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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01753856
First received: December 18, 2012
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Osteoporosis
Drug: Teriparatide
Drug: Denosumab
Drug: Demeclocyline
Drug: Tetracycline
Drug: Calcium Supplement
Drug: Vitamin D
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change from Baseline to 3 Months in Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Proportion of Bone with Remodeling-Based Formation and Modeling-Based Formation [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Proportion of Overfilled Remodeling Sites [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Change from Baseline to 3 Months in Label Length within each Basic Multicellular Unit (BMU) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Change from Baseline to 3 Months in Mineral Apposition Rate (MAR) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Change from Baseline to 3 Months in Bone Formation Rate (BFR) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Percent of Single or Double Tetracycline Labels per Bone Surface (sLS/BS), (dLS/BS) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Change from Baseline to 3 Months in Intact Parathyroid Hormone (PTH) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Change from Baseline to 3 Months in Serum Procollagen Type I N-terminal Propeptide (P1NP) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Change from Baseline to 3 Months in Serum Osteocalcin [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Change from Baseline to 3 Months in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) [ Time Frame: Baseline, 3 Months ] [ Designated as safety issue: No ]
  • Activation Frequency (Ac.f ) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Adjusted Apposition Rate (Aj.AR) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Number of Samples with Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Percentage of Osteoid Volume (OV)/Bone Volume (BV) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Percentage of Osteoid Surface (OS)/Bone Surface (BS) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Osteoid Thickness (O.Th) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Wall Thickness (W.Th) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
  • Percentage of Eroded Surface/Bone Surface (ES/BS) [ Time Frame: 3 Months ] [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: January 2013
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Teriparatide

20 micrograms (mcg) 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 milligram (mg) DEM will be taken orally every 6 hours; Days 4-15: 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 and 19 through 22: 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
Administered SC
Other Names:
  • LY333334
  • Forteo
  • Forsteo
Drug: Demeclocyline
Administered orally
Drug: Tetracycline
Administered orally
Drug: Calcium Supplement
Administered orally
Drug: Vitamin D
Administered orally
Active Comparator: Denosumab

60 mg denosumab administered SC once in 6 months.

Demeclocycline (DEM): Beginning 18 days prior to Randomization: Days 1, 2, 3 and 16, 17, 18: 150 milligram (mg) DEM will be taken orally every 6 hours; Days 4-15: 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 and 19 through 22: TET will not be administered.

Calcium: Approximately 1000 mg/day administered orally.

Vitamin D: Approximately 800 to 1200 IU/day administered orally.

Drug: Denosumab
Administered SC
Drug: Demeclocyline
Administered orally
Drug: Tetracycline
Administered orally
Drug: Calcium Supplement
Administered orally
Drug: Vitamin D
Administered orally

  Eligibility

Ages Eligible for Study:   55 Years to 89 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01753856

Locations
United States, Colorado
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, United States, 80227
United States, Georgia
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, United States, 30501
United States, Michigan
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, United States, 48202
United States, Nebraska
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, United States, 68131
Canada, British Columbia
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, Canada, V5Z 4E1
Canada, Quebec
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, Canada, G1V 3M7
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01753856     History of Changes
Other Study ID Numbers: 14592, B3D-US-GHDV
Study First Received: December 18, 2012
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Vitamins
Vitamin D
Ergocalciferols
Teriparatide
Tetracycline
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014