E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oral contraception for females aged 15-45 |
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E.1.1.1 | Medical condition in easily understood language |
Oral contraception for females aged 15-45 |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10042613 |
E.1.2 | Term | Surgical and medical procedures |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030970 |
E.1.2 | Term | Oral contraception |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the contraceptive efficacy of LPRI-424 |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the safety and tolerability of LPRI-424 and to assess the pharmacokinetics of LPRI-424 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Sexually active, postmenarcheal and premenopausal female subjects, at risk of pregnancy, aged between 15 and 45 years (inclusive) at the time of trial enrolment. (In some countries the lower age limit may be higher due to national legislation.) Female subjects at risk of pregnancy, between the ages of 15 and 17 (inclusive) provided that: a.Applicable national, state and local laws allow subjects in this age group to consent/assent to receive contraceptive services, b.All applicable laws and regulations regarding the informed consent/assent of the subjects to participate in clinical trials are observed. 2.Women who a.have never used hormonal contraceptives before consent/assent (naïve users), b.have used hormonal contraceptives in the past, but have had a hormonal contraceptive-free period before consent/assent and a full menstrual cycle (see Section 4.2) during the drug-free period (previous users) or c.directly switch from another hormonal contraceptive (switchers). 3.Only for subjects who were not pregnant and did not use hormonal contraception during the last six months before consent/assent: Regular cycles (i.e. cycle length between 24 and 35 days) during the last six months. 4.Only for women who were pregnant within the last six months before consent/assent: At least three complete menstrual cycles after pregnancy. 5.At screening, systolic blood pressure ≤ 140 mm Hg and diastolic blood pressure ≤ 90 mm Hg. 6.Be able and willing to provide written informed consent/assent, prior to undergoing any trial-related procedure. 7.Willing to use trial contraception for thirteen 28-day cycles. 8.Be willing to have intercourse in each cycle of the trial without the need to use back-up contraceptive. 9.Be willing to state that, to her best knowledge, her male sexual partner/partners has/have not had a vasectomy or been previously diagnosed as infertile. 10.Agree not to participate in any other clinical trials during the course of this trial (participation in a non-interventional study is allowed). |
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E.4 | Principal exclusion criteria |
1.Pregnancy. 2.Wish for pregnancy. 3.Breastfeeding. 4.Subject is known to or suspected of not being able to comply with the trial protocol, the use of the trial medication or the use of the trial diary. 5.History of infertility. 6.BMI > 35 kg/m2 7.Current smoker with age > 35 years and/or with BMI > 30 kg/m² (at the time of trial enrolment). 8.Abnormal finding on pelvic, breast or ultrasound examination that in the investigator’s opinion contraindicates participation in the trial. 9.Women ≥21 years of age with a Papanicolaou (Pap) smear reading low-grade squamous intraepithelial lesion (LGSIL) or higher at screening (or 6 months prior to screening date). Subjects with atypical squamous cells of undetermined significance (ASC-US) can be included if they are negative for high-risk human papilloma virus (HPV) strains. Subjects < 21 years of age do not require a Pap smear. 10.Known contraindication or hypersensitivity to ingredients or excipients of the IMP, including: a.Presence or risk of a venous thromboembolism (VTE) b.Presence or risk of an arterial thromboembolism (ATE) c.Presence or history of pancreatitis, if it is associated with severe hypertriglyceridemia d.Presence or history of liver diseases in which liver function has not returned to normal (also Dubin-Johnson and Rotor syndrome) e.Current or previous liver tumours f.Known or suspected sex hormone-dependent malignant tumours (e.g., breast or endometrium) g.Undiagnosed vaginal bleeding h.Unexplained amenorrhoea i.Concomitant use of medicinal products containing ombitasvir/paritaprevir/ritonavir or dasabuvir 11.Uncontrolled thyroid disorder (i.e., not on stable dose of thyroid replacement for at least two months at the time of assent/consent). 12.Uncontrolled concomitant diseases (i.e., not on a stable treatment dose for at least two months at the time of assent/consent). 13.Evidence or history of alcohol, medication or drug abuse (within the last 12 months prior to consent/assent). 14.Known HIV infection. 15.Known current or chronic hepatitis B or C. 16.Known HPV infection with strains 16, 18 or other high-risk strains as per screening examination. 17.Less than 3 menses after discontinuing dosing of depot medroxyprogesterone acetate (DMPA or Depo-Provera®) or any combined injectable contraceptive (e.g., Cyclofem®) prior to consent/assent. 18.Long-term treatment (longer than seven consecutive days within a month prior to V1b) of any medication that might interfere with the efficacy of hormonal contraceptives, e.g.: a.Anticonvulsants (e.g. phenytoin, carbamazepine, oxcarbazepine, topiramate, felbamate) b.Barbiturates (e.g. primidone) c.Specific antibiotics (such as rifampin or rifampicin [tuberculosis infection] and griseofulvin [fungal infections]) d.HIV medication (such as ritonavir, neviparine and efavirenz) e.Bosentan f.Griseofulvin g.St. John’s wort (hypericum perforatum) h.Metoclopramide 19.Prohibited medication including the use of oestrogens, progestogens, strong microsomal enzyme-inducing drugs (intensive and moderate frequency). 20.Administration of medication containing human chorionic gonadotropin (hCG) within a month prior to V1b. 21.Progestin-releasing intra-uterine device (IUD) or contraceptive implant received or in place within the last two months prior to consent/assent. 22.Planned regular concomitant use of barrier contraceptive methods, spermicides, IUDs or other contraceptive measures. 23.Evidence or history of clinically significant psychiatric illness, such as major depression or schizophrenia, that in the investigator’s opinion contraindicates participation in the trial. 24.Planned surgery during participation in this trial requiring withdrawal of an oral contraceptive. 25.Participation in another trial of an investigational drug or device in parallel to the current trial or less than 90 days before consent/assent, or previous participation in a clinical trial with LPRI-421 or LPRI-424 and dispensed trial medication. 26.Subject is a member of the investigator’s or sponsor’s staff or a relative or family member thereof. 27.Any condition that, in the opinion of the investigator, may jeopardize protocol compliance or the scientific integrity of the trial. 28.Severe Covid-19 disease or less than 3 months after hospitalisation due to a Covid-19 disease. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Pearl Index (PI) in women aged ≤ 35 years (at the time of trial enrolment) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary: 1.PI after correction for back-up contraception and sexual activity (evaluable cycles) in women aged ≤ 35 years (at the time of trial enrolment) 2.PI for method failures in women aged ≤ 35 years (at the time of trial enrolment) 3.Pregnancy ratio (life table analysis) in women aged ≤ 35 years (at the time of trial enrolment) 4.Overall PI, PI after correction for back-up contraception and sexual activity (evaluable cycles), PI for method failures and pregnancy ratio (life table analysis) in all women 5.Overall PI, PI after correction for back-up contraception and sexual activity (evaluable cycles), PI for method failures and pregnancy ratio (life table analysis) in women aged > 35 years (at the time of trial enrolment) Safety/Tolerability: 6.Adverse events (AEs) 7.Vital signs 8.Electrocardiogram (ECG) 9.Physical examination 10.Gynaecological examination 11.Transvaginal ultrasound examination 12.Mastodynia/mastalgia and dysmenorrhea characteristics as well as cervical cytology 13.Clinical laboratory parameters 14.Bleeding pattern 15.IMP acceptability 16.Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form (Q-LES-Q-SF) Pharmacokinetics (PK): 17.LPRI-424 (DNG and EE) plasma concentrations 18.Volume of distribution 19.Apparent clearance 20.Area under the curve (AUC) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 49 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Ukraine |
Bulgaria |
Germany |
Lithuania |
Spain |
Czechia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |