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

• ClinicalTrials.gov Identifier: NCT01293292
• Recruitment Status: Completed
• First Posted: February 10, 2011
• Last Update Posted: May 8, 2017
• Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Information provided by (Responsible Party): Sheffield Teaching Hospitals NHS Foundation Trust

Tracking Information

• First Submitted Date: February 4, 2011
• First Posted Date: February 10, 2011
• Last Update Posted Date: May 8, 2017
• Study Start Date: January 2011
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 9, 2011)

Volumetric bone mineral density (BMD) of the lumbar spine (mg hydroxyapatite/cm3) [ Time Frame: 0 to 104 weeks ]

Change in volumetric BMD of the lumbar spine (vertebrae L1-3) (mg hydroxyapatite/cm3) measured by quantitative computed tomography (QCT) from 0 to 104 weeks treatment.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 9, 2011)

• Lumbar spine, total hip and whole body bone mineral density (g/cm2) [ Time Frame: 0 to 104 weeks ]
  Changes in lumbar spine, total hip and whole body bone mineral density (g/cm2) measured by dual x-ray absorptiometry (DXA) from 0 to 104 weeks.
• Biochemical markers of bone turnover [ Time Frame: 0 to 104 weeks ]
  Changes in biochemcial markers of bone turnover (OC, PINP, bone ALP, urinary NTX, serum CTX, sclerostin, DKK-1) from 0 to 104 weeks.
• Distal tibia and radius volumetric body bone mineral density (BMD) (mg hydroxyapatite/cm3) [ Time Frame: 0 to 104 weeks ]
  Changes in distal tibia and radius volumetric bone mineral density (mg hydroxyapatite/cm3) measured by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) from 0 to 104 weeks.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Osteoporosis

Intervention

Drug: Teriparatide

Teriparatide (Forsteo) 20 mcg subcutaneous injection once daily. Duration 104 weeks.

Other Name: Forsteo

• Study Arms: Not Provided
• Publications *: Gossiel F, Scott JR, Paggiosi MA, Naylor KE, McCloskey EV, Peel NFA, Walsh JS, Eastell R. Effect of Teriparatide Treatment on Circulating Periostin and Its Relationship to Regulators of Bone Formation and BMD in Postmenopausal Women With Osteoporosis. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1302-1309. doi: 10.1210/jc.2017-00283.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 24, 2016): 19
• Original Estimated Enrollment (submitted: February 9, 2011): 20
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: up to 84 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01293292
• Other Study ID Numbers: STH15466; 2010-021009-19 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Sheffield Teaching Hospitals NHS Foundation Trust
• Study Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Collaborators: Not Provided

Investigators

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

• PRS Account: Sheffield Teaching Hospitals NHS Foundation Trust
• Verification Date: May 2017