Effect of Full Length Parathyroid Hormone, PTH(1-84) or Strontium Ranelate on Bone Markers in Postmenopausal Women With Primary Osteoporosis (FP-006-IM) - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Osteoporosis
Interventions:	Drug: Full Length Parathyroid Hormone, PTH(1-84) Drug: Strontium Ranelate

Participant Flow

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
82 subjects were randomized. Of these, one subject was randomized, but consent was withdrawn during the screening period; the subject did not receive any treatment. Therefore, the Intention to treat set (ITT) consisted of 81 subjects.

Reporting Groups

	Description
PTH(1-84)	Once daily subcutaneous injection
Strontium Ranelate	One sachet (2 g) per day, suspended in water

Participant Flow: Overall Study

	PTH(1-84)	Strontium Ranelate
STARTED	41	40
COMPLETED	38	34
NOT COMPLETED	3	6

Baseline Characteristics

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Reporting Groups

	Description
PTH(1-84)	Once daily subcutaneous injection
Strontium Ranelate	One sachet (2 g) per day, suspended in water
Total	Total of all reporting groups

Baseline Measures

	PTH(1-84)	Strontium Ranelate	Total
Number of Participants [units: participants]	41	40	81
Age [units: years] Mean ± Standard Deviation	64.0 ± 8.64	64.9 ± 8.49	64.4 ± 8.52
Gender, Customized [units: participants]
Female	41	40	81

Outcome Measures

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1. Primary:

Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial [ Time Frame: Baseline and 24 weeks of treatment ]

Measure Type	Primary
Measure Title	Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial
Measure Description	P1NP is a bone formation marker that is derived from the amino-terminal propeptides of type I collagen and is considered a quantitative measure of newly formed type I collagen. Bone marker measurements were done by blood analysis.
Time Frame	Baseline and 24 weeks of treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT (Intention to Treat) analysis. Number of participants analyzed = number of participants with data available.

Reporting Groups

	Description
PTH(1-84)	Once daily subcutaneous injection
Strontium Ranelate	One sachet (2 g) per day, suspended in water

Measured Values

	PTH(1-84)	Strontium Ranelate
Number of Participants Analyzed [units: participants]	41	40
Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial [units: percent change] Mean ± Standard Deviation	446.1 ± 355.3	-6.2 ± 36.9

Statistical Analysis 1 for Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.0001
Mean Difference (Net) ^[4]	360.3
95% Confidence Interval	( 256.5 to 494.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The bone marker values were log-transformed for the primary analysis as they were heavily skewed. Changes in log-transformed bone marker values were analyzed using an analysis of covariance (ANCOVA) with treatment and center as fixed effects and the baseline bone marker value as a covariate. An F-test was used to test the effect of treatment and the least square means were computed to assess the clinical difference between treatment groups.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-values corresponding to the tests of treatment effect for the primary endpoints were adjusted using the Hochberg procedure.
[4]	Other relevant estimation information:
	No text entered.

2. Primary:

Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial [ Time Frame: Baseline and 24 weeks of treatment ]

Measure Type	Primary
Measure Title	Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial
Measure Description	BSAP is a marker of bone formation that reflects the cellular activity of osteoblasts. Bone marker measurements were done by blood analysis.
Time Frame	Baseline and 24 weeks of treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT analysis. Number of participants analyzed = number of participants with data available.

Reporting Groups

	Description
PTH(1-84)	Once daily subcutaneous injection
Strontium Ranelate	One sachet (2 g) per day, suspended in water

Measured Values

	PTH(1-84)	Strontium Ranelate
Number of Participants Analyzed [units: participants]	41	40
Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial [units: percent change] Mean ± Standard Deviation	129.6 ± 100.3	4.9 ± 22.9

Statistical Analysis 1 for Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.0001
Mean Difference (Net) ^[4]	92.9
95% Confidence Interval	( 63.8 to 127.1 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The bone marker values were log-transformed for the primary analysis as they were heavily skewed. Changes in log-transformed bone marker values were analyzed using an analysis of covariance (ANCOVA) with treatment and center as fixed effects and the baseline bone marker value as a covariate. An F-test was used to test the effect of treatment and the least square means were computed to assess the clinical difference between treatment groups.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-values corresponding to the tests of treatment effect for the primary endpoints were adjusted using the Hochberg procedure.
[4]	Other relevant estimation information:
	No text entered.

3. Secondary:

Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial [ Time Frame: Baseline and 24 weeks of treatment ]

Measure Type	Secondary
Measure Title	Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial
Measure Description	CTX is a marker of bone resorption, which is a degradation product of bone collagen. Bone marker measurements were done by blood analysis.
Time Frame	Baseline and 24 weeks of treatment
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT analysis. Number of participants analyzed = number of participants with data available.

Reporting Groups

	Description
PTH(1-84)	Once daily subcutaneous injection
Strontium Ranelate	One sachet (2 g) per day, suspended in water

Measured Values

	PTH(1-84)	Strontium Ranelate
Number of Participants Analyzed [units: participants]	41	40
Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial [units: percent change] Mean ± Standard Deviation	153.3 ± 132.4	-3.7 ± 36.0

Statistical Analysis 1 for Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	<0.0001
Mean Difference (Net) ^[4]	138.5
95% Confidence Interval	( 94.8 to 191.8 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The bone marker values were log-transformed for the primary analysis as they were heavily skewed. Changes in log-transformed bone marker values were analyzed using an analysis of covariance (ANCOVA) with treatment and center as fixed effects and the baseline bone marker value as a covariate. An F-test was used to test the effect of treatment and the least square means were computed to assess the clinical difference between treatment groups.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	P-value corresponding to the tests of treatment effect was adjusted using the Hochberg procedure.
[4]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: After publication of the results or 24 months after Clinical Trial Report has been finalised, whichever comes first, Nycomed acknowledge the Investigator's rights to publish results from this trial. Any such scientific paper, presentation, communication, or other information concerning the investigation described in this protocol, must be submitted to Nycomed prior to submission for publication/presentation for review. Review comments will be given within a month from receipt of the manuscript.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
A limitation of the trial was the open label design, however this is not considered to affect the primary or secondary outcome of the trial.

Results Point of Contact:

Name/Title: Clinical Trial Operations
Organization: Nycomed
phone: +45 4677 1111
e-mail: clinicaltrials@nycomed.com

No publications provided

Responsible Party:	Nycomed
ClinicalTrials.gov Identifier:	NCT00479037 History of Changes
Other Study ID Numbers:	FP-006-IM, 2006-006065-16
Study First Received:	May 23, 2007
Results First Received:	March 31, 2011
Last Updated:	May 4, 2012
Health Authority:	Austria: Ethikkommission Spain: Spanish Agency of Medicines