8/27/2016
`
`RADO01 Therapy of Angiomyolipomata in Patients With TS Complex and Sporadic LAM - Full Text \fiew - C|inica|Tria|s.gov
`
`Clin icalTrials.gov
`A service of the U.S. National Institutes of Health
`
`Trial record 1 of 1 for: NCTOO457964
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`RAD001 Therapy of Angiomyolipomata in Patients With TS Complex and Sporadic LAM
`
`This study has been completed.
`
`Sponsor:
`Children's Hospital Medical Center, Cincinnati
`
`c°"ab°"at°"’
`Novartis Pharmaceuticals
`Information provided by (Responsible Party):
`Children's Hospital Medical Center, Cincinnati
`
`C|inicaITrials.gov Identifier:
`NCTO0457964
`
`First received: April 6. 2007
`Last updated: September 23, 2013
`Last verified: September 2013
`History of Changes
`
`Full Text View
`
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`
`No Study Results Posted
`
`Disclaimer
`
`How to Read a Study Record
`
`P Purpose
`
`The purpose of this research study is to find out what effects RAD001 has on angiomyolipomas of a person with Tuberous Sclerosis Complex
`and to determine the safe dose of RAD001 without toxicity.
`The hypothesis is that the drug will inhibit the growth of the angiomyolipomas and possibly even cause regression.
`
`Tuberous Sclerosis
`Lymphangioleiomyomatosis
`
`Drug: RADO01
`
`Interventional
`Study Type:
`Study Design: Endpoint Classification: Safety/Efficacy Study
`Intervention Model: Single Group Assignment
`Masking: Open Label
`Primary Purpose: Treatment
`
`Official Title:
`
`RAD001 Therapy of Angiomyolipomata in Patients With Tuberous Sclerosis Complex and Sporadic Lymphangioleiomyomatosis
`
`Resource links provided by NLM:
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`Further study details as provided by Children's Hospital Medical Center, Cincinnati:
`
`Primary Outcome Measures:
`- Patients will be considered responders if their angiomyolipoma volume decreases by thirty percent or more from baseline [Time Frame: 12
`months] [ Designated as safety issue: No]
`
`Enrollment:
`Study Start Date:
`
`36
`August 2005
`
`https://clinicaltrials.gov/ct2Ishow/N CT00457964?term= NCT00457964&rank=1
`
`Par Pharm., Inc.
`Exhibit 1096
`
`Par Pharm., Inc. v. Novartis AG
`Case lPR2016-00084
`
`Ex. 1096-0001
`
`

`
`RADO01 Therapy of Angiomyolipomata in Patients With TS Complex and Sporadic LAM - Full Text \fiew - C|inica|Tria|s.gov
`8/27/2016
`Study Completion Date:
`July 2013
`Primary Completion Date:
`July 2013 (Final data collection date for primary outcome measure)
`
`Experimental: Administration of RAD001
`
`Detailed Description:
`
`A§_§i.£.|_!!.§?_‘.!.__'__F!S§.!__‘.'__‘E_F‘t'.‘_?.'.‘___5_.
`
`Drug: RAD001
`5 and 10 mg/day or 30, 50, 70mg/week
`
`Tuberous sclerosis complex is a genetic disorder with a birth incidence of approximately one in six thousand. Angiomyolipomas occur in eighty
`percent of persons with TS, and in up to 60% of persons with LAM. They are fatty tumors that often occur in kidney or liver as well as other parts
`of the body. They can grow and cause damage to surrounding kidney tissue and even renal failure. They may also leak blood causing potentially
`life-threatening hemorrhage.
`Laboratory studies have shown that RAD001 suppresses the chemical that cause tumors to grow in tuberous sclerosis and sporadic LAM.
`
`The primary goal of this study is to evaluate the clinical effectiveness of RAD001 in a 24 month trial. Although the primary goal is to determine if
`the drug RAD001 has effects on angiomyolipomas, other diseases associated with tuberous sclerosis will be monitored too, specifically any
`change in involvement of your brain or lungs with tuberous sclerosis. The use of RAD001 to treat angiomyolipomas in tuberous sclerosis or
`sporadic LAM is considered experimental
`
`F Eligibility
`
`Ages Eligible for Study:
`Genders Eligible for Study:
`Accepts Healthy Volunteers:
`Criteria
`
`Inclusion Criteria:
`
`18 Years to 65 Years
`Both
`No
`
`(Adult)
`
`- Diagnosed with angiomyolipomas and have either Tuberous Sclerosis Complex or lymphangioleiomyomatosis
`- Angiomyolipoma one centimeter or greater in largest diameter
`- Between the ages of 18 and 65 years old.
`-
`If female, documentation of negative pregnancy test prior to enrollment and, where applicable, use of appropriate non-estrogen containing
`birth control contraceptive regimen while on study.
`- Adequate renal function (creatinine < 3 mg/dl)
`Exclusion Criteria:
`
`- Pregnant or lactating women
`- Continuous requirement for supplemental oxygen
`- Surgery within past 2 months
`- Use of an investigational drug within last 30 days.
`
`F Contacts and Locations
`
`Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a
`study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general
`information, see Learn About Clinical Studies.
`
`Please refer to this study by its C|inica|Tria|s.gov identifier: NCT00457964
`
`Locations
`
`United States, Ohio
`
`Cincinnati Children's Hospital Medical Center
`Cincinnati, Ohio, United States, 45229
`
`Sponsors and Collaborators
`
`Children's Hospital Medical Center, Cincinnati
`Novartis Pharmaceuticals
`
`Investigators
`Principal Investigator:
`
`John J. Bissler, M.D. LaBonheur Children's Hospital
`
`https://clinicaltrials.gov/ct2Ishow/N CT00457964?term= NCT00457964&rank=1
`
`2/3
`
`Ex. 1096-0002
`
`Ex. 1096-0002
`
`

`
`8/27/2016
`
`RAD001 Therapy of Angiomyolipomata in Patients With TS Complex and Sporadic LAM - Full Text \fiew - C|inica|Tria|s.gov
`
`F More Information
`
`Responsible Party:
`cnnicaITriaIs.gov Identifier:
`Other Study ID Numbers:
`Study First Received:
`Last Updated:
`Health Authority:
`
`Children's Hospital Medical Center, Cincinnati
`
`CCHMC IRB #2008-O812(O4-07-22)
`April 6, 2007
`September 23, 2013
`United States: Food and Drug Administration
`
`Keywords provided by Children's Hospital Medical Center, Cincinnati:
`Tuberous Sclerosis Complex (TSC)
`Lymyphangioleiomyomatosis
`Mammalian Target of Rapamycin (mTOR)
`RADO01
`Angiomyolipmas
`
`Additional relevant MeSH terms:
`Sclerosis
`Tuberous Sclerosis
`Lymphangioleiomyomatosis
`Angiomyolipoma
`Pathologic Processes
`Hamartoma
`Neoplasms
`Neoplasms, Multiple Primary
`Neoplastic Syndromes, Hereditary
`Malformations of Cortical Development, Group I
`Malformations of Cortical Development
`Nervous System Malformations
`Nervous System Diseases
`Neurocutaneous Syndromes
`Heredodegenerative Disorders, Nervous System
`
`C|inica|Tria|s.gov processed this record on August 25, 2016
`
`Neurodegenerative Diseases
`Congenital Abnormalities
`Genetic Diseases, lnborn
`Lymphangiomyoma
`Lymphatic Vessel Tumors
`Neoplasms by Histologic Type
`Perivascular Epithelioid Cell Neoplasms
`Neoplasms, Connective and Soft Tissue
`Lymphoproliferative Disorders
`Lymphatic Diseases
`lmmunoproliferative Disorders
`Immune System Diseases
`Neoplasms, Adipose Tissue
`Everolimus
`Sirolimus
`
`https://clinicaltrials.gov/ct2Ishow/N CT00457964?term= NCT00457964&rank=1
`
`3/3
`
`Ex. 1096-0003
`
`Ex. 1096-0003