Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis

Condition(s) targeted: Osteoporosis

Intervention: Teriparatide (Drug); Denosumab (Drug); Demeclocyline (Drug); Tetracycline (Drug); Calcium Supplement (Drug); Vitamin D (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Eli Lilly and Company

Official(s) and/or principal investigator(s):
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST), Study Director, Affiliation: Eli Lilly and Company

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).

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change from Baseline to 3 Months in Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies

Secondary outcome:

Change from Baseline to 3 Months in Mineralizing Surface/Bone Surface (MS/BS) in the Endocortical Compartment, Intracortical Compartment, and Periosteal Compartment of Iliac Crest Bone Biopsies

Proportion of Bone with Remodeling-Based Formation and Modeling-Based Formation

Proportion of Overfilled Remodeling Sites

Change from Baseline to 3 Months in Label Length within each Basic Multicellular Unit (BMU)

Change from Baseline to 3 Months in Mineral Apposition Rate (MAR)

Change from Baseline to 3 Months in Bone Formation Rate (BFR)

Percent of Single or Double Tetracycline Labels per Bone Surface (sLS/BS), (dLS/BS)

Change from Baseline to 3 Months in Intact Parathyroid Hormone (PTH)

Change from Baseline to 3 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP)

Change from Baseline to 3 Months in Serum Osteocalcin

Change from Baseline to 3 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX)

Activation Frequency (Ac.f )

Adjusted Apposition Rate (Aj.AR)

Number of Samples with Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels

Percentage of Osteoid Volume (OV)/Bone Volume (BV)

Percentage of Osteoid Surface (OS)/Bone Surface (BS)

Osteoid Thickness (O.Th)

Wall Thickness (W.Th)

Percentage of Eroded Surface/Bone Surface (ES/BS)

Minimum age: 55 Years. Maximum age: 89 Years. Gender(s): Female.

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) (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 demeclocycline (DEM) or tetracycline (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

due to the bone biopsy procedure (e. g. bleeding disorder)

- Has undergone 2 previous iliac crest bone biopsies (1 in each iliac crest)

- Has a 25-hydroxyvitamin D concentration of <10 nanogram 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 milligrams/day (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

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., Vancouver, British Columbia V5Z 4E1, Canada

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., Lakewood, Colorado 80227, United States

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., Gainesville, Georgia 30501, United States

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., Detroit, Michigan 48202, United States

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., Omaha, Nebraska 68131, United States

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., Sainte-Foy, Quebec G1V 3M7, Canada

Starting date: January 2013
Last updated: June 30, 2014