is a general practice
`that we try to -- well, one of the
`advantages of using IR is that you are
`using essentially the same active
`ingredient as is in the XR, of course, and
`that often works well. A Dexedrine
`Spansule given late in the day would hang
`around a long time and could well
`precipitate insomnia or cause too much
`late-day appetite suppression
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