A Study of Sapanisertib, Combination of Sapanisertib With MLN1117, Paclitaxel and Combination of Sapanisertib With Paclitaxel in Women With Endometrial Cancer

A Phase 2, Randomized Study of MLN0128 (a Dual TORC1/2 Inhibitor), MLN0128+MLN1117 (a PI3Kα Inhibitor), Weekly Paclitaxel, or the Combination of Weekly Paclitaxel and MLN0128 in Women With Advanced, Recurrent, or Persistent Endometrial Cancer

The primary purpose of this study is to determine if sapanisertib in combination with weekly paclitaxel improves progression-free survival (PFS) compared to weekly paclitaxel alone.

Study Overview

• Status: Completed
• Conditions: Endometrial Neoplasms
• Intervention / Treatment: Drug: MLN1117; Drug: Paclitaxel; Drug: Sapanisertib

Detailed Description

The drugs being evaluated in this study are sapanisertib and MLN1117. Sapanisertib is being evaluated as a single agent and in combination with paclitaxel or MLN1117 to treat women with advanced, recurrent, or persistent endometrial cancer. This study will evaluate the efficacy and safety of each drug or drug combination.

The study will enroll approximately 241 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of 4 treatment groups:

• Paclitaxel 80 mg/m^2
• Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
• Sapanisertib 30 mg
• Sapanisertib 4 mg + MLN1117 200 mg

Participants will receive either paclitaxel intravenous (IV) weekly, Paclitaxel IV along with sapanisertib orally, sapanisertib orally, or sapanisertib and MLN1117 orally.

This is a multicenter, multinational trial. Participants will make multiple visits to the clinic, with an end of treatment visit (EOT) which will occur 30 to 40 days after receiving their last dose of study drug or before the start of any subsequent anticancer therapy. After EOT, participants will be followed for PFS and overall survival (OS).

• Study Type: Interventional
• Enrollment (Actual): 241
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre Clayton
    • Footscray, Victoria, Australia, 3011
      • Sunshine Hospital
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital Malvern
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre-East Melbourne
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liege, Belgium, 4000
    • Centre Hospitalier Universitaire de Liège Site Sart Tilman
  • Wilrijk, Belgium, 2610
    • GasthuisZusters Antwerpen Sint-Augustinus
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • UZ Antwerpen
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Clinic
    • London, Ontario, Canada, N6A 4L6
      • LHSC - Victoria Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network - Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM Hopital Notre-Dame
• Germany
  • Berlin, Germany, 13353
    • Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
  • Mecklenburg Vorpommern
    • Greifswald, Mecklenburg Vorpommern, Germany, 17489
      • Universitaetsmedizin Greifswald
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Schleswig Holstein
    • Luebeck, Schleswig Holstein, Germany, 23538
      • Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
• Italy
  • Brescia, Italy, 25123
    • Spedali Civili di Brescia
  • Genova, Italy, 16128
    • Ente Ospedaliero Ospedali Galliera
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milano, Italy, 20141
    • Ieo Istituto Europeo Di Oncologia
  • Napoli, Italy, 80131
    • Istituto Tumori Napoli Fondazione G. Pascale
  • Ravenna, Italy, 48121
    • Azienda Unita Sanitaria Locale di Ravenna
  • Roma, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 00144
    • Istituto Nationale Tumori Regina Elena
  • Roma, Italy, 00161
    • Universita degli Studi di Roma "La Sapienza" - Umberto I Policlinico di Roma
  • Forli - Cesena
    • Meldola, Forli - Cesena, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
• Netherlands
  • Groningen, Netherlands, 9700 RB
    • Universitair Medisch Centrum Groningen
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht Universitair Medisch Centrum
  • Noord-holland
    • Amsterdam, Noord-holland, Netherlands, 1105 AZ
      • Academisch Medisch Centrum
  • Zuid-holland
    • Rotterdam, Zuid-holland, Netherlands, 3015 GD
      • Erasmus Medisch Centrum Daniel Den Hoed
• Norway
  • Bergen, Norway, 5021
    • Haukeland universitetssykehus, Kvinneklinikken
  • Oslo, Norway, 0310
    • Radiumhospitalet
  • Stavanger, Norway, 4011
    • Stavanger University Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain, 28050
    • Centro Integral Oncológico Clara Campal
  • Madrid, Spain, 28033
    • MD Anderson Cancer Centre
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia IVO
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Avon
    • Bristol, Avon, United Kingdom, BS2 8ED
      • Bristol Haematology and Oncology Centre
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital (Wonford)
  • Greater London
    • London, Greater London, United Kingdom, W12 0HS
      • Hammersmith Hospital
    • London, Greater London, United Kingdom, NW1 2BU
      • University College London Hospitals
    • London, Greater London, United Kingdom, SW3 6JJ
      • Royal Marsden Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • The Christie
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama Comprehensive Cancer Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • University of Arizona Cancer Center
  • California
    • Greenbrae, California, United States, 94904
      • Marin Cancer Care
    • La Jolla, California, United States, 92093-1503
      • University of California San Diego Medical Center
    • San Francisco, California, United States, 94115
      • University of California at San Francisco (PARENT)
    • Stanford, California, United States, 94305
      • Stanford School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612-9416
      • H. Lee Moffitt Cancer Center and Research Institute, Inc
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan St. Francis Health
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center Research Institute, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center Clinic
    • New York, New York, United States, 10065-6094
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center Cancer Center at Magee-Womens Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Histologic or cytologic diagnosis of endometrial carcinoma (including endometrioid, serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma).
2. Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy or established treatments.
3. At least 1 prior platinum-based chemotherapeutic regimen, but not more than 2 prior chemotherapeutic regimens, for management of endometrial carcinoma. Prior treatment may include chemotherapy, chemotherapy/radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitized therapy will be considered a systemic chemotherapy regimen.
4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be greater than or equal to (>=) 10 millimeter (mm) in long axis when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam. Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI.
5. Tumor accessible and participant consents to undergo fresh tumor biopsies.
6. Female participants 18 years or older.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

8. Female participants who:

   • Are postmenopausal for at least 1 year before the screening visit, OR
   • Are surgically sterile, OR
   • If they are of childbearing potential, agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labeling [example, United States Prescribing Information (USPI), Summary of Product Characteristics (SmPC), etc.]) after the last dose of study drug, OR
   • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

9. Clinical laboratory values as specified below within 4 weeks before the first dose of study drug:

   • Bone marrow reserve consistent with absolute neutrophil count (ANC) >= 1500 per micro liter (/mcL); platelet count >= 100,000/mcL; hemoglobin A1c (HbA1c) less than (<) 6.5 percent (%).
   • Total bilirubin must be less than or equal to (<=) 1.5 * the upper limit of normal (ULN).
   • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be <= 2.5 * the upper limit of the normal range. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of metastatic disease in liver.
   • Creatinine clearance >= 50 milliliter per minute per 1.73 square meter (mL/min/1.73 m^2) based either on Cockcroft-Gault estimate or based on a 12- or 24-hour urine collection.
   • Fasting serum glucose < 130 milligram per deciliter (mg/dL) and fasting triglycerides <= 300 mg/dL.
10. Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
11. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

Exclusion Criteria:

1. Positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug. Women who are lactating and breastfeeding are not eligible.
2. Previous treatment with any weekly taxane regimen.
3. History of severe hypersensitivity reactions to paclitaxel or any of its excipients.
4. Previous treatment with phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (AKT), dual PI3K/ mammalian (or mechanistic) target of rapamycin (mTOR) inhibitors, target of rapamycin complex 1/2 (TORC1/2) inhibitors or TORC1 inhibitors.
5. Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids (either intravenous [IV] or oral steroids, excluding inhalers) within 1 week before administration of the first dose of study drug (participants already receiving erythropoietin on a chronic basis for >=4 weeks are eligible).
6. Participants who are taking proton pump inhibitors (PPIs) within 7 days of the first dose of study drug or who require treatment with PPIs throughout the trial or those who are taking H2 receptor antagonists within 24 hours of the first dose of study drug.
7. A prothrombin time (PT) or activated partial thromboplastin time (aPTT) above the ULN or a history of a coagulopathy or bleeding disorder.
8. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
9. Sensory or motor neuropathy >= Grade 2.
10. Central nervous system (CNS) metastasis, endometrial leiomyosarcoma, or endometrial stromal sarcoma.
11. Manifestations of malabsorption due to prior gastrointestinal surgery, gastrointestinal disease, or for some other reason that may alter the absorption of sapanisertib or MLN1117. In addition, participants with enteric stomata are also excluded.
12. Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection, or any other condition that could compromise participation of the participant in the study.
13. Known human immunodeficiency virus infection.

14. History of any of the following within the last 6 months before administration of the first dose of study drug:

    • Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures.
    • Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures.
    • Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
    • Placement of a pacemaker for control of rhythm.
    • New York Heart Association Class III or IV heart failure.
    • Pulmonary embolism.

15. Significant active cardiovascular or pulmonary disease before administration of the first dose of study drug, including:

    • Uncontrolled hypertension (that is, either systolic blood pressure > 180 millimeter of mercury [mm Hg] or diastolic blood pressure > 95 mm Hg).
    • Pulmonary hypertension.
    • Uncontrolled asthma or oxygen saturation < 90% by arterial blood gas analysis or pulse oximetry on room air.
    • Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention; or history of valve replacement.
    • Medically significant (symptomatic) bradycardia.
    • History of arrhythmia requiring an implantable cardiac defibrillator.
    • Baseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval > 480 millisecond [ms], or history of congenital long QT syndrome, or torsades de pointes).
16. Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
17. Participants with endometrioid histology and histologically confirmed expression of estrogen receptors (ER) and/or progesterone receptors (PgR) who have not received prior endocrine therapy and for whom endocrine therapy is currently indicated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paclitaxel 80 mg/m^2; Paclitaxel 80 milligrams per square meter (mg/m^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).	Drug: Paclitaxel; Paclitaxel intravenous solution.
Experimental: Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg; Paclitaxel 80 mg/m^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).	Drug: Paclitaxel; Paclitaxel intravenous solution.; Drug: Sapanisertib; Sapanisertib capsules.; Other Names: INK128; MLN0128; TAK-228
Experimental: Sapanisertib 30 mg; Sapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).	Drug: Sapanisertib; Sapanisertib capsules.; Other Names: INK128; MLN0128; TAK-228
Experimental: Sapanisertib 4 mg + MLN1117 200 mg; Sapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).	Drug: MLN1117; MLN1117 capsules.; Other Names: TAK-117; INK1117; Drug: Sapanisertib; Sapanisertib capsules.; Other Names: INK128; MLN0128; TAK-228

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Up to approximately 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)	An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.	From the first dose of study drug through 30 days after the last dose of study drug (Up to approximately 54 months)
Overall Survival (OS)	OS is defined as the time in months from the date of randomization to the date of death.	Up to approximately 54 months
Time to Tumor Progression (TTP)	TTP is defined as the time in months from the date of randomization to the date of first documentation of progression. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Up to 30 months
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieved a best response of a complete response (CR) or partial response (PR). Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.	Up to 30 months
Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with CR or PR or SD (SD of any duration). Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Up to 30 months
Clinical Benefit Rate (CBR) at Week 16 (CBR-16)	CBR-16 is defined as the percentage of participants who achieved CR or PR of any duration or have SD with a duration of at least 16 weeks. Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.	Week 16

Collaborators and Investigators

• Sponsor: Millennium Pharmaceuticals, Inc.
• Collaborators: European Network of Translational Research in Ovarian Cancer - EUTROC; European Network of Individualized Treatment in Endometrial Cancer - ENITEC

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): July 2, 2019
• Study Completion (Actual): October 30, 2020

Study Registration Dates

• First Submitted: March 28, 2016
• First Submitted That Met QC Criteria: March 28, 2016
• First Posted (Estimate): March 31, 2016

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Serabelisib
• Other Study ID Numbers: C31004; U1111-1168-1824 (Other Identifier: WHO); 2014-005394-37 (EudraCT Number); 02725268 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No