Early Effects of Abaloparatide on Tissue-Based Indices of Bone Formation and Resorption
Condition: Osteoporosis, Postmenopausal; Osteoporosis; Osteoporosis Vertebral; Osteoporosis Risk; Osteoporosis Fracture; Osteoporosis Localized to Spine; Osteoporosis, Age-Related; Osteoporosis Senile; Osteoporosis of Vertebrae
MeSH terms: Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures
Intervention: Abaloparatide
Intervention description: Abaloparatide is a novel, synthetic, 34 amino acid peptide designed to be a potent and selective activator of the PTH/PTH-related protein (PTHrP) type 1 receptor (PTHR1) signaling pathway with 41% homology to PTH[1-34] and 76% homology to human PTHrP[1-34].
Intervention MeSH terms: Abaloparatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: Female
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: BA058; abaloparatide; TYMLOS®; Bone metabolism; Osteoporosis; Fracture; Bone loss

Summary:

      The objective of this study is to measure the early effects of abaloparatide on tissue-based
      bone formation using samples obtained by transiliac crest bone biopsy after quadruple
      fluorochrome labeling.
    

Eligibility criteria:

        Inclusion Criteria

        Participants must meet all of the following criteria to be eligible to participate in this
        study:

          1. The participant is a healthy ambulatory postmenopausal female from 50 to 85 years of
             age (inclusive) with osteoporosis.

          2. The participant has been postmenopausal for at least 5 years. Postmenopausal status
             will be established by a history of amenorrhea for at least 5 years and by an elevated
             follicle stimulating hormone (FSH) value of ≥30 international units(IU)/liter (L).

          3. The participant has a BMD T-score ≤-2.5 at the lumbar spine (L1-L4) or hip (femoral
             neck or total hip) by dual-energy x-ray absorptiometry (DXA) or lumbar spine or hip
             BMD T-score ≤-2.0 with a history of low trauma vertebral, forearm, humerus, sacral,
             pelvic, hip, femoral, or tibial fracture sustained within 5 years prior to enrollment.
             These fractures must be documented by radiograph or hospital report.

          4. The participant is in good general health as determined by medical history and
             physical examination (including vital signs), has a body mass index (BMI) of 18.5 to
             33, inclusive, and is without evidence of clinically significant abnormality in the
             opinion of the Investigator.

          5. The participant has serum calcium (albumin-corrected), parathyroid hormone (PTH)
             (1-84), phosphorus, and alkaline phosphatase levels all within the normal range during
             the Screening Period. Any participant with an elevated alkaline phosphatase value, and
             who meets all other entry criteria, is required to have a normal bone-specific
             alkaline phosphatase result to be enrolled.

          6. The participant has serum 25-hydroxyvitamin D values ≥ 20 nanograms (ng)/milliliter
             (mL) and within the normal range. Participants with serum 25-hydroxyvitamin D levels <
             20 ng/ml may be treated with vitamin D3 and re-tested once.

          7. The participant's resting 12-lead electrocardiogram (ECG) obtained during screening
             shows no clinically significant abnormality.

          8. The participant has read, understood, and signed the written informed consent form.

        Exclusion Criteria:

        Participants with any of the following characteristics are not eligible to participate in
        the study:

          1. Presence of abnormalities of the lumbar spine that would prohibit assessment of lumbar
             spine BMD, defined as having at least 2 radiologically evaluable vertebrae within
             L1-L4.

          2. Unevaluable hip BMD or participants who have undergone bilateral hip replacement
             (unilateral hip replacement is acceptable).

          3. History of bone disorders (for example, Paget's disease) other than postmenopausal
             osteoporosis.

          4. Clinically significant abnormality of serum hemoglobin, hematocrit, white blood cells
             (WBC) and platelets, coagulation, or usual serum chemistry: electrolytes, renal
             function, liver function and serum proteins.

          5. Unexplained elevation of serum alkaline phosphatase.

          6. History of radiotherapy (radiation therapy), other than radioiodine.

          7. History of bleeding disorder that would preclude a bone biopsy, in the opinion of the
             Investigator.

          8. History of chronic or recurrent renal, hepatic, pulmonary, allergic, cardiovascular,
             gastrointestinal, endocrine, central nervous system, hematologic or metabolic
             diseases, or immunologic, emotional and/or psychiatric disturbances to a degree that
             would interfere with the interpretation of study data or compromise the safety of the
             participant.

          9. History of Cushing's disease, hyperthyroidism, hypo- or hyperparathyroidism, or
             malabsorptive syndromes within the past year.

         10. History of significantly impaired renal function (serum creatinine > 177 micromoles
             [µmol]/L or >2.0 milligrams [mg]/deciliter [dL]). If the serum creatinine is >1.5 and
             ≤ 2.0 mg/dL, the calculated creatinine clearance (Cockcroft-Gault) must be ≥ 30
             mL/minute (min).

         11. History of any cancer within the past 5 years (other than basal cell or squamous cell
             cancer of the skin).

         12. History of osteosarcoma at any time or a history of hereditary disorders which could
             predispose the participant to osteosarcoma.

         13. History of nephrolithiasis or urolithiasis within the past 5 years.

         14. Participant known to be positive for hepatitis B, hepatitis C, or human
             immunodeficiency virus infection (HIV-1 or HIV-2). Testing is not required in the
             absence of clinical signs and symptoms suggestive of HIV infection or acute or chronic
             hepatitis.