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

• ClinicalTrials.gov Identifier: NCT01674621
• Recruitment Status: Completed
• First Posted: August 29, 2012
• Results First Posted: December 19, 2016
• Last Update Posted: June 16, 2020
• Sponsor: Radius Health, Inc.
• Collaborator: Nordic Bioscience A/S
• Information provided by (Responsible Party): Radius Health, Inc.

Tracking Information

• First Submitted Date: August 24, 2012
• First Posted Date: August 29, 2012
• Results First Submitted Date: October 25, 2016
• Results First Posted Date: December 19, 2016
• Last Update Posted Date: June 16, 2020
• Actual Study Start Date: September 25, 2012
• Actual Primary Completion Date: August 2, 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2020)

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

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

Original Primary Outcome Measures (submitted: August 28, 2012)

BMD (Lumbar Spine) [ Time Frame: 6 Months ]

Change in BMD, using DXA results; active compared to placebo.

Current Secondary Outcome Measures (submitted: May 7, 2020)

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

Original Secondary Outcome Measures (submitted: August 28, 2012)

• BMD (Hip and Forearm) [ Time Frame: 6 Months ]
  Change in BMD, using DXA results; active compared to placebo.
• Serum markers of bone formation and resorption [ Time Frame: 6 months ]
  Change in laboratory results; active compared to placebo.
• Safety and Tolerability [ Time Frame: 6 Months ]
  Physical examinations, vital signs, electrocardiograms, clinical laboratory tests, local tolerance, and adverse events.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 2 Study of BA058 (Abaloparatide) Transdermal Delivery in Postmenopausal Women With Osteoporosis
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

• Condition: Post Menopausal Osteoporosis

Intervention

• Drug: Abaloparatide Transdermal (50 mcg)
  Abaloparatide Transdermal Microneedle Active Patch
  Other Name: BA058 Transdermal (50 mcg)
• Drug: Abaloparatide Transdermal (100 mcg)
  Abaloparatide Transdermal Microneedle Active Patch
  Other Name: BA058 Transdermal (100 mcg)
• Drug: Abaloparatide Transdermal (150 mcg)
  Abaloparatide Transdermal Microneedle Active Patch
  Other Name: BA058 Transdermal (150 mcg)
• Drug: Abaloparatide Injection (80 mcg)
  Abaloparatide Subcutaneous Injection
  Other Name: BA058 Injection (80 mcg)
• Drug: Abaloparatide Placebo
  Abaloparatide Transdermal Microneedle Placebo Patch
  Other Name: BA058 Placebo

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 6, 2013): 250
• Original Estimated Enrollment (submitted: August 28, 2012): 240
• Actual Study Completion Date: August 2, 2013
• Actual Primary Completion Date: August 2, 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: up to 85 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Estonia, Poland, United States
• Removed Location Countries: Hong Kong

Administrative Information

• NCT Number: NCT01674621
• Other Study ID Numbers: BA058-05-007; 2012-001921-29 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Radius Health, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Radius Health, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Nordic Bioscience A/S
• Investigators: Not Provided
• PRS Account: Radius Health, Inc.
• Verification Date: May 2020