Teriparatide (Forsteo) Treatment in Postmenopausal Women: Mechanism of Action

Condition(s) targeted: Osteoporosis

Intervention: Teriparatide (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Sheffield Teaching Hospitals NHS Foundation Trust

Official(s) and/or principal investigator(s):
Richard Eastell, MD, FRCP, FRCPath, FMedSci, Study Director, Affiliation: University of Sheffield
Jennifer Walsh, PhD MRCP, Principal Investigator, Affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
Eugene McCloskey, MD, FRCPI, Principal Investigator, Affiliation: University of Sheffield
Nicola Peel, DM FRCP, Principal Investigator, Affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
Angela Rogers, BSc (Hons), PhD, MCSP, Principal Investigator, Affiliation: University of Sheffield
Margaret Paggiosi, Bsc (Hons), PhD, MICR, Principal Investigator, Affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
Lang Yang, PhD CSci, Principal Investigator, Affiliation: University of Sheffield
David Hughes, BMedSci MBChB PhD FRCPath, Principal Investigator, Affiliation: Sheffield Teaching Hospitals NHS Foundation Trust
Mark Wilkinson, PhD, FRCS (Tr&Orth), Principal Investigator, Affiliation: University of Sheffield

Overall contact:
Katharine Knight, PhD, Phone: +44 114 2266401, Email: katharine.knight@sth.nhs.uk

Previously the approach to treatment of osteoporosis has been to use medications which prevent excessive resorption of bone. More recently medications that build up new bone, i. e. anabolic treatments, have been, and are being, developed. The investigators would like to develop a strategy for evaluating the effectiveness of anabolic therapies by studying a currently available therapy (teriparatide). This strategy could then be used to assess new anabolic treatments as they are developed for use in humans. The aims of this study are 1) to fully describe the changes in bone turnover in response to teriparatide by biochemical marker type and by time; 2) to fully describe the changes in bone mineral density (BMD) in response to teriparatide by site, bone compartment and time. If this study is able to identify an early response to treatment, then this will help speed up drug development in this area, by allowing the identification of promising new anabolic drugs and enabling us to understand their mechanism of action. This will benefit the investigators patients as the investigators will have a better understanding of how these drugs work.

Official title: Teriparatide (Forsteo) Treatment in Postmenopausal Women: Mechanism of Action. A Two-year Open-label Single-arm Study of Teriparatide in Secondary Care

Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Volumetric bone mineral density (BMD) of the lumbar spine (mg hydroxyapatite/cm3)

Secondary outcome:

Lumbar spine, total hip and whole body bone mineral density (g/cm2)

Biochemical markers of bone turnover

Distal tibia and radius volumetric body bone mineral density (BMD) (mg hydroxyapatite/cm3)

Minimum age: N/A. Maximum age: 84 Years. Gender(s): Female.

Criteria:

Inclusion Criteria Subjects must:

- Have a bone mineral density T-score (at the lumbar spine or total hip) of less than

or equal to - 2. 5

- Be female

- Be at least 5 years post menopausal (more than 5 years since their last menstrual

period) but <85 years old.

- Be ambulatory

- Be able and willing to participate in the study and provide written informed consent

- Have a serum 25(OH)2 vitamin D3 >50 nmol/L (after vitamin D3 loading)

Exclusion Criteria Patients will not be admitted to the study if they exhibit any of the following:

- Evidence of a clinically significant organic disease which could prevent the patient

from completing the study

- A body mass index less than 18 or greater than 35

- Abuse of alcohol or use illicit drugs (information obtained from medical history) or

who consumed more than 4 servings of any alcoholic beverage one day prior to the visit (i. e., subjects who might be binge drinkers)

- Any history of cancer within the past 5 years excluding skin cancer non melanomas

- Any history of ongoing conditions or diseases known to cause abnormalities of calcium

metabolism or skeletal health including Paget's disease of bone

- Chronic renal disease (as defined by an estimated glomerular filtration rate of ≤

30mL/min)

- Acute or chronic hepatic disease

- Malabsorption syndromes

- Hyperthyroidism as manifested by TSH outside the lower limit of the normal range

- Hyperparathyroidism

- Hypocalcemia or hypercalcemia

- Osteomalacia

- Cushing's syndrome

- Current use of glucocorticoid therapy

- A corrected serum calcium less than 2. 2 mmol/L and a PTH above 100 ng/L (that

persists after testing and treatment for vitamin D deficiency)

- A history of any known condition that would interfere with the assessment of DXA at

either lumbar spine or femoral neck

- Markedly abnormal clinical laboratory parameters that are assessed as clinically

significant by the investigator

- Any previous use of bisphosphonate

- Use any of the following medications within 12 months of starting study drug

- Any fluoride with the exception of use for oral hygiene

- Strontium Ranelate

- Other bone agents (e. g. SERM, isoflavones, HRT)

- Participation in another clinical trial involving active therapy 3 months prior to

enrolment

- Less than 5 years since menopause

- Bilateral fractures in the measurement regions (hip, tibia and forearm)

- Recent fracture within the last 12 months

- Prior radiation therapy which may involve the skeleton

- Hypersensitivity to teriparatide or any of its excipients

- Unexplained elevations of alkaline phosphatase

- Any known contraindication to the use of teriparatide

Katharine Knight, PhD, Phone: +44 114 2266401, Email: katharine.knight@sth.nhs.uk

Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, South Yorkshire S5 7AU, United Kingdom; Recruiting
Richard Eastell, MD, FRCP, FRCPath, FMedSci, Principal Investigator

Starting date: January 2011
Last updated: December 14, 2012