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Clinical Trial Results:
An Extension Study to Evaluate 24 Months of Standard-of-Care Osteoporosis Management Following Completion of 18 Months of BA058 or Placebo Treatment in Protocol BA058-05-003

Summary
EudraCT number	2012-002216-10
Trial protocol	EE DK CZ PL LT
Global end of trial date	03 Oct 2016

Results information
Results version number	v2(current)
This version publication date	04 Dec 2020
First version publication date	16 Oct 2020
Other versions	v1
Version creation reason	Correction of full data set Updated based on changes made to the ClinicalTrials.gov posting

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

BA058-05-005

ISRCTN number

US NCT number

NCT01657162

WHO universal trial number (UTN)

Sponsor organisation name

Radius Health, Inc.

Sponsor organisation address

950 Winter Street, Waltham, United States, 02451

Public contact

Radius Head of Clinical Operations, Radius Health, Inc., +1 617-551-4700,

Scientific contact

VP, Osteoporosis Clinical Development, Radius Health, Inc., +1 617-444-1943,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

01 Dec 2016

Is this the analysis of the primary completion data?

Yes

Primary completion date

03 Oct 2016

Global end of trial reached?

Yes

Global end of trial date

03 Oct 2016

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to collect clinical information following 6 months of treatment with alendronate, in participants who have previously received 18 months of blinded treatment with abaloparatide-subcutaneous or placebo in Study BA058-05-003 (EudraCT Number 2012-002216-10). Following the initial 6 months of oral alendronate treatment in the study, participants entered the long-term phase of the study during which participants continued to receive alendronate treatment for an additional 18 months (for a total of 24 months).

Protection of trial subjects

The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki in its revised edition (Tokyo, 2004), the guidelines for current Good Clinical Practice (GCP), International Conference on Harmonization (ICH) [Committee for Proprietary Medicinal Products (CPMP)/ICH/135/95], the US Food and Drug Administration (FDA) Code of Federal Regulations (CFR) (21 CFR Parts 50, 54, 56 and 312), Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT) regulations (Argentinean Investigators only), and all other applicable local regulatory and ethical requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Nov 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 16

Country: Number of subjects enrolled

Argentina: 14

Country: Number of subjects enrolled

Brazil: 288

Country: Number of subjects enrolled

Czech Republic: 197

Country: Number of subjects enrolled

Denmark: 203

Country: Number of subjects enrolled

Estonia: 44

Country: Number of subjects enrolled

Hong Kong: 204

Country: Number of subjects enrolled

Lithuania: 33

Country: Number of subjects enrolled

Poland: 77

Country: Number of subjects enrolled

Romania: 63

Worldwide total number of subjects

1139

EEA total number of subjects

617

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

220

From 65 to 84 years

916

85 years and over

Subject disposition

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Recruitment details

Eligible participants who received abaloparatide or placebo in the double-blind study (BA058-05-003 [Study 003]), were enrolled to this open-label extension study. Complete results for Study 003 are reported in the EudraCT Study Record 2010-022576-30.

Screening details

The procedures performed for the Follow-up visit (Month 19) for Study 003 served as Baseline for Day 1 of Study BA058-05-005 (Study 005).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Even though this is an open-label study, participants and Investigators who will be participating in this study (BA058-05-005) will remain blinded to the prior treatment assignment in Study BA058-05-003 (2010-022576-30) until all participants completed the first 6 months of BA058-05-005 for prespecified data analysis. Complete data analysis for Study BA058-05-003 are reported in the EudraCT Study Record 2010-022576-30.

Are arms mutually exclusive

Yes

Abaloparatide-SC/Alendronate

Arm description

Participants received 70 milligrams (mg) of alendronate orally once per week beginning on Day 2 for up to 24 months after participating in Study BA058-05-003 during which participants received abaloparatide 80 micrograms (mcg) subcutaneous (SC) daily for 18 months.

Arm type

Experimental

Investigational medicinal product name

Alendronate

Investigational medicinal product code

Other name

Fosamax, alendronate sodium

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

70 mg orally once per week

Placebo/Alendronate

Arm description

Participants received 70 mg of alendronate orally once per week beginning on Day 2 for up to 24 months after participating in Study BA058-05-003 during which participants received abaloparatide-matching placebo daily for 18 months.

Arm type

Experimental

Investigational medicinal product name

Alendronate

Investigational medicinal product code

Other name

Fosamax, alendronate sodium

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

70 mg orally once per week

Number of subjects in period 1	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Started	558	581
Study 005 ITT Population	558	581
Study 005 Safety Population	553	580
Study 005 mITT Population	544	568
Completed	499	506
Not completed	59	75
Adverse event, serious fatal	2	3
Consent withdrawn by subject	13	13
Adverse event, non-fatal	26	36
Other than Specified	-	2
Lost to follow-up	3	4
Hypersensitivity to Alendronate	-	1
Refusal of Treatment	4	6
Continuing Significant Deterioration	9	3
Inability to Complete Study Procedures	1	7
Protocol deviation	1	-

Baseline characteristics

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Reporting group title

Abaloparatide-SC/Alendronate

Reporting group description

Reporting group title

Placebo/Alendronate

Reporting group description

Reporting group values	Abaloparatide-SC/Alendronate	Placebo/Alendronate	Total
Number of subjects	558	581	1139
Age Categorical
Units:
<65 years	106	114	220
65 to <74 years	351	370	721
≥75 years	101	97	198
Sex: Female, Male
Units:
Female	558	581	1139
Male	0	0	0
Lumbar Spine Bone Mineral Density (BMD) T-Score, n = 556, 581
BMD measured by a DXA instrument. At Baseline, participants were required to have a BMD T-score ≤2.5 to >-5.0 at the lumbar spine (L1-L4) or if the pre-specified fracture criteria were not met then T-score could be ≤3.0 to >-5.0. Osteoporosis status was based on the WHO 2007 criteria of normal (T-score >-1.0), osteopenia (T-score >-2.5 to ≤-1.0), and osteoporosis (T-score ≤-2.5). Study 003 ITT participants who enrolled in Study 005 (Study 005 ITT Population) with an evaluable femoral neck BMD T-score. Study 003 ITT population included all participants who randomized into Study 003.
Units: T-score
arithmetic mean (standard deviation)	-2.11 ± 0.997	-2.87 ± 0.867	-
Femoral Neck BMD T-Score, n = 555, 581
BMD measured by a DXA instrument. At Baseline, participants were required to have a BMD T-score ≤2.5 to >-5.0 at the lumbar spine (L1-L4) or if the pre-specified fracture criteria were not met then T-score could be ≤3.0 to >-5.0. Osteoporosis status was based on the WHO 2007 criteria of normal (T-score >-1.0), osteopenia (T-score >-2.5 to ≤-1.0), and osteoporosis (T-score ≤-2.5). Study 003 ITT participants who enrolled in Study 005 (Study 005 ITT Population) with an evaluable femoral neck BMD T-score. Study 003 ITT population included all participants who randomized into Study 003.
Units: T-score
arithmetic mean (standard deviation)	-1.951 ± 0.656	-2.196 ± 0.695	-
Total Hip BMD T-Score, n = 555, 581
BMD measured by a DXA instrument. At Baseline, participants were required to have a BMD T-score ≤2.5 to >-5.0 at the lumbar spine (L1-L4) or if the pre-specified fracture criteria were not met then T-score could be ≤3.0 to >-5.0. Osteoporosis status was based on the WHO 2007 criteria of normal (T-score >-1.0), osteopenia (T-score >-2.5 to ≤-1.0), and osteoporosis (T-score ≤-2.5). Study 003 ITT participants who enrolled in Study 005 (Study 005 ITT Population) with an evaluable femoral neck BMD T-score. Study 003 ITT population included all participants who randomized into Study 003.
Units: T-score
arithmetic mean (standard deviation)	-1.63 ± 0.742	-1.93 ± 0.758	-

End points

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Reporting group title

Abaloparatide-SC/Alendronate

Reporting group description

Reporting group title

Placebo/Alendronate

Reporting group description

Primary: Number of Participants With ≥1 New Vertebral Fracture Since Study BA058-05-003 Baseline

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End point title

Number of Participants With ≥1 New Vertebral Fracture Since Study BA058-05-003 Baseline ^[1]

End point description

Vertebral fractures were determined clinically and via protocol directed radiograph evaluation. Study BA058-05-005 mITT Population: all Study BA058-05-003 mITT participants with a Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25) evaluable radiologic assessment (spine X-ray). Study BA058-05-003 mITT population included all ITT participants with a pretreatment and postbaseline evaluable radiologic assessment during Study BA058-05-003. Complete results for Study BA058-05-003 are reported in the EudraCT Study Record 2010-022576-30.

End point type

Primary

End point timeframe

Study BA058-05-003 Baseline (Day 1) up to Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analyses is not applicable to this Endpoint.

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	544	568
Units: participants	3	25

No statistical analyses for this end point

Secondary: Number of Participants With a Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data from Studies BA058-05-005 and BA058-05-003 Combined)

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End point title

Number of Participants With a Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data from Studies BA058-05-005 and BA058-05-003 Combined)

End point description

Nonvertebral fractures were defined as clinical fractures that included: 1) those of the hip, wrist, forearm, shoulder, collar bone, upper arm, ribs, upper leg (not hip), knee, lower leg (not knee or ankle), foot, ankle, hand, pelvis (not hip), tailbone, and other; and 2) those associated with low trauma, defined as a fall from standing height or less; a fall on stairs, steps or curbs; a minimal trauma other than a fall; or moderate trauma other than a fall. Study BA058-05-005 ITT Population: all Study BA058-05-003 ITT participants who enrolled in the BA058-05-005 study. Study BA058-05-003 ITT population included all participants who were randomized into the study. Complete results for Study BA058-05-003 are reported in the EudraCT Study Record 2010-022576-30.

End point type

Secondary

End point timeframe

Study BA058-05-003 Baseline (Day 1) up to Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	558	581
Units: participants	15	32

No statistical analyses for this end point

Secondary: Percent Change From Study BA058-05-003 Baseline in Total Hip BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

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End point title

Percent Change From Study BA058-05-003 Baseline in Total Hip BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point description

Total hip BMD were measured via DXA. Study BA058-05-005 ITT Population: all Study BA058-05-003 ITT participants who enrolled in the BA058-05-005 study. Study BA058-05-003 ITT population included all participants who were randomized into Study BA058-05-003. Missing BMD data were imputed using last observation carried forward (LOCF). Complete results for Study BA058-05-003 are reported in the EudraCT Study Record 2010-022576-30.

End point type

Secondary

End point timeframe

Study BA058-05-003 Baseline (Day 1), Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	558	581
Units: percent change
arithmetic mean (standard deviation)	5.4737 ± 3.9884	1.3698 ± 2.9712

No statistical analyses for this end point

Secondary: Percent Change From Study BA058-05-003 Baseline in Femoral Neck BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

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End point title

Percent Change From Study BA058-05-003 Baseline in Femoral Neck BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point description

Femoral neck BMD were measured via DXA. Study BA058-05-005 ITT Population: all Study BA058-05-003 ITT participants who enrolled in the BA058-05-005 study. Study BA058-05-003 ITT population included all participants who were randomized into Study BA058-05-003. Missing BMD data were imputed using LOCF. Complete results for Study BA058-05-003 are reported in the EudraCT Study Record 2010-022576-30.

End point type

Secondary

End point timeframe

Study BA058-05-003 Baseline (Day 1), Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	558	581
Units: percent change
arithmetic mean (standard deviation)	4.5113 ± 4.8042	0.4649 ± 3.7913

No statistical analyses for this end point

Secondary: Percent Change From Study BA058-05-003 Baseline in Lumbar Spine BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

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End point title

Percent Change From Study BA058-05-003 Baseline in Lumbar Spine BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point description

Lumbar spine BMD were measured via DXA. Study BA058-05-005 ITT Population: all Study BA058-05-003 ITT participants who enrolled in the BA058-05-005 study. Study BA058-05-003 ITT population included all participants who were randomized into Study BA058-05-003. Missing BMD data were imputed using LOCF. Complete results for Study BA058-05-003 are reported in the EudraCT Study Record 2010-022576-30.

End point type

Secondary

End point timeframe

Study BA058-05-003 Baseline (Day 1), Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	558	581
Units: percent change
arithmetic mean (standard deviation)	12.7921 ± 7.9790	3.5133 ± 4.2765

No statistical analyses for this end point

Secondary: Kaplan-Meier Estimated Event Rate of the First Incident of Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data From Studies BA058-05-005 and BA058-05-003 Combined)

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End point title

Kaplan-Meier Estimated Event Rate of the First Incident of Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data From Studies BA058-05-005 and BA058-05-003 Combined)

End point description

End point type

Secondary

End point timeframe

Study BA058-05-003 Baseline (Day 1) up to Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	558	581
Units: percentage of events
number (not applicable)	2.7	5.6

No statistical analyses for this end point

Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Data From Study BA058-05-005 Only)

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End point title

Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Data From Study BA058-05-005 Only)

End point description

A TEAE is any untoward medical occurrence or undesirable event(s) experienced in a participant that begins or worsens following administration of study drug, whether or not considered related to study drug by Investigator. An SAE was 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), congenital anomaly/birth defect, or persistent or significant disability/incapacity. Intensity for each AE was defined as mild, moderate, or severe. AEs included both SAEs and non-serious AEs. AEs whose causal relation was characterized as Possible or Probable were considered as related to study drug. AEs were coded using MedDRA. A summary of serious and all other nonserious AEs, regardless of causality, is located in the Reported Adverse Events module. Study 005 Safety Population: all Study 005 ITT participants who received 1 or more doses of alendronate.

End point type

Secondary

End point timeframe

Study BA058-05-005 Baseline (Day 1) up to Study BA058-05-005 Month 24

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	553	580
Units: participants
TEAEs	452	466
TEAEs Related to Study Treatment	85	80
Severe TEAEs	38	40
Serious TEAEs	65	58
TEAEs Leading to Death	0	2
TEAEs Leading to Discontinuation	30	36

No statistical analyses for this end point

Secondary: Number of Participants With a Clinically Notable Serum Chemistry Laboratory Value (Data From Study BA058-05-005 Only)

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End point title

Number of Participants With a Clinically Notable Serum Chemistry Laboratory Value (Data From Study BA058-05-005 Only)

End point description

Serum Chemistry laboratory parameters that were evaluated via notable criteria (presented in parentheses) included: sodium (Low: ≤129; High: ≥148 milliequivalent per liter [mEq/L]), potassium (Low: ≤3.2; High: ≥5.5 mEq/L), albumin (<2.5 grams [g]/deciliter [dL]), total protein (<5 g/dL), glucose (Low: ≤54; High: >125 mg/dL [fasting] or >200 milligrams [mg]/dL [random]), creatinine (≥2.1 mg/dL), aspartate aminotransferase (AST) (≥5.1*upper limit of normal [ULN]), alanine aminotransferase (ALT) (≥5.1*ULN), alkaline phosphatase (AP) (≥3.1*ULN), total bilirubin (≥1.51*ULN [with any increase in liver function tests] ≥2.0*ULN [with normal liver function tests]), creatine kinase (≥3.1*ULN), total cholesterol (>226 mg/dL), and total calcium (Low: ≤7.4; High: ≥11.6 mg/dL). Only the serum chemistry parameters with at least 1 participant with a notable laboratory value are presented. Study 005 Safety Population: all Study 005 ITT participants who received 1 or more doses of alendronate.

End point type

Secondary

End point timeframe

Study BA058-05-005 Baseline (Day 1) up to Study BA058-05-005 Month 24

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	553	580
Units: participants
Alkaline Phosphatase, n = 545, 580	1	0
Cholesterol Total, n = 342, 358	75	73
Creatine Kinase, n = 545, 568	2	1
Glucose (Fasting; High), n = 515, 543	22	18
Glucose (Random), n = 515, 543	1	2
Potassium (Low), n = 541, 565	1	3
Potassium (High), n = 541, 565	4	3
Sodium (Low), n = 542, 570	1	1
Sodium (High), n = 542, 580	6	2

No statistical analyses for this end point

Secondary: Number of Participants With a Clinically Notable Hematology Laboratory Value (Data From Study BA058-05-005 Only)

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End point title

Number of Participants With a Clinically Notable Hematology Laboratory Value (Data From Study BA058-05-005 Only)

End point description

Hematology laboratory parameters that were evaluated via notable criteria (presented in parentheses) included: Absolute Eosinophils (>5000 cells/mm^3), Absolute Lymphocytes (≤499 cells/mm^3), Absolute Neutrophils (≤999 cells/mm^3), % Eosinophils (>50%), % Lymphocytes (≤5%), % Neutrophils (≤10%), Hemoglobin (Low: ≤9.4 g/dL; High: change from baseline ≥2.1 g/dL), Platelets (≤99000 cells/mm^3), and White Blood Cells (Low: ≤1499 cells/mm^3; High: ≥20001 cells/mm^3). Only the hematology parameters with at least 1 participant with a notable laboratory value are presented. Study 005 Safety Population: all Study 005 ITT participants who received 1 or more doses of alendronate.

End point type

Secondary

End point timeframe

Study BA058-05-005 Baseline (Day 1) up to Study BA058-05-005 Month 24

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	553	580
Units: participants
Absolute Lymphocytes, n = 380, 392	15	11
Lymphocytes (Absolute Count or %), n = 521, 540	15	11
Absolute Neutrophils, n = 392, 410	0	2
Neutrophils (Absolute Count or %), n = 533, 558	0	2
Hemoglobin (Low), n = 544, 580	7	2
Hemoglobin (High), n = 544, 580	19	17
Platelets, n = 545, 565	1	0

No statistical analyses for this end point

Secondary: Number of Participants With a Clinically Notable Coagulation Laboratory Value (Data From Study BA058-05-005 Only)

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End point title

Number of Participants With a Clinically Notable Coagulation Laboratory Value (Data From Study BA058-05-005 Only)

End point description

Coagulation laboratory parameters that were evaluated via notable criteria (presented in parentheses) included: Activated Partial Thromboplastin Time (≥1.41*ULN), Prothrombin Time (≥1.21*ULN). Because the Activated Partial Thromboplastin Time was the only coagulation laboratory parameter with at least 1 participant with a notable laboratory value, this is the only parameter presented below. Study 005 Safety Population: all Study 005 ITT participants who received 1 or more doses of alendronate.

End point type

Secondary

End point timeframe

Study BA058-05-005 Baseline (Day 1) up to Study BA058-05-005 Month 24

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	553	580
Units: participants	9	4

No statistical analyses for this end point

Secondary: Number of Participants With a Clinically Notable Urine Laboratory Value (Data From Study BA058-05-005 Only)

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End point title

Number of Participants With a Clinically Notable Urine Laboratory Value (Data From Study BA058-05-005 Only)

End point description

Urine laboratory parameters that were evaluated via notable criteria (presented in parentheses) included: Glucose (2+), Protein (2+), Blood (>50 red blood cells per high-power field [rbc/hpf]). Study 005 Safety Population: all Study 005 ITT participants who received 1 or more doses of alendronate.

End point type

Secondary

End point timeframe

Study BA058-05-005 Baseline (Day 1) up to Study BA058-05-005 Month 24

End point values	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Number of subjects analysed	553	580
Units: participants
Glucose, n = 553, 580	4	3
Protein, n = 543, 567	6	6
Blood, n = 482, 496	77	50

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Study BA058-05-005 Baseline (Day 1) up to Study BA058-05-005 Month 24

Adverse event reporting additional description

Study 005 Safety Population: all Study 005 ITT participants who received 1 or more doses of alendronate. Serious and Non-Serious TEAEs are presented. The "Total # of Deaths Resulting From Adverse Events" is reporting the number of deaths resulting from TEAEs. AEs for Study 003 are reported in the EudraCT Study Record 2010-022576-30.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.1

Reporting group title

Abaloparatide-SC/Alendronate

Reporting group description

Reporting group title

Placebo/Alendronate

Reporting group description

Serious adverse events	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Total subjects affected by serious adverse events
subjects affected / exposed	65 / 553 (11.75%)	58 / 580 (10.00%)
number of deaths (all causes)	2	3
number of deaths resulting from adverse events	0	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Brain neoplasm
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	2 / 553 (0.36%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colorectal adenocarcinoma
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Leiomyosarcoma
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	1 / 553 (0.18%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian adenoma
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ovarian epithelial cancer
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritoneal neoplasm
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal cancer
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vulval cancer
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Essential hypertension
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Temporal arteritis
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Varicose vein
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Medical device removal
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal septal operation
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Removal of internal fixation
subjects affected / exposed	1 / 553 (0.18%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tooth extraction
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	1 / 553 (0.18%)	2 / 580 (0.34%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Uterine prolapse
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Asthmatic crisis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cough
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Major depression
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychotic disorder
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Cervical vertebral fracture
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Clavicle fracture
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Concussion
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Head injury
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower limb fracture
subjects affected / exposed	1 / 553 (0.18%)	3 / 580 (0.52%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	1 / 553 (0.18%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 553 (0.18%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	2 / 553 (0.36%)	2 / 580 (0.34%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	1 / 553 (0.18%)	3 / 580 (0.52%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1
Angina pectoris
subjects affected / exposed	2 / 553 (0.36%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	2 / 553 (0.36%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure chronic
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular failure
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 553 (0.00%)	2 / 580 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1
Myocardial ischaemia
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Carpal tunnel syndrome
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebellar ischaemia
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral thrombosis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 553 (0.00%)	2 / 580 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical radiculopathy
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	2 / 553 (0.36%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	2 / 553 (0.36%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transient global amnesia
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	4 / 553 (0.72%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	4 / 553 (0.72%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Retinal detachment
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Visual impairment
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vitreous haemorrhage
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 553 (0.18%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric polyps
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	0 / 553 (0.00%)	2 / 580 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Irritable bowel syndrome
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Proctalgia
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestinal perforation
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	1 / 553 (0.18%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Drug induced liver injury
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stress urinary incontinence
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary incontinence
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	2 / 553 (0.36%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	5 / 553 (0.90%)	4 / 580 (0.69%)
occurrences causally related to treatment / all	0 / 6	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Bronchopneumonia
subjects affected / exposed	1 / 553 (0.18%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media chronic
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pericarditis infective
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 553 (0.18%)	2 / 580 (0.34%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis chronic
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 553 (0.00%)	1 / 580 (0.17%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Viral myositis
subjects affected / exposed	1 / 553 (0.18%)	0 / 580 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Abaloparatide-SC/Alendronate	Placebo/Alendronate
Total subjects affected by non serious adverse events
subjects affected / exposed	145 / 553 (26.22%)	158 / 580 (27.24%)
Vascular disorders
Hypertension
subjects affected / exposed	27 / 553 (4.88%)	33 / 580 (5.69%)
occurrences all number	29	33
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	54 / 553 (9.76%)	58 / 580 (10.00%)
occurrences all number	61	66
Back pain
subjects affected / exposed	36 / 553 (6.51%)	34 / 580 (5.86%)
occurrences all number	41	38
Pain in extremity
subjects affected / exposed	23 / 553 (4.16%)	31 / 580 (5.34%)
occurrences all number	23	35
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	40 / 553 (7.23%)	51 / 580 (8.79%)
occurrences all number	58	83

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Were there any global substantial amendments to the protocol? Yes

13 Feb 2013

In addition to administrative changes and editorial corrections, the protocol was amended to: - extend the duration of the study from 6 months to a total of 24 months - to revise inclusion criteria to extend the visit window from 33 days to 40 days to accommodate participant scheduling - to reflect the elimination of the option of an alternative osteoporosis treatment and to stipulate that only alendronate treatment could be administered.

31 Mar 2014

In addition to administrative changes and editorial corrections, the following changes to the protocol were made: - Modified to specify that formal statistical analyses (rather than general descriptive descriptions) were to be performed, as appropriate - Modified to clarify the correct alendronate dosage - Modified to provide flexibility in alendronate sourcing - Deleted the need to discuss supplement modification with the study medical monitor - Modified to more accurately describe the sequence of procedures in the protocol - Modified to clarify how the data were to be grouped in the analyses - Modified to clarify the participant populations to be analyzed - Clarified that AEs and clinical laboratory abnormalities at 24 months, rather than 6 months, were to be followed until they were resolved, become chronic, or stable - Definitions of protocol violation and protocol deviation were added to align the protocol with Radius' Protocol Deviation/Violation Procedure Manual (Version 3.0, 1 October 12).

24 Aug 2015

The following changes were implemented: - The Medical Monitor was changed. - The length of time with positive antibodies to abaloparatide that participants were to be followed was extended, to be continued until the antibody titer is negative.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
An Extension Study to Evaluate 24 Months of Standard-of-Care Osteoporosis Management Following Completion of 18 Months of BA058 or Placebo Treatment in Protocol BA058-05-003

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With ≥1 New Vertebral Fracture Since Study BA058-05-003 Baseline

Primary: Number of Participants With ≥1 New Vertebral Fracture Since Study BA058-05-003 Baseline

Secondary: Number of Participants With a Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data from Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Number of Participants With a Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data from Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Percent Change From Study BA058-05-003 Baseline in Total Hip BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Total Hip BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Femoral Neck BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Femoral Neck BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Lumbar Spine BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Lumbar Spine BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Kaplan-Meier Estimated Event Rate of the First Incident of Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data From Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Kaplan-Meier Estimated Event Rate of the First Incident of Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data From Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Serum Chemistry Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Serum Chemistry Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Hematology Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Hematology Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Coagulation Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Coagulation Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Urine Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Urine Laboratory Value (Data From Study BA058-05-005 Only)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: An Extension Study to Evaluate 24 Months of Standard-of-Care Osteoporosis Management Following Completion of 18 Months of BA058 or Placebo Treatment in Protocol BA058-05-003

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With ≥1 New Vertebral Fracture Since Study BA058-05-003 Baseline

Primary: Number of Participants With ≥1 New Vertebral Fracture Since Study BA058-05-003 Baseline

Secondary: Number of Participants With a Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data from Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Number of Participants With a Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data from Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Percent Change From Study BA058-05-003 Baseline in Total Hip BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Total Hip BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Femoral Neck BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Femoral Neck BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Lumbar Spine BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Percent Change From Study BA058-05-003 Baseline in Lumbar Spine BMD at Study BA058-05-005 Month 6 (Study BA058-05-003 Month 25)

Secondary: Kaplan-Meier Estimated Event Rate of the First Incident of Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data From Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Kaplan-Meier Estimated Event Rate of the First Incident of Nonvertebral Fracture Since Study BA058-05-003 Baseline (Data From Studies BA058-05-005 and BA058-05-003 Combined)

Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Serum Chemistry Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Serum Chemistry Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Hematology Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Hematology Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Coagulation Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Coagulation Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Urine Laboratory Value (Data From Study BA058-05-005 Only)

Secondary: Number of Participants With a Clinically Notable Urine Laboratory Value (Data From Study BA058-05-005 Only)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Extension Study to Evaluate 24 Months of Standard-of-Care Osteoporosis Management Following Completion of 18 Months of BA058 or Placebo Treatment in Protocol BA058-05-003