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Trial record 45 of 999 for:    BMD

A Multicenter Study to Evaluate the Effects of a 91-day Oral Contraceptive on Bone Mineral Density in Adolescent Females

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ClinicalTrials.gov Identifier: NCT00924560
Recruitment Status : Completed
First Posted : June 19, 2009
Results First Posted : October 9, 2014
Last Update Posted : October 22, 2014
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Duramed Research )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Bone Mineral Density
Interventions Drug: 91-day Levonorgestrel Oral Contraceptive
Drug: 28-day Levonorgestrel Oral Contraceptive
Enrollment 1361
Recruitment Details Healthy, postmenarcheal, adolescent females who were either willing to be randomly assigned to 1 of 2 open-label oral contraceptive (OC) treatment regimens or who were not seeking current treatment with hormonal contraceptives and agreed not to use hormonal contraception throughout the 12-month duration of the study (control group).
Pre-assignment Details

Eligible participants initiating treatment with OCs were randomly assigned to one of the two treatment groups; eligible participants not initiating treatment with hormonal contraceptives were assigned to the untreated control group.

Twenty-six participants at one clinic were excluded from all analyses as the site was closed due to audit findings.

Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles). Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles). Participants received no oral contraceptives during the study.
Period Title: Overall Study
Started 458 448 455
Received Treatment 422 [1] 411 [2] 0
Completed 247 240 372
Not Completed 211 208 83
Reason Not Completed
Did Not Meet Protocol Requirements             4             2             1
Non Compliance with the Protocol             20             15             4
Physician Decision             2             3             4
Withdrawal by Subject             50             44             18
Adverse Event             39             33             0
Pregnancy             5             7             1
Lost to Follow-up             78             94             45
Miscellaneous Reasons             13             10             10
[1]
Excludes 7 participants at 1 site that was closed. One participant received 28-day OC in error.
[2]
Excludes 9 participants from one site that was closed due to audit findings.
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control Total
Hide Arm/Group Description Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles). Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles). Participants received no oral contraceptives during the study. Total of all reporting groups
Overall Number of Baseline Participants 458 448 455 1361
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 458 participants 448 participants 455 participants 1361 participants
16.0  (1.61) 15.9  (1.71) 14.8  (1.72) 15.6  (1.77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 458 participants 448 participants 455 participants 1361 participants
Female
458
 100.0%
448
 100.0%
455
 100.0%
1361
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 458 participants 448 participants 455 participants 1361 participants
African-American 87 87 72 246
Asian 3 9 12 24
Caucasian 251 265 255 771
Hispanic 102 79 111 292
Other 15 8 5 28
1.Primary Outcome
Title Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD)
Hide Description

Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.

Percent change from Baseline was calculated as (BMD at Month 12 – BMD at Baseline)/BMD at Baseline * 100%.

Time Frame Baseline and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set, including all participants who received at least 1 dose of study treatment (does not apply to Control group), had both Baseline and one post-baseline assessment via DXA, and who completed all procedures at all scheduled study visits including the 12-month DXA scans, and did not have any major protocol violations.
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 229 362
Least Squares Mean (Standard Error)
Unit of Measure: percent change
2.26  (0.168) 1.45  (0.171) 2.50  (0.139)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments The primary efficacy endpoint (percent change from baseline to 12 months in lumbar spine BMD) was analyzed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 91-day levonorgestrel OC was declared to be non-inferior to the untreated control group if the lower bound of the 2-sided 95% confidence interval (CI) was greater than –3%.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-0.67 to 0.20
Estimation Comments Difference = OC group minus the untreated control
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments The primary efficacy endpoint (percent change from baseline to 12 months in lumbar spine BMD) was analyzed using an analysis of covariance (ANCOVA) model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Non-Inferiority or Equivalence
Comments 28-day levonorgestrel OC was declared to be non-inferior to the untreated control group if the lower bound of the 2-sided 95% confidence interval (CI) was greater than -3%.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.05
Confidence Interval (2-Sided) 95%
-1.49 to -0.61
Estimation Comments Difference = OC group minus the untreated control
2.Secondary Outcome
Title Change From Baseline in Lumbar Spine Bone Mineral Density
Hide Description Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 229 362
Least Squares Mean (Standard Error)
Unit of Measure: g/cm^2
Change from Baseline to Month 6 0.02  (0.001) 0.01  (0.001) 0.01  (0.001)
Change from Baseline to Month 12 0.02  (0.002) 0.01  (0.002) 0.03  (0.001)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.00 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.01 to -0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.01 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.02 to -0.01
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Lumbar Spine Bone Mineral Content (BMC)
Hide Description Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists.
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 229 362
Least Squares Mean (Standard Error)
Unit of Measure: g
Change from Baseline to Month 6 1.29  (0.095) 0.69  (0.097) 1.12  (0.079)
Change from Baseline to Month 12 1.86  (0.120) 1.20  (0.122) 1.94  (0.099)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
-0.08 to 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean Difference
Estimated Value -0.43
Confidence Interval (2-Sided) 95%
-0.68 to -0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.39 to 0.24
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.74
Confidence Interval (2-Sided) 95%
-1.05 to -0.42
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Proximal Femur Bone Mineral Density
Hide Description Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set with available Baseline proximal femur DXA scans; participants with available proximal femur DXA scans at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 228 362
Least Squares Mean (Standard Error)
Unit of Measure: g/cm^2
Change from Baseline to Month 6 (n=238, 227, 358) 0.01  (0.001) 0.00  (0.001) 0.01  (0.001)
Change from Baseline to Month 12 (n=238, 224, 359) 0.02  (0.002) 0.01  (0.002) 0.01  (0.001)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
0.00 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.01 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
0.00 to 0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 0.95%
-0.01 to 0.00
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Proximal Femur Bone Mineral Content (BMC)
Hide Description Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists.
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set with available Baseline proximal femur DXA scans; participants with available proximal femur DXA scans at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 228 362
Least Squares Mean (Standard Error)
Unit of Measure: g
Change from Baseline to Month 6 (n=238, 227, 358) 0.26  (0.059) 0.09  (0.061) 0.13  (0.049)
Change from Baseline to Month 12 (n=238, 224, 359) 0.59  (0.066) 0.28  (0.068) 0.43  (0.055)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean Difference
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
-0.03 to 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.20 to 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.01 to 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.32 to 0.03
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Total Body Bone Mineral Density
Hide Description Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists.
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set with Baseline total body DXA scans. Participants with available total body DXA scans at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 130 126 150
Least Squares Mean (Standard Error)
Unit of Measure: g/cm^2
Change from Baseline to Month 6 (n=130, 126, 149) 0.01  (0.001) 0.01  (0.001) 0.01  (0.001)
Change from Baseline to Month 12 (n=130, 126, 150) 0.01  (0.002) 0.01  (0.002) 0.02  (0.001)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.01 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.01 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.01 to -0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.01 to -0.00
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Total Body Bone Mineral Content (BMC)
Hide Description Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists.
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol analysis set with Baseline total body DXA scans. Participants with available total body DXA scans at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 130 126 150
Least Squares Mean (Standard Error)
Unit of Measure: g
Change from Baseline to Month 6 (n=130, 126, 149) 40.77  (6.571) 38.70  (6.638) 46.26  (6.231)
Change from Baseline to Month 12 (n=130, 126, 150) 72.86  (8.325) 63.78  (8.409) 84.95  (7.871)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -5.48
Confidence Interval (2-Sided) 95%
-23.57 to 12.61
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 6. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -7.55
Confidence Interval (2-Sided) 95%
-25.65 to 10.55
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 91-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -12.09
Confidence Interval (2-Sided) 95%
-34.99 to 10.81
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 28-day Levonorgestrel OC, Untreated Control
Comments Comparison of Change from Baseline to Month 12. ANCOVA model with treatment as a fixed effect and chronological age, body weight, and Baseline value as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -21.17
Confidence Interval (2-Sided) 95%
-44.08 to 1.74
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Bone-specific Alkaline Phosphatase
Hide Description [Not Specified]
Time Frame Baseline, Month 6 and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 227 356
Mean (Standard Deviation)
Unit of Measure: µg/L
Change from Baseline to Month 6 (n=236, 224, 353) -6.8  (8.31) -5.9  (7.84) -6.2  (10.42)
Change from Baseline to Month 12 (n=235, 225, 347) -6.9  (8.64) -6.6  (8.82) -10.3  (12.49)
9.Secondary Outcome
Title Change From Baseline in Serum Deoxypyridinoline
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Time Frame Baseline, Month 6 and Month 12
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Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
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Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 234 227 350
Mean (Standard Deviation)
Unit of Measure: nmol/L
Change from Baseline to Month 6 (n=234, 224, 349) -0.1  (2.43) -0.1  (1.95) 0.1  (2.33)
Change from Baseline to Month 12 (n=233, 226, 348) -0.1  (2.21) 0.1  (2.05) -0.1  (2.28)
10.Secondary Outcome
Title Change From Baseline in Serum Osteocalcin
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Time Frame Baseline, Month 6 and Month 12
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Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
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Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 227 357
Mean (Standard Deviation)
Unit of Measure: nmol/L
Change from Baseline to Month 6 (n=236, 224, 354) -4.8  (7.00) -3.9  (6.74) -5.1  (11.94)
Change from Baseline to Month 12 (n=235, 225, 348) -4.5  (6.69) -3.7  (7.19) -7.1  (11.74)
11.Secondary Outcome
Title Change From Baseline in Serum Procollagen 1 N-terminal Propeptide
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Time Frame Baseline, Month 6 and Month 12
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Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 238 227 356
Mean (Standard Deviation)
Unit of Measure: µg/L
Change from Baseline to Month 6 (n=237, 225, 355) -49.9  (58.55) -38.7  (51.14) -57.8  (92.58)
Change from Baseline to Month 12 (n=235, 226, 349) -50.4  (60.20) -39.8  (55.73) -86.0  (118.69)
12.Secondary Outcome
Title Change From Baseline in Serum Type I Collagen N-telopeptide
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Time Frame Baseline, Month 6 and Month 12
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Hide Analysis Population Description
Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by "n".
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets containing 100 μg LNG/20 μg EE followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 237 227 357
Mean (Standard Deviation)
Unit of Measure: nM bone collagen equivalents (BCE)
Change from Baseline to Month 6 (n=235, 224, 356) -4.8  (9.69) -3.9  (10.68) -0.7  (13.60)
Change from Baseline to Month 12 (n=236, 225, 350) -4.5  (10.22) -4.3  (10.71) -3.1  (12.64)
13.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
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An adverse event was any untoward medical occurrence in a clinical investigation subject participating in the clinical study, and did not necessarily need to have a causal relationship with treatment or the clinical study. The relationship of each adverse event to study treatment or procedures, and the severity and seriousness of each adverse event was judged by the investigator, as described below.

A severe AE is defined as incapacitating, with inability to perform usual activities.

A serious adverse event is an adverse event occurring at any dose that resulted in any of the following outcomes or actions:

  • fatal or life-threatening;
  • required or prolonged inpatient hospitalization;
  • resulted in persistent or significant disability/incapacity;
  • congenital anomaly or birth defect;
  • important medical event.
Time Frame 12 months
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Hide Analysis Population Description
The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description:
Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg LNG/30 μg EE, followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles).
Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets (containing 100 μg LNG/20 μg EE) followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles).
Participants received no oral contraceptives during the study.
Overall Number of Participants Analyzed 421 412 437
Measure Type: Number
Unit of Measure: participants
Any adverse event 252 258 274
Severe adverse event 14 20 10
Treat-related adverse event 100 95 7
Deaths 0 0 0
Other serious adverse events 9 12 0
Withdrawn from study due to adverse events 34 33 1
Time Frame 12 months
Adverse Event Reporting Description The safety analysis set includes data from all randomly assigned participants who received at least 1 dose of study treatment and from all participants enrolled in the control group who had baseline BMD measures via DXA. One participant randomly assigned to 91-day LNG received 21-day LNG instead and is included in the 21-day LNG group for safety.
 
Arm/Group Title 91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Hide Arm/Group Description Participants received a 91-day regimen consisting of 84 consecutive days of active combination tablets containing 150 μg levonorgestrel (LNG)/30 μg ethinyl estradiol (EE), followed by 7 days of 10 μg EE tablets for a total of 52 weeks (4 consecutive 91-day cycles). Participants received a 28-day regimen consisting of 21 consecutive days of active combination tablets (containing 100 μg LNG/20 μg EE) followed by 7 days of placebo tablets for a total of 52 weeks (13 consecutive 28-day cycles). Participants received no oral contraceptives during the study.
All-Cause Mortality
91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/421 (2.14%)      12/412 (2.91%)      0/437 (0.00%)    
Cardiac disorders       
Wolff-Parkinson-White syndrome * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
General disorders       
Serositis * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Infections and infestations       
Appendicitis * 1  2/421 (0.48%)  2 1/412 (0.24%)  1 0/437 (0.00%)  0
Clostridial infection * 1  0/421 (0.00%)  0 1/412 (0.24%)  2 0/437 (0.00%)  0
Hepatitis infectious mononucleosis * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Pyelonephritis * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Urinary tract infection * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Injury, poisoning and procedural complications       
Injury * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Post concussion syndrome * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Road traffic accident * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Knee deformity * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Nervous system disorders       
Dizziness * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Abortion incomplete * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Abortion spontaneous * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Ectopic pregnancy * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Psychiatric disorders       
Affective disorder * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Depression * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Drug abuse * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Drug dependence * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Major depression * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Suicide attempt * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Renal and urinary disorders       
Calculus ureteric * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
Hydronephrosis * 1  0/421 (0.00%)  0 1/412 (0.24%)  1 0/437 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism * 1  1/421 (0.24%)  1 0/412 (0.00%)  0 0/437 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
91-day Levonorgestrel OC 28-day Levonorgestrel OC Untreated Control
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   156/421 (37.05%)      160/412 (38.83%)      196/437 (44.85%)    
Gastrointestinal disorders       
Nausea * 1  18/421 (4.28%)  20 25/412 (6.07%)  28 14/437 (3.20%)  15
Infections and infestations       
Nasopharyngitis * 1  35/421 (8.31%)  46 52/412 (12.62%)  62 53/437 (12.13%)  91
Upper respiratory tract infection * 1  30/421 (7.13%)  44 27/412 (6.55%)  32 53/437 (12.13%)  79
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  9/421 (2.14%)  17 14/412 (3.40%)  26 22/437 (5.03%)  26
Nervous system disorders       
Headache * 1  65/421 (15.44%)  124 69/412 (16.75%)  120 88/437 (20.14%)  197
Reproductive system and breast disorders       
Dysmenorrhoea * 1  20/421 (4.75%)  31 26/412 (6.31%)  41 37/437 (8.47%)  88
Metrorrhagia * 1  29/421 (6.89%)  40 14/412 (3.40%)  21 0/437 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain * 1  14/421 (3.33%)  16 10/412 (2.43%)  12 30/437 (6.86%)  35
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
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.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor’s review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor’s designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
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Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
EMail: ustevatrials@tevapharm.com
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Responsible Party: Teva Pharmaceutical Industries ( Duramed Research )
ClinicalTrials.gov Identifier: NCT00924560     History of Changes
Other Study ID Numbers: DR-105-202
First Submitted: June 18, 2009
First Posted: June 19, 2009
Results First Submitted: October 3, 2014
Results First Posted: October 9, 2014
Last Update Posted: October 22, 2014