Single-center, open-label, adaptive design study to evaluate the influence on hormonal and ovarian function and vaginal bleeding pattern of different dosages of levonorgestrel administered once daily for 28 days over two consecutive treatment cycles in healthy, cyclic wome

Phase 1

• Conditions: Investigation of ovulation inhibition for indication of contraception; MedDRA version: 20.0Level: LLTClassification code 10073728Term: Hormonal contraceptionSystem Organ Class: 100000004865; Therapeutic area: Body processes [G] - Reproductive physiologi cal processes [G08]

• Registration Number: EUCTR2018-002700-14-DE
• Lead Sponsor: avad Life Sciences Pte Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-10-11
• Last Update Posted: 15 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 150

Inclusion Criteria

Per treatment group 30 healthy female subjects fulfilling the following inclusion criteria:
1. 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 subjects participating in the clinical trial
2. sex: female
3. age: 18 years to 45 years inclusive
4. body-mass index (BMI): =18.0 kg/m² (no upper limit has been set, instead at least 5 subjects per group with a BMI =30 kg/m² shall be enrolled)
5. good state of physical and mental health based on medical, surgical and gynaecological history, physical- and gynaecological examination at screening
6. 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
7. both ovaries visible upon transvaginal ultrasonography; observed at screening examination
8. ovulation in the pre-treatment cycle between Day 9±1 and Day 27±1 defined as:
-TVUS observation of follicle rupture or corpus luteum formation and
- a subsequent serum progesterone concentration of = 16nmol/l and
-next menstruation does not start within 6±1 days after suspected ovulation

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Safety concerns:
1. Any known severe systemic disease that might interfere with the conduct of the study or the interpretation of the results
2. existing cardiac and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability of the active ingredient
3. existing hepatic and/or renal diseases or pathological findings, which might interfere with the safety or tolerability, and/or pharmacokinetics of the active ingredient
4. existing gastrointestinal diseases or pathological findings, which might interfere with the safety, tolerability, absorption and/or pharmacokinetics of the active ingredient
5. 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])
6. 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)
7. presence or history of liver tumours (benign or malignant)
8. existing or previous hepatic disease as long as liver function values have not returned to normal
9. existing or history of pancreatitis, if associated with severe hypertriglyceridemia
10. 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
11. 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
12. 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])
13. specific heart diseases (e.g. valvular heart disease, atrial fibrillation)
14. cardiac dysfunction (NYHA I-IV)
15. pronounced varicose veins
16. history of phlebitis in combination with other risk factors for thromboembolic diseases
17. existing uncontrolled thyroid disorders
18. known diabetes mellitus
19. Sickle-cell anaemia
20. known severe disturbances of lipid metabolism
21. existing or history of known or suspected malignant or premalignant diseases, regardless of the hormone status
22. 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)
23. known hypersensitivity to any ingredients of the study medication (active ingredients used or to constituents of the pharmaceutical preparations), (e.g. subjects with rare hereditary problems or galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption)
24. subjects with severe allergies or multiple drug allergies unless it is judged as not relevant for the clinical trial by the investigator
25. systolic blood pressure < 90 or > 139 mmHg
26. diastolic blood pressure < 60 or > 89 mmHg
27. puls rate < 5

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified