Effects of Teriparatide or Zoledronic Acid Treatment on Bone in Postmenopausal Osteoporotic Women

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00927186
First received: June 22, 2009
Last updated: February 21, 2013
Last verified: February 2013
Results First Received: October 7, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Osteoporosis, Post-menopausal
Interventions: Drug: Teriparatide
Drug: Zoledronic Acid

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This was a Phase 4, multicenter, randomized, stratified, double-blind, active comparator-controlled study with the primary endpoint at 6 months. Following the bone biopsy visit at 6 months, the study became open label for an additional 6 months. All participants who complete 12 months of treatment are eligible for an additional 12-month extension.

Reporting Groups
  Description
Teriparatide

20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind.

After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.

Zoledronic Acid

5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind.

After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.


Participant Flow for 2 periods

Period 1:   12 Months Primary Study
    Teriparatide     Zoledronic Acid  
STARTED     34     35  
Completed 6 Months Double Blind Phase     28     31  
COMPLETED     27     31  
NOT COMPLETED     7     4  
Adverse Event                 5                 2  
Lost to Follow-up                 1                 0  
Protocol Violation                 0                 1  
Withdrawal by Subject                 1                 1  

Period 2:   12 - 24 Months Extension Treatment
    Teriparatide     Zoledronic Acid  
STARTED     10 [1]   11 [1]
COMPLETED     10     11  
NOT COMPLETED     0     0  
[1] Not all participants who completed 12 months of primary study chose to enter 12-month extension.



  Baseline Characteristics
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Reporting Groups
  Description
Teriparatide 20 microgram (mcg) subcutaneous (SC) injection per day for 12 months. Placebo intravenous (IV) infusions were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Zoledronic Acid 5 milligram (mg) intravenous (IV) infusion administered once during 1 year study. Placebo subcutaneous (SC) injections were given to maintain blind. After completing 12 months of treatment, all participants are eligible to participate in an additional 12-month extension.
Total Total of all reporting groups

Baseline Measures
    Teriparatide     Zoledronic Acid     Total  
Number of Participants  
[units: participants]
  34     35     69  
Age  
[units: years]
Mean ± Standard Deviation
  65.49  ± 6.93     64.20  ± 5.96     64.84  ± 6.44  
Gender  
[units: participants]
     
Female     34     35     69  
Male     0     0     0  
Race/Ethnicity, Customized  
[units: participants]
     
Black or African American     1     1     2  
White     33     34     67  
Region of Enrollment  
[units: participants]
     
United States     21     25     46  
Canada     13     10     23  
Height  
[units: centimeters (cm)]
Mean ± Standard Deviation
  159.28  ± 5.92     160.00  ± 7.38     159.64  ± 6.66  
Weight  
[units: kilograms (kg)]
Mean ± Standard Deviation
  61.25  ± 9.21     64.75  ± 11.66     63.03  ± 10.60  
Pulse  
[units: beats per minute (bpm)]
Mean ± Standard Deviation
  67.41  ± 7.15     70.60  ± 8.79     69.03  ± 8.13  
Blood Pressure - Systolic  
[units: millimeters of mercury (mmHg)]
Mean ± Standard Deviation
  125.71  ± 16.19     122.49  ± 16.25     124.07  ± 16.18  
Blood Pressure - Diastolic  
[units: mmHg]
Mean ± Standard Deviation
  74.79  ± 8.24     73.97  ± 10.15     74.38  ± 9.20  
Alcohol Use  
[units: participants]
     
Yes     21     17     38  
No     13     18     31  
Tobacco Use  
[units: participants]
     
Yes     5     5     10  
No     29     30     59  
Caffeine or Xanthine Use  
[units: participants]
     
Yes     29     30     59  
No     5     5     10  
Previous Osteoporosis Therapy  
[units: participants]
     
Yes     17     21     38  
No     17     14     31  
Fracture Status [1]
[units: participants]
     
Yes     14     17     31  
No     20     18     38  
Lumbar Spine T-Score [2]
[units: T-Score]
Mean ± Standard Deviation
  -2.79  ± 0.83     -2.93  ± 0.75     -2.86  ± 0.79  
Femoral Neck T-Score [3]
[units: T-Score]
Mean ± Standard Deviation
  -2.25  ± 0.68     -2.29  ± 0.74     -2.27  ± 0.70  
Total Hip T-Score [4]
[units: T-Score]
Mean ± Standard Deviation
  -1.78  ± 0.78     -1.88  ± 0.91     -1.83  ± 0.84  
Serum Procollagen Type I N-Terminal Propeptide (PINP) [5]
[units: microgram/Liter (µg/L)]
Mean ± Standard Deviation
  49.18  ± 18.28     52.88  ± 19.43     51.03  ± 18.81  
Serum Carboxyterminal Cross-Linking Telopeptide of Collagen Type I (CTX) [6]
[units: nanogram/milliliter (ng/mL)]
Mean ± Standard Deviation
  0.43  ± 0.23     0.42  ± 0.19     0.43  ± 0.21  
Serum Osteocalcin [7]
[units: microgram/Liter (µg/L)]
Mean ± Standard Deviation
  25.05  ± 8.37     24.92  ± 8.53     24.98  ± 8.39  
[1] Yes means a participant has already had fracture before study entry.
[2] The T-score at lumbar spine is a comparison of a participant's bone mineral density (BMD) to that of the mean BMD for a healthy population of women at peak bone mass (30 years). A normal T-score has a value of -1.0 or higher. Osteoporosis is defined as a T-score of -2.5 or lower, meaning a bone mineral density that is two and a half standard deviations below the mean BMD of a healthy population of women at peak bone mass (30 years).
[3] The T-score at femoral neck is a comparison of a participant's bone mineral density (BMD) to that of the mean BMD for a healthy population of women at peak bone mass (30 years). A normal T-score has a value of -1.0 or higher. Osteoporosis is defined as a T-score of -2.5 or lower, meaning a bone mineral density that is two and a half standard deviations below the mean BMD of a healthy population of women at peak bone mass (30 years).
[4] The T-score at total hip is a comparison of a participant's bone mineral density (BMD) to that of the mean BMD for a healthy population of women at peak bone mass (30 years). A normal T-score has a value of -1.0 or higher. Osteoporosis is defined as a T-score of -2.5 or lower, meaning a bone mineral density that is two and a half standard deviations below the mean BMD of a healthy population of women at peak bone mass (30 years).
[5] A measure of bone formation.
[6] A measure of bone resorption.
[7] A measure of osteoblast function.



  Outcome Measures
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1.  Primary:   Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

2.  Secondary:   Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

3.  Secondary:   Mineralizing Surface/Bone Surface(MS/BS) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

4.  Secondary:   Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

5.  Secondary:   Activation Frequency (Ac.f) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

6.  Secondary:   Activation Frequency (Ac.f) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

7.  Secondary:   Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

8.  Secondary:   Bone Formation Rate (BFR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

9.  Secondary:   Bone Formation Rate (BFR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

10.  Secondary:   Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

11.  Secondary:   Mineral Apposition Rate (MAR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

12.  Secondary:   Mineral Apposition Rate (MAR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

13.  Secondary:   Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

14.  Secondary:   Adjusted Apposition Rate (Aj.AR) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

15.  Secondary:   Adjusted Apposition Rate (Aj.AR) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

16.  Secondary:   Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

17.  Secondary:   Mineralization Lag Time (Mlt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

18.  Secondary:   Mineralization Lag Time (Mlt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

19.  Secondary:   Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

20.  Secondary:   Osteoid Maturation Time (Omt) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

21.  Secondary:   Osteoid Maturation Time (Omt) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 Months ]

22.  Secondary:   Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

23.  Secondary:   Total Formation Period (Tt.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

24.  Secondary:   Total Formation Period (Tt.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

25.  Secondary:   Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

26.  Secondary:   Active Formation Period (a.FP) in the Cancellous Compartment (CC) of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

27.  Secondary:   Active Formation Period (a.FP) in the Endocortical Compartment (EC) of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

28.  Secondary:   Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

29.  Secondary:   Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

30.  Secondary:   Percent of Single or Double Tetracycline Labels Per Bone Surface (sLS/BS), (dLS/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

31.  Secondary:   Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

32.  Secondary:   Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

33.  Secondary:   Number of Samples With Single or Double Tetracycline Labels, Single and Double Labels, or No Tetracycline Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

34.  Secondary:   Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

35.  Secondary:   Average Length of Tetracycline Double Labels in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

36.  Secondary:   Average Length of Tetracycline Double Labels in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

37.  Secondary:   Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

38.  Secondary:   Percentage of Osteoid Volume (OV)/Bone Volume (BV) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

39.  Secondary:   Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

40.  Secondary:   Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

41.  Secondary:   Percentage of Osteoid Surface (OS)/Bone Surface (BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

42.  Secondary:   Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

43.  Secondary:   Osteoid Thickness (OTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

44.  Secondary:   Osteoid Thickness (OTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

45.  Secondary:   Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

46.  Secondary:   Wall Thickness (WTh.) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

47.  Secondary:   Wall Thickness (WTh.) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

48.  Secondary:   Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 6 Months   [ Time Frame: 6 months ]

49.  Secondary:   Percentage of Eroded Surface/Bone Surface (ES/BS) in the Cancellous Compartment of Iliac Crest Bone Biopsies at 24 Months   [ Time Frame: 24 months ]

50.  Secondary:   Percentage of Eroded Surface/Bone Surface (ES/BS) in the Endocortical Compartment of Iliac Crest Bone Biopsies at 6 and 24 Months   [ Time Frame: 6 and 24 months ]

51.  Secondary:   Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 1, 3 and 6 Endpoint   [ Time Frame: Baseline, 1, 3, 6 months ]

52.  Secondary:   Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 12 Endpoint   [ Time Frame: Baseline, 12 months ]

53.  Secondary:   Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 1, 3 and 6 Endpoint   [ Time Frame: Baseline, 1, 3, 6 months ]

54.  Secondary:   Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 12 Endpoint   [ Time Frame: Baseline, 12 months ]

55.  Secondary:   Change From Baseline in Serum Osteocalcin (OC) at Month 1, 3, and 6 Endpoint   [ Time Frame: Baseline, 1, 3, 6 months ]

56.  Secondary:   Change From Baseline in Serum Osteocalcin (OC) at Month 12 Endpoint   [ Time Frame: Baseline, 12 months ]


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