A Randomized, Double-Blind, Placebo Controlled Proof-of-Concept Study Investigating the Safety and Efficacy of ZT-031 on Hip Fracture Healing in Men and Postmenopausal Women With Intertrochanteric Fracture of the Hip
Subjects are required to meet all of the following criteria for inclusion in the study:
1. Signed Institutional Review Board (IRB)/Research Ethics Board (REB)-approved informed
consent form (ICF).
2. Sustained an unstable low energy intertrochanteric (Evans Type II or higher) hip
fracture within 7 days prior to planned surgery date. Low energy is defined as a
fracture that occurs spontaneously or from a fall from a stationary height of ≤ 1
meter (3 feet) or missing one to three steps.
3. Women ≥ 55 years of age and men ≥ 30 years of age of any race. If female, subjects
must be post-menopausal for at least 5 years and weigh ≥ 110 lbs or 50 kg.
4. Subjects who are expected to undergo or have recently undergone (within two weeks)
open or closed repair of the fracture requiring a CHS.
5. By history, the subject was at least household ambulatory prior to hip fracture.
6. Serum calcium level within the normal range when corrected for albumin. Corrected
calcium (mg/dL) = Serum Ca (mg/dL) + 0.8 x (4.0 - albumin [g/dL])
7. Able and willing to comply with all protocol procedures.
8. Cognitive, visual, auditory and physical abilities adequate to undertake assessments.
9. Availability of a care partner to administer injections or demonstrated ability to
self-administer injections. Subjects planning to self-administer study drug will need
to show that they will be capable of accurately self-injecting study drug in rotating
quadrants of the abdomen, in the opinion of the Investigator.
10. Clinically acceptable medical history and physical examination, according to the
judgment of the Investigator.
11. Laboratory results within normal ranges or, if abnormal, considered by the
Investigator as not clinically significant for the well-being of the subject or for
the purpose of the study.
The following additional criteria are required for randomization and dosing with
ZT-031 or placebo to occur:
12. The most recent value for 25-hydroxy Vitamin D (25OHD) must be at or above the lower
limit of normal (LLN) for the laboratory reference range of the testing method used
for determination of 25OHD. NOTE: Randomization should be delayed until it is known
that 25OHD is ≥ LLN.
13. The most recent value for intact PTH must be ≤ ULN for the laboratory reference
14. Randomization and dosing must occur within 2 weeks post-op. Exclusion Criteria
Subjects who meet any of the following conditions are excluded from this clinical study:
1. Previous fracture(s) or bone or joint surgery in the currently fractured site
2. Intertrochanteric fracture with reverse obliquity
3. Pathologic fracture: A fracture occurring at a site of metabolic bone disease (other
than osteoporosis) or a benign or malignant tumor
4. Presence of a concurrent disease known to affect bone metabolism other than
post-menopausal osteoporosis, including but not limited to hyperparathyroidism,
hyperthyroidism, osteogenesis imperfecta, abnormalities of serum calcium, Paget's
disease, or osteomalacia
5. History of rheumatoid arthritis
6. Any significant neurologic disease including but not limited to any dementing illness
or other neurodegenerative disease, cerebrovascular disease, epilepsy or undiagnosed
7. Unstable or clinically significant cardiovascular disease resulting in:
1. Hemodynamic instability manifested as hypotension unresponsive to intravenous
2. Uncontrolled hypertension requiring administration of parenteral therapy.
8. Renal disease, defined by:
1. Creatinine level of >2.0 mg/dL
2. Urolithiasis or nephrolithiasis in the last 2 years
9. Hepatic disease or insufficiency, defined by liver function tests (ALT, AST or GGT) >
3 times the ULN or bilirubin > 34 mmol/L or 2.0 mg/dL
10. Currently receiving treatment for cancer
11. History of external beam radiation to the skeleton or a radiation therapy implant
12. Presence of substance abuse, including alcohol, within 1 year of Screening
13. Current or previous use of any PTH compound, including ZT-031
14. Use of any investigational compound within 4 weeks of Screening, or within 5
half-lives of compound, whichever is longer
15. Use of any bone substitutes, osteobiologics or any fracture healing drug.