Faslodex in McCune-Albright Syndrome (FMAS)

An Open-label, Non-Comparative Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Faslodex (Fulvestrant) in Girls With Progressive Precocious Puberty Associated With McCune-Albright Syndrome

The purpose of this study is to evaluate the safety, effectiveness and pharmacokinetics of a study drug called Faslodex (fulvestrant) in the treatment of progressive precocious puberty (PPP) (early puberty) in girls with McCune-Albright syndrome (MAS)

Study Overview

• Status: Completed
• Conditions: Puberty, Precocious; McCune-Albright Syndrome
• Intervention / Treatment: Drug: Fulvestrant

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33000
    • Research Site
  • Bron, France, 69677
    • Research Site
  • Paris Cedex 12, France, 75571
    • Research Site
• Germany
  • Erlangen, Germany, 91054
    • Research Site
  • Osnabrück, Germany, 49082
    • Research Site
• Italy
  • Torino, Italy, 10126
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 117036
    • Research Site
• United Kingdom
  • Liverpool, United Kingdom, L12 2AP
    • Research Site
  • London, United Kingdom, WC1N 3JH
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Research Site
  • Florida
    • Miami, Florida, United States, 33136
      • Research Site
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • Research Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Research Site
  • New York
    • Bronx, New York, United States, 10467
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females less than or equal to 10 years of age (prior to 11th birthday)
• Diagnosis of MAS
• PPP associated with MAS

Exclusion Criteria:

• Received any prior treatment for PPP associated with MAS with fulvestrant
• Abnormal platelet count or liver function tests
• Bleeding disorders
• Long term anticoagulation therapy
• Known hypersensitivity to any component of the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Fulvestrant; Participants will receive intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants will be dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants will be dosed at 4 mg/kg) into the buttock or thigh monthly for 12 months or until the participant demonstrates lack of efficacy based upon one or more of the primary endpoints or experiences a serious drug-related toxicity requiring treatment discontinuation.

Drug: Fulvestrant; Participants will receive intramuscular injection of fulvestrant as stated in arm description.; Other Names: Faslodex; ZD9238

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline	Vaginal bleeding days are defined as the number of days in which vaginal bleeding, (including spotting) occurred. In order to annualize, a 12-month period is defined as 360 days and a 6-month period is defined as 180 days. Frequency of annualized vaginal bleeding days = [(number of vaginal bleeding days)/(total number of days of the time interval under consideration)] multiplied by 360. Change in frequency is equal to the on-treatment frequency minus the baseline frequency. Diary cards will capture days of vaginal bleeding during the 12-month treatment period. Change in the frequency of annualized days of vaginal bleeding during the 12-month treatment period compared to the 6-month baseline period, based on a worst-case scenario calculation (ie, missing diary card days counted as bleeding days) are reported.	Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline	The percentage change in frequency is defined as 100% times the difference (the on-treatment period frequency minus the baseline period frequency), divided by the baseline period frequency. The percentage of participants with baseline vaginal bleeding days who experienced ≥ 50% reduction in the number of vaginal bleeding days during the 12 month treatment period compared to the 6 month baseline period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.	Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period	Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 6-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.	Baseline (6-month pre-treatment observation period) through Month 12 treatment period
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period	Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 12-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.	Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline	Change in rate of BA advancement over first 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in chronological age (CA) (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between BA radiograph dates. It is calculated as [(BA6 - BA0)/(CA6 - CA0)] - [(BA0 - BA*)/(CA0 - CA*)], where 6, 0, * stand for first Month 6 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.	Baseline (6-month pre-treatment observation period) through Month 6 of treatment period
Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline	Change in rate of BA advancement over second 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between the BA radiograph dates. It is calculated as [(BA6 - BA0)/(CA6 - CA0)] - [(BA0 - BA*)/(CA0 - CA*)], where 6, 0, * stand for second Month 6 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.	Baseline (6-month pre-treatment observation period) through second Month 6 of treatment period
Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline	Change in rate of BA advancement over whole 12-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment period is defined as increase in BA divided by change in CA (in fractional years) between the BA radiograph dates. It is calculated as [(BA12 - BA0) / (CA12 - CA0)] - [(BA0 - BA*) / (CA0 - CA*)], where 12, 0, * stand for Month 12 Visit, Month 0 Visit, and the 6-month retrospective visit, respectively.	Baseline (6-month pre-treatment observation period) through Month 12 of treatment period
Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over First 6-month Treatment Period Compared to Baseline	Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to first 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.	Baseline (6 month pre-treatment observation period) through first 6-month of treatment period
Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Second 6-month Treatment Period Compared to Baseline	Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to second 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.	Baseline (6 month pre-treatment observation period) through second 6-month treatment period (ie, through 12-month treatment period)
Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Whole 12-month Treatment Period Compared to Baseline	Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to the 12-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.	Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline	Change in growth velocity (Z-score) from baseline period to the first 6 months of treatment period is reported. The Z-score (also known as Standard Deviation Score [SDS]) is defined as [(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by standard deviation (SD)], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.	Baseline (6 month pre-treatment observation period) through first 6-month treatment period
Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline	Change in growth velocity (Z-score) from baseline period to the second 6 months of treatment period is reported. The Z-score (also known as SDS) is defined as [(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by SD], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.	Baseline (6 month pre-treatment observation period) through second 6-month treatment period
Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline	Change in growth velocity (Z-score) from baseline period to 12 months of treatment period is reported. The Z-score (also known as SDS) is defined as [(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by SD)], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean for growth velocity. For McCune-Albright Syndrome, Z-score below mean is a better outcome.	Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound	Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from baseline to Month 6 was calculated as Month 6 volume (by ultrasound) minus screening visit volume (by ultrasound). Baseline (screening visit) is the pre-treatment baseline visit.	Baseline (pre-treatment baseline visit) and Month 6 of treatment period
Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound	Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from Month 6 to Month 12/final visit was calculated as Month 12/finial visit volume (by ultrasound) minus Month 6 volume (by ultrasound).	At Month 6 and Month 12/final visit treatment period
Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound	Uterine volume was calculated via ultrasound using the formula: 0.5 multiplied by (longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated. Change in uterine volume from baseline to Month 12/final visit was calculated as End of Study volume (by ultrasound) minus Screening Visit volume (by ultrasound). Baseline (screening visit) is the pre-treatment baseline visit.	Baseline (pre-treatment screening visit) and Month 12 treatment period
Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound	The mean ovarian volume was the average of both ovaries. Average volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from baseline to Month 6 was calculated as Month 6 mean volume minus Screening Visit mean volume. Baseline (screening visit) is the pre-treatment baseline visit.	Baseline (pre-treatment screening visit) and Month 6 of treatment period
Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound	The mean ovarian volume was the average of both ovaries. Average volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from Month 6 to Month 12/final visit was calculated as Month 12/final visit mean volume minus Month 6 mean volume.	At Month 6 and Month 12/final visit treatment period
Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound	The mean ovarian volume was the average of both ovaries. Average ovarian volume was calculated as 0.5 multiplied by (volume of left ovary plus volume of right ovary) if both volumes were calculated; otherwise, average ovarian volume was considered missing. The volume of each ovary was calculated via ultrasound using the formula: 0.5 multiplied by longitudinal dimension multiplied by anterior-posterior dimension multiplied by transverse dimension. Change in mean ovarian volume from baseline to the end of the study was calculated as End of Study mean volume minus Screening Visit mean volume. Baseline (screening visit) is the pre-treatment baseline visit.	Baseline (pre-treatment baseline visit) and Month 12/final visit treatment period
Mean Clearance of Fulvestrant	Mean clearance of fulvestrant is reported.	Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
Mean Volume of Distribution (V1/F) of Fulvestrant	Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the first compartment and V2/F is the volume of the second compartment. V1/F of fulvestrant is reported. The measure of variability presented is the inter-individual error.	Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
Mean Volume of Distribution (V2/F) of Fulvestrant	Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the first compartment and V2/F is the volume of the second compartment. V2/F of fulvestrant is reported. The measure of variability presented is the inter-individual error.	Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	Day 1 through 68.7 weeks (maximum observed duration)
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs	Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Clinical laboratory parameter analysis included hematology and clinical chemistry.	Day 1 through 68.7 weeks (maximum observed duration)
Number of Participants With Compliance to Study Treatment	Number of participants with compliance to study treatment are reported. Treatment compliance was ensured at each treatment visit whether each participant received all protocol-defined injections up until the point they either withdrew from the study or completed the main study period. Compliance with study treatment for each participant for the 12-month treatment period was calculated as total number of injections divided by number of visits between first injection (Month 0) and last injection (at Month 11).	Day 1 through Month 12 of treatment period
Number of Participants With Withdrawals From Study Treatment Due to TEAE	Number of participants with withdrawals from study treatment due to TEAE are reported.	Day 1 through 68.7 weeks (maximum observed duration)
Hormone Assay: Serum Oestradiol Level	Serum oestradiol level at Month 12 (final visit) is reported.	Month 12 (final visit) of treatment period
Hormone Assay: Serum Luteinizing Hormone (LH) Level	Serum LH level collected at Month 12 (final visit) is reported.	Month 12 (final visit) of treatment period
Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level	Serum FSH level collected at Month 12 (final visit) is reported.	Month 12 (final visit) of treatment period
Hormone Assay: Serum Testosterone Level	Serum testosterone level at Month 12 (final visit) is reported.	Month 12 (final visit) of treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit	Change in Tanner stage (measure of pubertal progression) of breast from baseline to Month 12/last visit is reported. Tanner stage (breast) is a score of range 1-5 where 1 = no development and 5 = adult breast.	From Baseline (Month 0) through Month 12 treatment period
Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit	Change in Tanner stage (measure of pubertal progression) of pubic hair from baseline to Month 12/final visit is reported. Tanner stage (pubic hair) is a score of range 1-5 where 1 = no development and 5 = adult pubic hair.	From Baseline (Month 0) through Month 12 treatment period
Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit	Change in PAH for children over age 6 is reported. Bone age radiographs were collected retrospectively. PAH equals the current height divided by a factor (the fraction of final adult height) based on current bone age (central read) and current bone age relative to chronological age, classified as retarded, average or advanced. Retarded is defined as current bone age (years) < chronological age (years) minus 1; advanced is defined as current bone age (years) > chronological age (years) plus 1; otherwise, bone age is classified as average. The PAH was summarized using the Bayley and Pinneau method.	From Baseline (screening visit) through Month 12 treatment period
Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation	The MAS is caused by an activating mutation in the gene coding for the stimulatory subunit of the G protein, Gsα. The altered Gsα causes autonomous activation of G-protein stimulated cyclic adenosine monophosphate (cAMP) formation, which in the gonads, results in episodic uncontrolled sex steroid production and subsequent pubertal development. For participants who provided separate specific informed consent, the percentage of participants with a Gsα mutation at screening was assessed by molecular analysis of peripheral blood.	Baseline (screening)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: AstraZeneca Faslodex Medical Science Director, MD, AstraZeneca

Publications and helpful links

General Publications

• Sims EK, Garnett S, Guzman F, Paris F, Sultan C, Eugster EA; Fulvestrant McCune-Albright study group. Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome. Int J Pediatr Endocrinol. 2012 Sep 22;2012(1):26. doi: 10.1186/1687-9856-2012-26.

Helpful Links

• CSR-D6992C00044.pdf
• CSR Synopsis Redacted

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2006
• Primary Completion (Actual): December 8, 2009
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: January 17, 2006
• First Submitted That Met QC Criteria: January 17, 2006
• First Posted (Estimated): January 19, 2006

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: McCune-Albright Syndrome; MAS; PPP; Progressive Precocious Puberty
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Gonadal Disorders; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Developmental; Osteochondrodysplasias; Fibrous Dysplasia of Bone; Syndrome; Puberty, Precocious; Fibrous Dysplasia, Polyostotic; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: D6992C00044; 2005-004893-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests 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 approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP