The primary objective of this study is to evaluate the impact of LF111 and drospirenone (DRSP) 3.5 mg chewable tablets on bone mineral density (BMD) at the lumbar spine after 12 months (13 medication cycles) of investigation in comparison to non-hormonal contraceptive methods. Secondary objectives include further evaluating the impact of LF111 and DRSP 3.5 mg chewable tablets on BMD and bone turnover after 12 months (13 medication cycles) in comparison to non-hormonal contraceptive methods and assessing the general safety and tolerability of LF111 and DRSP 3.5 mg chewable tablets in comparison to non-hormonal contraceptive methods. Exploratory objectives include evaluating the impact of LF111 and DRSP 3.5 mg chewable tablets on body fat and lean mass after 12 months (13 medication cycles) of investigation.
This is a Phase IV, prospective, multicenter, open-label, controlled, non-randomized trial in female subjects between 14 to 45 years of age who are postmenarcheal for at least two years and premenopausal. Subjects who choose to take the trial medication (LF111 tablet or drospirenone \[DRSP\] 3.5 mg chewable tablet \[USA only\]) will be compared to subjects who choose to use non-hormonal contraceptive methods, enrolled in a 1:1 ratio. Subjects will also be separated into two cohorts: cohort 1 as adolescents aged 14-17, and cohort 2 as adults aged 18-45. At Visit 1 (screening), informed consent/assent will be obtained, and the screening procedures will be performed. At Visit 2 (allocation to treatment), after confirming the subject's eligibility, subjects who choose to use LF111 or DRSP 3.5 mg chewable tablets (USA only) for pregnancy prevention will be provided with LF111 or DRSP 3.5 mg chewable tablets. The subjects will attend additional on-site visits 6 months and 12 months after Visit 2 (end of investigational phase) or within one week after premature trial discontinuation for routine safety assessments. The primary objective of this study is to evaluate the impact of LF111 and DRSP 3.5 mg chewable tablets on bone mineral density (BMD) at the lumbar spine after 12 months (13 medication cycles) of investigation in comparison to non-hormonal contraceptive methods. Secondary objectives include further evaluating the impact of LF111 and DRSP 3.5 mg chewable tablets on BMD and bone turnover after 12 months (13 medication cycles) in comparison to non-hormonal contraceptive methods and assessing the general safety and tolerability of LF111 and DRSP 3.5 mg chewable tablets in comparison to non-hormonal contraceptive methods. Exploratory objectives include evaluating the impact of LF111 and DRSP 3.5 mg chewable tablets on body fat and lean mass after 12 months (13 medication cycles) of investigation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
SCREENING
Masking
NONE
Enrollment
1,536
Drospirenone 4 mg tablet (LF1111) orally daily on days 1-24, followed by placebo tablet orally daily on days 25-28 (available in USA and Europe) or drospirenone 3.5 mg chewable tablet chewed daily on days 1-24, followed by placebo tablet chewed daily on days 25-28) (available in USA only).
Phoenix Childrens Hospital
Phoenix, Arizona, United States
University of Colorado Denver - School of Medicine - Anschutz Medical Campus
Aurora, Colorado, United States
Encore Medical Research of Boynton Beach LLC
Boynton Beach, Florida, United States
Advanced Clinical Research Network
Coral Gables, Florida, United States
BioMD Research
Coral Gables, Florida, United States
Cohort 1: Mean absolute change in lumbar spine (L1-L4) Z-score in adolescents
Measured by dual-energy X-ray absorptiometry (DXA)
Time frame: Baseline to 12 months
Cohort 2: Mean percentage change in lumbar spine (L1-L4) BMD in adults
Measured by DXA
Time frame: Baseline to 12 months
Cohort 1: Mean absolute changes in lumbar spine (L1-L4) Z-score in adolescents (hormonal treatment arm only)
Measured by DXA
Time frame: Baseline to 6 months
Cohort 1: Mean absolute changes in Z-scores (femoral neck, total hip, and total body less head [TBLH]) in adolescents
Measured by DXA
Time frame: Baseline to 6 months (hormonal treatment arm only) and to 12 months
Cohort 1: Mean absolute and percentage changes in lumbar spine, femoral neck, total hip, and TBLH BMD in adolescents
Measured by DXA
Time frame: Baseline to 6 months (hormonal treatment arm only) and to 12 months
Cohort 1: Mean absolute and percentage changes in TBLH bone mineral content (BMC) in adolescents
Measured by DXA
Time frame: Baseline to 6 months (hormonal treatment arm only) and to 12 months
Cohort 1: Proportion of adolescent subjects with percentage changes in lumbar spine, femoral neck, total hip, and TBLH BMD by categories
Categories are ≥ 0%, \< 0% to -1.5%, \< -1.5% to -3%, \< -3% to -5%, \< -5% to -8% and \< -8%
Time frame: Baseline to 12 months
Cohort 1: Proportion of adolescent subjects with absolute changes in Z-scores (lumbar spine, femoral neck, total hip, and TBLH) by categories
Categories are ≥ 0.50, \< 0.50 to 0.30, \< 0.30 to 0, \< 0 to -0.30, \< -0.30 to -0.50 and \< -0.50
Time frame: Baseline to 6 months (hormonal treatment arm only) and to 12 months
Cohort 2: Mean absolute changes in lumbar spine (L1-L4) BMD in adults
Measured by DXA
Time frame: Baseline to 12 months
Cohort 2: Mean absolute and percentage changes in femoral neck, total hip, and total body BMD in adults
Measured by DXA
Time frame: Baseline to 12 months
Cohort 2: Mean absolute and percentage changes in BMD (lumbar spine, femoral neck, total hip, and total body) in adults (hormonal treatment arm only)
Measured by DXA
Time frame: Baseline to 6 months
Cohort 2: Proportion of adult subjects with percentage changes in lumbar spine, femoral neck, total hip, and total body BMD by categories
Categories are ≥ 0%, \< 0% to -1.5%, \< -1.5% to -3%, \< -3% to -5%, \< -5% to -8% and \< -8%
Time frame: Baseline to 12 months
Cohort 2: Mean absolute changes in Z-scores (lumbar spine, femoral neck, total hip, and total body) in adults
Measured by DXA
Time frame: Baseline to 6 months (hormonal treatment arm only) and to 12 months
Cohort 2: Proportion of adult subjects with absolute changes in Z-scores (lumbar spine, femoral neck, total hip, and total body) by categories
Categories are ≥ 0.5, \< 0.5 to 0.3, \< 0.3 to 0, \< 0 to -0.3, \< -0.3 to -0.5 and \< -0.5
Time frame: Baseline to 6 months (hormonal treatment arm only) and to 12 months
Changes in body weight and body mass index (BMI)
Changes in body weight and body mass index (BMI)
Time frame: Baseline to 12 months
Routine laboratory values
Mean absolute and relative changes in routine laboratory values
Time frame: Baseline to 6 months and to 12 months
Serum estradiol (E2) levels (hormonal treatment arm only)
Mean absolute and relative changes in serum estradiol (E2) levels
Time frame: Baseline to 6 months and to 12 months
Number of subjects with adverse events as a measure of safety
Adverse events include laboratory and vital sign abnormalities that are considered clinically significant, require treatment, fulfill any serious adverse event criterion, or cause the subject to change the trial schedule and are judged by either the reporting investigator or the sponsor as having a reasonable causal relationship to the trial medication (drospirenone) or placebo comparator (non-hormonal contraceptive methods).
Time frame: Up to 12 months following treatment
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