Investigation of Ovulation Inhibition with Levonorgestrel 0.135 mg Tablet in Contraception Despite Scheduled Intake Delays
- Trial ID
- 2025-521236-12-00
- Protocol
- 1460lng24ct
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the efficacy of **ovulation** inhibition using LNG-POP (Levonorgestrel 0.135 mg tablet) despite scheduled delays in tablet intake. This investigation is clinically relevant as it assesses the reliability of the contraceptive method under conditions of intentional intake errors, which can occur in real-world settings. Understanding the robustness of ovulation inhibition under these circumstances is crucial for ensuring effective contraception and providing guidance on the management of missed doses.
Participants
The clinical trial focuses on the **investigation of ovulation inhibition** after intentional intake errors of the investigational medicinal product for contraception purposes. The study population comprises **female** participants who are premenopausal, with an age range of 18 to 35 years. Participants are required to have a body mass index (BMI) of at least 18.0 kg/m² and must be in a good state of physical and mental health, as determined by medical, surgical, and gynecological history, as well as physical and gynecological examinations. Lifestyle considerations include being a non-smoker or an ex-smoker for at least three months if over 30 years of age, or a moderate smoker if 30 years or younger. Both ovaries must be visible upon transvaginal ultrasonography, and ovulation in the pre-treatment cycle is confirmed by a serum progesterone concentration greater than 10.0 nmol/l. The total number of participants is not provided by the sponsor. The trial population was selected based on these criteria to ensure the reliability and validity of the study outcomes.
Plans and Procedures
The clinical trial is designed to evaluate the **inhibition of ovulation** using LNG-POP Levonorgestrel 0.135 mg tablets over three 28-day cycles, with continuous treatment and intentional intake errors. This is a mono-centre, non-comparative study, classified as a Phase IV trial. The primary objective is to determine if ovulation inhibition is maintained despite scheduled delays in tablet intake. The trial will involve premenopausal female participants aged 18 to 35 years, with a body mass index of at least 18.0 kg/m², who are in good physical and mental health. Participants must be non-smokers or moderate smokers, with both ovaries visible upon transvaginal ultrasonography and evidence of ovulation in the pre-treatment cycle.
The trial will commence with a screening visit to assess eligibility based on the inclusion criteria. Participants will then undergo a series of study visits corresponding to each 28-day cycle, during which the primary endpoint of ovulation under treatment will be evaluated. Ovulation during treatment is defined by a Hoogland-Skouby score of 5 or 6, combined with a Landgren criterion of progesterone concentration greater than 16.0 nmol/l for at least five consecutive days. The trial is expected to conclude with an end-of-study visit, where final assessments will be conducted.
The total duration of the trial is estimated to be 84 days, with participant involvement spanning the same period. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse events, or withdrawal of consent. The trial is scheduled to start recruitment on June 2, 2025, and is anticipated to end by December 31, 2025. The study will be conducted under controlled conditions, ensuring the safety and well-being of all participants throughout the trial duration.
Treatment
The clinical trial involves the administration of **LNG-POP Levonorgestrel 0.135 mg Tablet**, which is an experimental medication designed to inhibit ovulation. The active substance in this medication is **levonorgestrel**, a chemical compound. The pharmaceutical form of the medication is a tablet, and it is administered orally. The dosage is 0.135 mg per tablet, with a maximum daily dose of 135 micrograms. The treatment is continuous over three 28-day cycles, with a total maximum treatment period of 84 days. The study includes intentional intake errors to assess the maintenance of ovulation inhibition despite scheduled delays in tablet intake. The total maximum dose over the treatment period is 11,340 micrograms.
No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The trial is mono-centre and non-comparative, focusing solely on the effects of the **LNG-POP Levonorgestrel 0.135 mg Tablet**. Participant compliance with the dosing schedule is monitored to ensure adherence to the treatment regimen. The medication is not a paediatric formulation and is not classified as an orphan drug. The study is conducted under the sponsorship of SOCRATEC R&D GMBH, with the product authorized for use in this clinical trial.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the primary endpoint, which is the occurrence of **ovulation** under treatment. Ovulation during treatment is specifically defined as a Hoogland-Skouby score (HSS) of 5 or 6, combined with the fulfillment of the Landgren criterion, which requires a progesterone concentration greater than 16.0 nmol/l for at least five consecutive days. These parameters will be measured and collected throughout the trial to determine the effectiveness of the LNG-POP Levonorgestrel 0.135 mg Tablet in inhibiting ovulation, even with scheduled delays in tablet intake.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the participants in the clinical trial
- Sex: female, premenopausal
- Age: 18 years to 35 years inclusive, at screening
- Body mass index (BMI): ≥ 18.0 kg/m² at screening
- Good state of physical and mental health based on medical, surgical and gynaecological history, physical and gynaecological examination at screening
- Non-smoker or ex-smoker for at least 3 months if aged > 30 years or moderate smoker (10 cigarettes or 2 cigars or 2 pipes per day) if aged ≤ 30 years only; questioned at screening examination
- Both ovaries visible upon transvaginal ultrasonography (TVUS); observed at screening examination
- Ovulation in the pre-treatment cycle, defined as a serum progesterone concentration > 10.0 nmol/l on cycle day 20 (±4) or 25 (±4)
Exclusion Criteria
- Any known severe systemic disease that might interfere with the conduct of the study or the interpretation of the results
- Existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
- Existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient
- Existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient
- History of relevant CNS and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders (e.g. clinically significant depression [current or in the last year])
- Acute and chronic progressive liver diseases (e.g. disturbances of the bilirubin excretion of the bile [Dubin-Johnson and Rotor syndromes], disturbances of the bile secretion, disturbances in the bile flow, idiopathic icterus or pruritus during a previous pregnancy or estrogen-progestogen treatment)
- Presence or history of liver tumours (benign or malignant)
- Existing or previous hepatic disease as long as liver function values have not returned to normal
- Existing or history of pancreatitis, if associated with severe hypertriglyceridemia
- Presence or history of venous or arterial thromboembolic diseases (e.g. deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke) or prodromal conditions (e.g. transient ischemic attack, angina pectoris), cerebrovascular accident
- Presence of any hereditary or acquired predisposition for venous or arterial thrombosis that could increase the risk of any of the conditions listed in Exclusion Criterion No. 10 (e.g. APC-resistance, Antithrombin III deficiency, Protein-C and/or Protein-S deficiency, hyperhomocysteinaemia and antiphospholipid-antibodies
- Anamnestic hints for increased risk of thrombosis events in family history (e.g. any venous thromboembolic event that occurred in a close relative at a young age [≤ 50 years])
- Specific heart diseases (e.g. valvular heart disease, atrial fibrillation)
- Cardiac dysfunction (NYHA I-IV)
- Pronounced varicose veins
- History of phlebitis in combination with other risk factors for thromboembolic diseases
- Existing uncontrolled thyroid disorders
- Known diabetes mellitus
- Sickle-cell anaemia
- Known severe disturbances of lipid metabolism
- Existing or history of known or suspected malignant or premalignant diseases, regardless of the hormone status
- Abnormal, clinically significant findings which, according to the assessment of the investigator, may worsen under hormonal treatment (e.g. pemphigoid gestationis during a previous pregnancy, middle-ear deafness (otosclerosis); Sydenham’s chorea, porphyria, systemic lupus erythematosus, haemolytic-uremic syndrome)
- Known hypersensitivity to any ingredients of the study medication (active ingredients used or to constituents of the pharmaceutical preparations), (e.g. participants with rare hereditary problems or galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption)
- Participants with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
- Systolic blood pressure < 90 or > 139 mmHg
- Diastolic blood pressure < 60 or > 89 mmHg
- Pulse rate < 50 bpm or > 90 bpm
- Clinical laboratory values out of normal range at screening unless the minor deviation from normal is judged as not relevant for the clinical trial by the investigator
- ASAT > 20 % ULN, ALAT > 10 % ULN, bilirubin > 20% ULN (except in case of existing Morbus Gilbert-Meulengracht deduced from anamnesis/medical history) and creatinine > 0.1 mg/dL ULN (limit of > 0.1 mg/dL correspondents to of > 9 µmol/l ULN).
- Positive anti-HIV-test (if positive to be verified by western blot), HBs-AG-test or anti-HCV-test
- Diagnosis of latest PAP smear: findings classified higher than score II (Munich Nomenclature III)
- Other diseases: migraine with neurologic symptoms (complicated migraine), undiagnosed vaginal bleeding, manifest kidney disease with impaired renal function, worsening of epilepsy or chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) under hormonal treatment
- Acute or chronic diseases which may interfere with the aims of the clinical trial
- History of or current drug, alcohol or medicine abuse (e.g. laxatives)
- Participants who are on a diet which could affect the pharmacokinetics of the active ingredient
- Blood donation or other blood loss more than 400 ml after individual enrolment (signed informed consent) of the participant
- Participation in another clinical study or administration of any investigational medicinal product within 1 cycle prior to start of the pre-treatment cycle
- Surgery scheduled in the study period (minor surgical procedures [e.g. day case surgery] are permissible)
- Treatment with any systemically available medication within 2 weeks prior to start of the pre-treatment cycle which might interfere with pharmacodynamics, pharmacokinetics or safety of the IMPs (see chapter 13.2.1 of the clinical trial protocol)
- Use of any hormonal contraception preceding the pre-treatment cycle as follows: shortly acting hormonal contraceptives as oral, patch, ring or intra uterine system within one cycle; injectable (intramuscularly or subcutaneously) within 10-month (three-month treatment duration), 6-month (two-month treatment duration) or 3-month (one-month treatment duration)
- In case of washout phase, if no spontaneous menses started within 46 days after stop of short-acting hormonal contraceptive
- Participants with known cycle irregularities during the last year, prior to screening examination, if not caused by hormonal contraceptives
- Positive pregnancy test at screening examination or any time during the study
- Pregnant or lactating women (less than 3 cycles following delivery, abortion, or lactation before start of pre-treatment cycle)
- In case of heterosexual activity, female participants who do not agree to apply a barrier method for contraception (e.g. male condom) or hetero-sexual abstinence from screening onward until the final visit
- Participants, who actually desire to be pregnant
- Non-availability of prompt access to eDiary at any time
- Participants suspected or known not to follow instructions
- Participants who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial
- Participant is a dependent person, e.g. a relative, family member, or member of the investigator’s staff
- Participants who are in custody by order of an authority or a court of law
- Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the participant’s safety
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Recruiting | 02 Jun 2025 | 34 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
LNG-POP Levonorgestrel 0.135 mg Tablet | Test | TABLET | ORAL | 135 | 84 | PRD12216762 |