E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Endometriosis is a condition in which tissue similar to the lining of the uterus (the endometrium, womb) grows outside the uterus. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10014778 |
E.1.2 | Term | Endometriosis |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
|
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 efficacy of LPRI-CF113 in the management of Endometriosis Associated Pelvic Pain (EAPP) as assessed on a numeric rating scale (NRS). |
|
E.2.2 | Secondary objectives of the trial |
To assess the efficacy of LPRI-CF113 versus placebo in terms of response to treatment. To assess the safety and tolerability of LPRI-CF113 in comparison to placebo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Postmenarcheal and premenopausal female subjects ≥ 15 and ≤ 45 years of age at screening, not seeking pregnancy. 2. Endometriosis was diagnosed by laparoscopy at least 6 weeks before Visit 1a and either a. histological confirmation was documented, OR b. in cases where histological confirmation is not available, the complete laparoscopy report with a visual confirmation of the diagnosis is available to the investigator. 3. EAPP of ≥ 3 points on an NRS during the last 3 months before screening. 4. Be able and willing to provide written informed consent or assent before any trial-related procedure will be performed. 5. In females not using a hormonal contraceptive at screening: regular menstrual cycles (i.e. cycle length between 21 and 35 days) during the last 3 months before screening. 6. Willing to agree to one wash-out cycle of hormonal therapies, if applicable. 7. Willing to use one agreed NSAID or paracetamol as rescue medication throughout the trial. No switching or start of an additional pain killer should be planned after Visit 1a until the end of the trial. 8. Systolic blood pressure ≤ 140 mmHg and diastolic blood pressure ≤ 90 mmHg at screening, in a sitting position after 5 minutes of rest. 9. Willing to use IP for six 28-day cycles. 10. Willing to use reliable non-hormonal contraceptive methods (condoms, female or male sterilisation or sexual abstinence [if in line with the preferred and usual lifestyle of the subject]) during the course of the trial. 11. Be in good physical (apart from endometriosis) and mental health according to medical history and general physical examination performed at screening. 12. Willing to adhere to the prohibitions and restrictions specified in the protocol. 13. Agree not to participate in any other clinical trials during the course of this trial.
Inclusion criteria at Visit 1b: 14. Have completed the e-diary in accordance with the e-diary instructions and with no more than 1 missed entry per each week during the last 28 days before Visit 1b. 15. Have regular menstrual cycles (i.e. cycle length between 21 and 35 days) during the screening period. 16. A mean EAPP score of ≥ 3 points on an NRS within the last 28 days before Visit 1b as assessed by e-diary entries.
|
|
E.4 | Principal exclusion criteria |
1. Ongoing pregnancy, wish for pregnancy, and breastfeeding subjects. 2. Subject is known to or suspected of not being able to comply with the trial protocol, the use of IP or trial e-diary. 3. Abnormal finding on pelvic, breast or ultrasound examination other than those related to endometriosis that in the investigator’s opinion contraindicates participation in the trial. 4. Pelvic pain not caused by endometriosis (e.g. interstitial cystitis, presumptive adenomyosis, fibroids, post-surgery pain, etc.). In case of a recent (< 3 months prior to Visit 1a) surgery, incl. low invasive laparoscopy, the investigator should confirm that the subject has fully recovered. 5. Any other pathology associated with chronic pain (e.g. fibromyalgia, chronic back pain, chronic headaches, etc.). 6. Laboratory values, heart rate and/or electrocardiogram assessment at screening which are considered clinically significant and which in the opinion of the investigator would be detrimental for participation in the trial. 7. Known contraindication to the use of LPRI-CF113: a) Active venous thromboembolic disorder. b) Presence or history of severe hepatic disease as long as liver function values have not returned to normal. c) Severe renal insufficiency or acute renal failure. d) Known or suspected sex-steroid sensitive malignancies. e) Undiagnosed vaginal bleeding. f) Hypersensitivity to the active substance or to any of the excipients. 8. Currently ongoing conditions or previous history of: a) Cerebral-vascular or coronary-artery disease which includes myocardial infarction, angina pectoris. b) Valvular heart disease with thrombogenic complications. c) Headaches with focal neurological symptoms. d) Known or suspected carcinoma of the breast. e) Arterial and cardiovascular disease, past or present (e.g. myocardial infarction, cerebrovascular accident, ischemic heart disease). f) Diabetes mellitus with vascular involvement. g) Adrenal insufficiency. h) History of cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use. i) Hyperkalaemia. j) Hysterectomy. 9. Major surgery with more than 7 days of immobilisation within the 2 weeks prior to screening. 10. Uncontrolled concomitant diseases (i.e. not on a stable treatment dose for at least 2 months before screening). 11. Evidence or history of alcohol, medication or drug abuse (within the last 12 months prior to screening). 12. Known or suspected human immunodeficiency virus (HIV) and/or hepatitis infection at screening. 13. Received a dose of depot medroxyprogesterone acetate (DMPA or Depo-Provera®) within the last 10 months prior to screening, or received any combined injectable contraceptive (e.g. Cyclofem®) within the last 6 months prior to screening, or no spontaneous menses since last injection. 14. Long-term treatment (> 7 consecutive days within a month prior to Visit 1b) of any medication that might interfere with the efficacy of hormonal contraceptives, e.g.: a) Anticonvulsants (e.g. phenytoin, carbamazepine, oxcarbazepine, topiramate, felbamate, primidone, lamotrigine) b) Potent inhibitors of CYP3A4 (fluconazole, ketoconazole, itraconazole or voriconazole). c) Barbiturates d) Antibiotics (such as rifampicin) e) HIV medication (such as ritonavir, nelfinavir, neviparine and efavirenz) f) Hepatitis C virus (HCV) medication (e.g. boceprevir, telaprevir) g) Macrolides (clarithromycin and erythromycin) h) Bosentan i) Griseofulvin j) Verapamil k) Diltiazem l) Cyclosporin m) St. John’s wort (hypericum perforatum) n) Opioids 15. Administration of human chorionic gonadotropin (hCG) or intake of co-medication containing hCG within the month prior to screening. 16. Progestin-releasing intrauterine device (IUD) or contraceptive implant received or in place within the last 2 months prior to screening. 17. Known inherited or acquired predisposition to venous thromboembolism (VTE) e.g. factor V Leiden, prothrombin mutation, antiphospholipid antibodies) or bruising within the last 12 months prior to screening. 18. Previous or current use of a drospirenone-containing progestogen-only-pill. 19. Evidence or history of clinically significant psychiatric illness or suicide risk according to the diagnosis from a psychiatrist. 20. Planned surgery during the anticipated time of participation in this trial requiring withdrawal of an oral contraceptive. 21. Participation in any other drug or medical device investigational trial or observational study within the past 30 days (or five half-lives of IP whichever is longer) prior to Visit 1a until last visit. 22. Subject is a member of the investigator’s or sponsor’s staff or a relative or family member thereof. 23. Any condition that, in the opinion of the investigator, may jeopardize protocol compliance or the scientific integrity of the trial. 24. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Changes from baseline in EAPP by the assessment of subject reported pain score on an NRS after 3 medication cycles.
Intercurrent events (ICEs) and strategies • Change in rescue medication during 3 medication cycles compared to baseline. • Treatment non-compliance (< 80% or > 120%). • Discontinuation of treatment (due to lack of efficacy, adverse events [AEs] or safety concerns).
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Number of days corresponding to subjects average menstruation cycle duration, prior to and including Day 28 of medication cycle 3 (or last intake of IP in case of early discontinuation). |
|
E.5.2 | Secondary end point(s) |
1. Changes after 1, 3 and 6 medication cycle(s) compared to baseline in dysmenorrhoea (assessed via NRS pain score). 2. Changes after 1, 3 and 6 medication cycle(s) compared to baseline in NMPP (assessed via NRS pain score). 3. Changes after 1, 3 and 6 medication cycle(s) compared to baseline in rescue medication intake. 4. Changes after 1 and 6 medication cycle(s) compared to baseline in EAPP (assessed via an NRS pain score). 5. Changes after 1, 3 and 6 medication cycle(s) compared to baseline in dyspareunia. 6. Number and percentage of subjects with amenorrhoea. 7. Vaginal bleeding pattern 8. The number and percentage of responders at 3 months (responder will be defined by a 50% EAPP reduction measured through an NRS). 9. Withdrawals due to lack of efficacy (pain relief). 10. Changes after 3 and 6 medication cycles compared to baseline in quality of life (30-item Endometriosis Health Profile Questionnaire [EHP-30]). 11. Patient’s Global Impression of Change (PGIC). 12. Adverse events. 13. Mean absolute and relative changes in laboratory values. 14. Vital signs. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1, 3 and 6 medication cycles, respectively |
|
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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
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 |
Lithuania |
Poland |
Czechia |
Germany |
Slovakia |
Ukraine |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |