McCune-Albright Syndrome, Puberty, Precocious
Conditions
Keywords
Progressive Precocious Puberty, PPP, McCune-Albright Syndrome, MAS
Brief summary
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)
Interventions
DRUGFulvestrant
Participants will receive intramuscular injection of fulvestrant as stated in arm description.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
1 Years to 10 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hormone Assay: Serum Testosterone Level | Month 12 (final visit) of treatment period | Serum testosterone level at Month 12 (final visit) is reported. |
| Number of Participants With Withdrawals From Study Treatment Due to TEAE | Day 1 through 68.7 weeks (maximum observed duration) | Number of participants with withdrawals from study treatment due to TEAE are reported. |
| Hormone Assay: Serum Oestradiol Level | Month 12 (final visit) of treatment period | Serum oestradiol level at Month 12 (final visit) is reported. |
| Hormone Assay: Serum Luteinizing Hormone (LH) Level | Month 12 (final visit) of treatment period | Serum LH level collected at Month 12 (final visit) is reported. |
| Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level | Month 12 (final visit) of treatment period | Serum FSH level collected at Month 12 (final visit) is reported. |
| Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline | Baseline (6 month pre-treatment observation period) through Month 12 treatment period | 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. |
| Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline | Baseline (6 month pre-treatment observation period) through Month 12 treatment period | 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. |
| Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period | 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 days over a 6-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported. |
| Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period | 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 days over a 12-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported. |
| Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline | Baseline (6-month pre-treatment observation period) through Month 6 of treatment period | 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. |
| Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline | Baseline (6-month pre-treatment observation period) through second Month 6 of treatment period | 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. |
| Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline | Baseline (6-month pre-treatment observation period) through Month 12 of treatment period | 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. |
| Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over First 6-month Treatment Period Compared to 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) 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. |
| Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Second 6-month Treatment Period Compared to 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) 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. |
| Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Whole 12-month Treatment Period Compared to Baseline | Baseline (6 month pre-treatment observation period) through Month 12 of treatment period | 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. |
| Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline | Baseline (6 month pre-treatment observation period) through first 6-month treatment period | 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. |
| Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline | Baseline (6 month pre-treatment observation period) through second 6-month treatment period | 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. |
| Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline | Baseline (6 month pre-treatment observation period) through Month 12 of treatment period | 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. |
| Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound | Baseline (pre-treatment baseline visit) and Month 6 of treatment period | 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. |
| Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound | At Month 6 and Month 12/final visit treatment period | 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). |
| Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound | Baseline (pre-treatment screening visit) and Month 12 treatment period | 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. |
| Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound | Baseline (pre-treatment screening visit) and Month 6 of treatment period | 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. |
| Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound | At Month 6 and Month 12/final visit treatment period | 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. |
| Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound | Baseline (pre-treatment baseline visit) and Month 12/final visit treatment period | 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. |
| Mean Clearance of Fulvestrant | 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 clearance of fulvestrant is reported. |
| Mean Volume of Distribution (V1/F) of Fulvestrant | 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 | 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. |
| Mean Volume of Distribution (V2/F) of Fulvestrant | 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 | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 through 68.7 weeks (maximum observed duration) | 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. |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Day 1 through 68.7 weeks (maximum observed duration) | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Clinical laboratory parameter analysis included hematology and clinical chemistry. |
| Number of Participants With Compliance to Study Treatment | Day 1 through Month 12 of treatment period | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit | From Baseline (Month 0) through Month 12 treatment period | 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. |
| Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit | From Baseline (screening visit) through Month 12 treatment period | 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. |
| Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation | Baseline (screening) | 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. |
| Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit | From Baseline (Month 0) through Month 12 treatment period | 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. |
Countries
France, Germany, Italy, Russia, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at study sites located in France, Germany, Italy, Russian Federation, United Kingdom, and the United States of America.
Pre-assignment details
A total of 30 participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant Participants received intramuscular injection of fulvestrant 2 mg/kg or 4 mg/kg (First 10 participants were dosed at 2 mg/kg then increased to 4 mg/kg. All subsequent participants were 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. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Disease progression | 1 |
Baseline characteristics
| Characteristic | Fulvestrant |
|---|---|
| Age, Continuous | 5.86 Years STANDARD_DEVIATION 1.846 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 23 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 25 / 30 |
| serious Total, serious adverse events | 9 / 30 |
Outcome results
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Population: The full-analysis set (FAS) population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline | -3.6 Days per year |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through first 6-month of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over First 6-month Treatment Period Compared to Baseline | -1.7 cm/year | Standard Deviation 4.35 |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through second 6-month treatment period (ie, through 12-month treatment period)
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Second 6-month Treatment Period Compared to Baseline | -0.8 cm/year | Standard Deviation 4.49 |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Whole 12-month Treatment Period Compared to Baseline | -1.4 cm/year | Standard Deviation 3.69 |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through first 6-month treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline | -1.60 Unit on a score | Standard Deviation 4.616 |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through second 6-month treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline | -0.64 Unit on a score | Standard Deviation 4.606 |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline | -1.14 Unit on a score | Standard Deviation 4.078 |
Primary
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.
Time frame: Baseline (pre-treatment baseline visit) and Month 12/final visit treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound | 1.01 Cubic centimetres |
Primary
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.
Time frame: Baseline (pre-treatment screening visit) and Month 6 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound | 0.10 Cubic centimetres |
Primary
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.
Time frame: Baseline (6-month pre-treatment observation period) through second Month 6 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline | -1.10 Ratio | Standard Deviation 1.383 |
Primary
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.
Time frame: Baseline (6-month pre-treatment observation period) through Month 12 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline | -0.93 Ratio | Standard Deviation 1.343 |
Primary
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.
Time frame: Baseline (6-month pre-treatment observation period) through Month 6 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline | -0.83 Ratio | Standard Deviation 1.507 |
Primary
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.
Time frame: Baseline (pre-treatment screening visit) and Month 12 treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound | -2.44 Cubic centimeters |
Primary
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.
Time frame: Baseline (pre-treatment baseline visit) and Month 6 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound | -1.10 Cubic centimeters |
Primary
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).
Time frame: At Month 6 and Month 12/final visit treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound | -0.13 Cubic centimetres |
Primary
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.
Time frame: At Month 6 and Month 12/final visit treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants with data at both time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound | 0.76 Cubic centimetres |
Primary
Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level
Serum FSH level collected at Month 12 (final visit) is reported.
Time frame: Month 12 (final visit) of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level | 1.13 IU/L | Standard Deviation 1.024 |
Primary
Hormone Assay: Serum Luteinizing Hormone (LH) Level
Serum LH level collected at Month 12 (final visit) is reported.
Time frame: Month 12 (final visit) of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Hormone Assay: Serum Luteinizing Hormone (LH) Level | 0.11 IU/L | Standard Deviation 0.042 |
Primary
Hormone Assay: Serum Oestradiol Level
Serum oestradiol level at Month 12 (final visit) is reported.
Time frame: Month 12 (final visit) of treatment period
Population: he FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Hormone Assay: Serum Oestradiol Level | 25.95 pmol/L | Standard Deviation 30.718 |
Primary
Hormone Assay: Serum Testosterone Level
Serum testosterone level at Month 12 (final visit) is reported.
Time frame: Month 12 (final visit) of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were evaluable at the specified time point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Hormone Assay: Serum Testosterone Level | 0.65 nmol/L | Standard Deviation 0.273 |
Primary
Mean Clearance of Fulvestrant
Mean clearance of fulvestrant is reported.
Time frame: 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
Population: Population pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study drug and have evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Mean Clearance of Fulvestrant | 38.4 Litres/hour | Standard Deviation 11.56 |
Primary
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.
Time frame: 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
Population: Population PK analysis set included all participants who received at least 1 dose of study drug and have evaluable PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fulvestrant | Mean Volume of Distribution (V1/F) of Fulvestrant | 33000 Litres |
Primary
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.
Time frame: 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
Population: Population PK analysis set included all participants who received at least 1 dose of study drug and have evaluable PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fulvestrant | Mean Volume of Distribution (V2/F) of Fulvestrant | 32700 Litres |
Primary
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.
Time frame: Day 1 through 68.7 weeks (maximum observed duration)
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fulvestrant | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Anemia | 1 Participants |
| Fulvestrant | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | Vitamin D Deficiency | 1 Participants |
Primary
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).
Time frame: Day 1 through Month 12 of treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fulvestrant | Number of Participants With Compliance to Study Treatment | 30 Participants |
Primary
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.
Time frame: Day 1 through 68.7 weeks (maximum observed duration)
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Fulvestrant | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAEs | 27 Participants |
| Fulvestrant | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAEs | 9 Participants |
Primary
Number of Participants With Withdrawals From Study Treatment Due to TEAE
Number of participants with withdrawals from study treatment due to TEAE are reported.
Time frame: Day 1 through 68.7 weeks (maximum observed duration)
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fulvestrant | Number of Participants With Withdrawals From Study Treatment Due to TEAE | 0 Participants |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who had bleeding during the 6 month baseline period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant | Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline | 73.9 Percentage of Participants |
Primary
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.
Time frame: Baseline (6-month pre-treatment observation period) through Month 12 treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who had bleeding during the 6-month baseline period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant | Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period | 78.3 Percentage of Participants |
Primary
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.
Time frame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who had bleeding during the 6 month baseline period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant | Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period | 34.8 Percentage of Participants |
Secondary
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.
Time frame: From Baseline (screening visit) through Month 12 treatment period
Population: The FAS population included participants who received at least 1 dose of study drug. Here, number of participants analyzed denotes those participants who were analyzed for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fulvestrant | Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit | 0.5 Centimeter | Standard Deviation 4.1 |
Secondary
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.
Time frame: From Baseline (Month 0) through Month 12 treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit | 0.0 Unit on a scale |
Secondary
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.
Time frame: From Baseline (Month 0) through Month 12 treatment period
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant | Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit | 0.0 Unit on a scale |
Secondary
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.
Time frame: Baseline (screening)
Population: The FAS population included participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant | Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation | 23.3 Percentage of participants |