Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non gBRCAm Ovarian Cancer Patients
OPINION
A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed Non-Germline BRCA Mutated Ovarian Cancer Patients Who Are in Complete or Partial Response Following Platinum Based Chemotherapy
2 other identifiers
interventional
279
19 countries
91
Brief Summary
The purpose of the study is to assess the efficacy and safety of single-agent olaparib as a maintenance treatment in patients with relapsed High Grade Serous Ovarian Cancer (including patients with primary peritoneal and/or fallopian tube cancer) or high grade endometrioid cancer who do not have known deleterious or suspected deleterious germline BRCA mutations (non-gBRCAm) and who had responded following platinum based chemotherapy
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2018
Typical duration for phase_3
91 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 3, 2018
CompletedFirst Posted
Study publicly available on registry
January 18, 2018
CompletedStudy Start
First participant enrolled
January 30, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 2, 2020
CompletedResults Posted
Study results publicly available
October 11, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 10, 2022
CompletedAugust 21, 2024
July 1, 2024
2.7 years
January 3, 2018
September 14, 2021
July 25, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
PFS is defined as the time from date of first dose until the date of objective radiological disease progression. Assessed according to modified Response Evaluation Criteria In Solid Tumours Version 1.1 (RECIST 1.1) or death (by any cause in the absence of progression). Progression was determined by investigator assessment, RECIST 1.1. Calculated using the Kaplan-Meier technique. Confidence intervals (CI) for median PFS was derived based on Brookmeyer-Crowley method.
Up to maximum of 32 months
Secondary Outcomes (7)
Time to First Subsequent Therapy or Death (TFST)
Up to a maximum of 43 months
Time to Treatment Discontinuation or Death (TDT)
Up to a maximum of 43 months
PFS by Homologous Recombination Deficiency (HRD)/ Breast Cancer Susceptibility Gene Mutation (Mutated) (BRCAm) Status
Up to maximum of 32 months
Chemotherapy-free Interval (CT-FI)
Up to a maximum of 43 months
Overall Survival (OS)
Up to a maximum of 43 months
- +2 more secondary outcomes
Study Arms (1)
Olaparib
EXPERIMENTALOlaparib will be supplied as film-coated tablets containing 150 mg or 100 mg of olaparib. Patients will be administered olaparib orally twice daily (bid) at 300 mg.
Interventions
Eligibility Criteria
You may qualify if:
- Female patients with histologically diagnosed relapsed HGSOC (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid ovarian cancer
- Documented gBRCA1/2 mutation status
- Patients must have completed at least 2 previous courses of platinum containing therapy
- Patients must have normal organ and bone marrow function measured within 28 days of starting study treatment
- ECOG performance status 0-1 (see Appendix E)
- Patients must have a life expectancy ≥16 weeks
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1
- At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment OR No evidence of disease following a complete response to chemotherapy
- An appropriately prepared tumour sample from the cancer, of sufficient quantity and quality (as specified in the Central Laboratory Services Manual) must be available for future central testing of tumour genetic status
You may not qualify if:
- Patients receiving any systemic hormonal therapy, chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to start of study treatment
- Any previous treatment with PARP inhibitor, including olaparib
- Patients with a germline BRCA mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function)
- Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
- Concomitant use of known strong CYP3A inhibitors and strong (or moderate CYP3A inducers
- Persistent toxicities (≥ Grade 2 Common Terminology Criteria for Adverse Event (CTCAE) adverse event) caused by previous cancer therapy, excluding alopecia
- Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML
- Patients with symptomatic uncontrolled brain metastases
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Iqvia Pty Ltdcollaborator
- Myriad Genetics, Inc.collaborator
- Covancecollaborator
- Theradexcollaborator
- Parexelcollaborator
Study Sites (91)
Research Site
Graz, 8036, Austria
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Innsbruck, 6020, Austria
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Vienna, 1090, Austria
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Wein, 1130, Austria
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Brussels, 1200, Belgium
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Leuven, 3000, Belgium
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Loverval, 6280, Belgium
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Namur, 5000, Belgium
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Wilrijk, 2610, Belgium
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Plovdiv, 4000, Bulgaria
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Plovdiv, 4004, Bulgaria
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Sofia, 1330, Bulgaria
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Victoria, British Columbia, V8R 6V5, Canada
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London, Ontario, N6A 5W9, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M5G2M9, Canada
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Montreal, Quebec, H2X 0A9, Canada
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Sherbrooke, Quebec, J1H 5N4, Canada
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Brno, 625 00, Czechia
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Nový Jičín, 74101, Czechia
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Olomouc, 775 20, Czechia
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Ostrava, 708 52, Czechia
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Prague, 128 08, Czechia
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Aalborg, 9100, Denmark
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Aarhus, 8200, Denmark
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Kuopio, 70210, Finland
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Oulu, 90029, Finland
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Tampere, 33520, Finland
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Afula, 18101, Israel
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Beersheba, Israel
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Haifa, 91096, Israel
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Jerusalem, 91031, Israel
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Kfar Saba, 4428164, Israel
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Ramat Gan, 52621, Israel
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Ancona, 60020, Italy
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Brescia, 25123, Italy
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Lecco, 23900, Italy
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Milan, 20141, Italy
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Padua, 35128, Italy
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Torino, 10126, Italy
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Torino, 10128, Italy
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Breda, 4818 CK, Netherlands
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Tilburg, 5022 GC, Netherlands
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Bergen, 5053, Norway
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Oslo, 424, Norway
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Gdynia, 81-519, Poland
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Krakow, 31-501, Poland
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Lublin, 20-090, Poland
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Olsztyn, 10-513, Poland
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Poznan, 60-569, Poland
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Warsaw, 02-781, Poland
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Warsaw, 04-141, Poland
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Coimbra, 3000-073, Portugal
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Lisbon, 1400-048, Portugal
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Bucharest, 031422, Romania
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Cluj-Napoca, 400015, Romania
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Cluj-Napoca, 400058, Romania
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Ljubljana, 1000, Slovenia
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Badalona, 08916, Spain
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Barcelona, 08036, Spain
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Barcelona, 08041, Spain
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Barcelona, 8035, Spain
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Córdoba, 14004, Spain
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Girona, 17007, Spain
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Hospitalet deLlobregat, 08907, Spain
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Madrid, 28027, Spain
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Madrid, 28046, Spain
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Málaga, 29011, Spain
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Pamplona, 31008, Spain
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Seville, 41009, Spain
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Valencia, 46009, Spain
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Valencia, 46026, Spain
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Linköping, 581 85, Sweden
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Lund, 221 85, Sweden
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Basel, 4031, Switzerland
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Bellinzona, 6500, Switzerland
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Bern, 3010, Switzerland
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Frauenfeld, 8501, Switzerland
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Geneva, 1205, Switzerland
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Lausanne, 1011, Switzerland
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Zurich, 8091, Switzerland
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Aberdeen, AB25 2ZN, United Kingdom
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Colchester, CO4 5JL, United Kingdom
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Exeter, EX2 5DW, United Kingdom
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Leeds, LS9 7TF, United Kingdom
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Leicester, LE1 5WW, United Kingdom
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London, SE1 9RT, United Kingdom
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London, WC1N 3BG, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Northampton, NN1 5BD, United Kingdom
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Scarborough, YO12 6QL, United Kingdom
Related Publications (11)
Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. doi: 10.1056/NEJMoa0900212. Epub 2009 Jun 24.
PMID: 19553641BACKGROUNDRottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, Derksen PW, de Bruin M, Zevenhoven J, Lau A, Boulter R, Cranston A, O'Connor MJ, Martin NM, Borst P, Jonkers J. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17079-84. doi: 10.1073/pnas.0806092105. Epub 2008 Oct 29.
PMID: 18971340BACKGROUNDMurai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, Ji J, Takeda S, Pommier Y. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res. 2012 Nov 1;72(21):5588-99. doi: 10.1158/0008-5472.CAN-12-2753.
PMID: 23118055BACKGROUNDMirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Madry R, Christensen RD, Berek JS, Dorum A, Tinker AV, du Bois A, Gonzalez-Martin A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7.
PMID: 27717299BACKGROUNDHelleday T. The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol. 2011 Aug;5(4):387-93. doi: 10.1016/j.molonc.2011.07.001. Epub 2011 Jul 22.
PMID: 21821475BACKGROUNDHay T, Matthews JR, Pietzka L, Lau A, Cranston A, Nygren AO, Douglas-Jones A, Smith GC, Martin NM, O'Connor M, Clarke AR. Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin. Cancer Res. 2009 May 1;69(9):3850-5. doi: 10.1158/0008-5472.CAN-08-2388. Epub 2009 Apr 21.
PMID: 19383921BACKGROUNDLedermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, Matei D, Macpherson E, Watkins C, Carmichael J, Matulonis U. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012 Apr 12;366(15):1382-92. doi: 10.1056/NEJMoa1105535. Epub 2012 Mar 27.
PMID: 22452356BACKGROUNDPujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25.
PMID: 28754483BACKGROUNDBarnicle A, Ray-Coquard I, Rouleau E, Cadoo K, Simpkins F, Aghajanian C, Leary A, Poveda A, Lheureux S, Pujade-Lauraine E, You B, Ledermann J, Matulonis U, Gourley C, Timms KM, Lai Z, Hodgson DR, Elks CE, Dearden S, Egile C, Lao-Sirieix P, Harrington EA, Brown JS. Patterns of genomic instability in > 2000 patients with ovarian cancer across six clinical trials evaluating olaparib. Genome Med. 2024 Dec 18;16(1):145. doi: 10.1186/s13073-024-01413-5.
PMID: 39695768DERIVEDPoveda A, Lheureux S, Colombo N, Cibula D, Lindemann K, Weberpals J, Bjurberg M, Oaknin A, Sikorska M, Gonzalez-Martin A, Madry R, Perez MJR, Ledermann J, Davidson R, Blakeley C, Bennett J, Barnicle A, Skof E. Olaparib maintenance monotherapy in platinum-sensitive relapsed ovarian cancer patients without a germline BRCA1/BRCA2 mutation: OPINION primary analysis. Gynecol Oncol. 2022 Mar;164(3):498-504. doi: 10.1016/j.ygyno.2021.12.025. Epub 2022 Jan 19.
PMID: 35063276DERIVEDPoveda AM, Davidson R, Blakeley C, Milner A. Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design. Future Oncol. 2019 Nov;15(32):3651-3663. doi: 10.2217/fon-2019-0343. Epub 2019 Sep 25.
PMID: 31553234DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- STUDY DIRECTOR
Chris Wilks
AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Masking Details
- Open
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 3, 2018
First Posted
January 18, 2018
Study Start
January 30, 2018
Primary Completion
October 2, 2020
Study Completion
March 10, 2022
Last Updated
August 21, 2024
Results First Posted
October 11, 2021
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.