A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerabili... | NCT02055157 | Trialant
NCT02055157
Sponsor
BioMarin Pharmaceutical
Status
Completed
Last Update Posted
Jan 15, 2021Actual
Enrollment
35Actual
Phase
Phase 2
Conditions
Achondroplasia
Interventions
BMN 111
Countries
United States
Australia
France
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02055157
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
111-202
Secondary IDs
ID
Type
Description
Link
2013-004137-32
EudraCT Number
Brief Title
A Phase 2 Study of BMN 111 to Evaluate Safety, Tolerability, and Efficacy in Children With Achondroplasia
Official Title
A Phase 2, Open-label, Sequential Cohort Dose-escalation Study of BMN 111 in Children With Achondroplasia
Acronym
ACH
Organization
BioMarin PharmaceuticalINDUSTRY
Status Module
Record Verification Date
Dec 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jan 13, 2014Actual
Primary Completion Date
Oct 2, 2017Actual
Completion Date
Oct 2, 2017Actual
First Submitted Date
Apr 18, 2013
First Submission Date that Met QC Criteria
Feb 3, 2014
First Posted Date
Feb 5, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Sep 18, 2020
Results First Submitted that Met QC Criteria
Dec 22, 2020
Results First Posted Date
Jan 15, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Sep 19, 2018
Certification/Extension First Submitted that Passed QC Review
Sep 19, 2018
Certification/Extension First Posted Date
Sep 24, 2018Actual
Last Update Submitted Date
Dec 22, 2020
Last Update Posted Date
Jan 15, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
BioMarin PharmaceuticalINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a Phase 2, open-label, sequential cohort dose-escalation study of BMN 111 in children with achondroplasia. The primary objective is to assess the safety and tolerability of daily BMN 111 administered to children with achondroplasia.
Detailed Description
Not provided
Conditions Module
Conditions
Achondroplasia
Keywords
Achondroplasia
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
35Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort 1
Experimental
Cohort 1: 2.5 ug/kg
Drug: BMN 111
Cohort 2
Experimental
Cohort 2: 7.5 ug/kg,
Drug: BMN 111
Cohort 3
Experimental
Cohort 3: 15 ug/Kg
Drug: BMN 111
Cohort 4
Experimental
Cohort 4: 30 ug/kg
Drug: BMN 111
Interventions
Name
Type
Description
Arm Group Labels
Other Names
BMN 111
Drug
BMN 111 will be administered daily for 24 months in an open-label sequential dose adjustment fashion.
Cohort 1
Cohort 2
Cohort 3
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Overall Summary of Adverse Events During Initial 6-Month Period
A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Serious adverse event (SAE).
Up to Month 6 ± 7 Days
Overall Summary of Adverse Events During Entire Study Period
A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Change From Baseline in Annualized Growth Velocity (AGV) During Initial 6-Month
Annualized Growth Velocity at Day 183 is assessed on standing height as ((Height at Day 183 Visit - Height at Baseline Visit)/(Date at Day 183 Visit - Baseline Visit Date)) x 365.25.
At 6 month (Day 183)
Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 3 and 4
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Parent(s) or guardian(s) are willing and able to provide written, signed informed consent
5 to 14 years old at end of study
ACH, documented by clinical grounds, confirmed by genetic testing
At least 6-month of pretreatment growth assessment in Study 111-901 before study entry, and one standing height at least 6 months prior to screening for 111-202
Negative pregnancy test at the Screening Visit for females ≥ 10 years old or who have begun menses
If sexually active, willing to use a highly effective method of contraception while participating in the study
Ambulatory, able to stand without assistance
Willing and able to perform all study procedures as physically possible
Parents/caregivers willing to administer daily injections to the subjects
Hypochondroplasia or short stature condition other than ACH
Have any of the following:
Hypothyroidism or hyperthyroidism
Insulin-requiring diabetes mellitus
Autoimmune inflammatory disease
Inflammatory bowel disease
Autonomic neuropathy
Recent acute illness associated with volume dehydration not completely resolved prior to the first dose of study drug
Unstable condition requiring surgical intervention during the study
Growth plates have fused
Have a history of any of the following:
Renal insufficiency, defined as creatinine > 2 mg/dl
Anemia
Baseline systolic BP < 75 mm Hg or recurrent symptomatic hypotension or recurrent symptomatic hypotension, recurrent symptomatic orthostatic hypotension
Cardiac or vascular disease, including the following:
Cardiac dysfunction (abnormal echocardiogram [ECHO] including left ventricle [LV] mass) at Screening Visit
Hypertrophic cardiomyopathy
Pulmonary Hypertension
Congenital heart disease with ongoing cardiac dysfunction
Cerebrovascular disease
Aortic insufficiency
Clinically significant atrial or ventricular arrhythmias
Have an ECG showing any of the following:
Right or left atrial enlargement or ventricular hypertrophy
PR (period of time from the beginning of atrial depolarization until the beginning of ventricular depolarization) interval > 200 msec
QRS (The Q, R, and S heart waves that are measured on an electrocardiogram) interval > 110 msec
Corrected QTc-F (Measure of the corrected time between the start of the Q wave and end of the T wave in the heart's electrical cycle) > 450 msec
Second- or third-degree atrioventricular block
Documented Vitamin D deficiency
Require any investigational agent prior to completion of study period
Have received another investigational product or investigational medical device within 30 days before the Screening visit
Use of any other investigational product or investigational medical device for the treatment of ACH or short stature
Current chronic therapy with antihypertensive medications, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, diuretics, beta-blockers, calcium-channel blockers, cardiac glycosides, systemic anticholinergic agents, any medication that may impair or enhance compensatory tachycardia, diuretics, or other drugs known to alter renal or tubular function
Treatment with growth hormone, IGF-1 (Insulin-like growth factor), or anabolic steroids in the previous 6 months or long-term treatment (> 3 months) at any time
Long-term treatment (> 1 month) with oral corticosteroids
Concomitant medication that prolongs the QT/QTc-F interval within 14 days or 5 half-lives, whichever is longer, before the Screening visit
Pregnant or breastfeeding at the Screening Visit or planning to become pregnant (self or partner) at any time during the study
Limb-lengthening or bone-related surgery < 18 months prior to study enrollment
Had a fracture of the long bones or spine within 6 months prior to screening (except for fracture of digits or toes)
AST (Aspartate Transaminase) or ALT (Alanine Transaminase) at least 3x upper limit of normal (ULN) or total bilirubin at least 2x ULN
Evidence of severe sleep apnea requiring surgery or new initiation of CPAP (Continuous positive airway pressure).
History of malignancy and chemotherapy/radiation or currently under work-up for suspected malignancy
Known hypersensitivity to BMN 111 or its excipients
Have a condition or circumstance that, in the view of the Investigator, places the subject at high risk for poor treatment compliance or for not completing the study
Concurrent disease or condition that would interfere with study participation or safety
Have abnormal findings on baseline clinical hip exam or imaging assessments that are determined to be clinically significant as determined by the PI.
Have a history of hip surgery or severe hip dysplasia
Have a history of clinically significant hip injury in the 30 days prior to screening.
History of slipped capital femoral epiphysis or avascular necrosis of the femoral head.
Are unable to lie flat when in prone position
Additional Exclusion Criteria for Optional, Open-label Extension Phase:
Use of restricted therapies during the initial 6 months of the study
Permanently discontinued BMN 111 during the initial 6 months of the study
Qi Y, Chan ML, Mould DR, Larimore K, Fisheleva E, Cherukuri A, Day J, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Bober MB, Henshaw J. Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model. Clin Pharmacokinet. 2024 May;63(5):707-719. doi: 10.1007/s40262-024-01371-6. Epub 2024 Apr 23.
This study was conducted at nine study centers in United States, Australia, United Kingdom and France.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Periods
Title
Milestones
Reasons Not Completed
Initial 6 Months
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Aug 22, 2016
Sep 18, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Cohort 4
Modified recombinant human C-type natriuretic peptide
Vosoritide
Annualized Growth Velocity at Day 183 visit is assessed on standing height as ((Height at Day 183 Visit - Height at Baseline Visit)/(Date at Day 183 Visit - Baseline Visit Date)) x 365.25.
At month 24
Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 1 and 2 Switchers
Annualized Growth Velocity at 1st visit with >= 12 months on 15ug/kg is assessed on standing height as ((Height at 1st Visit with >= 12 Months on 15 μg/kg - Height at 1st Visit on 15 μg/kg)/(Date of the 1st Visit with >= 12 months on 15 μg/kg - Date of at 1st Visit on 15 μg/kg)) x 365.25.
At month 24
Change From Baseline in Height Z-Scores Using Centers for Disease Control and Prevention (CDC) Reference Standard During Initial 6-Months
Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 Standard Deviation Scores (SDs) indicate a child's height is no longer within normal height range for average stature children of the same sex and age.
Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC).
At month 6 (Day 183)
Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 3 and 4
Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 SDs indicate a child's height is no longer within normal height range for average stature children of the same sex and age.
Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC).
At month 24
Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 1 and 2 Switchers
Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 SDs indicate a child's height is no longer within normal height range for average stature children of the same sex and age.
Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC).
At month 24
Change From Baseline in Upper to Lower Body Ratios During Initial 6-Months
The Upper to Lower Body ratio prior to treatment, at baseline, and through 6 months is assessed on Sitting Height / (Standing Height - Sitting Height)
At month 6 (Day 183)
Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 3 and 4
The Upper to Lower Body ratio prior to treatment, at baseline, and through 24 months is assessed on Sitting Height / (Standing Height - Sitting Height)
At month 24
Change From Baseline in Upper Arm Length to Lower Arm (Forearm) Length Ratio During Initial 6-Months
The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 6 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length.
At month 6 (Day 183)
Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 3 and 4
The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 24 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length.
At month 24
Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 1 and 2 Switchers
The Upper to Lower Body ratio prior to treatment, at baseline, and through 24 months is assessed on Sitting Height / (Standing Height - Sitting Height)
At month 24
Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 24 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length.
At month 24
Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Initial 6-months
The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 6 months is assessed on Upper Leg Length (Thigh) / Knee to Heel Length.
At month 6 (Day 183)
Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 3 and 4
The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh) / Knee to Heel Length.
At month 24
Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh) / Knee to Heel Length.
At month 24
Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Initial 6-months
The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 6 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length.
At month 6 (Day 183)
Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 3 and 4
The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length.
At month 24
Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length.
At month 24
Change From Baseline in Arm Span to Height Ratio During Initial 6-months
The Arm Span to Height Ratio prior to treatment, at baseline, and through 6 months is assessed by Arm Span / Standing Height.
At month 6 (Day 183)
Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 3 and 4
The Arm Span to Height Ratio prior to treatment, at baseline, and through 24 months is assessed by Arm Span / Standing Height.
At month 24
Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Arm Span to Height Ratio prior to treatment, at baseline, and through 24 months is assessed by Arm Span / Standing Height.
Values are not available for participants in cohort 1 switchers for Change from Baseline to >=12 Months on 15ug/kg.
At month 24
Torrance
California
90509
United States
Ann and Robert H. Lurie Childrens Hospital of Chicago
Chicago
Illinois
60611
United States
Johns Hopkins McKusick - Institute of Genetic Medicine
Baltimore
Maryland
21287
United States
Vanderbilt University
Nashville
Tennessee
37232-2578
United States
Baylor College of Medicine
Houston
Texas
77030
United States
Murdoch Children's Research Institute
Parkville
Victoria
3052
Australia
Institut Necker
Paris
75015
France
Guys & St. Thomas NHS Foundation Trust Evelina Hospital
London
SE1 9RT
United Kingdom
Derived
Chan ML, Qi Y, Larimore K, Cherukuri A, Seid L, Jayaram K, Jeha G, Fisheleva E, Day J, Huntsman-Labed A, Savarirayan R, Irving M, Bacino CA, Hoover-Fong J, Ozono K, Mohnike K, Wilcox WR, Horton WA, Henshaw J. Pharmacokinetics and Exposure-Response of Vosoritide in Children with Achondroplasia. Clin Pharmacokinet. 2022 Feb;61(2):263-280. doi: 10.1007/s40262-021-01059-1. Epub 2021 Aug 25.
Savarirayan R, Irving M, Bacino CA, Bostwick B, Charrow J, Cormier-Daire V, Le Quan Sang KH, Dickson P, Harmatz P, Phillips J, Owen N, Cherukuri A, Jayaram K, Jeha GS, Larimore K, Chan ML, Huntsman Labed A, Day J, Hoover-Fong J. C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia. N Engl J Med. 2019 Jul 4;381(1):25-35. doi: 10.1056/NEJMoa1813446. Epub 2019 Jun 18.
FG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
FG002
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
FG003
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
FG0008 subjects
FG0018 subjects
FG00210 subjects
FG0039 subjects
COMPLETED
FG0007 subjects
FG0017 subjects
FG00210 subjects
FG0038 subjects
NOT COMPLETED
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
Type
Comment
Reasons
Subject discontinued due to NeedlePhobia
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
Consent withdrawn by subject
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
18-month Extension
Type
Comment
Milestone Data
STARTED
FG0007 subjects
FG0017 subjects
FG00210 subjects
FG0038 subjects
COMPLETED
FG0006 subjects
FG0016 subjects
FG00210 subjects
FG0038 subjects
NOT COMPLETED
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
Type
Comment
Reasons
Investigator decision
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG003
Safety Analysis Population consists of all subjects who received at least one dose of study treatment and were used for safety analysis in the initial 6-month period and entire study period.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
BG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
BG002
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
BG003
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0008
BG0018
BG00210
BG0039
BG00435
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
yrs
Title
Denominators
Categories
Title
Measurements
BG0007.3± 1.58
BG0018.3± 2.19
BG0028.0± 1.63
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0005
BG0013
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
White
Title
Measurements
BG0007
BG0016
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Overall Summary of Adverse Events During Initial 6-Month Period
A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Serious adverse event (SAE).
Safety Analysis Population includes all subjects who received at least one dose of study treatment and were used for safety analysis in the initial 6-month period and entire study period.
Posted
Count of Participants
Participants
Up to Month 6 ± 7 Days
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG002
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG003
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG0008
OG0018
OG00210
OG003
Title
Denominators
Categories
Subjects with at Least 1 Reported TEAE
Title
Measurements
OG0008
OG0018
OG00210
OG003
Primary
Overall Summary of Adverse Events During Entire Study Period
A treatment-emergent Adverse Events (TEAE) is any Adverse Events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG002
Cohort 3
Secondary
Change From Baseline in Annualized Growth Velocity (AGV) During Initial 6-Month
Annualized Growth Velocity at Day 183 is assessed on standing height as ((Height at Day 183 Visit - Height at Baseline Visit)/(Date at Day 183 Visit - Baseline Visit Date)) x 365.25.
Efficacy Analysis Population includes all subjects who received at least one dose of study treatment and who had post treatment data for any efficacy endpoint in the corresponding period were included in the Efficacy Analysis and Extension Efficacy Analysis population.
Posted
Mean
Standard Deviation
cm/year
At 6 month (Day 183)
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 3 and 4
Annualized Growth Velocity at Day 183 visit is assessed on standing height as ((Height at Day 183 Visit - Height at Baseline Visit)/(Date at Day 183 Visit - Baseline Visit Date)) x 365.25.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
cm/year
At month 24
ID
Title
Description
OG000
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Annualized Growth Velocity (AGV) During Entire Study Period - Cohort 1 and 2 Switchers
Annualized Growth Velocity at 1st visit with >= 12 months on 15ug/kg is assessed on standing height as ((Height at 1st Visit with >= 12 Months on 15 μg/kg - Height at 1st Visit on 15 μg/kg)/(Date of the 1st Visit with >= 12 months on 15 μg/kg - Date of at 1st Visit on 15 μg/kg)) x 365.25.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
cm/year
At month 24
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Height Z-Scores Using Centers for Disease Control and Prevention (CDC) Reference Standard During Initial 6-Months
Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 Standard Deviation Scores (SDs) indicate a child's height is no longer within normal height range for average stature children of the same sex and age.
Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC).
Efficacy Analysis Population
Posted
Mean
Standard Deviation
z score
At month 6 (Day 183)
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 3 and 4
Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 SDs indicate a child's height is no longer within normal height range for average stature children of the same sex and age.
Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC).
Efficacy Analysis Population
Posted
Mean
Standard Deviation
z score
At month 24
ID
Title
Description
OG000
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Height Z-Scores Using CDC Reference Standard During Entire Study Period - Cohort 1 and 2 Switchers
Height Z scores indicates how far a particular child is from the average height for children of the same sex and age. A positive height Z score indicates the child's height is above average whilst a negative Z score indicates the child's height is below average. Height Z scores below -2 SDs indicate a child's height is no longer within normal height range for average stature children of the same sex and age.
Z-scores are derived using non-ACH age-sex-specific reference data (means and standard deviations) per Centers for Disease Control and Prevention (CDC).
Efficacy Analysis Population
Posted
Mean
Standard Deviation
z score
At month 24
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Upper to Lower Body Ratios During Initial 6-Months
The Upper to Lower Body ratio prior to treatment, at baseline, and through 6 months is assessed on Sitting Height / (Standing Height - Sitting Height)
Efficacy Analysis Population
Posted
Mean
Standard Deviation
Ratio
At month 6 (Day 183)
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG002
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 3 and 4
The Upper to Lower Body ratio prior to treatment, at baseline, and through 24 months is assessed on Sitting Height / (Standing Height - Sitting Height)
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Upper Arm Length to Lower Arm (Forearm) Length Ratio During Initial 6-Months
The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 6 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 6 (Day 183)
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG002
Cohort 3
Secondary
Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 3 and 4
The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 24 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Upper to Lower Body Ratios During Entire Study Period - Cohort 1 and 2 Switchers
The Upper to Lower Body ratio prior to treatment, at baseline, and through 24 months is assessed on Sitting Height / (Standing Height - Sitting Height)
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Secondary
Change From Baseline in Upper Arm to Lower Arm Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Upper Arm Length to Lower Arm (Forearm) Length ratio prior to treatment, at baseline, and through 24 months is assessed on Upper Arm Length / Lower Arm (Forearm) Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Initial 6-months
The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 6 months is assessed on Upper Leg Length (Thigh) / Knee to Heel Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 6 (Day 183)
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG002
Cohort 3
Secondary
Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 3 and 4
The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh) / Knee to Heel Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Upper Leg Length (Thigh) to Knee to Heel Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Upper Leg Length (Thigh) to Knee to Heel Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh) / Knee to Heel Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Initial 6-months
The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 6 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 6 (Day 183)
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG002
Cohort 3
Secondary
Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 3 and 4
The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Upper Leg Length (Thigh) to Tibial Length Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Upper Leg Length (Thigh) to Tibial Length Ratio prior to treatment, at baseline, and through 24 months is assessed by Upper Leg Length (Thigh)/ Tibial Leg Length.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Secondary
Change From Baseline in Arm Span to Height Ratio During Initial 6-months
The Arm Span to Height Ratio prior to treatment, at baseline, and through 6 months is assessed by Arm Span / Standing Height.
Efficacy Analysis Population
Arm span measurement was optional until July 2015. Therefore data was not collected for all subjects for this outcome measure.
Posted
Mean
Standard Deviation
ratio
At month 6 (Day 183)
ID
Title
Description
OG000
Cohort 1
Initial 6 months: BMN 111 at 2.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 2.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, 7 subjects escalated to 7.5 μg/kg daily subcutaneous injection, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG002
Cohort 3
Secondary
Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 3 and 4
The Arm Span to Height Ratio prior to treatment, at baseline, and through 24 months is assessed by Arm Span / Standing Height.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 3
Initial 6 months: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
OG001
Cohort 4
Initial 6 months: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 30.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG000
Secondary
Change From Baseline in Arm Span to Height Ratio During Entire Study Period - Cohort 1 and 2 Switchers
The Arm Span to Height Ratio prior to treatment, at baseline, and through 24 months is assessed by Arm Span / Standing Height.
Values are not available for participants in cohort 1 switchers for Change from Baseline to >=12 Months on 15ug/kg.
Efficacy Analysis Population
Posted
Mean
Standard Deviation
ratio
At month 24
ID
Title
Description
OG000
Cohort 2
Initial 6 months: BMN 111 at 7.5 μg/kg daily subcutaneous injection, over a period of 6 months.
18-month extension: BMN 111 at 7.5 μg/kg daily subcutaneous injection, dose determined to be suboptimal after the end of the initial 6 months, discontinued 1 subject escalating 6 subjects to BMN 111 at 15.0 μg/kg daily subcutaneous injection, over a period of 18 months.
Units
Counts
Participants
OG000
Time Frame
Up to Month 25 ± 7 Days
Description
Safety Analysis Population consists of all subjects who received at least one dose of study treatment and were used for safety analysis in the initial 6-month period and entire study period.
Extension Safety Analysis Population consists of all subjects who received at least one dose of study treatment in the extension period and were used for safety analysis in the extension period.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Initial 6-Months Period 2.5 µg/kg.
BMN 111 at 2.5 μg/kg subcutaneous injection, once daily in the morning for initial 6-month period.
0
8
0
8
8
8
EG001
Initial 6-Months Period 7.5 µg/kg.
BMN 111 at 7.5 μg/kg subcutaneous injection, once daily in the morning for initial 6-month period.
0
8
0
8
8
8
EG002
Initial 6-Months Period 15 µg/kg.
BMN 111 at 15 μg/kg subcutaneous injection, once daily in the morning for initial 6-month period.
0
10
0
10
10
10
EG003
Initial 6-Months Period 30 µg/kg.
BMN 111 at 30 μg/kg subcutaneous injection, once daily in the morning for initial 6-month period.
0
9
0
9
9
9
EG004
Extension Period 2.5 µg/kg.
BMN 111 at 2.5 μg/kg subcutaneous injection, once daily in the morning for mean duration of 135.4 days.
0
7
1
7
7
7
EG005
Extension Period 7.5 µg/kg.
BMN 111 at 7.5 μg/kg subcutaneous injection, once daily in the morning for mean duration of 83.1 days.
0
14
0
14
13
14
EG006
Extension Period 15 µg/kg.
BMN 111 at 15 μg/kg subcutaneous injection, once daily in the morning for mean duration of 464.7 days.
0
22
1
22
22
22
EG007
Extension Period 30 µg/kg.
BMN 111 at 30 μg/kg subcutaneous injection, once daily in the morning for mean duration of 546.4 days.
0
8
1
8
8
8
EG008
Entire Study Period 2.5 µg/kg.
BMN 111 at 2.5 μg/kg subcutaneous injection, once daily in the morning for mean duration of 298.8 days.
0
8
1
8
8
8
EG009
Entire Study Period 7.5 µg/kg.
BMN 111 at 7.5 μg/kg subcutaneous injection, once daily in the morning for mean duration of 175.5 days.
0
15
0
15
14
15
EG010
Entire Study Period 15 µg/kg.
BMN 111 at 15 μg/kg subcutaneous injection, once daily in the morning for mean duration of 549.6 days.
0
22
1
22
22
22
EG011
Entire Study Period 30 µg/kg.
BMN 111 at 30 μg/kg subcutaneous injection, once daily in the morning for mean duration of 650.9 days.
0
9
1
9
9
9
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Sleep apnoea syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG0030 affected9 at risk
EG004
Tonsillar hypertrophy
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Thyroglossal cyst
Congenital, familial and genetic disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Injection site reaction
General disorders
MedDRA (19.1)
Systematic Assessment
EG0002 affected8 at risk
EG0016 affected8 at risk
EG0028 affected10 at risk
EG0039 affected9 at risk
EG0042 affected7 at risk
EG0055 affected14 at risk
EG00615 affected22 at risk
EG0076 affected8 at risk
EG0082 affected8 at risk
EG0098 affected15 at risk
EG01017 affected22 at risk
EG0119 affected9 at risk
Injection site erythema
General disorders
MedDRA (19.1)
Systematic Assessment
EG0004 affected8 at risk
EG0017 affected8 at risk
EG0029 affected10 at risk
EG003
Injection site swelling
General disorders
MedDRA (19.1)
Systematic Assessment
EG0004 affected8 at risk
EG0012 affected8 at risk
EG0024 affected10 at risk
EG003
Injection site urticaria
General disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0011 affected8 at risk
EG0022 affected10 at risk
EG003
Injection site pain
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Pyrexia
General disorders
MedDRA (19.1)
Systematic Assessment
EG0004 affected8 at risk
EG0011 affected8 at risk
EG0023 affected10 at risk
EG003
Injection site bruising
General disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0012 affected8 at risk
EG0020 affected10 at risk
EG003
Fatigue
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Injection site pruritus
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0022 affected10 at risk
EG003
Injection site haemorrhage
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Application site erythema
General disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Cyst
General disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Influenza like illness
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Injection site discolouration
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Injection site induration
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Malaise
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Medical device site reaction
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Pain
General disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0013 affected8 at risk
EG0023 affected10 at risk
EG003
Ear infection
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0013 affected8 at risk
EG0022 affected10 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0023 affected10 at risk
EG003
Otitis media
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Viral upper respiratory tract infection
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Gastroenteritis viral
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Viral infection
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Sinusitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Conjunctivitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Influenza
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Otitis externa
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Pharyngitis streptococcal
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Rhinitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Acute sinusitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Atypical pneumonia
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Croup infectious
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Eye abscess
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Gastrointestinal viral infection
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Incision site infection
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Onychomycosis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Rash pustular
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Scarlet fever
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Varicella
Infections and infestations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0004 affected8 at risk
EG0010 affected8 at risk
EG0022 affected10 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0012 affected8 at risk
EG0022 affected10 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0012 affected8 at risk
EG0020 affected10 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Sleep apnoea syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Sneezing
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Tonsillar hypertrophy
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Nasal dryness
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Snoring
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0002 affected8 at risk
EG0011 affected8 at risk
EG0021 affected10 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0021 affected10 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0002 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Malpositioned teeth
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Aphthous ulcer
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Parotid gland enlargement
Gastrointestinal disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Headache
Nervous system disorders
MedDRA (19.1)
Systematic Assessment
EG0004 affected8 at risk
EG0012 affected8 at risk
EG0022 affected10 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0011 affected8 at risk
EG0021 affected10 at risk
EG003
Presyncope
Nervous system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Syncope
Nervous system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Tremor
Nervous system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0012 affected8 at risk
EG0021 affected10 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Procedural anxiety
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Procedural pain
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Thermal burn
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Excoriation
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Joint injury
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Meniscus injury
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Muscle strain
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Post-traumatic pain
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Soft tissue injury
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Sunburn
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Wound
Injury, poisoning and procedural complications
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0011 affected8 at risk
EG0021 affected10 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Groin pain
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Joint range of motion decreased
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Hypotension
Vascular disorders
MedDRA (19.1)
Systematic Assessment
EG0003 affected8 at risk
EG0014 affected8 at risk
EG0024 affected10 at risk
EG003
Haematoma
Vascular disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Haemorrhage
Vascular disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Hypertension
Vascular disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Pallor
Vascular disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0012 affected8 at risk
EG0020 affected10 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Rash generalised
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Miliaria
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Skin exfoliation
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Skin striae
Skin and subcutaneous tissue disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0012 affected8 at risk
EG0021 affected10 at risk
EG003
Ear swelling
Ear and labyrinth disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Otorrhoea
Ear and labyrinth disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Middle ear effusion
Ear and labyrinth disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Tympanic membrane hyperaemia
Ear and labyrinth disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Body temperature increased
Investigations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Eosinophil count increased
Investigations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Vitamin D decreased
Investigations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Blood immunoglobulin E increased
Investigations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Respiratory rate increased
Investigations
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Sleep study abnormal
Investigations
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Emotional disorder
Psychiatric disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Irritability
Psychiatric disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Aggression
Psychiatric disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Attention deficit/hyperactivity disorder
Psychiatric disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Enuresis
Psychiatric disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Frustration tolerance decreased
Psychiatric disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0011 affected8 at risk
EG0020 affected10 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Eye pain
Eye disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Eye discharge
Eye disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Eye inflammation
Eye disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0021 affected10 at risk
EG003
Eye irritation
Eye disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Hypermetropia
Eye disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA (19.1)
Systematic Assessment
EG0001 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Ear tube insertion
Surgical and medical procedures
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Tooth extraction
Surgical and medical procedures
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Cyanosis
Cardiac disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Wolff-Parkinson-White syndrome
Cardiac disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA (19.1)
Systematic Assessment
EG0002 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Thyroglossal cyst
Congenital, familial and genetic disorders
MedDRA (19.1)
Systematic Assessment
EG0000 affected8 at risk
EG0010 affected8 at risk
EG0020 affected10 at risk
EG003
Skin papilloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)