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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Chemo Research S.L.

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years, 18-64 years

Gender

Female

Therapeutic area

Phenomena and Processes [G] - Musculoskeletal and Neural Physiological Phenomena [G11]

Trial duration

22 Aug 2022 → ongoing

Decision date (initial)

2024-06-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Chemo Research S.L.

External identifiers

EU CT number

2024-512347-23-00

EudraCT number

2020-000412-30

WHO UTN

U1111-1301-8973

ClinicalTrials.gov

NCT05303636

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

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 2

1. To further evaluate the impact of LF111 and DRSP 3.5 mg chewable tablets on BMD and bone turnover after 12 months (13 medication cycles) of investigation in comparison to non-hormonal contraceptive methods
2. To assess general safety and tolerability of LF111 and DRSP 3.5 mg chewable tablets in comparison to non-hormonal contraceptive methods

Conditions and MedDRA coding

Oral contraception

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 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.
2. 2. Systolic blood pressure < 140 mmHg, diastolic blood pressure < 90 mmHg at Visit 1, in sitting position after 5 minutes of rest.
3. 3. Menstruation restarted for at least 6 months since last pregnancy (only applicable for women that were pregnant)
4. 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.
5. 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 18

1. 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).
2. 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.
3. 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.
4. 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).
5. 5. In adolescents only: Short stature defined as height-for-age percentile less than the fifth percentile.
6. 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.
7. 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.
8. 8. Ongoing pregnancy or wish for pregnancy.
9. 9. Currently lactating or stopped lactating within the past year.
10. 10. Eating disorders (e.g., anorexia nervosa, bulimia).
11. 11. Celiac disease.
12. 12. Endocrine disorders (e.g., diabetes, hypothyroidism or hyperthyroidism, hyperparathyroidism, Cushing's disease).
13. 13. Rheumatoid arthritis.
14. 14. Current or ever use of medications or supplements known to increase BMD including bisphosphonates, denosumab, teriparatide, abaloparatide, romosozumab, calcitonin, fluoride and strontium.
15. 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.
16. 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.
17. 17. Any condition that, in the opinion of the investigator, may jeopardize the trial conduct according to the protocol.
18. 18. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 5

1. Please refer to the Protocol for Cohort 1 & 2 (Section 7)
2. Changes in body weight and body mass index (BMI)
3. Mean absolute and relative changes in routine laboratory values from baseline to 6 months and to 12 months
4. Mean absolute and relative changes in serum estradiol (E2) levels in the hormonal treatment arm from baseline to 6 months and to 12 months
5. Adverse events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Chemo Research S.L.

Sponsor organisation

Chemo Research S.L.

Address

3rd Floor, Calle De Manuel Pombo Angulo 28 Calle De Manuel Pombo Angulo 28

City

Madrid

Postcode

28050

Country

Spain

Scientific contact point

Organisation

Chemo Research S.L.

Contact name

Chief Scientific Officer

Public contact point

Organisation

Chemo Research S.L.

Contact name

Chief Scientific Officer

Third parties 3

Locations

2 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications