Clinical trial NCT01753856: Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis
Official title: Anabolism Versus Antiresorption: A Quadruple Labeling Histomorphometry Study to Compare the Mechanism of Action of Teriparatide and Denosumab in Postmenopausal Women With Osteoporosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoporosis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2012-12-20
Enrollment: 69
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine how teriparatide or denosumab affects the bone of postmenopausal women with osteoporosis after 3 months of treatment, as determined by a bone biopsy sample taken from the iliac crest (upper part of the pelvis).


Eligibility criteria: Inclusion Criteria:

* Ambulatory, postmenopausal women (no vaginal bleeding for at least 2 years prior to screening) with osteoporosis
* Bone mineral density (BMD) T-score of at least -2.5 at femoral neck (FN), total hip (TH), or lumbar spine (LS) (Lumbar vertebrae L1-L4, with at least 2 evaluable vertebrae), with or without atraumatic fracture after menopause, OR
* BMD T-score of at least -1.5 at FN, TH, or LS (L1-L4, with at least 2 evaluable vertebrae), and 1 or more atraumatic fractures after menopause (vertebral or nonvertebral). Nonvertebral fracture sites allowed are wrist, hip, pelvis, rib, humerus, clavicle, leg (femur, tibia, and fibula, excluding ankle)
* Laboratory values for serum calcium, parathyroid hormone (PTH), and alkaline phosphatase must be within the normal reference range

Exclusion Criteria:

* Has an increased risk of osteosarcoma (bone tumor); this includes Paget's disease of bone, a previous bone tumor, or radiation involving the skeleton
* Has an allergy or intolerance to teriparatide or denosumab and/or is a poor candidate for teriparatide or denosumab treatment (investigator should refer to local product prescribing information)
* Has a history of exposure to DEM or TET therapy in the 12 months prior to screening or a known allergy to DEM or TET
* Has a condition that could put the participant at additional risk of an adverse event (AE) due to the bone biopsy procedure (for example, bleeding disorder)
* Has undergone 2 previous iliac crest bone biopsies (1 in each iliac crest)
* Has a 25-hydroxyvitamin D concentration of \<10 nanograms per milliliter (ng/mL)
* Has currently active or suspected (within 1 year prior to enrollment) diseases that affect bone metabolism, other than osteoporosis (such as renal osteodystrophy, hyperthyroidism, osteomalacia, or hyperparathyroidism)
* Has a history of certain cancers within 5 years prior to trial entry
* Current or recent (within 1 year prior to enrollment) celiac disease, inflammatory bowel disease, gastric bypass, or other malabsorption syndrome
* Has significantly impaired hepatic or renal function
* Has had treatment with systemic glucocorticoids in doses ≥5 mg/day prednisone/day or equivalent in the 6 calendar months prior to screening
* Has taken any intravenous osteoporosis medication
* Has had prior treatment with other bisphosphonates and not been off of them for a specific period of time before trial entry
* Has participated in any other clinical trial studying teriparatide, PTH, PTH analog, or denosumab, or prior or current treatment with teriparatide, PTH, PTH analog, or denosumab

Primary outcomes:
measure: Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies
timeFrame: Baseline, 3 months post first dose of study drug
Secondary outcomes:
measure: Number of Samples With Single or Double Tetracycline Labels, SL and DL, or No Tetracycline Labels in the CC, Endocortical Compartment (EC), Intracortical Compartment (IC) and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies
timeFrame: 3 months post first dose of study drug
measure: Change From Baseline to 3 Months in MS/BS in the Endocortical Compartment (EC), Intracortical Compartment (IC), and Periosteal Compartment (PC) of the Iliac Crest Bone Biopsies
timeFrame: Baseline, 3 months post first dose of study drug
measure: MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug
timeFrame: 3 months post first dose of study drug
measure: Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies
timeFrame: 3 months post first dose of study drug
measure: Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies
timeFrame: 3 months post first dose of study drug
measure: Percentage of Overfilled Remodeling Sites in the CC, EC and PC of the Iliac Crest Bone Biopsies
timeFrame: 3 months post first dose of study drug
measure: Change From Baseline to 3 Months in Label Length Within Each Basic Multicellular Unit (BMU) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
timeFrame: Baseline, 3 months post first dose of study drug
measure: Change From Baseline to 3 Months in Mineral Apposition Rate (MAR) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
timeFrame: Baseline, 3 months post first dose of study drug
measure: Change From Baseline to 3 Months in Bone Formation Rate/Bone Surface (BFR/BS ) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
timeFrame: Baseline, 3 months post first dose of study drug
measure: Percentage of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS or dLS/BS) in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies
timeFrame: 3 months post first dose of study drug
measure: Percentage Change From Baseline to 1, 3, and 6 Months in Intact Parathyroid Hormone (PTH)
timeFrame: Baseline, 1, 3, and 6 months post first dose of study drug
measure: Percentage Change From Baseline to 1, 3, and 6 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP)
timeFrame: Baseline, 1, 3, and 6 months post first dose of study drug
measure: Percentage Change From Baseline to 1, 3, and 6 Months in Serum Osteocalcin
timeFrame: Baseline, 1, 3, and 6 months post first dose of study drug
measure: Percentage Change From Baseline to 1, 3, and 6 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX)
timeFrame: Baseline, 1, 3, and 6 months post first dose of study drug
measure: Activation Frequency (Ac.f) in the CC, EC and IC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
measure: Adjusted Apposition Rate (Aj.AR) in the CC, EC and IC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
measure: Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the CC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
measure: Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the CC, EC and IC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
measure: Osteoid Thickness (O.Th) in the CC, EC and IC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
measure: Wall Thickness (W.Th) in the CC, EC and IC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
measure: Percentage of Eroded Surface/Bone Surface (ES/BS) in the CC, EC and IC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
Other outcomes:
measure: Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest
timeFrame: 3 months post first dose of study drug
Locations:
city: Lakewood
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Colorado
city: Gainesville
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Georgia
city: Detroit
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Michigan
city: Omaha
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Nebraska
city: Vancouver
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: British Columbia
city: Sainte-Foy
country: Canada
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Quebec
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Dempster DW, Zhou H, Recker RR, Brown JP, Recknor CP, Lewiecki EM, Miller PD, Rao SD, Kendler DL, Lindsay R, Krege JH, Alam J, Taylor KA, Melby TE, Ruff VA. Remodeling- and Modeling-Based Bone Formation With Teriparatide Versus Denosumab: A Longitudinal Analysis From Baseline to 3 Months in the AVA Study. J Bone Miner Res. 2018 Feb;33(2):298-306. doi: 10.1002/jbmr.3309. Epub 2017 Nov 15.