DROSPIRENONE for Decreased bone mineral density | Oral contraception

Inclusion criteria

• {"criterion_text":"- 1. 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 a. Applicable national, state and local laws allow subjects in this age group to consent/assent to receive contraceptive services, and b. All applicable laws and regulations regarding the informed consent/assent of the subjects to participate in clinical trials are observed."}
• {"criterion_text":"- 2. Systolic blood pressure < 140 mmHg, diastolic blood pressure < 90 mmHg at Visit 1, in sitting position after 5 minutes of rest."}
• {"criterion_text":"- 3. Menstruation restarted for at least 6 months since last pregnancy (only applicable for women that were pregnant)"}
• {"criterion_text":"- 4. Be able and willing to provide written informed consent, or assent if the subject is an adolescent, prior to undergoing any trial-related procedures."}
• {"criterion_text":"- 5. Willing to use trial contraception for thirteen 28-day cycles (LF111 arm) or to use non-hormonal contraceptive methods for the duration of the trial (non-hormonal contraceptive arm), respectively."}

Exclusion criteria

• {"criterion_text":"- 1. Contraindications to the use of LF111 (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 LF111 arm only)."}
• {"criterion_text":"- 10. Eating disorders (e.g., anorexia nervosa, bulimia)."}
• {"criterion_text":"- 11. Celiac disease."}
• {"criterion_text":"- 12. Endocrine disorders (e.g., diabetes, hypothyroidism or hyperthyroidism, hyperparathyroidism, Cushing's disease)."}
• {"criterion_text":"- 13. Rheumatoid arthritis."}
• {"criterion_text":"- 14. Current or ever use of medications or supplements known to increase BMD including bisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab, calcitonin, fluoride and strontium."}
• {"criterion_text":"- 15. Treatment with medications that are known to decrease bone mass: • Glucocorticoids (oral, intravenous, chronic inhaled or 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 consecutive 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."}
• {"criterion_text":"- 16. 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."}
• {"criterion_text":"- 17. Any condition that, in the opinion of the investigator, may jeopardize the trial conduct according to the protocol."}
• {"criterion_text":"- 18. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities."}
• {"criterion_text":"- 2. BMD Z-score below -1.50 at any anatomic location. 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."}
• {"criterion_text":"- 3. 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."}
• {"criterion_text":"- 4. Medical conditions associated with low bone mass: a. Metabolic bone disease such as osteogenesis imperfecta, Paget's disease of the bone, osteomalacia/rickets b. Collagen vascular diseases such as Marfan's syndrome and Erhlos- Danlos syndrome c. 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 d. Gastrointestinal (malabsorptive) disease including inflammatory bowel disease, gastric bypass surgery and current postgasrectomy syndrome e. Liver disease f. Abnormal bone mineral metabolism (hypocalcemia/hypercalcemia, hypophosphatemia/hyperphosphatemia, hypomagnesemia)."}
• {"criterion_text":"- 5. In adolescents only: Short stature defined as height-for-age percentile less than the fifth percentile."}
• {"criterion_text":"- 6. Use of oral, transdermal, vaginal or intrauterine hormonal contraceptives in the previous month (within the previous 3 months in case of containing estrogen) or use of injectable or implantable hormonal contraceptives in the previous 6 months."}
• {"criterion_text":"- 7. 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."}
• {"criterion_text":"- 8. Ongoing pregnancy or wish for pregnancy."}
• {"criterion_text":"- 9. Currently lactating or stopped lactating within the past year."}

Primary endpoints

• {"endpoint_text":"- Cohort 1: Adolescents Mean absolute change in lumbar spine (L1-L4) Z-score from baseline to 12 months as measured by dual-energy X-ray absorptiometry (DXA) Cohort 2: Adults Mean percentage change in lumbar spine (L1-L4) BMD from baseline to 12 months as measured by DXA","definition_or_measurement_approach":"Lumbar spine (L1-L4) measurement by dual-energy X-ray absorptiometry (DXA); Cohort 1 (adolescents) endpoint uses mean absolute change in Z-score from baseline to 12 months; Cohort 2 (adults) endpoint uses mean percentage change in BMD from baseline to 12 months."}

Secondary endpoints

• {"endpoint_text":"- Please refer to the Protocol for Cohort 1 & 2 (Section 7)","definition_or_measurement_approach":"Details provided in protocol Section 7 (protocol document referenced in trial documents)."}
• {"endpoint_text":"- Changes in body weight and body mass index (BMI)","definition_or_measurement_approach":"Change from baseline in measured body weight and BMI at prespecified visits (e.g., 6 and 12 months) as described in protocol."}
• {"endpoint_text":"- Mean absolute and relative changes in routine laboratory values from baseline to 6 months and to 12 months","definition_or_measurement_approach":"Routine laboratory tests measured at baseline, 6 months and 12 months; endpoints are mean absolute and relative changes vs baseline."}
• {"endpoint_text":"- Mean absolute and relative changes in serum estradiol (E2) levels in the hormonal treatment arm from baseline to 6 months and to 12 months","definition_or_measurement_approach":"Serum estradiol (E2) measured in hormonal treatment arm at baseline, 6 months and 12 months; endpoints are mean absolute and relative changes vs baseline."}
• {"endpoint_text":"- Adverse events","definition_or_measurement_approach":"All adverse events collected and reported per protocol safety reporting; incidence and severity summarised."}

Methods

• Site-based recruitment using recruitment materials listed in trial documents (K2 recruitment materials: Dear Participant Letter, Brochure, Leaflet, Participant Quick Reference, Poster) and country-specific recruitment arrangements (K1 documents) — materials available for Poland and Czechia; target audience: adolescent and adult women considering contraception.

Czechia

Earliest CTIS Part Ii Submission Date

21-05-2024

Latest Decision Or Authorization Date

02-10-2024

Processing Time Days

134

Number Of Sites

6

Number Of Participants

376

Poland

Earliest CTIS Part Ii Submission Date

21-05-2024

Latest Decision Or Authorization Date

04-09-2025

Processing Time Days

471

Number Of Sites

8

Number Of Participants

564

Primary sponsor

Full Name

Chemo Research S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Multiple sponsor duties codes including clinical site agreement negotiations and signing CSAs with sites; operational support (contact: RS-Advisor-Support@medpace.com)

Name

MEDPACE LABORATORIES

Responsibilities

Sponsor duties code 4 (laboratory services noted in sponsor third-parties listing); contact: MRL-BE-PM@medpace.com

Name

Bioclinica Inc.

Responsibilities

Medical image analysis/review (DXA scans); contact: support@bioclinica.com

Third parties

• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Sponsor duties codes listed in record: 1,10,12,15 (including: Clinical site agreement(CSA) negotiations and signing CSAS with sites),2,3,5,6,7,9; contact: RS-Advisor-Support@medpace.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"Sponsor duties codes listed in record: 4; contact: MRL-BE-PM@medpace.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image analysis/review (DXA scans); contact: support@bioclinica.com","organisation_type":"Laboratory/Research/Testing facility"}