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

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.

• 91-day Levonorgestrel Oral Contraceptive (Drug), also known as levonorgestrel/ethinyl estradiol, DR-105, Seasonique®: Levonorgestrel/ethinyl estradiol 0.15/0.03 mg and ethinyl estradiol 0.01 mg tablet. Take 1 tablet daily
• 28-day Levonorgestrel Oral Contraceptive (Drug), also known as levonorgestrel/ethinyl estradiol, Lessina®: Levonorgestrel/ethinyl estradiol 0.10/0.02 mg tablet and placebo. Take 1 tablet daily

Primary outcomes

• 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 outcomes

• 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.
• 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.
• 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]
• 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.

Sex: Female, ages: 12 Years to 18 Years, accepts healthy volunteers

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

Participant flow

Outcome results

• Percent Change From Baseline to 12 Months in Lumbar Spine Bone Mineral Density (BMD) (Primary), Least squares mean, percent change: 91-day Levonorgestrel OC 2.26 +/- 0.168; 28-day Levonorgestrel OC 1.45 +/- 0.171; Untreated Control 2.50 +/- 0.139
• Change From Baseline in Lumbar Spine Bone Mineral Density (Secondary), Least squares mean, g/cm^2: 91-day Levonorgestrel OC 0.02 +/- 0.001; 28-day Levonorgestrel OC 0.01 +/- 0.001; Untreated Control 0.01 +/- 0.001
• Change From Baseline in Lumbar Spine Bone Mineral Content (BMC) (Secondary), Least squares mean, g: 91-day Levonorgestrel OC 1.29 +/- 0.095; 28-day Levonorgestrel OC 0.69 +/- 0.097; Untreated Control 1.12 +/- 0.079
• Change From Baseline in Proximal Femur Bone Mineral Density (Secondary), Least squares mean, g/cm^2: 91-day Levonorgestrel OC 0.01 +/- 0.001; 28-day Levonorgestrel OC 0.00 +/- 0.001; Untreated Control 0.01 +/- 0.001
• Change From Baseline in Proximal Femur Bone Mineral Content (BMC) (Secondary), Least squares mean, g: 91-day Levonorgestrel OC 0.26 +/- 0.059; 28-day Levonorgestrel OC 0.09 +/- 0.061; Untreated Control 0.13 +/- 0.049
• Change From Baseline in Total Body Bone Mineral Density (Secondary), Least squares mean, g/cm^2: 91-day Levonorgestrel OC 0.01 +/- 0.001; 28-day Levonorgestrel OC 0.01 +/- 0.001; Untreated Control 0.01 +/- 0.001
• Change From Baseline in Total Body Bone Mineral Content (BMC) (Secondary), Least squares mean, g: 91-day Levonorgestrel OC 40.77 +/- 6.571; 28-day Levonorgestrel OC 38.70 +/- 6.638; Untreated Control 46.26 +/- 6.231
• Change From Baseline in Bone-specific Alkaline Phosphatase (Secondary), Mean, µg/L: 91-day Levonorgestrel OC -6.8 +/- 8.31; 28-day Levonorgestrel OC -5.9 +/- 7.84; Untreated Control -6.2 +/- 10.42
• Change From Baseline in Serum Deoxypyridinoline (Secondary), Mean, nmol/L: 91-day Levonorgestrel OC -0.1 +/- 2.43; 28-day Levonorgestrel OC -0.1 +/- 1.95; Untreated Control 0.1 +/- 2.33
• Change From Baseline in Serum Osteocalcin (Secondary), Mean, nmol/L: 91-day Levonorgestrel OC -4.8 +/- 7.00; 28-day Levonorgestrel OC -3.9 +/- 6.74; Untreated Control -5.1 +/- 11.94
• Change From Baseline in Serum Procollagen 1 N-terminal Propeptide (Secondary), Mean, µg/L: 91-day Levonorgestrel OC -49.9 +/- 58.55; 28-day Levonorgestrel OC -38.7 +/- 51.14; Untreated Control -57.8 +/- 92.58
• Change From Baseline in Serum Type I Collagen N-telopeptide (Secondary), Mean, nM bone collagen equivalents (BCE): 91-day Levonorgestrel OC -4.8 +/- 9.69; 28-day Levonorgestrel OC -3.9 +/- 10.68; Untreated Control -0.7 +/- 13.60
• Number of Participants With Adverse Events (AEs) (Secondary), Number, participants: 91-day Levonorgestrel OC 252; 28-day Levonorgestrel OC 258; Untreated Control 274

Adverse events

Time frame: 12 months

Serious adverse events by term

Other adverse events by term

• Jen Henrick, Study chair, Teva GBP