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

NCT01753856 | Completed Phase 4 Results

• 2 other identifiers: 14592B3D-US-GHDV
• Study Type: interventional
• Target: 69
• Locations: 2 countries
• Sites: 6

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).

Conditions

Osteoporosis

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to 3 Months in Mineralizing Surface (MS) /Bone Surface (BS) in the Cancellous Compartment (CC) of the Iliac Crest Bone Biopsies

  MS /BS is a measure of the proportion of BS on which new mineralized bone is deposited at the time of DEM or TET labeling, and calculated as the sum of the total extent of double label (DL) plus half the extent of single label (SL) divided by BS. At baseline (18 days prior to randomization / study drug administration), DEM was administered (3 days on, 12 days off, 3 days on). 22 days prior to the biopsy procedure (biopsy obtained 3 months post first dose of study drug), TET was administered (same dosing schedule as DEM). Both DEM and TET temporarily bind to new bone and fluoresce under UV light. New bone in the biopsy was seen as the amount of bone between the 2 fluorescently DEM- or TET-labeled lines under a microscope. A DL indicated active bone formation and a SL or no label (NL) suggested varying degrees of suppression of bone formation.

  Baseline, 3 months post first dose of study drug

Secondary Outcomes (21)

• 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

  3 months post first dose of study drug

• 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

  Baseline, 3 months post first dose of study drug

• MS/BS in the CC, EC, IC and PC of the Iliac Crest Bone Biopsies 3 Months Post First Dose of Study Drug

  3 months post first dose of study drug

• Percentage of Bone With Remodeling-Based and Modeling-Based Formations in the CC, EC and PC of the Iliac Crest Bone Biopsies

  3 months post first dose of study drug

• Percentage of Mineralizing Surface With Remodeling-Based Formation and Modeling-Based Formation in the CC, EC and PC of the Iliac Crest Bone Biopsies

  3 months post first dose of study drug

Other Outcomes (1)

• Average Length of DLs in the CC, EC, IC and PC of the Iliac Crest

  3 months post first dose of study drug

Study Arms (2)

Teriparatide

EXPERIMENTAL

20 micrograms (µg) teriparatide administered subcutaneously (SC) once every day for 6 months. Demeclocycline (DEM): Beginning 18 days prior to randomization: Days 1, 2, 3 and 16, 17, 18: 150 milligrams (mg) DEM will be taken orally every 6 hours; Days 4 to15: DEM will not be administered. Tetracycline (TET): Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15: TET will not be administered. Calcium: Approximately 1000 milligrams per day (mg/day) administered orally. Vitamin D: Approximately 800 to 1200 International Units per day (IU/day) administered orally.

Drug: Teriparatide; Drug: Demeclocycline; Drug: Tetracycline; Drug: Calcium Supplement; Drug: Vitamin D

Denosumab

ACTIVE COMPARATOR

60 mg denosumab administered SC once in 6 months. DEM: Beginning 18 days prior to randomization: Days 1, 2, 3 and 16, 17, 18: 150 mg DEM will be taken orally every 6 hours; Days 4 to 15: DEM will not be administered. TET: Beginning 22 days prior to the biopsy procedure: Days 1, 2, 3 and 16, 17, 18: 250 mg TET will be taken orally every 6 hours; Days 4 through 15: TET will not be administered. Calcium: Approximately 1000 mg/day administered orally. Vitamin D: Approximately 800 to 1200 IU/day administered orally.

Drug: Denosumab; Drug: Demeclocycline; Drug: Tetracycline; Drug: Calcium Supplement; Drug: Vitamin D

Interventions

Teriparatide DRUG

Administered SC

Also known as: LY333334, Forteo, Forsteo

Teriparatide

Denosumab DRUG

Administered SC

Denosumab

Demeclocycline DRUG

Administered orally

Denosumab; Teriparatide

Tetracycline DRUG

Administered orally

Denosumab; Teriparatide

Calcium Supplement DRUG

Administered orally

Denosumab; Teriparatide

Vitamin D DRUG

Administered orally

Denosumab; Teriparatide

Eligibility Criteria

• Age: 55 Years - 89 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (6)

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

Location

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

Location

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

Location

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

Location

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

Location

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

Location

Related Publications (1)

• 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.

  PMID: 29024120 DERIVED

MeSH Terms

Conditions

Osteoporosis

Interventions

Teriparatide; Denosumab; Demeclocycline; Tetracycline; Vitamin D

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Parathyroid Hormone; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Secosteroids; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2012
• First Posted: December 20, 2012
• Study Start: January 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: October 8, 2015
• Results First Posted: October 8, 2015

Record last verified: 2015-09

Locations

CA (2); US (4)