E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
As the trial is intended to investigate a new contraceptive medicinal product, the study subjects included are not characterized by a specific medical condition.
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010808 |
E.1.2 | Term | Contraception |
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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 evaluate one-year data on the contraceptive efficacy and safety of the 150/15 NES/EE CVR as the basis for regulatory approvals of this CVR as a new delivery system for contraception. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the cycle control, bleeding patterns, side effects, and acceptability of a 21-day continuous use regimen of the CVR, followed by one week off per cycle. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
A multicenter, open-label study on the acceptability of a contraceptive vaginal ring delivering a daily dose of 150 mg of Nestorone and 15 mg of Ethinyl estradiol (150/15 NES/EE CVR): An addendum to Protocol 300 A/B: A multicenter, open-label study on the efficacy, cycle control and safety of a contraceptive vaginal ring delivering a daily dose of 150µg of Nestorone and 15 mg of Ethinyl estradiol (150/15 NES/EE CVR). Date and Version are the same as for the main study protocol. Primary Objective: To evaluate method acceptability among women who are enrolled in the phase 3 safety and efficacy trial for the 150/15 µg NES/EE CVR.
Secondary Objectives: a) To determine characteristics of women who are satisfied and successful users of the CVR; b) To determine characteristics and properties of the NES/EE CVR that appeal to women and their partners seeking contraception including affects on sexual activity: c) To describe women’s’ perspectives regarding use of vaginal rings to deliver other therapies important to women’s health, e.g. anti-infective agents. |
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E.3 | Principal inclusion criteria |
a. Healthy women, aged 18-<40 years who wish to use a combined hormonal contraceptive. b. Women not intending to become pregnant for 13 months. c. Intact uterus and both ovaries. d. Prior history of regular menstrual cycles of 28 ± 7 days when not using hormonal contraception; if postpartum or postabortal, history of regular menstrual cycles of 21-35 days in length and at least one cycle (2 menses) with a cycle length consistent with her past cycles. e. Sexually active (currently) and willing to discontinue current contraceptive method to participate in the study. f. In the opinion of the investigator, able to comply with the protocol, e.g. live within the clinic catchment area or within a reasonable distance from the clinic. g. Do not meet any of the exclusion criteria. h. Signed informed consent prior to entry into the trial. |
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E.4 | Principal exclusion criteria |
a. Known hypersensitivity to estrogens or progestins. b. Known hypersensitivity to silicone rubber. c. Known or suspected pregnancy. d. History of infertility of >1.0 year in woman or her male partner. e. History of vasectomy or sterility in male partner. f. Undiagnosed abnormal genital bleeding. g. Undiagnosed vaginal discharge or vaginal lesions or abnormalities. (Subjects diagnosed at screening with a chlamydia or gonococcus infection may be included in the trial following treatment; partner treatment is also recommended. Subjects at high risk for reinfection can be included or excluded per investigator’s discretion.) h. History of pelvic inflammatory disease since last pregnancy episode. i. History of toxic shock syndrome. j. Current abnormal Pap smear (women who have abnormal Pap smears but are ASCUS HPV negative may participate provided there is follow-up for this finding per standard of care). k. Cystoceles or rectoceles or other anatomical abnormality that would preclude use of a vaginal ring. l. Women planning to undergo major surgery. m. Smoking more than 15 cigarettes per day if < 35yrs; any amount of smoking if 35 years and over. n. Breastfeeding. o. Current or past thrombophlebitis or thromboembolic disorders. p. History of venous thrombosis or embolism in a first-degree relative, <55 years of age suggesting familial defect in blood coagulation system q. Cerebrovascular or cardiovascular disease. r. History of retinal vascular lesions, unexplained partial or complete loss of vision. s. Known or suspected carcinoma of the breast. t. Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia. u. Past history of any other carcinoma unless in remission for more than 5 years. v. Current or history of medically diagnosed severe depression, which, in the opinion of the investigator, could be exacerbated by use of a hormonal contraceptive. w. Headaches with focal neurological symptoms. x. Severe constipation. y. History of cholestatic jaundice of pregnancy or jaundice with prior steroid use. z. Benign or malignant liver tumors; active liver disease. aa. Diastolic blood pressure (BP) >= 85 mm Hg and/or systolic BP >=135 mm Hg after 5-10 min. rest. bb. Known or suspected alcoholism or drug abuse. cc. Abnormal serum chemistry values according to the physician’s judgment. dd. Participation in another clinical trial within last 30 days. ee. Weight >95 kg or >209 lbs. ff. Use of liver enzyme inducers on a regular basis. gg. Use of monthly injectable contraceptives (e.g. cyclofem) unless suspended 2 months before initiation of treatment. Use of Depo-Provera(R) [depo-medroxyprogesterone (DMPA)] unless suspended 6 months before treatment. hh. Current use of implanted hormonal contraceptives, including Mirena(R) [progestin containing intrauterine system (IUS)], Jadelle(R), Norplant(R) or Implanon(R). Subjects using these hormonal products who request removal for reasons unrelated to the purpose of enrollment in this study may be considered for participation. ii. Current use of a non-hormonal IUD. Subjects with IUDs who request removal for reasons unrelated to the purpose of enrollment in this study may be considered for participation. jj. Known HIV infection. kk. Women at high risk of contracting HIV, e.g. women with multiple sex partners who need to use condoms consistently, injection drug users. If women enrolled in the study do use condoms to protect against STIs, they should be instructed that this occasional use should be with non-N-9 containing condoms and they should record condom use in their diaries. Women found to have an STI at screening will be treated prior to inclusion in the study (with the exception of those infected with HIV). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint: the cumulative pregnancy rate will be the primary endpoint and will be assessed at one year (13 cycles of ring use). The Pearl indices and Kaplan-Meier life table analyses will be assessed for all subjects and all subjects ≤ 35 years. Pearl indices will be based on all cycles and on all cycles for which back-up contraception was not used.
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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 | Yes |
E.6.3 | Therapy | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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The end of the study will be when the last subject enrolled in Protocol 300A or 300B has completed her last visit or follow-up period. This definition is preferred to the definition that the end of the study is the last visit of the last subject undergoing the trial in an EU member state because that might mean to prepare a report on the subsection of the data collected from a subset of participating states, where a final report based on the data of the whole trial is more appropriate. |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |