Phase 2 Study of BA058 (Abaloparatide) Transdermal Delivery in Postmenopausal Women With Osteoporosis

• Sponsor: Radius Health, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01674621
• Collaborator: Nordic Bioscience A/S (Industry)
• Enrollment: 250
• Locations: 9
• Arms: 5
• Actual Duration (Months): 10.2
• Patients Per Site: 27.8
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

To determine the clinical safety and efficacy of abaloparatide transdermal in otherwise healthy postmenopausal women with osteoporosis as assessed by changes in bone mineral density (BMD) and serum markers of bone metabolism when compared to transdermal placebo and abaloparatide injection for 6 months of treatment.

Condition or Disease	Intervention/Treatment	Phase
Post Menopausal Osteoporosis	Drug: Abaloparatide Transdermal (50 mcg); Drug: Abaloparatide Transdermal (100 mcg); Drug: Abaloparatide Transdermal (150 mcg); Drug: Abaloparatide Injection (80 mcg); Drug: Abaloparatide Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Since the abaloparatide injection arm was administered subcutaneously (SC), it was not possible to blind this arm of the study. Therefore, abaloparatide-SC was considered a reference drug, but the centralized BMD assessments and bone marker evaluations remained blinded to all treatment assignments.
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study of BA058 Administered Via a Coated Transdermal Microarray Delivery System (BA058 Transdermal) in Healthy Postmenopausal Women With Osteoporosis
• Actual Study Start Date: Sep 25, 2012
• Actual Primary Completion Date: Aug 2, 2013
• Actual Study Completion Date: Aug 2, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abaloparatide Transdermal (50 mcg) Abaloparatide Transdermal Microneedle Patch - 50 microgram (mcg) daily applications for up to 6 months	Drug: Abaloparatide Transdermal (50 mcg); Abaloparatide Transdermal Microneedle Active Patch; Other Names: BA058 Transdermal (50 mcg)
Experimental: Abaloparatide Transdermal (100 mcg) Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Drug: Abaloparatide Transdermal (100 mcg); Abaloparatide Transdermal Microneedle Active Patch; Other Names: BA058 Transdermal (100 mcg)
Experimental: Abaloparatide Transdermal (150 mcg) Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Drug: Abaloparatide Transdermal (150 mcg); Abaloparatide Transdermal Microneedle Active Patch; Other Names: BA058 Transdermal (150 mcg)
Active Comparator: Abaloparatide Injection (80 mcg) Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Drug: Abaloparatide Injection (80 mcg); Abaloparatide Subcutaneous Injection; Other Names: BA058 Injection (80 mcg)
Placebo Comparator: Abaloparatide Transdermal Placebo (0 mcg) Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months	Drug: Abaloparatide Placebo; Abaloparatide Transdermal Microneedle Placebo Patch; Other Names: BA058 Placebo

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at 6 Months [Baseline, 6 Months]

   Percent change in BMD as specified by dual energy x-ray absorptiometry (DXA) scans of the lumbar spine.

Secondary Outcome Measures

1. Percent Change From Baseline in BMD of Total Hip at 6 Months [Baseline, 6 Months]

   Percent change in BMD as specified by DXA scans of the total hip.

2. Percent Change From Baseline in BMD of Forearm at 6 Months [Baseline, 6 Months]

   Percent change in BMD as specified by DXA scans of the forearm.

3. Percent Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (BSAP) at 6 Months [Baseline, 6 Months]

4. Percent Change From Baseline in Serum Procollagen Type I C Propeptide (PICP) at 6 Months [Baseline, 6 Months]

5. Percent Change From Baseline in Serum Osteocalcin at 6 Months [Baseline, 6 Months]

6. Percent Change From Baseline in Serum Procollagen Type I N Propeptide (PINP) at 6 Months [Baseline, 6 Months]

7. Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (CTXI) at 6 Months [Baseline, 6 Months]

8. Number of Participants With Abnormal Physical Examinations at Screening and End of Treatment (6 Months) [Baseline up to 6 Months]

   A full physical examination included, at a minimum: general appearance, skin, head/ears/eyes/nose/throat, lungs/chest, breasts, heart, abdomen, lymph nodes, musculoskeletal, extremities, and neurologic. Physical examination results that were considered abnormal were determined by the Investigator. A summary of other non-serious adverse events (AEs) and all serious AEs (SAEs), regardless of causality is located in Reported AE section.

9. Number of Participants With Treatment Emergent Adverse Events (TEAEs) That Occurred During the Study That Were Associated With Vital Sign Changes [Baseline up to 7 Months]

   Vital sign parameters included respiration rate (breaths/minute), body temperature (°C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHg), and heart rate (bpm). Number of participants for each TEAE is presented. The same participant may be included in more than one TEAE category. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

10. Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Result [Baseline up to 7 Months]

    The following ECG parameters were recorded: rhythm, heart rate, PR interval, QRS duration and QT/QTc. ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

11. Number of Participants With an Abnormal Clinical Hematology Laboratory Parameter With an Eastern Cooperative Oncology Group (ECOG) Score of Grade 3 or Grade 4 [Baseline up to 6 Months]

    Hematology laboratory parameters that were evaluated via ECOG Grade 3 and Grade 4 criteria (presented in parentheses) included: white blood cell (Grade 3: 1.0-1.9*10^9/liter [L]; Grade 4 <1.0*10^9/L), platelets (Grade 3: 25.0-49.9*10^9/L; Grade 4: <25.0*10^9/L), haemoglobin (Grade 3: 65.0-79.0 grams [g]/L or 4.0-4.9 mmol/L; Grade 4: <65.0 g/L or <4.0 millimole [mmol]/L), granulocytes/bands (Grade 3: 0.5-0.9*10^9/L; Grade 4: <0.5*10^9/L), lymphocytes (Grade 3: 0.5-0.9*10^9/L; Grade 4: <0.5 *10^9/L), haemorrhage (Grade 3: gross, 3 - 4 units transfusion per episode; Grade 4: massive, > 4 units transfusion per episode). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

12. Number of Participants With an Abnormal Clinical Chemistry Laboratory Parameter With an ECOG Score of Grade 3 or Grade 4 [Baseline up to 6 Months]

    Chemistry laboratory parameters that were evaluated via ECOG Grade 3 and Grade 4 criteria (presented in parentheses) included: sodium, potassium, chloride, inorganic phosphorus, albumin, total protein (Grade 3: 4 (+), >1.0 g%, or >10 g/L; Grade 4: nephrotic syndrome), glucose, blood urea nitrogen (BUN), creatinine (Grade 3: 3.1-6.0*normal; Grade 4: >6.0*normal), uric acid, aspartate aminotransferase (AST) (Grade 3: 5.1-20.0 units [U]/L*normal, Grade 4: >20.0 U/L*normal), alanine aminotransferase (ALT) (Grade 3: 5.1-20.0 U/L*normal; Grade 4: >20.0 U/L*normal), gamma-glutamyltranspeptidase (GGT), creatine phosphokinase (CPK), alkaline phosphatase (Grade 3: 5.1-20.0 U/L*normal; Grade 4: >20.0 U/L*normal), total bilirubin (Grade 3: 1.5-3.0*normal; Grade 4: >3.0*normal), lactate dehydrogenase (LDH), cholesterol, triglycerides, total calcium. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

13. Number of Participants With an Abnormal Clinical Coagulation Laboratory Parameter With an ECOG Score of Grade 3 or Grade 4 [Baseline up to 6 Months]

    Coagulation laboratory parameters that were evaluated via ECOG Grade 3 and Grade 4 criteria (presented in parentheses) included: prothrombin time (quick) (Grade 3: 1.51%-2.00%*normal, Grade 4: >2.00%*normal), partial thromboplastin time (Grade 3: 2.34-3.00 seconds [sec], Grade 4: >3.00 secs*normal). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Postmenopausal woman, less than 85 years old.

• BMD T-score ≤-2.5 of spine or hip (femoral neck) or ≤-2.0 with previous fracture (within 5 years).

• Normal physical exam, vital signs, electrocardiogram (ECG), and medical history.

• Laboratory tests within the normal range, including serum calcium, Vitamin D, parathyroid hormone (PTH) (1-84), serum phosphorus, and alkaline phosphatase.

Exclusion Criteria:

• BMD T-score ≤-5.0 at the lumbar spine or hip.

• History of bone disorders (for example, Paget's disease) other than postmenopausal osteoporosis.

• Significantly impaired renal function.

• History of any cancer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Lakewood	Colorado	United States	80227
2		Atlanta	Georgia	United States	30319
3		Bethesda	Maryland	United States	20817
4		Aalborg		Denmark
5		Ballerup		Denmark
6		Vejle		Denmark
7		Tallinn		Estonia
8		Lodz		Poland
9		Warsaw		Poland

Sponsors and Collaborators

• Radius Health, Inc.
• Nordic Bioscience A/S

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Radius Health, Inc.
• ClinicalTrials.gov Identifier: NCT01674621
• Other Study ID Numbers: BA058-05-007; 2012-001921-29
• First Posted: Aug 29, 2012
• Last Update Posted: Jun 16, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Radius Health, Inc.: BA058; Abaloparatide-SC; abaloparatide; Abaloparatide-TD; Osteo; Osteoporosis; Transdermal; Patch
• Additional relevant MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Abaloparatide; Parathyroid Hormone-Related Protein

Study Results

Participant Flow

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 microgram (mcg) daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-Subcutaneous (SC) Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Period Title: Overall Study
STARTED	50	51	48	51	50
Modified Intent-to-Treat Population	47	46	43	49	46
Safety Population	50	51	47	51	50
COMPLETED	45	43	41	45	44
NOT COMPLETED	5	8	7	6	6

Baseline Characteristics

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)	Total
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months	Total of all reporting groups
Overall Participants	47	46	43	49	46	231
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.9 (4.83)	65.7 (5.26)	66.3 (6.46)	66.4 (5.48)	66.5 (7.27)	66.2 (5.87)
Sex: Female, Male (Count of Participants)
Female	47 100%	46 100%	43 100%	49 100%	46 100%	231 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at 6 Months
Description	Percent change in BMD as specified by dual energy x-ray absorptiometry (DXA) scans of the lumbar spine.
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	1.87 (2.87)	2.33 (2.96)	2.95 (3.13)	5.80 (4.21)	0.04 (2.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0066
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.930
	Confidence Interval	(2-Sided) 95%; -5.555 to -2.305
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change of BMD from baseline to end-of-treatment between treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.470
	Confidence Interval	(2-Sided) 95%; -5.104 to -1.837
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change of BMD from baseline to end-of-treatment between treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.856
	Confidence Interval	(2-Sided) 95%; -4.519 to -1.193
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change of BMD from baseline to end-of-treatment between treatment groups (transdermal and SC injection).

2. Secondary Outcome

Title	Percent Change From Baseline in BMD of Total Hip at 6 Months
Description	Percent change in BMD as specified by DXA scans of the total hip.
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pre-treatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 microgram (mcg) daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	0.97 (1.95)	1.32 (1.96)	1.49 (1.73)	2.74 (3.05)	-0.02 (2.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0547
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0056
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.768
	Confidence Interval	(2-Sided) 95%; -2.864 to -0.672
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change off BMD from baseline to end-of-treatment between active treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.420
	Confidence Interval	(2-Sided) 95%; -2.522 to -0.318
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change of BMD from baseline to end-of-treatment between treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.247
	Confidence Interval	(2-Sided) 95%; -2.368 to -0.126
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change of BMD from baseline to end-of-treatment between treatment groups (transdermal and SC injection).

3. Secondary Outcome

Title	Percent Change From Baseline in BMD of Forearm at 6 Months
Description	Percent change in BMD as specified by DXA scans of the forearm.
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	-0.24 (2.74)	-0.16 (3.71)	0.84 (2.96)	0.33 (3.41)	0.05 (3.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9493
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of treatment to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9806
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of treatment to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5191
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BMD from baseline to end-of treatment to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.564
	Confidence Interval	(2-Sided) 95%; -2.168 to 1.040
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change off BMD from baseline to end-of-treatment between active treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.483
	Confidence Interval	(2-Sided) 95%; -2.115 to 1.150
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change off BMD from baseline to end-of-treatment between active treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.517
	Confidence Interval	(2-Sided) 95%; -1.106 to 2.139
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change off BMD from baseline to end-of-treatment between active treatment groups (transdermal and SC injection).

4. Secondary Outcome

Title	Percent Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (BSAP) at 6 Months
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	-4.84 (23.87)	5.22 (43.66)	-5.52 (37.86)	17.30 (42.76)	10.23 (64.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2549
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BSAP from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9115
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BSAP from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2390
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of BSAP from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-22.146
	Confidence Interval	(2-Sided) 95%; -40.501 to -3.790
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end-of-treatment between active treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.086
	Confidence Interval	(2-Sided) 95%; -30.543 to 6.372
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end-of-treatment between active treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-22.828
	Confidence Interval	(2-Sided) 95%; -41.614 to -4.041
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end-of-treatment between active treatment groups (transdermal and SC injection).

5. Secondary Outcome

Title	Percent Change From Baseline in Serum Procollagen Type I C Propeptide (PICP) at 6 Months
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	-17.26 (22.86)	-8.42 (29.51)	-16.63 (25.11)	10.28 (72.31)	-6.76 (31.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1632
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of PICP from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9834
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of PICP from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2179
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of PICP from baseline to end-of-treatment (EOT) to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-27.541
	Confidence Interval	(2-Sided) 95%; -48.557 to -6.525
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-18.702
	Confidence Interval	(2-Sided) 95%; -39.835 to 2.430
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-26.914
	Confidence Interval	(2-Sided) 95%; -48.424 to -5.405
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

6. Secondary Outcome

Title	Percent Change From Baseline in Serum Osteocalcin at 6 Months
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	-4.37 (19.36)	6.67 (33.38)	-3.83 (22.01)	69.54 (81.79)	-4.21 (27.55)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of serum osteocalcin from baseline to EOT to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1200
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of serum osteocalcin from baseline to EOT to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9998
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of serum osteocalcin from baseline to EOT to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-73.906
	Confidence Interval	(2-Sided) 95%; -96.926 to -50.886
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-62.872
	Confidence Interval	(2-Sided) 95%; -86.019 to -39.725
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-73.367
	Confidence Interval	(2-Sided) 95%; -96.927 to -49.807
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

7. Secondary Outcome

Title	Percent Change From Baseline in Serum Procollagen Type I N Propeptide (PINP) at 6 Months
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	-12.76 (26.81)	1.52 (57.29)	-6.78 (38.91)	97.64 (172.52)	-7.26 (35.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.8569
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of PINP from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6091
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of PINP from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9999
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of PINP from baseline to EOT to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-110.398
	Confidence Interval	(2-Sided) 95%; -156.966 to -63.831
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-96.115
	Confidence Interval	(2-Sided) 95%; -142.940 to -49.290
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-104.418
	Confidence Interval	(2-Sided) 95%; -152.079 to -56.758
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

8. Secondary Outcome

Title	Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (CTXI) at 6 Months
Time Frame	Baseline, 6 Months

Outcome Measure Data

Analysis Population Description

mITT population included all participants with pretreatment and end-of-treatment evaluable radiologic assessments. The participants were analyzed as randomized.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	47	46	43	49	46
Mean (Standard Deviation) [Percent change]	-2.61 (28.77)	1.65 (48.66)	-8.22 (54.84)	41.11 (104.12)	9.42 (22.57)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3483
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of CTXI from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6839
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of CTXI from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Transdermal Placebo (0 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1067
	Comments	Threshold for significance at 0.05 level.
	Method	Dunnett's test
	Comments	P-value from Dunnett's test comparing percent change of CTXI from baseline to end-of-treatment to each transdermal dose group versus placebo.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (50 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-43.721
	Confidence Interval	(2-Sided) 95%; -75.748 to -11.694
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (100 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-39.461
	Confidence Interval	(2-Sided) 95%; -71.665 to -7.257
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Abaloparatide Transdermal (150 mcg), Abaloparatide Injection (80 mcg)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-49.334
	Confidence Interval	(2-Sided) 95%; -82.113 to -16.555
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference of percent change from baseline to end of treatment between the active treatment groups (transdermal and SC injection).

9. Secondary Outcome

Title	Number of Participants With Abnormal Physical Examinations at Screening and End of Treatment (6 Months)
Description	A full physical examination included, at a minimum: general appearance, skin, head/ears/eyes/nose/throat, lungs/chest, breasts, heart, abdomen, lymph nodes, musculoskeletal, extremities, and neurologic. Physical examination results that were considered abnormal were determined by the Investigator. A summary of other non-serious adverse events (AEs) and all serious AEs (SAEs), regardless of causality is located in Reported AE section.
Time Frame	Baseline up to 6 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received 1 or more doses of study medication. The participants were analyzed as treated.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	50	51	47	51	50
General appearance at Screening	0 0%	0 0%	0 0%	1 2%	0 0%
General appearance at 6 months	0 0%	0 0%	1 2.3%	1 2%	0 0%
Skin at Screening	28 59.6%	24 52.2%	17 39.5%	14 28.6%	21 45.7%
Skin at 6 months	29 61.7%	26 56.5%	16 37.2%	14 28.6%	17 37%
Head at Screening	6 12.8%	3 6.5%	2 4.7%	5 10.2%	1 2.2%
Head at 6 months	6 12.8%	4 8.7%	3 7%	4 8.2%	2 4.3%
Lungs at Screening	0 0%	0 0%	0 0%	1 2%	1 2.2%
Lungs at 6 months	0 0%	0 0%	0 0%	1 2%	0 0%
Breasts at Screening	4 8.5%	7 15.2%	3 7%	3 6.1%	11 23.9%
Breasts at 6 months	4 8.5%	7 15.2%	3 7%	4 8.2%	10 21.7%
Abdomen at Screening	7 14.9%	8 17.4%	4 9.3%	9 18.4%	4 8.7%
Abdomen at 6 months	6 12.8%	7 15.2%	3 7%	9 18.4%	3 6.5%
Lymph nodes at Screening	0 0%	0 0%	1 2.3%	0 0%	0 0%
Lymph nodes at 6 months	0 0%	0 0%	0 0%	0 0%	1 2.2%
Columna at Screening	1 2.1%	3 6.5%	7 16.3%	4 8.2%	1 2.2%
Columna at 6 months	1 2.1%	2 4.3%	7 16.3%	3 6.1%	1 2.2%
Extremities at Screening	21 44.7%	13 28.3%	14 32.6%	23 46.9%	21 45.7%
Extremities at 6 months	23 48.9%	10 21.7%	14 32.6%	25 51%	21 45.7%
Neurologic at Screening	0 0%	0 0%	0 0%	2 4.1%	1 2.2%
Neurologic at 6 months	0 0%	0 0%	0 0%	3 6.1%	1 2.2%

10. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) That Occurred During the Study That Were Associated With Vital Sign Changes
Description	Vital sign parameters included respiration rate (breaths/minute), body temperature (°C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (mmHg), and heart rate (bpm). Number of participants for each TEAE is presented. The same participant may be included in more than one TEAE category. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to 7 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received 1 or more doses of study medication. The participants were analyzed as treated.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	50	51	47	51	50
Hypertension	0 0%	1 2.2%	0 0%	0 0%	0 0%
Blood Pressure Increased	0 0%	0 0%	1 2.3%	1 2%	0 0%
Heart Rate increased	0 0%	0 0%	1 2.3%	0 0%	0 0%
Dyspnoea	0 0%	0 0%	0 0%	1 2%	0 0%
Dizziness	0 0%	0 0%	0 0%	1 2%	0 0%

11. Secondary Outcome

Title	Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Result
Description	The following ECG parameters were recorded: rhythm, heart rate, PR interval, QRS duration and QT/QTc. ECG results that were considered clinically meaningful were to be determined by the Investigator. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to 7 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received 1 or more doses of study medication. The participants were analyzed as treated.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	50	51	47	51	50
Count of Participants [Participants]	0 0%	0 0%	1 2.3%	2 4.1%	0 0%

12. Secondary Outcome

Title	Number of Participants With an Abnormal Clinical Hematology Laboratory Parameter With an Eastern Cooperative Oncology Group (ECOG) Score of Grade 3 or Grade 4
Description	Hematology laboratory parameters that were evaluated via ECOG Grade 3 and Grade 4 criteria (presented in parentheses) included: white blood cell (Grade 3: 1.0-1.9*10^9/liter [L]; Grade 4 <1.0*10^9/L), platelets (Grade 3: 25.0-49.9*10^9/L; Grade 4: <25.0*10^9/L), haemoglobin (Grade 3: 65.0-79.0 grams [g]/L or 4.0-4.9 mmol/L; Grade 4: <65.0 g/L or <4.0 millimole [mmol]/L), granulocytes/bands (Grade 3: 0.5-0.9*10^9/L; Grade 4: <0.5*10^9/L), lymphocytes (Grade 3: 0.5-0.9*10^9/L; Grade 4: <0.5 *10^9/L), haemorrhage (Grade 3: gross, 3 - 4 units transfusion per episode; Grade 4: massive, > 4 units transfusion per episode). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to 6 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received 1 or more doses of study medication. The participants were analyzed as treated.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	50	51	47	51	50
Count of Participants [Participants]	6 12.8%	5 10.9%	4 9.3%	1 2%	5 10.9%

13. Secondary Outcome

Title	Number of Participants With an Abnormal Clinical Chemistry Laboratory Parameter With an ECOG Score of Grade 3 or Grade 4
Description	Chemistry laboratory parameters that were evaluated via ECOG Grade 3 and Grade 4 criteria (presented in parentheses) included: sodium, potassium, chloride, inorganic phosphorus, albumin, total protein (Grade 3: 4 (+), >1.0 g%, or >10 g/L; Grade 4: nephrotic syndrome), glucose, blood urea nitrogen (BUN), creatinine (Grade 3: 3.1-6.0*normal; Grade 4: >6.0*normal), uric acid, aspartate aminotransferase (AST) (Grade 3: 5.1-20.0 units [U]/L*normal, Grade 4: >20.0 U/L*normal), alanine aminotransferase (ALT) (Grade 3: 5.1-20.0 U/L*normal; Grade 4: >20.0 U/L*normal), gamma-glutamyltranspeptidase (GGT), creatine phosphokinase (CPK), alkaline phosphatase (Grade 3: 5.1-20.0 U/L*normal; Grade 4: >20.0 U/L*normal), total bilirubin (Grade 3: 1.5-3.0*normal; Grade 4: >3.0*normal), lactate dehydrogenase (LDH), cholesterol, triglycerides, total calcium. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to 6 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received 1 or more doses of study medication. The participants were analyzed as treated.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	50	51	47	51	50
Count of Participants [Participants]	1 2.1%	0 0%	0 0%	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants With an Abnormal Clinical Coagulation Laboratory Parameter With an ECOG Score of Grade 3 or Grade 4
Description	Coagulation laboratory parameters that were evaluated via ECOG Grade 3 and Grade 4 criteria (presented in parentheses) included: prothrombin time (quick) (Grade 3: 1.51%-2.00%*normal, Grade 4: >2.00%*normal), partial thromboplastin time (Grade 3: 2.34-3.00 seconds [sec], Grade 4: >3.00 secs*normal). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to 6 Months

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received 1 or more doses of study medication. The participants were analyzed as treated.

Arm/Group Title	Abaloparatide Transdermal (50 mcg)	Abaloparatide Transdermal (100 mcg)	Abaloparatide Transdermal (150 mcg)	Abaloparatide Injection (80 mcg)	Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months	Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months	Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
Measure Participants	50	51	47	51	50
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Baseline up to 7 Months
Adverse Event Reporting Description	Safety population included all participants who received 1 or more doses of study medication. The participants were analyzed as treated.
Arm/Group Title	Abaloparatide Transdermal (50 mcg)		Abaloparatide Transdermal (100 mcg)		Abaloparatide Transdermal (150 mcg)		Abaloparatide Injection (80 mcg)		Abaloparatide Transdermal Placebo (0 mcg)
Arm/Group Description	Abaloparatide Transdermal Microneedle Patch - 50 mcg daily applications for up to 6 months		Abaloparatide Transdermal Microneedle Patch - 100 mcg daily applications for up to 6 months		Abaloparatide Transdermal Microneedle Patch - 150 mcg daily applications for up to 6 months		Abaloparatide-SC Subcutaneous Injection - 80 mcg daily injections for up to 6 months		Abaloparatide Transdermal Microneedle Patch - 0 mcg daily applications for up to 6 months
All Cause Mortality
	Abaloparatide Transdermal (50 mcg)		Abaloparatide Transdermal (100 mcg)		Abaloparatide Transdermal (150 mcg)		Abaloparatide Injection (80 mcg)		Abaloparatide Transdermal Placebo (0 mcg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Abaloparatide Transdermal (50 mcg)		Abaloparatide Transdermal (100 mcg)		Abaloparatide Transdermal (150 mcg)		Abaloparatide Injection (80 mcg)		Abaloparatide Transdermal Placebo (0 mcg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/50 (0%)		2/51 (3.9%)		2/47 (4.3%)		4/51 (7.8%)		1/50 (2%)
Cardiac disorders
Coronary artery disease	0/50 (0%)		0/51 (0%)		0/47 (0%)		1/51 (2%)		0/50 (0%)
Gastrointestinal disorders
Abdominal Pain	0/50 (0%)		0/51 (0%)		0/47 (0%)		1/51 (2%)		0/50 (0%)
Colitis	0/50 (0%)		0/51 (0%)		1/47 (2.1%)		0/51 (0%)		0/50 (0%)
Injury, poisoning and procedural complications
Radius fracture	0/50 (0%)		1/51 (2%)		0/47 (0%)		0/51 (0%)		0/50 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/50 (0%)		0/51 (0%)		1/47 (2.1%)		1/51 (2%)		0/50 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	0/50 (0%)		0/51 (0%)		0/47 (0%)		1/51 (2%)		0/50 (0%)
Cervix carcinoma	0/50 (0%)		1/51 (2%)		0/47 (0%)		0/51 (0%)		0/50 (0%)
Malignant melanoma	0/50 (0%)		0/51 (0%)		0/47 (0%)		0/51 (0%)		1/50 (2%)
Other (Not Including Serious) Adverse Events
	Abaloparatide Transdermal (50 mcg)		Abaloparatide Transdermal (100 mcg)		Abaloparatide Transdermal (150 mcg)		Abaloparatide Injection (80 mcg)		Abaloparatide Transdermal Placebo (0 mcg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/50 (80%)		40/51 (78.4%)		37/47 (78.7%)		41/51 (80.4%)		39/50 (78%)
Cardiac disorders
Palpitations	0/50 (0%)		2/51 (3.9%)		0/47 (0%)		3/51 (5.9%)		0/50 (0%)
Gastrointestinal disorders
Diarrhoea	4/50 (8%)		0/51 (0%)		3/47 (6.4%)		1/51 (2%)		0/50 (0%)
Nausea	2/50 (4%)		3/51 (5.9%)		6/47 (12.8%)		3/51 (5.9%)		2/50 (4%)
General disorders
Application site erythema	4/50 (8%)		5/51 (9.8%)		4/47 (8.5%)		0/51 (0%)		2/50 (4%)
Application site pruritus	0/50 (0%)		1/51 (2%)		4/47 (8.5%)		0/51 (0%)		0/50 (0%)
Influenza like illness	1/50 (2%)		3/51 (5.9%)		1/47 (2.1%)		1/51 (2%)		2/50 (4%)
Injection site erythema	0/50 (0%)		0/51 (0%)		0/47 (0%)		3/51 (5.9%)		0/50 (0%)
Infections and infestations
Bronchitis	0/50 (0%)		0/51 (0%)		4/47 (8.5%)		1/51 (2%)		1/50 (2%)
Cystitis	2/50 (4%)		0/51 (0%)		4/47 (8.5%)		1/51 (2%)		1/50 (2%)
Influenza	4/50 (8%)		4/51 (7.8%)		2/47 (4.3%)		5/51 (9.8%)		4/50 (8%)
Nasopharyngitis	11/50 (22%)		10/51 (19.6%)		8/47 (17%)		13/51 (25.5%)		9/50 (18%)
Upper respiratory tract infection	0/50 (0%)		1/51 (2%)		0/47 (0%)		3/51 (5.9%)		1/50 (2%)
Metabolism and nutrition disorders
Hypocalcaemia	3/50 (6%)		3/51 (5.9%)		1/47 (2.1%)		1/51 (2%)		2/50 (4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/50 (2%)		0/51 (0%)		4/47 (8.5%)		3/51 (5.9%)		3/50 (6%)
Back pain	1/50 (2%)		4/51 (7.8%)		3/47 (6.4%)		3/51 (5.9%)		5/50 (10%)
Nervous system disorders
Dizziness	2/50 (4%)		2/51 (3.9%)		3/47 (6.4%)		8/51 (15.7%)		1/50 (2%)
Headache	2/50 (4%)		2/51 (3.9%)		5/47 (10.6%)		5/51 (9.8%)		5/50 (10%)
Renal and urinary disorders
Hypercalciuria	0/50 (0%)		1/51 (2%)		2/47 (4.3%)		3/51 (5.9%)		3/50 (6%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	3/50 (6%)		1/51 (2%)		3/47 (6.4%)		0/51 (0%)		1/50 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Results may not be published prior to the Study Report completion. Investigators may publish results, providing a manuscript to the Sponsor =/> 30 days prior to its submission to a publisher. Sponsor will provide manuscript to Investigators =/> 30 days prior to its submission. Investigator shall comply with Sponsor's policy, withholding publication for an additional 60 days to permit the Sponsor to obtain patent or other proprietary rights protection, if deemed necessary.