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

NCT05303636 | Active Not Recruiting Phase 4 FDA Drug

• 2 other identifiers: LF111/4012020-000412-30
• Study Type: interventional
• Target: 1,536
• Locations: 3 countries
• Sites: 37

Brief 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.

Conditions

Change in Bone Mineral Density; Bone Loss

Keywords

Osteoporosis

Outcome Measures

Primary Outcomes (2)

• Cohort 1: Mean absolute change in lumbar spine (L1-L4) Z-score in adolescents

  Measured by dual-energy X-ray absorptiometry (DXA)

  Baseline to 12 months

• Cohort 2: Mean percentage change in lumbar spine (L1-L4) BMD in adults

  Measured by DXA

  Baseline to 12 months

Secondary Outcomes (16)

• Cohort 1: Mean absolute changes in lumbar spine (L1-L4) Z-score in adolescents (hormonal treatment arm only)

  Baseline to 6 months

• Cohort 1: Mean absolute changes in Z-scores (femoral neck, total hip, and total body less head [TBLH]) in adolescents

  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

  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

  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

  Baseline to 12 months

Other Outcomes (1)

• Changes in body fat and lean mass

  Baseline to 12 months

Study Arms (4)

Cohort 1 (adolescents aged 14-17) Hormonal Treatment Arm

EXPERIMENTAL

Subjects in the USA who choose to use the hormonal contraceptive method may choose between LF111 tablets or drospirenone (DRSP) 3.5 mg chewable tablets. 1/3 of subjects in the USA should receive DRSP 3.5 mg chewable tablets. The DRSP 3.5 mg chewable tablets are not available to subjects in Europe; subjects in Europe who choose to use the hormonal contraceptive method will only receive LF111.

Drug: drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tablet

Cohort 1 (adolescents aged 14-17) Non-Hormonal Contraceptive Arm

NO INTERVENTION

Subjects in this group will not receive any investigational product. They will be free to use a non-hormonal contraceptive method of their choice. Non-hormonal contraceptive methods include barrier contraceptive methods (condoms, female condoms, cervical caps, diaphragms, and contraceptive sponges), double barrier methods, non-hormonal IUD (e.g., copper IUD), surgical female sterilization, vasectomized partner, spermicides, and sexual abstinence.

Cohort 2 (adults aged 18-45) Hormonal Treatment Arm

EXPERIMENTAL

Subjects in the USA who choose to use the hormonal contraceptive method may choose between LF111 tablets or drospirenone (DRSP) 3.5 mg chewable tablets. 1/3 of subjects in the USA should receive DRSP 3.5 mg chewable tablets. The DRSP 3.5 mg chewable tablets are not available to subjects in Europe; subjects in Europe who choose to use the hormonal contraceptive method will only receive LF111.

Drug: drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tablet

Cohort 2 (adults aged 18-45) Non-Hormonal Contraceptive Method Arm

NO INTERVENTION

Subjects in this group will not receive any investigational product. They will be free to use a non-hormonal contraceptive method of their choice. Non-hormonal contraceptive methods include barrier contraceptive methods (condoms, female condoms, cervical caps, diaphragms, and contraceptive sponges), double barrier methods, non-hormonal IUD (e.g., copper IUD), surgical female sterilization, vasectomized partner, spermicides, and sexual abstinence.

Interventions

drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tablet DRUG

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).

Also known as: LF111 (drospirenone 4 mg tablet)

Cohort 1 (adolescents aged 14-17) Hormonal Treatment Arm; Cohort 2 (adults aged 18-45) Hormonal Treatment Arm

Eligibility Criteria

• Age: 14 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Female subjects with regular menstrual cycles (postmenarcheal for at least two years and premenopausal) aged 14 to 45 years.
• Female subjects aged between 14 to 17 years (inclusive) will only be included provided that:
• Applicable national, state, and local laws allow subjects in this age group to consent/assent to receive contraceptive services, and
• All applicable laws and regulations regarding the informed consent/assent of the subjects to participate in clinical trials are observed.
• Systolic blood pressure \< 140 mmHg, diastolic blood pressure \< 90 mmHg at Visit 1, in sitting position after 5 minutes of rest.
• Menstruation restarted for at least 6 months since last pregnancy (only applicable for women that were pregnant).
• Be able and willing to provide written informed consent, or assent if the subject is an 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.

You may not qualify if:

• Contraindications to the use of LF111 or DRSP 3.5 mg chewable tablets (such as active arterial or venous thromboembolic disorders, liver tumors benign or malignant, hepatic impairment, renal impairment, adrenal insufficiency, presence or history of cervical cancer or progestin-sensitive cancers, known or suspected sex-steroid sensitive malignancies, undiagnosed abnormal uterine bleeding, undiagnosed vaginal bleeding, hypersensitivity to active substance or excipient) or adverse effects due to previous contraceptive use (for the hormonal treatment arm only).
• BMD Z-score below -1.50. The TBLH Z-score applies only to Cohort 1 (adolescents) and the total body Z-score applies only to Cohort 2 (adults) when assessing study eligibility.
• Low trauma fracture(s) defined as a fracture that results from a fall from a standing height 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 the bone, 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 the Modification 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 the fifth percentile.
• Use of progestin-only contraceptive pills in the previous month or use of implantable hormonal contraceptives in the previous 6 months.
• Laboratory values at screening which are considered clinically significant and which in the opinion of the investigator would be detrimental for participation in the study.
• Ongoing pregnancy or wish for pregnancy.
• Currently lactating or stopped lactating within the last 12 months.

Sponsors & Collaborators

• Insud Pharma: lead
• Chemo Research: collaborator

Study Sites (37)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

University of Colorado Denver - School of Medicine - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Encore Medical Research of Boynton Beach LLC

Boynton Beach, Florida, 33436, United States

Location

Advanced Clinical Research Network

Coral Gables, Florida, 33134, United States

Location

BioMD Research

Coral Gables, Florida, 33134, United States

Location

Direct Helpers Research Center

Hialeah, Florida, 33012, United States

Location

Health Care Family Rehab & Research Center

Hialeah, Florida, 33015, United States

Location

Vital Pharma Research

Hialeah, Florida, 33016, United States

Location

Encore Medical Research, LLC

Hollywood, Florida, 33021, United States

Location

Cornerstone Research Institute

Longwood, Florida, 32750, United States

Location

D&H National Research Centers

Miami, Florida, 33155, United States

Location

Miami Clinical Research

Miami, Florida, 33155, United States

Location

Felicidad Medical Research, LLC

Miami, Florida, 33184, United States

Location

New Age Medical Research Corporation

Miami, Florida, 33186, United States

Location

KM International Research Operation LLC

Saint Cloud, Florida, 34769, United States

Location

Florida Pharmaceutical Research and Associates, Inc.

South Miami, Florida, 33143, United States

Location

Encore Medical Research of Weston LLC

Weston, Florida, 33331, United States

Location

Clinical Trials Management, LLC - Southshore

Metairie, Louisiana, 70006, United States

Location

University of Michigan C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48103, United States

Location

Meridian Clinical Research

Norfolk, Nebraska, 68701, United States

Location

Lillestol Research LLC

Fargo, North Dakota, 58104, United States

Location

OB/GYN Associates of Erie

Erie, Pennsylvania, 16502, United States

Location

Signature Gyn Services

Fort Worth, Texas, 76104, United States

Location

TMC Life Research, Inc.

Houston, Texas, 77054, United States

Location

Tidewater Clinical Research, Inc.

Norfolk, Virginia, 23502, United States

Location

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23510, United States

Location

Seattle Clinical Research Center

Seattle, Washington, 98105, United States

Location

Lékárna Devetsil JST s.r.o.

Slovany, Czechia

Location

Lékárna U Zvonice

Vysoké Mýto, Czechia

Location

Centrum Bocian Sp Z O. O. Spólka Komandytowa

Bialystok, Poland

Location

Centrum Bocian Sp z o.o. Sp.

Katowice, Poland

Location

GynCentrum Sp. z o.o.

Katowice, Poland

Location

Vita Longa Sp. z o.o.

Katowice, Poland

Location

Centrum Medyczne Linden

Krakow, Poland

Location

Grazyna Bogutyn Medico Praktyka Lekarska

Krakow, Poland

Location

CM Medyceusz, Apteka szpitalna

Lodz, Poland

Location

Klinika Leczenia Nieplodnosci, Ginekologii i Poloznictwa Bocian

Warsaw, Poland

Location

Related Publications (8)

• Rosenbaum P, Schmidt W, Helmerhorst FM, Wuttke W, Rossmanith W, Freundl F, Thomas K, Grillo M, Wolf A, Heithecker R. Inhibition of ovulation by a novel progestogen (drospirenone) alone or in combination with ethinylestradiol. Eur J Contracept Reprod Health Care. 2000 Mar;5(1):16-24. doi: 10.1080/13625180008500376.

  PMID: 10836659 BACKGROUND

• Cibula D, Skrenkova J, Hill M, Stepan JJ. Low-dose estrogen combined oral contraceptives may negatively influence physiological bone mineral density acquisition during adolescence. Eur J Endocrinol. 2012 Jun;166(6):1003-11. doi: 10.1530/EJE-11-1047. Epub 2012 Mar 21.

  PMID: 22436400 BACKGROUND

• Beksinska ME, Smit JA. Hormonal contraception and bone mineral density. Expert Rev of Obstet Gynecol. 2011;6(3);305-319.

  BACKGROUND

• Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O'Karma M, Wallace TC, Zemel BS. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-1386. doi: 10.1007/s00198-015-3440-3. Epub 2016 Feb 8.

  PMID: 26856587 BACKGROUND

• Rizzo ADCB, Goldberg TBL, Biason TP, Kurokawa CS, Silva CCD, Corrente JE, Nunes HRC. One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives. J Pediatr (Rio J). 2019 Sep-Oct;95(5):567-574. doi: 10.1016/j.jped.2018.05.011. Epub 2018 Jun 28.

  PMID: 29959901 BACKGROUND

• Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009 Mar;20(3):629-37. doi: 10.1681/ASN.2008030287. Epub 2009 Jan 21.

  PMID: 19158356 BACKGROUND

• Pierce CB, Munoz A, Ng DK, Warady BA, Furth SL, Schwartz GJ. Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease. Kidney Int. 2021 Apr;99(4):948-956. doi: 10.1016/j.kint.2020.10.047. Epub 2020 Dec 8.

  PMID: 33301749 BACKGROUND

• Carr B, Dmowski WP, O'Brien C, Jiang P, Burke J, Jimenez R, Garner E, Chwalisz K. Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density. Reprod Sci. 2014 Nov;21(11):1341-51. doi: 10.1177/1933719114549848. Epub 2014 Sep 23.

  PMID: 25249568 BACKGROUND

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis

Interventions

drospirenone; Tablets

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Enrico Colli, MD

  Chemo Research SL

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two cohorts: Cohort 1 (adolescents); Cohort 2 (adults)

Study Record Dates

• First Submitted: March 22, 2022
• First Posted: March 31, 2022
• Study Start: March 28, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 9, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (27); CZ (2); PL (8)