Change in Bone Mineral DensityPhase 4NCT05303636

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

A Phase 4 study testing drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tablet in people with Change in Bone Mineral Density and Bone Loss, run by Insud Pharma at 37 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 14 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for: Change in Bone Mineral Density, Bone Loss
What is being tested?: drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tablet
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,536 participants
Where: 37 sitesin 3 countries
Study dates: 28 Mar 2022to Jun 2028
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 14 to 45 years
Women only
Healthy volunteers accepted
Child, Adult

Who may be able to join

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.

Who cannot join

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.

Show all 28Show fewer

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.
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 stable treatment regiment for > 2 months.
Rheumatoid arthritis.
Current or ever use of medications or supplements known to increase BMD including bisphosphonates, 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 chronic oral/intravenous glucocorticoids (prednisone ≥ 2.5 mg daily for ≥ 3 months, or the equivalent) will have a washout period of 12 months.
Depo-medroxyprogesterone acetate within the previous 24 months (if duration of use was less than 2 consecutive years). Note: Subjects using depo-medroxyprogesterone acetate for a duration of use greater than 2 years will be 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 proton pump 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 with hardware in place, abdominal clips, umbilical ring (not willing to remove) or weight that exceeds the DXA machine limitation.
Any condition that, in the opinion of the investigator, may jeopardize the trial conduct according to the protocol.
Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.

Trial locations and contacts

37 sites in 3 countries.

Country

City, postcode or hospital

37 sites in 3 countries

United States27 sites

University of Michigan C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48103
University of Colorado Denver - School of Medicine - Anschutz Medical Campus
Aurora, Colorado, 80045
Encore Medical Research of Boynton Beach LLC
Boynton Beach, Florida, 33436
Advanced Clinical Research Network
Coral Gables, Florida, 33134
BioMD Research
Coral Gables, Florida, 33134
OB/GYN Associates of Erie
Erie, Pennsylvania, 16502
Lillestol Research LLC
Fargo, North Dakota, 58104
Signature Gyn Services
Fort Worth, Texas, 76104
Direct Helpers Research Center
Hialeah, Florida, 33012
Health Care Family Rehab & Research Center
Hialeah, Florida, 33015
Vital Pharma Research
Hialeah, Florida, 33016
Encore Medical Research, LLC
Hollywood, Florida, 33021
TMC Life Research, Inc.
Houston, Texas, 77054
Cornerstone Research Institute
Longwood, Florida, 32750
Clinical Trials Management, LLC - Southshore
Metairie, Louisiana, 70006
D&H National Research Centers
Miami, Florida, 33155
Miami Clinical Research
Miami, Florida, 33155
Felicidad Medical Research, LLC
Miami, Florida, 33184
New Age Medical Research Corporation
Miami, Florida, 33186
Meridian Clinical Research
Norfolk, Nebraska, 68701
Tidewater Clinical Research, Inc.
Norfolk, Virginia, 23502
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23510
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
KM International Research Operation LLC
Saint Cloud, Florida, 34769
Seattle Clinical Research Center
Seattle, Washington, 98105
Florida Pharmaceutical Research and Associates, Inc.
South Miami, Florida, 33143
Encore Medical Research of Weston LLC
Weston, Florida, 33331

Other trials in United States

Poland8 sites

Centrum Bocian Sp Z O. O. Spólka Komandytowa
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Centrum Bocian Sp z o.o. Sp.
Katowice
GynCentrum Sp. z o.o.
Katowice
Vita Longa Sp. z o.o.
Katowice
Centrum Medyczne Linden
Krakow
Grazyna Bogutyn Medico Praktyka Lekarska
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Czechia2 sites

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Slovany
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About this study

Official title: A Multicenter, Open-label, Controlled Study to Investigate the Effect of Either LF111 or Drospirenone Chewable Tablets on Bone Mineral Density (BMD) in Adolescent and Adult Women in Comparison With Non-users of Hormonal Contraceptive Methods

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.

Read the detailed 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.

Conditions: Change in Bone Mineral Density, Bone Loss
Being tested: drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tablet
Keywords: Osteoporosis
Medical subject headings: Bone Diseases, Metabolic, Osteoporosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tabletDrug
Also called LF111 (drospirenone 4 mg tablet)
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).

Study groups in NCT05303636
Study group	Role	What they receive
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. Receives: 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. Receives: 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

Cohort 1: Mean absolute change in lumbar spine (L1-L4) Z-score in adolescents
Measured by dual-energy X-ray absorptiometry (DXA)
Measured: Baseline to 12 months
Cohort 2: Mean percentage change in lumbar spine (L1-L4) BMD in adults
Measured by DXA
Measured: 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)
Measured by DXA
Measured: 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
Measured: 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
Measured: 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
Measured: 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%
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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%
Measured: 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
Measured: 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
Measured: 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)
Measured: Baseline to 12 months
Routine laboratory values
Mean absolute and relative changes in routine laboratory values
Measured: 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
Measured: 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).
Measured: Up to 12 months following treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Mar 2022Jun 2028

First posted31 Mar 2022
Study start28 Mar 2022
Primary completionDec 2027 (estimated)
Study completionJun 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (8)Papers the sponsor has linked to this study.
Other trials for Change in Bone Mineral DensityStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Screening
Allocation: Non-randomised
Intervention model: Factorial
Model description: Two cohorts: Cohort 1 (adolescents); Cohort 2 (adults)
Masking: None (open label)
Enrolment: 1,536 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05303636
Sponsor's protocol ID: LF111/401
Other IDs: 2020-000412-30
Status last verified: Apr 2026
First submitted: 22 Mar 2022
Last updated: 9 Apr 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 10836659
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.
PubMed 22436400
Beksinska ME, Smit JA. Hormonal contraception and bone mineral density. Expert Rev of Obstet Gynecol. 2011;6(3);305-319.
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.
PubMed 26856587
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.
PubMed 29959901
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.
PubMed 19158356
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.
PubMed 33301749
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.
PubMed 25249568

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Open-label, Controlled Study to Investigate the Effect of Either LF111 or Drospirenone Chewable Tablets on Bone Mineral Density (BMD) in Adolescent and Adult Women in Comparison With Non-users of Hormonal Contraceptive Methods
ClinicalTrials.gov ID: NCT05303636
Acronym / sponsor ID: LF111/401
Conditions: Change in Bone Mineral Density, Bone Loss
Keywords: Osteoporosis
Phase: Phase 4
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 1,536 participants (actual)
Lead sponsor: Insud PharmaIndustry (pharma, biotech, devices)
Collaborators: Chemo Research
Study start: 28 Mar 2022 (actual)
Primary completion: Dec 2027 (estimated)
Study completion: Jun 2028 (estimated)
First posted: 31 Mar 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Screening
Allocation: Non-randomised
Intervention model: Factorial
Masking: None (open label)
Number of arms: 4
Model description: Two cohorts: Cohort 1 (adolescents); Cohort 2 (adults)

Arm	Type	Receives
Cohort 1 (adolescents aged 14-17) Hormonal Treatment Arm	Experimental	Drug: drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tabletSubjects 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.
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	Drug: drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tabletSubjects 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.
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.

Who may qualify

Ages: 14 to 45 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (8 listed)

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:
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.

Key exclusion criteria (28 listed)

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:
In adolescents only: Short stature defined as height-for-age percentile less than the fifth percentile.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
drospirenone 4 mg oral tablet or drospirenone 3.5 mg chewable tabletAlso: LF111 (drospirenone 4 mg tablet)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).	Drug	Cohort 1 (adolescents aged 14-17) Hormonal Treatment Arm, Cohort 2 (adults aged 18-45) Hormonal Treatment Arm

Primary outcome

Cohort 1: Mean absolute change in lumbar spine (L1-L4) Z-score in adolescents
Time frame: Baseline to 12 months
Measured by dual-energy X-ray absorptiometry (DXA)
Cohort 2: Mean percentage change in lumbar spine (L1-L4) BMD in adults
Time frame: Baseline to 12 months
Measured by DXA

16 secondary outcomes

Cohort 1: Mean absolute changes in lumbar spine (L1-L4) Z-score in adolescents (hormonal treatment arm only)
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
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
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
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
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
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
Time frame: Baseline to 12 months
Cohort 2: Mean absolute and percentage changes in femoral neck, total hip, and total body BMD in adults
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)
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
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
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
Time frame: Baseline to 6 months (hormonal treatment arm only) and to 12 months
Changes in body weight and body mass index (BMI)
Time frame: Baseline to 12 months
Routine laboratory values
Time frame: Baseline to 6 months and to 12 months
Serum estradiol (E2) levels (hormonal treatment arm only)
Time frame: Baseline to 6 months and to 12 months
Number of subjects with adverse events as a measure of safety
Time frame: Up to 12 months following treatment

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
Background: PubMed 10836659Rosenbaum 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.
Background: PubMed 22436400Cibula 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.
BackgroundBeksinska ME, Smit JA. Hormonal contraception and bone mineral density. Expert Rev of Obstet Gynecol. 2011;6(3);305-319.
Background: PubMed 26856587Weaver 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.
Background: PubMed 29959901Rizzo 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.
Background: PubMed 19158356Schwartz 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.
Background: PubMed 33301749Pierce 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.
Background: PubMed 25249568Carr 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Enrico Colli, MD study director

Chemo Research SL

37 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Poland, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cohort 1: Mean absolute change in lumbar spine (L1-L4) Z-score in adolescents (time frame: Baseline to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05303636, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.