Effect of Teriparatide on Hip Fracture Healing

This is a 24-month, phase 3, prospective, randomized, parallel, double-blind,
placebo-controlled, multicenter, multinational study to evaluate the effect of 6 months of
treatment with teriparatide on fracture healing in participants who have sustained a recent
low-trauma, unilateral, femoral neck fracture stabilized by internal fixation. The study has
3 periods:

1. A screening period that must be completed in ≤ 14 days after operative treatment of the
femoral neck fracture

2. A 6-month double-blind treatment period (teriparatide 20 µg or placebo given once daily
by subcutaneous injection)

3. An 18-month observation period.

The primary objective is to determine the effect of 6 months of treatment with teriparatide
20 µg/day versus placebo on the percentage of participants with successful fracture healing
24 months after internal fixation of a low-trauma femoral neck fracture (after 12 months for
non-US regions).

All participants will receive supplements of calcium and vitamin D beginning at screening
and continuing for 24 months.

Inclusion Criteria:

- Community dwelling men and postmenopausal women who were ambulatory before sustaining
a low-trauma, unilateral femoral neck fracture (displaced or nondisplaced)

- Other than femoral neck fracture, be free of incapacitating conditions and have a
life expectancy of at least 2 years

- Have received or are eligible for treatment with internal fixation (sliding hip screw
or multiple cancellous screws) for the femoral neck fracture (the surgical procedure
itself is not performed as part of this study)

- Have given written informed consent (participant or proxy) after being informed of
the risks, medications, and study procedures

Exclusion Criteria:

- Increased baseline risk of osteosarcoma

- History of unresolved skeletal diseases affecting bone metabolism other than primary
osteoporosis

- Abnormally elevated serum calcium at screening

- Abnormally elevated serum intact parathyroid hormone (PTH) (1-84) at screening

- Severe vitamin D deficiency at screening

- Active liver disease or jaundice

- Significantly impaired renal function

- Abnormal thyroid function not corrected by therapy

- History of malignant neoplasm in the 5 years prior to screening

- History of bone marrow or solid organ transplantation

- History of symptomatic nephrolithiasis or urolithiasis in the 1 year prior to
screening

- Previous treatment with the following bone active drugs is allowed but must be
discontinued at screening: oral bisphosphonates, selective estrogen receptor
modulators (SERMs), calcitonin, estrogen (oral, transdermal, or injectable),
progestin, estrogen analog, estrogen agonist, estrogen antagonist or tibolone, and
active vitamin D3 analogs. Androgen or other anabolic steroid use must be
discontinued, except for use of physiologic replacement testosterone

- Previous treatment with the following bone active drugs is exclusionary, if the
stated treatment durations have been met: strontium ranelate for any duration,
intravenous bisphosphonates in the 12 months preceding screening, and/or denosumab in
the 6 months preceding screening

- Prior treatment with PTH, teriparatide, or other PTH analogs, or prior participation
in any other clinical trial studying PTH, teriparatide, or other PTH analogs

- Local or systemic treatment with bone morphogenic proteins or any other growth factor

- Previous fracture(s) or bone surgery in the currently fractured hip

- Soft-tissue infection at the operation site

- Treatment with bone grafting or osteotomies

- Treatment with augmentation using any type of degradable cement,
hydroxyapatite-coated implants, or with noninvasive interventions

- Associated major injuries of a lower extremity including fractures of the foot,
ankle, tibia, fibula, knee, femur, femoral head or pelvis; dislocations of the ankle,
knee or hip