LF111 or Drospirenone Chew vs Non-hormonal Contraceptive Methods on Bone Mineral Density in Adolescent and Adult Women

Last updated: June 15, 2023
Sponsor: Insud Pharma
Overall Status: Active - Recruiting

Phase

4

Condition

Bone Density

Osteoporosis

Osteopenia

Treatment

LF111 (drospirenone 4 mg oral tablet) or drospirenone (DRSP) 3.5 mg chewable tablet

Clinical Study ID

NCT05303636
LF111/401
2020-000412-30
  • Ages 14-45
  • Female
  • Accepts Healthy Volunteers

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Female subjects with regular menstrual cycles (postmenarcheal for at least two yearsand premenopausal) aged 14 to 45 years.
  • Female subjects aged between 14 to 17 years (inclusive) will only be included providedthat:
  • Applicable national, state, and local laws allow subjects in this age group toconsent/assent to receive contraceptive services, and
  • All applicable laws and regulations regarding the informed consent/assent of thesubjects to participate in clinical trials are observed.
  • Systolic blood pressure < 140 mmHg, diastolic blood pressure < 90 mmHg at Visit 1, insitting position after 5 minutes of rest.
  • Menstruation restarted for at least 6 months since last pregnancy (only applicable forwomen that were pregnant).
  • Be able and willing to provide written informed consent, or assent if the subject isan adolescent, prior to undergoing any trial-related procedures.
  • Willing to use trial contraception for thirteen 28-day cycles (hormonal treatment arm)or to use non-hormonal contraceptive methods for the duration of the trial (non-hormonal contraceptive arm), respectively.

Exclusion

Exclusion Criteria:

  • Contraindications to the use of LF111 or DRSP 3.5 mg chewable tablets (such as activearterial or venous thromboembolic disorders, liver tumors benign or malignant, hepaticimpairment, renal impairment, adrenal insufficiency, presence or history of cervicalcancer or progestin-sensitive cancers, known or suspected sex-steroid sensitivemalignancies, undiagnosed abnormal uterine bleeding, undiagnosed vaginal bleeding,hypersensitivity to active substance or excipient) or adverse effects due to previouscontraceptive use (for the hormonal treatment arm only).
  • BMD Z-score below -1.50. The TBLH Z-score applies only to Cohort 1 (adolescents) andthe total body Z-score applies only to Cohort 2 (adults) when assessing studyeligibility.
  • Low trauma fracture(s) defined as a fracture that results from a fall from a standingheight or less, excluding fingers, toes, face, and skull.
  • Medical conditions associated with low bone mass:
  • Metabolic bone disease such as osteogenesis imperfecta, Paget's disease of thebone, osteomalacia/rickets.
  • Collagen vascular diseases such as Marfan syndrome and Ehlers-Danlos syndrome.
  • Chronic kidney disease stage 3 with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 using the Bedside Schwartz equation for adolescents and theModification of Diet in Renal Disease (MDRD) method for adult subjects.
  • Gastrointestinal (malabsorptive) disease including inflammatory bowel disease,gastric bypass surgery and current post-gastrectomy syndrome.
  • Liver disease.
  • Abnormal bone mineral metabolism (hypocalcemia/hypercalcemia,hypophosphatemia/hyperphosphatemia, hypomagnesemia).
  • In adolescents only: Short stature defined as height-for-age percentile less than thefifth percentile.
  • Use of progestin-only contraceptive pills in the previous month or use of implantablehormonal contraceptives in the previous 6 months.
  • Laboratory values at screening which are considered clinically significant and whichin the opinion of the investigator would be detrimental for participation in thestudy.
  • Ongoing pregnancy or wish for pregnancy.
  • Currently lactating or stopped lactating within the last 12 months.
  • Eating disorders (e.g., anorexia nervosa, bulimia).
  • Celiac disease.
  • Endocrine disorders (e.g., diabetes, hypothyroidism or hyperthyroidism,hyperparathyroidism, Cushing's disease) not adequately controlled with a stabletreatment regiment for > 2 months.
  • Rheumatoid arthritis.
  • Current or ever use of medications or supplements known to increase BMD includingbisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab, calcitonin,fluoride and strontium.
  • Treatment with medications that are known to decrease bone mass:
  • Glucocorticoids (oral, intravenous, chronic inhaled, chronic extensive topical [> 3 months]) within the previous 3 months. Note: Subjects taking chronicoral/intravenous glucocorticoids (prednisone ≥ 2.5 mg daily for ≥ 3 months, orthe equivalent) will have a washout period of 12 months.
  • Depo-medroxyprogesterone acetate within the previous 24 months (if duration ofuse was less than 2 consecutive years). Note: Subjects usingdepo-medroxyprogesterone acetate for a duration of use greater than 2 years willbe excluded.
  • Aromatase inhibitors and/or raloxifene within the previous 24 months.
  • Anticonvulsants (phenytoin, phenobarbital, carbamazepine and valproate),anti-retroviral protease inhibitors, cyclosporine, heparin, warfarin,thiazolidinedione, SGLT-2 inhibitors, tricyclic antidepressants, chronic protonpump inhibitor (PPI) use (> 3 months), or selective serotonin reuptake inhibitors (SSRIs) within the previous 3 months.
  • Conditions that preclude BMD measurement i.e. lumbar spine/bilateral hip surgery withhardware in place, abdominal clips, umbilical ring (not willing to remove) or weightthat exceeds the DXA machine limitation.
  • Any condition that, in the opinion of the investigator, may jeopardize the trialconduct according to the protocol.
  • Persons committed to an institution by virtue of an order issued either by thejudicial or other authorities.

Study Design

Total Participants: 1710
Treatment Group(s): 1
Primary Treatment: LF111 (drospirenone 4 mg oral tablet) or drospirenone (DRSP) 3.5 mg chewable tablet
Phase: 4
Study Start date:
March 28, 2022
Estimated Completion Date:
March 31, 2027

Study Description

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.

Connect with a study center

  • Cactus Clinical Research, Inc.

    Phoenix, Arizona 85014
    United States

    Active - Recruiting

  • Women's Health Care Research

    San Diego, California 92111
    United States

    Site Not Available

  • Velocity Clinical Research

    Denver, Colorado 80209
    United States

    Active - Recruiting

  • Velocity Clinical Research - Denver

    Denver, Colorado 80209
    United States

    Site Not Available

  • Advanced Clinical Research Network

    Coral Gables, Florida 33134
    United States

    Active - Recruiting

  • Health Care Family Rehab & Research Center

    Hialeah, Florida 33015
    United States

    Active - Recruiting

  • Vital Pharma Research

    Hialeah, Florida 33016
    United States

    Active - Recruiting

  • Vital Pharma Research, Inc.

    Hialeah, Florida 33016
    United States

    Site Not Available

  • University of Florida - Jacksonville

    Jacksonville, Florida 32209
    United States

    Site Not Available

  • Cornerstone Research Institute

    Longwood, Florida 32750
    United States

    Active - Recruiting

  • New Age Medical Research Corporation

    Miami, Florida 33186
    United States

    Active - Recruiting

  • Florida Pharmaceutical Research and Associates, Inc.

    South Miami, Florida 33143
    United States

    Active - Recruiting

  • Comprehensive Clinical Research, LLC

    West Palm Beach, Florida 33409
    United States

    Active - Recruiting

  • M3 Wake Research, Inc.

    Sandy Springs, Georgia 30328
    United States

    Active - Recruiting

  • Family Care Research

    Boise, Idaho 83704
    United States

    Active - Recruiting

  • Tandem Clinical Research

    Marrero, Louisiana 70072
    United States

    Active - Recruiting

  • Clinical Trials Management, LLC - Southshore

    Metairie, Louisiana 70006
    United States

    Active - Recruiting

  • Meridian Clinical Research

    Norfolk, Nebraska 68701
    United States

    Active - Recruiting

  • Meridian Clinical Research - Norfolk

    Norfolk, Nebraska 68701
    United States

    Site Not Available

  • M3 Wake Research

    Raleigh, North Carolina 27612
    United States

    Active - Recruiting

  • Lillestol Research LLC

    Fargo, North Dakota 58104
    United States

    Active - Recruiting

  • Corpus Christi Women's Clinic

    Corpus Christi, Texas 78412
    United States

    Active - Recruiting

  • Signature Gyn Services

    Fort Worth, Texas 76104
    United States

    Active - Recruiting

  • TMC Life Research, Inc.

    Houston, Texas 77054
    United States

    Active - Recruiting

  • FMC Science - Lampasas

    Lampasas, Texas 76550
    United States

    Site Not Available

  • Seattle Clinical Research Center

    Seattle, Washington 98105
    United States

    Active - Recruiting

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