Trial Outcomes & Findings for A Study Using Imaging Technology to Measure Changes in Bone Structure After Treatment With Teriparatide (NCT NCT00557310)

NCT ID: NCT00557310

Last Updated: 2011-11-11

Results Overview

SCR is a measure of the computed ratio of plate-like to rod-like structures in a given volume of trabecular bone and reflects the integrity of the trabecular network. The higher the value for SCR, the more intact the trabecular network. Least squares (LS) mean of the percent change from baseline to 18 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 35 participants
• Primary outcome timeframe: Baseline, 18 months
• Results posted on: 2011-11-11

Participant Flow

Participants who completed the 18 month main study had an option to continue treatment for an additional 6 months (Extension Phase).

Participant milestones

Measure	Teriparatide 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Main Study (0 - 18 Months) STARTED	35
Main Study (0 - 18 Months) COMPLETED	30
Main Study (0 - 18 Months) NOT COMPLETED	5
Extension Phase (18 - 24 Months) STARTED	30
Extension Phase (18 - 24 Months) COMPLETED	25
Extension Phase (18 - 24 Months) NOT COMPLETED	5

Reasons for withdrawal

Measure	Teriparatide 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Main Study (0 - 18 Months) Adverse Event	4
Main Study (0 - 18 Months) Withdrawal by Subject	1
Extension Phase (18 - 24 Months) Adverse Event	1
Extension Phase (18 - 24 Months) Lost to Follow-up	1
Extension Phase (18 - 24 Months) Physician Decision	2
Extension Phase (18 - 24 Months) Protocol Violation	1

Baseline Characteristics

A Study Using Imaging Technology to Measure Changes in Bone Structure After Treatment With Teriparatide

Baseline characteristics by cohort

Measure	Teriparatide n=34 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Age Continuous	61.96 years STANDARD_DEVIATION 8.14 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	31 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	2 participants n=5 Participants
Race/Ethnicity, Customized West Asian	1 participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants
Region of Enrollment Canada	6 participants n=5 Participants
Dominant Hand Left	1 participants n=5 Participants
Dominant Hand Right	33 participants n=5 Participants
Prevalent Fractures None	14 participants n=5 Participants
Prevalent Fractures Any vertebral fracture	4 participants n=5 Participants
Prevalent Fractures Any non-vertebral fracture	17 participants n=5 Participants
Years Postmenopausal	16.97 years STANDARD_DEVIATION 12.10 • n=5 Participants
Prior Bisphosphonate Use Yes	21 participants n=5 Participants
Prior Bisphosphonate Use No	13 participants n=5 Participants
Lumbar Spine T-Score	-2.91 units on a scale STANDARD_DEVIATION 1.04 • n=5 Participants
Femoral Neck T-Score	-2.38 units on a scale STANDARD_DEVIATION 0.67 • n=5 Participants
Total Hip T-Score	-1.80 units on a scale STANDARD_DEVIATION 0.81 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 18 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

SCR is a measure of the computed ratio of plate-like to rod-like structures in a given volume of trabecular bone and reflects the integrity of the trabecular network. The higher the value for SCR, the more intact the trabecular network. Least squares (LS) mean of the percent change from baseline to 18 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=25 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Surface-to-Curve Ratio (SCR) in the Distal Radius at Month 18 Endpoint	4.53 percent (%) change of ratio Standard Error 4.89

SECONDARY outcome

Timeframe: Baseline, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

SCR is a measure of the computed ratio of plate-like to rod-like structures in a given volume of trabecular bone and reflects the integrity of the trabecular network. The higher the value for SCR, the more intact the trabecular network. Least squares (LS) mean of the percent change from baseline to 24 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=21 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Surface-to-Curve Ratio (SCR) in the Distal Radius at Month 24 Endpoint	1.44 % change of ratio Standard Error 6.88

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Cortical thickness (CT) is the thickness of both cortices in a given volume of bone. Least squares (LS) mean of the percent change from baseline to 18, 24 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=32 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Cortical Thickness (CT) in the Distal Radius at Month 18 and 24 Endpoint 18 month percent change (n=25)	-0.61 % change of millimeter (mm) Standard Error 2.56
Percent Change From Baseline in Cortical Thickness (CT) in the Distal Radius at Month 18 and 24 Endpoint 24 month percent change (n=21)	-0.22 % change of millimeter (mm) Standard Error 2.59

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

TEI is the ratio of the sum of topological parameters expected to increase with bone erosion compared to the sum of those expected to decrease. The lower the value for TEI, the more intact the trabecular network. Least squares (LS) mean of the percent change from baseline to 18, 24 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=32 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Topological Erosion Index (TEI) in the Distal Radius at Month 18 and 24 Endpoint 18 month percent change (n=25)	3.36 % change of ratio Standard Error 3.31
Percent Change From Baseline in Topological Erosion Index (TEI) in the Distal Radius at Month 18 and 24 Endpoint 24 month percent change (n=21)	8.46 % change of ratio Standard Error 4.63

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

BV/TV is the estimate of the ratio of detectable bone relative to the total volume of the region of interest. Least squares (LS) mean of the percent change from baseline to 18, 24 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=32 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Bone Volume (BV)/Total Volume (TV) Ratio in the Distal Radius at Month 18 and 24 Endpoint 18 month percent change (n=25)	0.36 % change of ratio Standard Error 1.85
Percent Change From Baseline in Bone Volume (BV)/Total Volume (TV) Ratio in the Distal Radius at Month 18 and 24 Endpoint 24 month percent change (n=21)	-3.14 % change of ratio Standard Error 2.40

SECONDARY outcome

Timeframe: Baseline, 3, 6, 12, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

SCR is a measure of the computed ratio of plate-like to rod-like structures in a given volume of trabecular bone and reflects the integrity of the trabecular network. The higher the value for SCR, the more intact the trabecular network. Least squares (LS) mean of the percent change from baseline to 3, 6, 12, 18, 24 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=32 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Surface-to-Curve Ratio (SCR) at Month 3, 6, 12, 18 and 24 Endpoint 3 month percent change (n=32)	-3.38 % change of ratio Standard Error 3.46
Percent Change From Baseline in Surface-to-Curve Ratio (SCR) at Month 3, 6, 12, 18 and 24 Endpoint 6 month percent change (n=30)	0.43 % change of ratio Standard Error 4.05
Percent Change From Baseline in Surface-to-Curve Ratio (SCR) at Month 3, 6, 12, 18 and 24 Endpoint 12 month percent change (n=28)	2.36 % change of ratio Standard Error 4.56
Percent Change From Baseline in Surface-to-Curve Ratio (SCR) at Month 3, 6, 12, 18 and 24 Endpoint 18 month percent change (n=25)	4.53 % change of ratio Standard Error 4.89
Percent Change From Baseline in Surface-to-Curve Ratio (SCR) at Month 3, 6, 12, 18 and 24 Endpoint 24 month percent change (n=21)	1.44 % change of ratio Standard Error 6.88

SECONDARY outcome

Timeframe: Baseline, 18 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Volumetric BMD is a measure of the amount of mineral in a given volume of bone, expressed as milligram per cubic centimeter (mg/cm³). Least squares (LS) mean of the percent change from baseline to 18 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=28 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Volumetric Bone Mineral Density (BMD) of Lumbar Spine at Month 18 Endpoint	10.05 % change of mg/cm³ Standard Error 1.55

SECONDARY outcome

Timeframe: Baseline, 18 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Volumetric BMD is a measure of the amount of mineral in a given volume of bone. Least squares (LS) mean of the percent change from baseline to 18 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=25 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Volumetric Bone Mineral Density (BMD) of Hip at Month 18 Endpoint	2.22 % change of mg/cm³ Standard Error 0.88

SECONDARY outcome

Timeframe: Baseline, 18 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Finite Element Analysis of computed tomography (CT) data from spine is used to estimate the strength of a vertebral body using a virtual axial load. Least squares (LS) mean of the percent change from baseline to 18 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=28 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in the Estimate of Bone Strength of Lumbar Spine at Month 18 Endpoint	17.43 % change of Newtons Standard Error 2.57

SECONDARY outcome

Timeframe: Baseline, 18 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Finite Element Analysis of computed tomography (CT) data from hip is used to estimate the strength of the proximal femur with a virtual sideways fall. Least squares (LS) mean of the percent change from baseline to 18 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=25 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in the Estimate of Bone Strength of Hip at Month 18 Endpoint	2.54 % change of Newtons Standard Error 1.18

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Areal BMD is a measure of the amount of mineral in a given area of bone. Least squares (LS) mean of the percent change from baseline to 18 and 24 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=29 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Areal BMD at the Lumbar Spine at Month 18 and 24 Endpoint 18 month percent change (n=28)	7.215 % change of g/square centimeter (g/cm²) Standard Error 1.166
Percent Change From Baseline in Areal BMD at the Lumbar Spine at Month 18 and 24 Endpoint 24 month percent change (n=25)	8.702 % change of g/square centimeter (g/cm²) Standard Error 0.939

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Areal BMD is a measure of the amount of mineral in a given area of bone. Least squares (LS) mean of the percent change from baseline to 18 and 24 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=29 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Areal BMD at the Femoral Neck at Month 18 and 24 Endpoint 24 month percent change (n=25)	2.762 % change of g/cm² Standard Error 1.312
Percent Change From Baseline in Areal BMD at the Femoral Neck at Month 18 and 24 Endpoint 18 month percent change (n=28)	2.792 % change of g/cm² Standard Error 0.998

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Areal BMD is a measure of the amount of mineral in a given area of bone. Least squares (LS) mean of the percent change from baseline to 18 and 24 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=29 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Areal BMD Responses at Total Hip at Month 18 and 24 Endpoint 18 month percent change (n=28)	0.292 % change of g/cm² Standard Error 0.747
Percent Change From Baseline in Areal BMD Responses at Total Hip at Month 18 and 24 Endpoint 24 month percent change (n=25)	1.482 % change of g/cm² Standard Error 0.836

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Areal BMD is a measure of the amount of mineral in a given area of bone. Least squares (LS) mean of the percent change from baseline to 18 and 24 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=29 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Areal BMD at ⅓ Distal Radius at Month 18 and 24 Endpoint 18 month percent change (n=28)	-2.068 % change of g/cm² Standard Error 0.763
Percent Change From Baseline in Areal BMD at ⅓ Distal Radius at Month 18 and 24 Endpoint 24 month percent change (n=25)	-2.733 % change of g/cm² Standard Error 0.864

SECONDARY outcome

Timeframe: Baseline, 18, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

Areal BMD is a measure of the amount of mineral in a given area of bone. Least squares (LS) mean of the percent change from baseline to 18 and 24 months is from an analysis of variance (ANOVA). The model included terms for investigator site and prior bisphosphonate use.

Outcome measures

Measure	Teriparatide n=29 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Areal BMD at Ultra-Distal Radius at Month 18 and 24 Endpoint 18 month percent change (n=28)	-1.891 % change of g/cm² Standard Error 1.122
Percent Change From Baseline in Areal BMD at Ultra-Distal Radius at Month 18 and 24 Endpoint 24 month percent change (n=25)	0.776 % change of g/cm² Standard Error 0.975

SECONDARY outcome

Timeframe: Baseline, 3, 6, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

PINP is a measure of bone formation. Least squares (LS) mean of the percent change from baseline to 3, 6, 24 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=32 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 3, 6 and 24 Endpoint 3 month percent change (n=32)	145.35 % change of microgram/Liter (µg/L) Standard Error 23.36
Percent Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 3, 6 and 24 Endpoint 6 month percent change (n=30)	238.04 % change of microgram/Liter (µg/L) Standard Error 44.29
Percent Change From Baseline in Serum Procollagen Type I N-Terminal Propeptide (PINP) at Month 3, 6 and 24 Endpoint 24 month percent change (n=23)	118.91 % change of microgram/Liter (µg/L) Standard Error 22.72

SECONDARY outcome

Timeframe: Baseline, 3, 6, 24 months

Population: Participants who were assigned to treatment, had non-missing baseline and at least one non-missing post-baseline measurement value.

CTX is a measure of bone resorption. Least squares (LS) mean of the percent change from baseline to 3, 6, 24 months is from a mixed model repeated measurements analysis. The model included terms for investigator site, prior bisphosphonate use, visit and baseline.

Outcome measures

Measure	Teriparatide n=32 Participants 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Percent Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 3, 6 and 24 Endpoint 3 month percent change (n=32)	63.53 % change of nanogram/milliliter (ng/mL) Standard Error 23.78
Percent Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 3, 6 and 24 Endpoint 6 month percent change (n=30)	102.56 % change of nanogram/milliliter (ng/mL) Standard Error 38.42
Percent Change From Baseline in Serum Carboxyterminal Cross-Linking Telopeptide of Type I Collagen (CTX) at Month 3, 6 and 24 Endpoint 24 month percent change (n=23)	48.28 % change of nanogram/milliliter (ng/mL) Standard Error 18.36

Adverse Events

Teriparatide

Serious events: 5 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Teriparatide n=35 participants at risk 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Cardiac disorders Cardiomyopathy	2.9% 1/35 • Number of events 1
Cardiac disorders Coronary artery disease	2.9% 1/35 • Number of events 1
Eye disorders Visual impairment	2.9% 1/35 • Number of events 1
Gastrointestinal disorders Crohn's disease	2.9% 1/35 • Number of events 1
Infections and infestations Arthritis bacterial	2.9% 1/35 • Number of events 1
Infections and infestations Gastroenteritis viral	2.9% 1/35 • Number of events 1
Infections and infestations Pneumonia	2.9% 1/35 • Number of events 1
Infections and infestations Staphylococcal infection	2.9% 1/35 • Number of events 1
Injury, poisoning and procedural complications Fall	2.9% 1/35 • Number of events 1
Metabolism and nutrition disorders Dehydration	2.9% 1/35 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neurilemmoma	2.9% 1/35 • Number of events 1

Other adverse events

Measure	Teriparatide n=35 participants at risk 20 microgram (mcg) teriparatide subcutaneous injection per day for 18 months, with possibility to continue for 24 months
Gastrointestinal disorders Abdominal discomfort	5.7% 2/35 • Number of events 2
Gastrointestinal disorders Constipation	8.6% 3/35 • Number of events 3
Gastrointestinal disorders Diarrhoea	8.6% 3/35 • Number of events 3
Gastrointestinal disorders Nausea	5.7% 2/35 • Number of events 2
Gastrointestinal disorders Vomiting	5.7% 2/35 • Number of events 2
General disorders Injection site haematoma	5.7% 2/35 • Number of events 2
General disorders Malaise	5.7% 2/35 • Number of events 2
Immune system disorders Seasonal allergy	5.7% 2/35 • Number of events 2
Infections and infestations Bronchitis	5.7% 2/35 • Number of events 2
Infections and infestations Diverticulitis	5.7% 2/35 • Number of events 2
Infections and infestations Influenza	8.6% 3/35 • Number of events 4
Infections and infestations Upper respiratory tract infection	5.7% 2/35 • Number of events 2
Injury, poisoning and procedural complications Contusion	5.7% 2/35 • Number of events 4
Injury, poisoning and procedural complications Fall	5.7% 2/35 • Number of events 3
Investigations Weight decreased	8.6% 3/35 • Number of events 3
Musculoskeletal and connective tissue disorders Arthralgia	11.4% 4/35 • Number of events 6
Musculoskeletal and connective tissue disorders Muscle spasms	11.4% 4/35 • Number of events 5
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.7% 2/35 • Number of events 3
Musculoskeletal and connective tissue disorders Neck pain	5.7% 2/35 • Number of events 2
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 2/35 • Number of events 3
Nervous system disorders Dizziness	5.7% 2/35 • Number of events 2
Nervous system disorders Headache	8.6% 3/35 • Number of events 4
Psychiatric disorders Anxiety	5.7% 2/35 • Number of events 2
Psychiatric disorders Insomnia	8.6% 3/35 • Number of events 3
Respiratory, thoracic and mediastinal disorders Cough	5.7% 2/35 • Number of events 2
Skin and subcutaneous tissue disorders Ecchymosis	5.7% 2/35 • Number of events 4
Skin and subcutaneous tissue disorders Onychoclasis	5.7% 2/35 • Number of events 2

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60