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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Post Menopausal Osteoporosis

Intervention / Treatment
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* Drug: Abaloparatide Transdermal (50 mcg)
* Drug: Abaloparatide Transdermal (100 mcg)
* Drug: Abaloparatide Transdermal (150 mcg)
* Drug: Abaloparatide Injection (80 mcg)
* Drug: Abaloparatide Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in BMD of Total Hip at 6 Months | Percent change in BMD as specified by DXA scans of the total hip. | Baseline, 6 Months | 
| Percent Change From Baseline in BMD of Forearm at 6 Months | Percent change in BMD as specified by DXA scans of the forearm. | Baseline, 6 Months | 
| Percent Change From Baseline in Serum Bone-Specific Alkaline Phosphatase (BSAP) at 6 Months |  | Baseline, 6 Months | 
| Percent Change From Baseline in Serum Procollagen Type I C Propeptide (PICP) at 6 Months |  | Baseline, 6 Months | 
| Percent Change From Baseline in Serum Osteocalcin at 6 Months |  | Baseline, 6 Months | 
| Percent Change From Baseline in Serum Procollagen Type I N Propeptide (PINP) at 6 Months |  | Baseline, 6 Months | 
| Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (CTXI) at 6 Months |  | Baseline, 6 Months | 
| Number of Participants With Abnormal Physical Examinations at Screening and End of Treatment (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. | Baseline up to 6 Months | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) That Occurred During the Study That Were Associated With Vital Sign Changes | 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. | Baseline up to 7 Months | 
| Number of Participants With a Clinically Meaningful Abnormal Electrocardiogram (ECG) Test Result | 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. | Baseline up to 7 Months | 
| Number of Participants With an Abnormal Clinical Hematology Laboratory Parameter With an Eastern Cooperative Oncology Group (ECOG) Score of Grade 3 or Grade 4 | 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. | Baseline up to 6 Months | 
| Number of Participants With an Abnormal Clinical Chemistry Laboratory Parameter With an ECOG Score of Grade 3 or Grade 4 | 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. | Baseline up to 6 Months | 
| Number of Participants With an Abnormal Clinical Coagulation Laboratory Parameter With an ECOG Score of Grade 3 or Grade 4 | 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. | Baseline up to 6 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BA058, Abaloparatide-SC, abaloparatide, Abaloparatide-TD, Osteo, Osteoporosis, Transdermal, Patch