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

Launched by INSUD PHARMA · Mar 22, 2022

Keywords

ClinConnect Summary

This clinical trial is studying the effects of two types of chewable hormonal contraceptives, LF111 and drospirenone (DRSP), on bone health in women aged 14 to 45. The main goal is to see how these medications impact bone mineral density (BMD) in the lower back after one year of use compared to women using non-hormonal contraceptive methods. The trial is also looking at how these treatments affect overall bone health and body composition, while ensuring they are safe and well-tolerated.

To participate, women must have regular menstrual cycles and be between the ages of 14 and 45. Participants will need to agree to use either the hormonal treatments or non-hormonal methods for 13 cycles, which is about a year. During the trial, participants can expect regular check-ins to monitor their bone health and overall well-being. It's important to know that certain medical conditions and previous medications may prevent eligibility, so a thorough screening will take place to ensure safety.

Gender

FEMALE

Eligibility criteria

• 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.