BA058 Transdermal Phase 3 Study in Women with Osteoporosis

Phase 1

Conditions: Osteoporosis in postmenopausal women
MedDRA version: 20.0Level: PTClassification code 10031285Term: Osteoporosis postmenopausalSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2019-004807-11-BG

Lead Sponsor: Radius Health Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 474

Inclusion Criteria

1. Healthy ambulatory female from 50 to 85 years of age (inclusive) with postmenopausal osteoporosis

2. Postmenopausal for at least 5 years as demonstrated by a history of amenorrhea for at least 5 years

3. BMD T-score based on the female reference range as assessed by the central imaging vendor of:
a. Less than or equal to -2.5 and greater than -5.0 at the lumbar spine (L1–L4) or hip (femoral neck or total hip) by dual energy X-ray absorptiometry (DXA) and: i) Radiological evidence of 2 or more mild or 1 or more moderate lumbar or thoracic vertebral fractures, or ii) History of fragility fracture to the forearm, humerus, sacrum, pelvis, hip, femur, or tibia within the past 5 years.
b. Postmenopausal women older than 65 years who meet the fracture criteria (i or ii) but have a T-score of = -2.0 and > -5.0 may be enrolled
c. Postmenopausal women older than 65 years who do NOT meet the fracture criteria may be enrolled if they have a BMD T-score = -3.0 and >-5 at the lumbar spine (L1-L4) or hip (femoral neck or total hip) by DXA

4. In good general health as determined by medical history and physical examination (including vital signs), has a body mass index of 18.5 to 33 kg/m2, inclusive, and is without evidence of clinically significant abnormality in the opinion of the Investigator.

5. Serum calcium (albumin-corrected), PTH (1-84), serum phosphorus, alkaline phosphatase, and thyroid stimulating hormone (TSH) values all within the normal range during the Screening Period. Any subject with an elevated alkaline phosphatase value and who meets all other entry criteria would be required to have a normal bone-specific alkaline phosphatase in order to be enrolled. Any subject with a TSH value outside of the normal range may be enrolled if their T3 and free T4 values are within the normal range

6. Serum 25-hydroxyvitamin D values must be = 20 ng/mL

7. Resting 12-lead ECG at Screening shows no clinically significant abnormality

8. Systolic blood pressure is = 100 and = 155 mmHg, diastolic blood pressure is = 40 and = 95 mmHg, and pulse rate is = 45 and = 100 beats per minute (taken sitting or supine)

9. Has no clinically significant abnormality of serum hemoglobin, hematocrit, white blood cells, and platelets, or usual serum biochemistry, including electrolytes, renal function, liver function and serum proteins, that might be expected to interfere with the subject’s health and/or medical treatment during the study.

10. Read, understood, and signed the written Informed Consent Form (ICF)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 379

Exclusion Criteria

1. History of more than 4 spine fractures, mild or moderate, or any severe fractures based on Genant Semi-quantitative Scoring method on radiographic findings

2. Presence of abnormalities of the lumbar spine that would prohibit assessment of spinal BMD, defined as having at least 2 radiologically-evaluable vertebrae within L1–L4 as assessed by the central imaging review of the DXA images
Anatomically abnormal vertebrae are excluded if:
- They are clearly abnormal and non-assessable within the resolution of the system; or
- There is a more than 1.0 T-score difference between the vertebra in question and adjacent vertebrae

3. Unevaluable hip BMD or subjects who have undergone bilateral hip replacement (unilateral hip replacement is acceptable)

4. History of bone disorders (eg, Paget’s disease) other than postmenopausal osteoporosis

5. History of prior external beam or implant radiation therapy involving the skeleton, other than radioiodine

6. History of Cushing’s disease, hyperthyroidism, hypo- or hyperparathyroidism, or malabsorptive syndromes within the past year

7. History of significantly impaired renal function (serum creatinine > 177 µmol/L or > 2.0 mg/dL). If serum creatinine is > 1.5 and = 2.0 mg/dL, the calculated creatinine clearance (Cockcroft-Gault) must be = 37 mL/minute

8. History of any cancer within the past 5 years (other than basal cell or squamous cancer of the skin)

9. History of osteosarcoma at any time

10. Hereditary disorders predisposing to osteosarcoma

11. History of nephrolithiasis or urolithiasis within the past 5 years

12. Decrease of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure from supine to standing (5 minutes laying and 3 minutes standing) or any symptomatic hypotension at Screening

13. Application site is compromised by scars, inflammation, or skin conditions that may compromise uniformity of patch application or drug delivery (nevi, plaques, tattoos, scars, piercing, etc)

14. Any other medical condition, that, in the opinion of the Investigator, renders the subject unable or unlikely to complete the study, would interfere with the interpretation of study data, or produce significant risk to the subject

15. Known history of hypersensitivity to any of the test materials or related compounds

16. Prior treatment with PTH- or PTHrP-derived drugs or bone anabolic drugs including abaloparatide, teriparatide, or PTH (1-84)

17. Prior treatment with intravenous bisphosphonates at any time or oral bisphosphonates within the past 3 years. Subjects who have received a short course of oral bisphosphonate therapy (3 months or less) may be enrolled as long as the treatment occurred 6 or more months prior to enrollment

18. Prior treatment with selective estrogen receptor modulators (such as raloxifene or tamoxifen) in the past 6 months. Estrogens administered as hormone replacement therapy, with or without progestins, are not exclusionary

19. Treatment with fluoride or strontium in the past 5 years or prior treatment with gallium nitrate or bone-acting investigational agents at any time

20. Prior treatment with calcitonin or tibolone in the past 6 months

21. Treatment with denosumab within the past 18 months

22. Treatment with anticonvulsants that affect vitamin D metabolism (phenobarbital, phenytoin, carbamazepine, or primidone) or with chronic heparin within the 6 months prior to the Screening Period

23. Tr

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the non-inferiority of abaloparatide-sMTS 300 µg compared to abaloparatide-SC 80 µg based on lumbar spine BMD at 12 months.<br>;Secondary Objective: Percent change from baseline in total hip BMD at 12 months<br>Percent change from baseline in femoral neck BMD at 12 months<br>Determine safety and tolerability of 12 months of dosing with abaloparatide-sMTS;Primary end point(s): The primary efficacy endpoint is the percent change from baseline in lumbar spine BMD. <br>;Timepoint(s) of evaluation of this end point: 12 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Percent change from baseline in total hip BMD<br>- Percent change from baseline in femoral neck BMD <br>- Treatment-emergent AEs (TEAEs), AEs of special interest (AESI), vital signs (orthostatic blood pressure, pulse rate, body temperature, and respiration rate), electrocardiograms (ECGs), laboratory tests (chemistry, hematology, coagulation, and urinalysis), local tolerance, and presence of anti-drug antibodies (ADAs);Timepoint(s) of evaluation of this end point: 12 months

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