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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01897571
Registration number
NCT01897571
Ethics application status
Date submitted
21/06/2013
Date registered
12/07/2013
Date last updated
26/03/2024
Titles & IDs
Public title
Study of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL
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Scientific title
An Open-Label, Multicenter, Phase 1/2 Study of Tazemetostat as a Single Agent in Subjects With Advanced Solid Tumors or With B-cell Lymphomas and Tazemetostat in Combination With Prednisolone in Subjects With Diffuse Large B Cell Lymphoma
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Secondary ID [1]
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2012-004083-21
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Secondary ID [2]
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E7438-G000-101
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
B-cell Lymphomas (Phase 1)
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Advanced Solid Tumors (Phase 1)
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Diffuse Large B-cell Lymphoma (Phase 2)
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Follicular Lymphoma (Phase 2)
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Transformed Follicular Lymphoma
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Primary Mediastinal Large B-Cell Lymphoma
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Condition category
Condition code
Cancer
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Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
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Cancer
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Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Tazemetostat
Treatment: Drugs - Prednisolone
Treatment: Drugs - Tazemetostat
Experimental: Phase 1 - Patients in the Phase 1 portion of the study.
Experimental: Phase 2 Group 1: Tazemetostat in R/R FL with Mutant EZH2 - Patients with R/R FL with mutant EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.
Experimental: Phase 2 Group 2: Tazemetostat in R/R FL with Wild-Type EZH2 - Patients with R/R FL with wild-type EZH2 treated with tazemetostat as a single agent in Phase 2 of the study.
Experimental: Phase 2 Group 3: Tazemetostat in R/R DLBCL - Patients with R/R DLBCL treated with tazemetostat as a single agent or tazemetostat in combination with prednisolone in Phase 2 of the study.
Treatment: Drugs: Tazemetostat
Patients who received 800 mg of tazemetostat, BID, administered in continuous 28-day cycles.
Treatment: Drugs: Prednisolone
Patients who received 40 mg/m^2 prednisolone once daily on Days 1-5 and 15-19 of Cycles 1-4.
Treatment: Drugs: Tazemetostat
Patients who received 100 mg to 1600 mg of tazemetostat, BID, administered in continuous 28-day cycles.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Recommended Phase 2 Dose (RP2D) of Tazemetostat as a Single-Agent and in Combination With Prednisolone (Phase 1 Only)
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Assessment method [1]
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Recommended Phase 2 dose (RP2D) of tazemetostat as administered orally twice daily (BID), continuously in 28-day cycles in subjects with advanced solid tumors or with relapsed and/or refractory B cell lymphomas as determined by incidence, seriousness, toxicity grade, and relatedness of treatment emergent dose limiting toxicities
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Timepoint [1]
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The first 28-day cycle of therapy
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Primary outcome [2]
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Objective Response Rate (ORR; Complete Response + Partial Response [CR + PR]) (Phase 2)
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Assessment method [2]
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Number of patients achieving an objective response (CR or PR)/number of patients treated x 100%. ORR was calculated as the percentage of patients with a confirmed complete response (CR) or partial response (PR) relative to the total number of patients in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
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Timepoint [2]
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Radiologic tumor assessments performed at baseline(within 28 days before start of study treatment)and every 8 weeks during Cycles 2 to 6,and then every 12 weeks thereafter until confirmed disease progression (PD)/death,a maximum of approximately 82 months
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Secondary outcome [1]
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Duration of Response for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)
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Assessment method [1]
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The time (in months) from the date of the initial response (CR or PR, whichever was first) until the date of the first documented disease progression per an Independent Review Committee (for Groups 1 and 2), per Investigator (Group 3), or death due to any cause. Patients who were alive and progression free at the time of the analysis were censored at the last date where the patient was known to be in response. Note: the DOR was censored, meaning data collection was stopped early for analysis, making the top limit of the 95% confidence interval not estimable (NE). Per RECIST v.1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
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Timepoint [1]
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Radiologic tumor assessments performed at baseline (within 28 days before start of study treatment) and every 8 weeks during Cycles 2 to 6, and then every 12 weeks thereafter until confirmed PD/death, a maximum of approximately 82 months
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Secondary outcome [2]
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Progression Free Survival for Tazemetostat as a Single Agent or in Combination With Prednisolone (Phase 2 Only)
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Assessment method [2]
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The time (in months) from the date of first dose of tazemetostat until the earliest date of disease progression or death from any cause. Per RECIST v1.0, CR was defined as disappearance of all target and non-target lesions and any pathological lymph nodes must be <10 mm in the short axis. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
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Timepoint [2]
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Radiologic tumor assessments performed at baseline (within 28 days before start of study treatment) and every 8 weeks during Cycles 2 to 6, and then every 12 weeks thereafter until confirmed PD/death, a maximum of approximately 82 months
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Eligibility
Key inclusion criteria
1. Phase 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Phase
2: ECOG performance status of 0 to 2.
2. Life expectancy of at least 3 months before starting tazemetostat.
3. Voluntary agreement to provide written informed consent and willing to adhere to all
protocol requirements
4. Subjects with Hepatitis B or C are eligible on the condition that subjects have
adequate liver function and are hepatitis B surface antigen negative and/or have
undetectable hepatitis C virus (HCV) RNA.
5. Adequate renal and liver function
6. Phase 1: Males or females aged = 16 years at time of informed consent. Phase 2: Males
or females aged = 18 years at the time of informed consent .
7. Females must not be lactating or pregnant at screening or baseline as documented by a
negative pregnancy test All females will be considered to be of childbearing potential
unless they are postmenopausal (at least 12 months consecutive amenorrheic, in the
appropriate age group, and without other known or suspected cause) or have been
sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral
oophorectomy, all with surgery at least 1 month before dose). Females of childbearing
potential must not have had unprotected sexual intercourse within 30 days prior to
study entry and must agree to use a highly effective method of contraception, from the
last menstrual period prior to randomization, during Treatment Cycles, and for 6
months after the last final dose of study drug; any male partner must use a condom.
8. Male subjects must have had a successful vasectomy (with confirmed azoospermia) or
they and their female partner must meet the criteria above (ie, not of childbearing
potential or practicing highly effective contraception and use a condom throughout the
study period and for 3 months after study drug discontinuation). Nonvasectomized male
subjects must also agree to refrain from donating sperm from first dose of
tazemetostat until 3 months following the last dose of tazemetostat
9. Phase 1 only: Histologically and/or cytologically confirmed advanced or metastatic
solid tumor or B-cell lymphomas that have progressed after treatment with approved
therapies or for which there are no standard therapies available.
10. Phase 2, Groups 1-6 only: Subjects must satisfy all of the following criteria:
1. Have histologically confirmed DLBCL (including primary mediastinal B-cell
lymphoma), with relapsed or refractory disease following at least 2 lines of
prior standard therapy, including alkylator/anthracycline (unless
anthracycline-based chemotherapy is contraindicated)/anti-CD20-based therapy
(rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone
[R-CHOP] or equivalent) AND must be considered unable to benefit from
intensification treatment with autologous hematopoietic stem cell transplantation
(ASCT) as defined by meeting at least 1 of the following criteria:
- Relapsed following, or refractory to, previous ASCT
- Did not achieve at least a partial response to a standard salvage regimen
(eg, rituximab, ifosfamide, carboplatin, and etoposide phosphate [R-ICE] or
rituximab, dexamethasone, cytarabine, and cisplatin [R-DHAP])
- Ineligible for intensification treatment due to age or significant
comorbidity
- Ineligible for intensification treatment due to failure to mobilize an
acceptable number of hematopoietic stem cells
- Refused intensification treatment and/or ASCT or
2. Have histologically confirmed Follicular Lymphoma (FL), all grades. Subjects may
have relapsed/refractory disease following at least 2 standard prior systemic
treatment regimens where at least 1 anti-CD20-based regimen was used. Subjects
with prior radiotherapy will be included; however, radiotherapy alone will not be
considered a systemic treatment regimen.
3. Have provided sufficient archival tumor tissue that has been successfully tested
for EZH2 mutation status and cell of origin (DLBCL only)
4. Have measurable disease as defined by International Working Group-Non-Hodgkin's
Lymphoma (IWG-NHL)
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Minimum age
16
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Prior exposure to tazemetostat or other inhibitor(s) of EZH2.
2. Subjects with leptomeningeal metastases or brain metastases or history of previously
treated brain metastases.
3. Has thrombocytopenia, neutropenia, or anemia of Grade =3 (per CTCAE 4.03 criteria) and
any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS).
4. Has a prior history of T-cell lymphoblastic lymphoma(T-LBL) or T-cell lymphoblastic
leukemia (T-ALL).
5. Subjects taking medications that are known strong CYP3A inhibitors and strong or
moderate CYP3A inducers (including St. Johns Wort) 6. Subjects unwilling to remove
Seville oranges, grapefruit juice and grapefruit from their diet.
6. Any unstable or unresolved prior treatment-related (i.e. chemotherapy, immunotherapy,
radiotherapy) toxicities at time of enrollment.
7. Major surgery within 4 weeks before the first dose of study drug. .
8. Inability to take oral medication, or malabsorption syndrome or any other uncontrolled
gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the
bioavailability of tazemetostat.
9. Significant cardiovascular impairment: history of congestive heart failure greater
than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension,
unstable angina, myocardial infarction, or stroke within 6 months of the first dose of
study drug; or cardiac ventricular arrhythmia.
10. Venous thrombosis or pulmonary embolism within the last 3 months before starting
tazemetostat.
11. Active infection requiring systemic therapy.
12. Immunocompromised patients, including patients known to be infected with human
immunodeficiency virus (HIV).
13. Any other major illness that, in the investigator's judgment, will substantially
increase the risk associated with the subject's participation in this study.
14. Females who are pregnant or breastfeeding.
15. Phase 2 only: Subjects with noncutaneous malignancies other than B-cell lymphomas.
Exception: Subjects with another malignancy who have been disease-free for 5 years, or
subjects with a history of a completely resected non-melanoma skin cancer or
successfully treated in situ carcinoma are eligible.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
13/06/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
2/11/2021
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Sample size
Target
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Accrual to date
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Final
400
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Recruitment in Australia
Recruitment state(s)
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- Clayton
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- Geelong
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- Melbourne
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- Clayton
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- Geelong
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Recruitment postcode(s) [3]
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- Melbourne
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Recruitment outside Australia
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Alabama
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California
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Colorado
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District of Columbia
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Toronto
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Nantes
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Paris
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France
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Pierre Benite
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Rennes
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Gottingen
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Uzhgorod
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Zhytomyr
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Glasgow
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Manchester
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Southampton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Epizyme, Inc.
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Ethics approval
Ethics application status
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Summary
Brief summary
This is an open-label, multicenter, Phase 1/2 study of tazemetostat as a single agent in
subjects with advanced solid tumors or with B-cell lymphomas and tazemetostat in combination
with prednisolone in subjects with diffuse large B-cell lymphoma (DLBCL).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01897571
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
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Ipsen Medical Director
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Ipsen
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01897571
Download to PDF