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

NCT ID: NCT05303636

Last Updated: 2023-06-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1710 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-28

Study Completion Date

2027-03-31

Brief Summary

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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.

Detailed Description

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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

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Change in Bone Mineral Density Bone Loss

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

FACTORIAL

Two cohorts: Cohort 1 (adolescents); Cohort 2 (adults)
Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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

Subjects in the USA will choose to use the 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. Only LF111 will be available to subjects in Europe.

Group Type EXPERIMENTAL

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

Intervention Type DRUG

LF111 (drospirenone 4 mg tablet orally daily on days 1-24, followed by placebo tablet orally daily on days 25-28) or drospirenone (DRSP) 3.5 mg chewable tablet chewed daily on days 1-24, followed by placebo tablet chewed daily on days 25-28) (USA only). Subjects in the USA who choose to use the hormonal contraceptive method may choose between LF111 and 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

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

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

Subjects in the USA will choose to use the 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. Only LF111 will be available to subjects in Europe.

Group Type EXPERIMENTAL

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

Intervention Type DRUG

LF111 (drospirenone 4 mg tablet orally daily on days 1-24, followed by placebo tablet orally daily on days 25-28) or drospirenone (DRSP) 3.5 mg chewable tablet chewed daily on days 1-24, followed by placebo tablet chewed daily on days 25-28) (USA only). Subjects in the USA who choose to use the hormonal contraceptive method may choose between LF111 and 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

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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

LF111 (drospirenone 4 mg tablet orally daily on days 1-24, followed by placebo tablet orally daily on days 25-28) or drospirenone (DRSP) 3.5 mg chewable tablet chewed daily on days 1-24, followed by placebo tablet chewed daily on days 25-28) (USA only). Subjects in the USA who choose to use the hormonal contraceptive method may choose between LF111 and 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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* 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.
Minimum Eligible Age

14 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Chemo Research

INDUSTRY

Sponsor Role collaborator

Insud Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Enrico Colli, MD

Role: STUDY_DIRECTOR

Chemo Research SL

Locations

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Cactus Clinical Research, Inc.

Phoenix, Arizona, United States

Site Status RECRUITING

Velocity Clinical Research

Denver, Colorado, United States

Site Status RECRUITING

Advanced Clinical Research Network

Coral Gables, Florida, United States

Site Status RECRUITING

Health Care Family Rehab & Research Center

Hialeah, Florida, United States

Site Status RECRUITING

Vital Pharma Research

Hialeah, Florida, United States

Site Status RECRUITING

Cornerstone Research Institute

Longwood, Florida, United States

Site Status RECRUITING

New Age Medical Research Corporation

Miami, Florida, United States

Site Status RECRUITING

Florida Pharmaceutical Research and Associates, Inc.

South Miami, Florida, United States

Site Status RECRUITING

Comprehensive Clinical Research, LLC

West Palm Beach, Florida, United States

Site Status RECRUITING

M3 Wake Research, Inc.

Sandy Springs, Georgia, United States

Site Status RECRUITING

Family Care Research

Boise, Idaho, United States

Site Status RECRUITING

Tandem Clinical Research

Marrero, Louisiana, United States

Site Status RECRUITING

Clinical Trials Management, LLC - Southshore

Metairie, Louisiana, United States

Site Status RECRUITING

Meridian Clinical Research

Norfolk, Nebraska, United States

Site Status RECRUITING

M3 Wake Research

Raleigh, North Carolina, United States

Site Status RECRUITING

Lillestol Research LLC

Fargo, North Dakota, United States

Site Status RECRUITING

Corpus Christi Women's Clinic

Corpus Christi, Texas, United States

Site Status RECRUITING

Signature Gyn Services

Fort Worth, Texas, United States

Site Status RECRUITING

TMC Life Research, Inc.

Houston, Texas, United States

Site Status RECRUITING

Seattle Clinical Research Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Study Director

Role: CONTACT

+34 - 91 771 15 00

Facility Contacts

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Ernesto Gomez, MD

Role: primary

602-363-3043

Kevin O'Brien, MD

Role: primary

303-293-3733

Gil Fernandez-Yera, MD

Role: primary

305-702-1594

Jose Lopez

Role: primary

Rafael Garcia-Ocasio, MD

Role: primary

786-666-0592

Michael Akpeke, MD

Role: primary

407-257-8102

Janet Gersten, MD

Role: primary

305-274-6002

Ana Roig-Cantisano, MD

Role: primary

954-538-5102

Jamie S Ackerman

Role: primary

561-478-3177

Stephen Blank, MD

Role: primary

404-843-4400

Richard Radnovich, DO

Role: primary

208-621-2503

Gary Reiss, MD

Role: primary

504-934-8424

Allison Rodriguez, MD

Role: primary

504-455-1310

Keith Vrbicky, MD

Role: primary

402-371-0797

Pouru Bhiwandi, MD

Role: primary

919-781-2514

Michael J Lillestol, MD

Role: primary

701-232-7705

Charles Kirkham, MD

Role: primary

361-851-5000

John Whitfield, MD

Role: primary

817-927-2229

Mark Jacobs, MD

Role: primary

713-799-1635 ext. 101

Rebecca Dunsmoor-Su, MD

Role: primary

206-522-3330

References

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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.

Reference Type BACKGROUND
PMID: 10836659 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22436400 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 26856587 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29959901 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19158356 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33301749 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25249568 (View on PubMed)

Other Identifiers

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2020-000412-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LF111/401

Identifier Type: -

Identifier Source: org_study_id

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