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

December 18, 2012
June 30, 2014
January 2013
June 2014   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01753856 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Effects of Teriparatide or Denosumab on Bone in Postmenopausal Women With Osteoporosis
Anabolism Versus Antiresorption: A Quadruple Labeling Histomorphometry Study to Compare the Mechanism of Action of Teriparatide and Denosumab in Postmenopausal Women With Osteoporosis

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).

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Osteoporosis
  • Drug: Teriparatide
    Administered SC
    Other Names:
    • LY333334
    • Forteo
    • Forsteo
  • Drug: Denosumab
    Administered SC
  • Drug: Demeclocyline
    Administered orally
  • Drug: Tetracycline
    Administered orally
  • Drug: Calcium Supplement
    Administered orally
  • Drug: Vitamin D
    Administered orally
  • 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.

    Interventions:
    • Drug: Teriparatide
    • Drug: Demeclocyline
    • Drug: Tetracycline
    • Drug: Calcium Supplement
    • Drug: Vitamin D
  • 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.

    Interventions:
    • Drug: Denosumab
    • Drug: Demeclocyline
    • Drug: Tetracycline
    • Drug: Calcium Supplement
    • Drug: Vitamin D
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
68
June 2014
June 2014   (final data collection date for primary outcome measure)

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
Female
55 Years to 89 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01753856
14592, B3D-US-GHDV
No
Eli Lilly and Company
Eli Lilly and Company
Not Provided
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
Eli Lilly and Company
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP