Bone Mineral Density
Conditions
Keywords
Adolescents, Bone Mineral Density, Oral Contraceptive
Brief summary
This study is being conducted to compare the effects of a 91-day oral contraceptive (OC) to a 28-day OC regimen on bone mineral density (BMD) in adolescent females.
Detailed description
Participants will be randomized to either a 91-day OC or a 28-day OC. Participants not seeking hormonal contraception who meet eligibility criteria will serve as a control group. Duration of the study for each study participant will be approximately 13 months.
Interventions
Levonorgestrel/ethinyl estradiol 0.15/0.03 mg and ethinyl estradiol 0.01 mg tablet. Take 1 tablet daily
Levonorgestrel/ethinyl estradiol 0.10/0.02 mg tablet and placebo. Take 1 tablet daily
Sponsors
Duramed Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
12 Years to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy postmenarchal adolescent female 12-18 years old, non-pregnant, nonlactating * Regular spontaneous menstrual cycles * Body mass index (BMI): 18 kg/m² to \<30 kg/m², weight \< 200 lbs * Others as dictated by the Food and Drug Administration (FDA)-approved protocol
Exclusion criteria
* Any contraindication to the use of oral contraceptives * History of previous clinically significant adverse event while taking hormonal contraceptives * Use of any medication which could significantly interfere with study assessments * Others as dictated by FDA-approved protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD) | Baseline and Month 12 | 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%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lumbar Spine Bone Mineral Density | Baseline, Month 6 and Month 12 | Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists. |
| Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) | Baseline, Month 6 and Month 12 | Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists. |
| Change From Baseline in Proximal Femur Bone Mineral Density | Baseline, Month 6 and Month 12 | Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists. |
| Change From Baseline in Proximal Femur Bone Mineral Content (BMC) | Baseline, Month 6 and Month 12 | Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists. |
| Change From Baseline in Total Body Bone Mineral Density | Baseline, Month 6 and Month 12 | Bone mineral density was measured by dual energy X-ray absorptiometry (DXA) scan. DXA scans were interpreted centrally by blinded, certified technologists. |
| Number of Participants With Adverse Events (AEs) | 12 months | 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. |
| Change From Baseline in Bone-specific Alkaline Phosphatase | Baseline, Month 6 and Month 12 | — |
| Change From Baseline in Serum Deoxypyridinoline | Baseline, Month 6 and Month 12 | — |
| Change From Baseline in Serum Osteocalcin | Baseline, Month 6 and Month 12 | — |
| Change From Baseline in Serum Procollagen 1 N-terminal Propeptide | Baseline, Month 6 and Month 12 | — |
| Change From Baseline in Serum Type I Collagen N-telopeptide | Baseline, Month 6 and Month 12 | — |
| Change From Baseline in Total Body Bone Mineral Content (BMC) | Baseline, Month 6 and Month 12 | Bone mineral content was measured by dual energy X-ray absorptiometry (DXA) scans and interpreted centrally by blinded, certified technologists. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 91-day Levonorgestrel OC 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). | 458 |
| 28-day Levonorgestrel OC 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). | 448 |
| Untreated Control Participants received no oral contraceptives during the study. | 455 |
| Total | 1,361 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 39 | 33 | 0 |
| Overall Study | Did Not Meet Protocol Requirements | 4 | 2 | 1 |
| Overall Study | Lost to Follow-up | 78 | 94 | 45 |
| Overall Study | Miscellaneous Reasons | 13 | 10 | 10 |
| Overall Study | Non Compliance with the Protocol | 20 | 15 | 4 |
| Overall Study | Physician Decision | 2 | 3 | 4 |
| Overall Study | Pregnancy | 5 | 7 | 1 |
| Overall Study | Withdrawal by Subject | 50 | 44 | 18 |
Baseline characteristics
| Characteristic | 91-day Levonorgestrel OC | 28-day Levonorgestrel OC | Untreated Control | Total |
|---|---|---|---|---|
| Age, Continuous | 16.0 years STANDARD_DEVIATION 1.61 | 15.9 years STANDARD_DEVIATION 1.71 | 14.8 years STANDARD_DEVIATION 1.72 | 15.6 years STANDARD_DEVIATION 1.77 |
| Race/Ethnicity, Customized African-American | 87 participants | 87 participants | 72 participants | 246 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 9 participants | 12 participants | 24 participants |
| Race/Ethnicity, Customized Caucasian | 251 participants | 265 participants | 255 participants | 771 participants |
| Race/Ethnicity, Customized Hispanic | 102 participants | 79 participants | 111 participants | 292 participants |
| Race/Ethnicity, Customized Other | 15 participants | 8 participants | 5 participants | 28 participants |
| Sex: Female, Male Female | 458 Participants | 448 Participants | 455 Participants | 1361 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 156 / 421 | 160 / 412 | 196 / 437 |
| serious Total, serious adverse events | 9 / 421 | 12 / 412 | 0 / 437 |
Outcome results
Primary
Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD)
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
Population: 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 | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 91-day Levonorgestrel OC | Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD) | 2.26 percent change | Standard Error 0.168 |
| 28-day Levonorgestrel OC | Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD) | 1.45 percent change | Standard Error 0.171 |
| Untreated Control | Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD) | 2.50 percent change | Standard Error 0.139 |
Comparison: 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.95% CI: [-0.67, 0.2]
Comparison: 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.95% CI: [-1.49, -0.61]
Secondary
Change From Baseline in Bone-specific Alkaline Phosphatase
Time frame: Baseline, Month 6 and Month 12
Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by n.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Bone-specific Alkaline Phosphatase | Change from Baseline to Month 6 (n=236, 224, 353) | -6.8 µg/L | Standard Deviation 8.31 |
| 91-day Levonorgestrel OC | Change From Baseline in Bone-specific Alkaline Phosphatase | Change from Baseline to Month 12 (n=235, 225, 347) | -6.9 µg/L | Standard Deviation 8.64 |
| 28-day Levonorgestrel OC | Change From Baseline in Bone-specific Alkaline Phosphatase | Change from Baseline to Month 6 (n=236, 224, 353) | -5.9 µg/L | Standard Deviation 7.84 |
| 28-day Levonorgestrel OC | Change From Baseline in Bone-specific Alkaline Phosphatase | Change from Baseline to Month 12 (n=235, 225, 347) | -6.6 µg/L | Standard Deviation 8.82 |
| Untreated Control | Change From Baseline in Bone-specific Alkaline Phosphatase | Change from Baseline to Month 12 (n=235, 225, 347) | -10.3 µg/L | Standard Deviation 12.49 |
| Untreated Control | Change From Baseline in Bone-specific Alkaline Phosphatase | Change from Baseline to Month 6 (n=236, 224, 353) | -6.2 µg/L | Standard Deviation 10.42 |
Secondary
Change From Baseline in Lumbar Spine Bone Mineral Content (BMC)
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
Population: Per-protocol analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) | Change from Baseline to Month 6 | 1.29 g | Standard Error 0.095 |
| 91-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) | Change from Baseline to Month 12 | 1.86 g | Standard Error 0.12 |
| 28-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) | Change from Baseline to Month 6 | 0.69 g | Standard Error 0.097 |
| 28-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) | Change from Baseline to Month 12 | 1.20 g | Standard Error 0.122 |
| Untreated Control | Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) | Change from Baseline to Month 6 | 1.12 g | Standard Error 0.079 |
| Untreated Control | Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) | Change from Baseline to Month 12 | 1.94 g | Standard Error 0.099 |
Comparison: 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.95% CI: [-0.08, 0.42]
Comparison: 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.95% CI: [-0.68, -0.18]
Comparison: 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.95% CI: [-0.39, 0.24]
Comparison: 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.95% CI: [-1.05, -0.42]
Secondary
Change From Baseline in Lumbar Spine Bone Mineral Density
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
Population: Per-protocol analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Density | Change from Baseline to Month 6 | 0.02 g/cm^2 | Standard Error 0.001 |
| 91-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Density | Change from Baseline to Month 12 | 0.02 g/cm^2 | Standard Error 0.002 |
| 28-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Density | Change from Baseline to Month 6 | 0.01 g/cm^2 | Standard Error 0.001 |
| 28-day Levonorgestrel OC | Change From Baseline in Lumbar Spine Bone Mineral Density | Change from Baseline to Month 12 | 0.01 g/cm^2 | Standard Error 0.002 |
| Untreated Control | Change From Baseline in Lumbar Spine Bone Mineral Density | Change from Baseline to Month 6 | 0.01 g/cm^2 | Standard Error 0.001 |
| Untreated Control | Change From Baseline in Lumbar Spine Bone Mineral Density | Change from Baseline to Month 12 | 0.03 g/cm^2 | Standard Error 0.001 |
Comparison: 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.95% CI: [0, 0.01]
Comparison: 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.95% CI: [-0.01, 0]
Comparison: 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.95% CI: [-0.01, 0]
Comparison: 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.95% CI: [-0.02, -0.01]
Secondary
Change From Baseline in Proximal Femur Bone Mineral Content (BMC)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Content (BMC) | Change from Baseline to Month 6 (n=238, 227, 358) | 0.26 g | Standard Error 0.059 |
| 91-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Content (BMC) | Change from Baseline to Month 12 (n=238, 224, 359) | 0.59 g | Standard Error 0.066 |
| 28-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Content (BMC) | Change from Baseline to Month 6 (n=238, 227, 358) | 0.09 g | Standard Error 0.061 |
| 28-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Content (BMC) | Change from Baseline to Month 12 (n=238, 224, 359) | 0.28 g | Standard Error 0.068 |
| Untreated Control | Change From Baseline in Proximal Femur Bone Mineral Content (BMC) | Change from Baseline to Month 6 (n=238, 227, 358) | 0.13 g | Standard Error 0.049 |
| Untreated Control | Change From Baseline in Proximal Femur Bone Mineral Content (BMC) | Change from Baseline to Month 12 (n=238, 224, 359) | 0.43 g | Standard Error 0.055 |
Comparison: 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.95% CI: [-0.03, 0.28]
Comparison: 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.95% CI: [-0.2, 0.11]
Comparison: 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.95% CI: [-0.01, 0.34]
Comparison: 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.95% CI: [-0.32, 0.03]
Secondary
Change From Baseline in Proximal Femur Bone Mineral Density
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Density | Change from Baseline to Month 6 (n=238, 227, 358) | 0.01 g/cm^2 | Standard Error 0.001 |
| 91-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Density | Change from Baseline to Month 12 (n=238, 224, 359) | 0.02 g/cm^2 | Standard Error 0.002 |
| 28-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Density | Change from Baseline to Month 6 (n=238, 227, 358) | 0.00 g/cm^2 | Standard Error 0.001 |
| 28-day Levonorgestrel OC | Change From Baseline in Proximal Femur Bone Mineral Density | Change from Baseline to Month 12 (n=238, 224, 359) | 0.01 g/cm^2 | Standard Error 0.002 |
| Untreated Control | Change From Baseline in Proximal Femur Bone Mineral Density | Change from Baseline to Month 6 (n=238, 227, 358) | 0.01 g/cm^2 | Standard Error 0.001 |
| Untreated Control | Change From Baseline in Proximal Femur Bone Mineral Density | Change from Baseline to Month 12 (n=238, 224, 359) | 0.01 g/cm^2 | Standard Error 0.001 |
Comparison: 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.95% CI: [0, 0.01]
Comparison: 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.95% CI: [-0.01, 0]
Comparison: 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.95% CI: [0, 0.01]
Comparison: 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.0.95% CI: [-0.01, 0]
Secondary
Change From Baseline in Serum Deoxypyridinoline
Time frame: Baseline, Month 6 and Month 12
Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by n.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Serum Deoxypyridinoline | Change from Baseline to Month 6 (n=234, 224, 349) | -0.1 nmol/L | Standard Deviation 2.43 |
| 91-day Levonorgestrel OC | Change From Baseline in Serum Deoxypyridinoline | Change from Baseline to Month 12 (n=233, 226, 348) | -0.1 nmol/L | Standard Deviation 2.21 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Deoxypyridinoline | Change from Baseline to Month 6 (n=234, 224, 349) | -0.1 nmol/L | Standard Deviation 1.95 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Deoxypyridinoline | Change from Baseline to Month 12 (n=233, 226, 348) | 0.1 nmol/L | Standard Deviation 2.05 |
| Untreated Control | Change From Baseline in Serum Deoxypyridinoline | Change from Baseline to Month 6 (n=234, 224, 349) | 0.1 nmol/L | Standard Deviation 2.33 |
| Untreated Control | Change From Baseline in Serum Deoxypyridinoline | Change from Baseline to Month 12 (n=233, 226, 348) | -0.1 nmol/L | Standard Deviation 2.28 |
Secondary
Change From Baseline in Serum Osteocalcin
Time frame: Baseline, Month 6 and Month 12
Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by n.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Serum Osteocalcin | Change from Baseline to Month 6 (n=236, 224, 354) | -4.8 nmol/L | Standard Deviation 7 |
| 91-day Levonorgestrel OC | Change From Baseline in Serum Osteocalcin | Change from Baseline to Month 12 (n=235, 225, 348) | -4.5 nmol/L | Standard Deviation 6.69 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Osteocalcin | Change from Baseline to Month 6 (n=236, 224, 354) | -3.9 nmol/L | Standard Deviation 6.74 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Osteocalcin | Change from Baseline to Month 12 (n=235, 225, 348) | -3.7 nmol/L | Standard Deviation 7.19 |
| Untreated Control | Change From Baseline in Serum Osteocalcin | Change from Baseline to Month 6 (n=236, 224, 354) | -5.1 nmol/L | Standard Deviation 11.94 |
| Untreated Control | Change From Baseline in Serum Osteocalcin | Change from Baseline to Month 12 (n=235, 225, 348) | -7.1 nmol/L | Standard Deviation 11.74 |
Secondary
Change From Baseline in Serum Procollagen 1 N-terminal Propeptide
Time frame: Baseline, Month 6 and Month 12
Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by n.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Serum Procollagen 1 N-terminal Propeptide | Change from Baseline to Month 12 (n=235, 226, 349) | -50.4 µg/L | Standard Deviation 60.2 |
| 91-day Levonorgestrel OC | Change From Baseline in Serum Procollagen 1 N-terminal Propeptide | Change from Baseline to Month 6 (n=237, 225, 355) | -49.9 µg/L | Standard Deviation 58.55 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Procollagen 1 N-terminal Propeptide | Change from Baseline to Month 12 (n=235, 226, 349) | -39.8 µg/L | Standard Deviation 55.73 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Procollagen 1 N-terminal Propeptide | Change from Baseline to Month 6 (n=237, 225, 355) | -38.7 µg/L | Standard Deviation 51.14 |
| Untreated Control | Change From Baseline in Serum Procollagen 1 N-terminal Propeptide | Change from Baseline to Month 12 (n=235, 226, 349) | -86.0 µg/L | Standard Deviation 118.69 |
| Untreated Control | Change From Baseline in Serum Procollagen 1 N-terminal Propeptide | Change from Baseline to Month 6 (n=237, 225, 355) | -57.8 µg/L | Standard Deviation 92.58 |
Secondary
Change From Baseline in Serum Type I Collagen N-telopeptide
Time frame: Baseline, Month 6 and Month 12
Population: Per protocol analysis set with Baseline data available; participants with available data at each time point are indicated by n.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Serum Type I Collagen N-telopeptide | Change from Baseline to Month 6 (n=235, 224, 356) | -4.8 nM bone collagen equivalents (BCE) | Standard Deviation 9.69 |
| 91-day Levonorgestrel OC | Change From Baseline in Serum Type I Collagen N-telopeptide | Change from Baseline to Month 12 (n=236, 225, 350) | -4.5 nM bone collagen equivalents (BCE) | Standard Deviation 10.22 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Type I Collagen N-telopeptide | Change from Baseline to Month 6 (n=235, 224, 356) | -3.9 nM bone collagen equivalents (BCE) | Standard Deviation 10.68 |
| 28-day Levonorgestrel OC | Change From Baseline in Serum Type I Collagen N-telopeptide | Change from Baseline to Month 12 (n=236, 225, 350) | -4.3 nM bone collagen equivalents (BCE) | Standard Deviation 10.71 |
| Untreated Control | Change From Baseline in Serum Type I Collagen N-telopeptide | Change from Baseline to Month 6 (n=235, 224, 356) | -0.7 nM bone collagen equivalents (BCE) | Standard Deviation 13.6 |
| Untreated Control | Change From Baseline in Serum Type I Collagen N-telopeptide | Change from Baseline to Month 12 (n=236, 225, 350) | -3.1 nM bone collagen equivalents (BCE) | Standard Deviation 12.64 |
Secondary
Change From Baseline in Total Body Bone Mineral Content (BMC)
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Content (BMC) | Change from Baseline to Month 12 (n=130, 126, 150) | 72.86 g | Standard Error 8.325 |
| 91-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Content (BMC) | Change from Baseline to Month 6 (n=130, 126, 149) | 40.77 g | Standard Error 6.571 |
| 28-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Content (BMC) | Change from Baseline to Month 12 (n=130, 126, 150) | 63.78 g | Standard Error 8.409 |
| 28-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Content (BMC) | Change from Baseline to Month 6 (n=130, 126, 149) | 38.70 g | Standard Error 6.638 |
| Untreated Control | Change From Baseline in Total Body Bone Mineral Content (BMC) | Change from Baseline to Month 12 (n=130, 126, 150) | 84.95 g | Standard Error 7.871 |
| Untreated Control | Change From Baseline in Total Body Bone Mineral Content (BMC) | Change from Baseline to Month 6 (n=130, 126, 149) | 46.26 g | Standard Error 6.231 |
Comparison: 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.95% CI: [-23.57, 12.61]
Comparison: 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.95% CI: [-25.65, 10.55]
Comparison: 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.95% CI: [-34.99, 10.81]
Comparison: 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.95% CI: [-44.08, 1.74]
Secondary
Change From Baseline in Total Body Bone Mineral Density
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 91-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Density | Change from Baseline to Month 6 (n=130, 126, 149) | 0.01 g/cm^2 | Standard Error 0.001 |
| 91-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Density | Change from Baseline to Month 12 (n=130, 126, 150) | 0.01 g/cm^2 | Standard Error 0.002 |
| 28-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Density | Change from Baseline to Month 12 (n=130, 126, 150) | 0.01 g/cm^2 | Standard Error 0.002 |
| 28-day Levonorgestrel OC | Change From Baseline in Total Body Bone Mineral Density | Change from Baseline to Month 6 (n=130, 126, 149) | 0.01 g/cm^2 | Standard Error 0.001 |
| Untreated Control | Change From Baseline in Total Body Bone Mineral Density | Change from Baseline to Month 12 (n=130, 126, 150) | 0.02 g/cm^2 | Standard Error 0.001 |
| Untreated Control | Change From Baseline in Total Body Bone Mineral Density | Change from Baseline to Month 6 (n=130, 126, 149) | 0.01 g/cm^2 | Standard Error 0.001 |
Comparison: 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.95% CI: [-0.01, 0]
Comparison: 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.95% CI: [-0.01, 0]
Comparison: 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.95% CI: [-0.01, 0]
Comparison: 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.95% CI: [-0.01, 0]
Secondary
Number of Participants With Adverse Events (AEs)
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 91-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Other serious adverse events | 9 participants |
| 91-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Severe adverse event | 14 participants |
| 91-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Treat-related adverse event | 100 participants |
| 91-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| 91-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Any adverse event | 252 participants |
| 91-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Withdrawn from study due to adverse events | 34 participants |
| 28-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Treat-related adverse event | 95 participants |
| 28-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Severe adverse event | 20 participants |
| 28-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Any adverse event | 258 participants |
| 28-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| 28-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Other serious adverse events | 12 participants |
| 28-day Levonorgestrel OC | Number of Participants With Adverse Events (AEs) | Withdrawn from study due to adverse events | 33 participants |
| Untreated Control | Number of Participants With Adverse Events (AEs) | Other serious adverse events | 0 participants |
| Untreated Control | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Untreated Control | Number of Participants With Adverse Events (AEs) | Withdrawn from study due to adverse events | 1 participants |
| Untreated Control | Number of Participants With Adverse Events (AEs) | Severe adverse event | 10 participants |
| Untreated Control | Number of Participants With Adverse Events (AEs) | Treat-related adverse event | 7 participants |
| Untreated Control | Number of Participants With Adverse Events (AEs) | Any adverse event | 274 participants |