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protocol_id stringclasses 263 values	section_number stringlengths 1 12	title stringlengths 1 1.88k	content stringlengths 0 866k	merged_titles listlengths 0 491
NCT03400943	9.6.3.3	Cervical smear	9.6.3.3 Cervical smear This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) The cervical smear should be obtained with the gynecological examination at the safety closeout visit in subjects who did not have this performed with normal result after end of treatment. As a guidance, a cervical smear sh...	[]
NCT03400943	9.6.3.4	Physical and gynecological examinations	9.6.3.4 Physical and gynecological examinations Complete physical examinations will be done in all subjects. Gynecological examinations, including breast palpation, will be performed in subjects who did not have this performed with normal result after end of treatment. In case of any suspicious finding, further diagnos...	[]
NCT03400943	9.6.3.5	Vital signs, weight, and height	9.6.3.5 Vital signs, weight, and height Vital signs (blood pressure in triplicates and heart rate) should be documented at the safety closeout visit. Blood pressure should be measured in triplicates after 5 minutes of rest, while the subject is sitting. Measurements should be made at least 1 minute apart using the same...	[]
NCT03400943	9.6.3.6	Ultrasound (safety)	9.6.3.6 Ultrasound (safety) If possible, the same examiner should conduct all ultrasound examinations of a subject throughout the study and the same ultrasound machine (per site) should be used throughout the study. Preferably the safety evaluation should be performed by transvaginal ultrasound (TVU). However, if deeme...	[]
NCT03400943	9.6.3.7	Contraception and pregnancy test	9.6.3.7 Contraception and pregnancy test With the implementation of protocol amendment 5 (version 5.0) no further restrictions apply to the use of contraception. New placement of intrauterine devices should only happen once it is clear that no further biopsies are needed. At safety closeout visit a urine pregnancy test...	[]
NCT03400943	9.6.3.8	Adrenal monitoring	9.6.3.8 Adrenal monitoring A robust adrenal safety monitoring program is implemented in all ongoing vilaprisan studies with this protocol amendment. Version 6.0 Page: 60 of 113 A plan for subjects showing adrenal neoplasms or hormonal abnormalities has been developed with the input of external endocrinology experts, se...	[]
NCT03400943	9.6.3.8.1	Timing of adrenal monitoring	9.6.3.8.1 Timing of adrenal monitoring Subjects will undergo scheduled adrenal monitoring at the safety closeout visit. Signs and symptoms possibly related to hypercortisolism (such as Cushing's syndrome, and hirsutism/virilization) or hyperaldosteronism will be documented on a dedicated CRF page (see Section [9.6.3.8....	[]
NCT03400943	9.6.3.8.2	Adrenal MRI	9.6.3.8.2 Adrenal MRI Non-contrast-enhanced (native) MRI will be implemented as the standard adrenal imaging modality. Due to the associated radiation exposure, non-contrast-enhanced (native) CT scan is permitted as an alternative option only if an MRI is not feasible, e.g., due to a subject having a contraindication t...	[]
NCT03400943	9.6.3.8.3	Laboratory testing	9.6.3.8.3 Laboratory testing Adrenal monitoring: - Serum cortisol, to be measured between 6 am and 10 am - o ACTH will be assessed from the same sample if the cortisol measurement yields an abnormal value. - Late night salivary cortisol (to be obtained between 11 PM and midnight) Subjects will be instructed to use the ...	[]
NCT03400943	9.6.3.8.4	Adrenal signs and symptom inquiry	9.6.3.8.4 Adrenal signs and symptom inquiry Vital signs (blood pressure in triplicates and heart rate) will be documented at the safety closeout visit. Blood pressure should be measured in triplicates after 5 minutes of rest, while the subject is sitting. Measurements should be made at least 1 minute apart using the sa...	[]
NCT03400943	9.6.3.9	Liver symptom inquiry	9.6.3.9 Liver symptom inquiry Investigators, subjects and their family members should be alert for non-specific symptoms which may be associated with liver dysfunction including anorexia, nausea, fatigue, right upper abdominal discomfort, vomiting, malaise, jaundice, fever, and rash. Before the implementation of protoc...	[]
NCT03400943	9.6.3.10	Liver monitoring	9.6.3.10 Liver monitoring In the past, investigators, subjects and their family members were instructed to be alert for non-specific symptoms which may be associated with liver dysfunction. In addition, the liver inquiry had to be completed at regular intervals. Based on the long interval between implementation of prot...	[]
NCT03400943	9.6.3.11	Skin monitoring	9.6.3.11 Skin monitoring All subjects who have taken at least one dose of the study medication will undergo a thorough skin examination by a dermatology expert. The outcome of the dermatology expert's examinations will be reported in the CRF. Any dermatology expert´s diagnosis of a pre-cancerous or malignant skin lesio...	[]
NCT03400943	9.7	Other procedures and variables	9.7 Other procedures and variables	[]
NCT03400943	9.7.1	Iron supplementation	9.7.1 Iron supplementation This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) Subjects in whom causes for anemia unrelated to HMB are suspected should not have been enrolled. Moderate anemia is defined as hemoglobin 10.9 g/dL [\(4](#page-80-8)). Iron supplementation should be offered to subjects ...	[]
NCT03400943	9.7.2	Algorithm for monitoring of endometrial safety	9.7.2 Algorithm for monitoring of endometrial safety See Section [9.6.3.2.1](#page-53-2).	[]
NCT03400943	9.7.3	Heavy menstrual bleeding / suspicious bleeding pattern	9.7.3 Heavy menstrual bleeding / suspicious bleeding pattern See Section [9.6.3.2.7](#page-57-0).	[]
NCT03400943	9.7.4	Unscheduled endometrial biopsy	9.7.4 Unscheduled endometrial biopsy See Section [9.6.3.2.8](#page-58-2).	[]
NCT03400943	9.7.5	Monitoring of ovarian cysts	9.7.5 Monitoring of ovarian cysts If cyst like structures >30 mm without suspicious appearance (ie, functional ovarian cysts) are visualized in the ovaries, unscheduled ultrasound examinations should be performed every 4 weeks or more frequently, if required due to symptoms, to document the regression/ outcome. If the ...	[]
NCT03400943	9.8	Appropriateness of procedures / measurements	9.8 Appropriateness of procedures / measurements All efficacy and safety parameters, as well as the methods to measure them, are standard variables/methods in clinical studies and/or clinical/gynecological practice. They are widely used and generally recognized as reliable, accurate, and relevant.	[]
NCT03400943	10	Statistical methods and determination of sample size	10. Statistical methods and determination of sample size	[]
NCT03400943	10.1	General considerations	10.1 General considerations Statistical analyses will be conducted by or under the supervision of the sponsor's study statistician, except for the analysis of PK/PD data, which will be performed and reported under the supervision of the sponsor´s pharmacometrics group. Statistical analyses will be performed using Stati...	[]
NCT03400943	10.2	Analysis sets	10.2 Analysis sets The documentation of important deviations from the protocol and validity findings and the assignment of subjects to analysis sets will be performed according to the sponsor's applicable Standard Operating Procedures and/or Instruction Manuals. The definition for important deviations and validity find...	[]
NCT03400943	10.3	Variables and planned statistical analyses	10.3 Variables and planned statistical analyses	[]
NCT03400943	10.3.1	Variables	10.3.1 Variables This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) The primary efficacy variable and secondary efficacy variables will be calculated based on the alkaline hematin method (unless otherwise specified). Other efficacy variables related to menstrual blood loss will be calculated base...	[]
NCT03400943	10.3.1.1	Primary efficacy variable	10.3.1.1 Primary efficacy variable This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) The primary efficacy variable is amenorrhea (yes/no), defined as MBL <2 mL during the last 28 days of treatment. If an endometrial biopsy was conducted during this time period, bleeding on the day of biopsy and ...	[]
NCT03400943	10.3.1.2	Secondary efficacy variables	10.3.1.2 Secondary efficacy variables This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) The secondary efficacy variables are: - HMB response defined as blood loss 50% reduction compared to baseline - Time to onset of amenorrhea. Onset of amenorrhea is defined by the first day for which the menst...	[]
NCT03400943	10.3.1.3	Other efficacy variables	10.3.1.3 Other efficacy variables This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) Other efficacy variables are: - Treatment success rate defined as percentage of subjects who fulfill the criteria of HMB response (50% reduction in menstrual blood loss as compared to baseline) and who have not b...	[]
NCT03400943	10.3.1.4	Pharmacokinetics (PK)	10.3.1.4 Pharmacokinetics (PK) For details, see Section [9.5.2](#page-42-1) and [9.5.3](#page-42-0) and the separate M&S Analysis plan.	[]
NCT03400943	10.3.1.5	Secondary safety variables	10.3.1.5 Secondary safety variables - Endometrial histology (eg, benign endometrium, presence or absence of hyperplasia or malignancy) - Endometrial thickness	[]
NCT03400943	10.3.1.6	Other safety variables	10.3.1.6 Other safety variables This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) - Endometrial histology (diagnosis of PAEC, individual features of PAEC) - Ovarian cysts (number, size) - Laboratory parameters - AEs - Cervical smear Version 6.0 Page: 69 of 113 - Vital signs - Percentage of subje...	[]
NCT03400943	10.3.2	Statistical and analytical plans	10.3.2 Statistical and analytical plans	[]
NCT03400943	10.3.2.1	Demographic and other baseline characteristics	10.3.2.1 Demographic and other baseline characteristics Demographic variables and baseline characteristics will be summarized overall by means of descriptive statistics and/or frequency tables as appropriate. Medical history findings and AEs will be coded by Medical Dictionary for Regulatory Activities (MedDRA) codes a...	[]
NCT03400943	10.3.2.2	Efficacy analysis	10.3.2.2 Efficacy analysis This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) For the confirmatory efficacy analysis, a hierarchical testing approach will be applied, involving the primary efficacy variable amenorrhea (yes/no) and the first three secondary efficacy variables HMB response, time to...	[ "Amenorrhea (yes/no), defined as MBL <2 mL during the last 28 days of treatment", "HMB response defined as blood loss 50% reduction compared to baseline", "Time to onset of amenorrhea", "Time to onset of controlled bleeding" ]
NCT03400943	10.3.2.3	Pharmacokinetic analysis	10.3.2.3 Pharmacokinetic analysis For details, see Sections [9.5.1](#page-41-0) and [9.5.3](#page-42-0) and the separate M&S Analysis Plan. Results will be reported in a separate M&S Report, if applicable.	[]
NCT03400943	10.3.2.4	Safety analysis	10.3.2.4 Safety analysis Safety analyses will be performed on the SAF. AEs and other safety variables will be summarized descriptively by treatment group. The incidence of treatment-emergent AEs and drug-related AEs will be summarized using MedDRA preferred term and the primary system organ class.	[]
NCT03400943	10.3.2.5	Subgroup analysis	10.3.2.5 Subgroup analysis This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) Subgroup analyses are planned using descriptive statistics for the primary and secondary Version 6.0 Page: 71 of 113 efficacy variables separately for each country (China and the US), race and ethnicity. Further subgrou...	[]
NCT03400943	10.3.3	Missing data/drop outs	10.3.3 Missing data/drop outs This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) For the primary efficacy variable and secondary efficacy variables included in the testing strategy described in Section [10.3.2.2](#page-69-0) it is assumed that data measured with the AH method will be only availab...	[]
NCT03400943	10.4	Determination of sample size	10.4 Determination of sample size This section was changed in Amendment 2, see Section [15.1.1](#page-80-1) No longer applicable as with the implementation of protocol amendment 5 (version 5.0) no new subjects will be recruited and no study medication will be given to the subjects who have been enrolled in the study. T...	[]
NCT03400943	10.5	Planned interim analyses	10.5 Planned interim analyses With the implementation of protocol amendment 5 (version 5.0) a safety and efficacy analysis is planned after all subjects have completed their treatment period. Data of the follow-up period available at that time point will also be included in the analysis. Remaining data of the follow-up...	[]
NCT03400943	11	Data handling and quality assurance	11. Data handling and quality assurance	[]
NCT03400943	11.1	Data recording	11.1 Data recording The data collection tool for this study is a validated, internet-based, electronic data capture (EDC) software system called RAVE. Subject data necessary for analysis and reporting will be entered/transmitted into a validated database or data system (Clinical Information Environment). RAVE, which Ba...	[ "Source documentation", "Data recorded from screening failures (screening failure confirmed at Visit 1)" ]
NCT03400943	11.2	Monitoring	11.2 Monitoring In accordance with applicable regulations, GCP, and sponsor's/CRO's procedures, monitors contacted the site prior to the start of the study to review with the site staff the protocol, study requirements, and their responsibilities to satisfy regulatory, ethical, and sponsor's requirements. When reviewin...	[]
NCT03400943	11.3	Data processing	11.3 Data processing Data management is performed consistent with applicable sponsor's standards and data cleaning procedures. This is applicable for data recorded in the eCRF as well as for data from other sources (eg, IVRS/IWRS, laboratory, ePRO). For data coding (eg, AEs, medication), internationally recognized and ...	[]
NCT03400943	11.4	Missing data	11.4 Missing data Most important is to avoid missing data (eg, by monitoring in time for completeness; see Section [11.2](#page-74-0)) and by training the investigators, especially instructing them to motivate subjects to be compliant with the study protocol. Study site personnel has been trained to monitor the complet...	[]
NCT03400943	11.5	Audit and inspection	11.5 Audit and inspection To ensure compliance with GCP and regulatory requirements, a member of the sponsor's (or a designated CRO's) quality assurance unit may arrange to conduct an audit to assess the performance of the study at the study site and of the study documents originating there. The investigator/institutio...	[]
NCT03400943	11.6	Archiving	11.6 Archiving Essential documents shall be archived safely and securely in such a way that ensures that they are readily available upon authorities' request. Subject (hospital) files will be archived according to local regulations and in accordance with the maximum period of time permitted by the hospital, institution...	[]
NCT03400943	12	Premature termination of the study	12. Premature termination of the study The sponsor has the right to close this study (or, if applicable, individual segments thereof [eg, treatment arms; dose steps; centers]) at any time, which may be due but not limited to the following reasons: - If risk-benefit ratio becomes unacceptable owing to, for example, - Sa...	[]
NCT03400943	13	Ethical and legal aspects	13. Ethical and legal aspects	[]
NCT03400943	13.1	Investigators and other study personnel	13.1 Investigators and other study personnel Study Medical Expert is identified on the Title Page of this protocol (see Section [1\)](#page-2-0). From among the participating investigators, the Global Clinical Leader will select the coordinating investigator, who will be responsible for signing the clinical study repor...	[]
NCT03400943	13.2	Funding and financial disclosure	13.2 Funding and financial disclosure Funding This study will be funded by its sponsor. Financial disclosure Each investigator (including principal and/or any sub investigators) who is directly involved in the treatment or evaluation of research subjects has to provide a financial disclosure according to all applicab...	[ "Funding", "Financial disclosure" ]
NCT03400943	13.3	Ethical and legal conduct of the study	13.3 Ethical and legal conduct of the study The procedures set out in this protocol, pertaining to the conduct, evaluation, and documentation of this study, are designed to ensure that the sponsor and investigator abide by GCP guidelines and the guiding principles detailed in the Declaration of Helsinki. The study will...	[]
NCT03400943	13.4	Subject information and consent	13.4 Subject information and consent All relevant information on the study will be summarized in an integrated subject information sheet and informed consent provided by the sponsor or the study center. A sample subject information and informed consent is provided as a document separate to this protocol. Based on this ...	[]
NCT03400943	13.5	Publication policy and use of data	13.5 Publication policy and use of data All relevant aspects regarding publication will be part of the contract between the sponsor and the investigator/institution. The sponsor has made the information regarding the study protocol publicly available on the internet at www.clinicaltrials.gov. All data and results and a...	[]
NCT03400943	13.6	Compensation for health damage of subjects / insurance	13.6 Compensation for health damage of subjects / insurance The sponsor maintains clinical trial insurance coverage for this study in accordance with the laws and regulations of the country in which the study is performed.	[]
NCT03400943	13.7	Confidentiality	13.7 Confidentiality All records identifying the subject will be kept confidential and, to the extent permitted by the applicable laws and/or regulations, will not be made publicly available. Subject names will not be supplied to the sponsor. Only the SID number will be recorded in the eCRF, and if the subject name app...	[]
NCT03400943	14	Reference list	14. Reference list - 1. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev. 1995;16(4):460-84. - 2. Hallberg L, Nilsson L. Determination of Menstrual Blood Loss. Scand J Clin Lab Invest. 1964;16:244-8. - 3. Emons G, Beckmann MW, Schmidt D, Mallmann P, for the Uteru...	[]
NCT03400943	15	Protocol amendments	15. Protocol amendments	[]
NCT03400943	15.1	Amendment 2 – Dated 15 NOV 2017	15.1 Amendment 2 – Dated 15 NOV 2017 Amendment 2 is the first global amendment. The following is an overview of the changes made to the original protocol Version 1.0.	[]
NCT03400943	15.1.1	Overview of the changes to the study	15.1.1 Overview of the changes to the study The protocol was amended to maintain consistency across Vilaprisan Phase 3 studies and to modify the collection period of the sanitary products.	[]
NCT03400943	15.1.1.1	Change 1: Modification of the collection periods of sanitary products	15.1.1.1 Change 1: Modification of the collection periods of sanitary products The collection period for sanitary products was extended to cover the entire study. Rationale Currently, the alkaline hematin method is the only validated method to collect information on menstrual blood loss volume accepted by the FDA. In ...	[ "Rationale", "Affected sections:" ]
NCT03400943	15.1.1.2	Change 2: Changes in the statistical analysis	15.1.1.2 Change 2: Changes in the statistical analysis Statistical sections of the protocol were updated. Rationale: In order to consider feedback from Authorities and to support label claims on the endpoints HMB response, time to onset of amenorrhea and time to onset of controlled bleeding, time to onset of amenorrhe...	[ "Rationale:", "Affected sections:" ]
NCT03400943	15.1.1.3	Change 3: Modifications of the tabular schedule of evaluations	15.1.1.3 Change 3: Modifications of the tabular schedule of evaluations Footnotes were modified. Rationale: Footnotes were revised to reflect the actual requirements correctly. Affected sections: [Section 9.1 Tabular schedule of evaluations](#page-85-1)	[]
NCT03400943	15.1.1.4	Change 4: Minor clarifications for consistency	15.1.1.4 Change 4: Minor clarifications for consistency Clarifications were made throughout the document to ensure readability, logic and consistency of the protocol and across studies. Affected sections: - [Section 2 Synopsis](#page-82-0) - [Section 5 Study design](#page-83-0) - [Section 6.2 Exclusion criteria](#page...	[ "Affected sections:" ]
NCT03400943	15.1.2	Changes to the protocol text	15.1.2 Changes to the protocol text In this section, all changes are detailed by presenting the "old text" and the "new text", and the sequence of the sections follows the structure of the protocol. Deletions are crossed out and additions are underlined. Corrections of typos or omissions, as well as automatic update of...	[]
NCT03400943	15.1.2.1	Section 2 Synopsis	15.1.2.1 Section 2 Synopsis \| \| […] \| \|-------------------------------\|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------...	[]
NCT03400943	15.1.2.2	Section 5 Study design	15.1.2.2 Section 5 Study design Old text: […] Overview of the study design is shown in Figure 5–1. Figure 5–1 Design overview \| TreatmentGroup A1 \| Screeningabout 120 days \| RND \| Vilaprisan 2 mg12 week \| B \| Vilaprisan 2 mg12 week \| 12-weekfollow-up \| \|-----------------------\|-----------------------------\|-----\|-----...	[ "Old text:", "[…]", "[…]", "Dose and regimen:", "New text:", "[…]", "Dose and regimen:" ]
NCT03400943	15.1.2.3	Section 6.2 Exclusion criteria	15.1.2.3 Section 6.2 Exclusion criteria Old text: […] 8. Use of other treatments that might interfere with the conduct of the study or the interpretation of the results including […] Contraceptive devices with or without hormone release (implant, intra-uterine device), if not removed at Visit […] New text: […] 8. Use...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.4	Section 9.1 Tabular schedule of evaluations	15.1.2.4 Section 9.1 Tabular schedule of evaluations Old text: Version 6.0 Page: 86 of 113 Table 9—1: Schedule of procedures \| Study Phase \| \| Screening \| \| TP 1 \| a \| TP 2 \| b \| FUP \| \|-------------------------------------------------------------------------------------------------------------------------------------...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.5	Section 9.2.2 Optional pre-screening phone contact	15.1.2.5 Section 9.2.2 Optional pre-screening phone contact Old text: […] After the telephone discussion, the patient information and informed consent form may be sent to the subject for further information. Regardless of whether the patient information and informed consent form is sent to the subject, it must be thor...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.6	Section 9.2.3 Scheduled visits	15.1.2.6 Section 9.2.3 Scheduled visits Old text: For timing of the visits see Table 9—1. Site personnel will determine the start of each treatment period from the eDiary provider web portal. Subjects must be contacted (eg, via phone call) after the first dose is taken in each treatment period to schedule the subseque...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.7	Section 9.2.3.1 Visit 1 Screening	15.1.2.7 Section 9.2.3.1 Visit 1 Screening Old text: […] - Dispense AH kit - Dispense sanitary protection. Explain procedure for collection of sanitary protection items for measurement of menstrual blood loss. - Remind the subject to return all used sanitary protection items as soon as the bleeding episode has been co...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.8	Section 9.2.3.2 Visit 2 Screening	15.1.2.8 Section 9.2.3.2 Visit 2 Screening Old text: […] - Dispense AH kit - Dispense sanitary protection […] Remind the subject to return all used sanitary protection items as soon as a bleeding episode has been completed [...] New text: […] Dispense AH kit and sanitary protection. Explain procedure for collection o...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.9	Section 9.2.3.3 Visit 3 Randomization	15.1.2.9 Section 9.2.3.3 Visit 3 Randomization Old text: […] Dispense sanitary protection […] Complete ClinRO (RAVE): CGI\I (see Section 9.4.2) New text: […] Dispense AH kit and sanitary protection. Explain procedure for collection of sanitary protection items for measurement of menstrual blood loss Version 6.0 Page:...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.10	Section 9.2.3.4 Visits 4, 5, and 6	15.1.2.10 Section 9.2.3.4 Visits 4, 5, and 6 Old text: […] - Dispense AH kit - Dispense sanitary protection - Visit 4: Remind subjects randomized to Treatment Groups A1, B1, and B2 to start collecting sanitary items on day 50 of the TP1; collection to be continued until the end of this TP. - Remind the subject to retu...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.11	Section 9.2.3.5 EoT visit	15.1.2.11 Section 9.2.3.5 EoT visit Old text: […] - Collect used sanitary protection items, if they have not yet been provided to the site. If a subject is continuing her treatment after the visit, remind her to continue collecting the used sanitary items until the end of her treatment and remind the subject to return...	[ "Old text:", "[…]", "New text:" ]
NCT03400943	15.1.2.12	Section 9.4.3 Alkaline hematin method to assess HMB	15.1.2.12 Section 9.4.3 Alkaline hematin method to assess HMB Old text: During the duration of the study, subjects will be required to use selected types of sanitary products provided (pads and/or tampons). During specified periods of the study, subjects need to collect their used sanitary products and return them to ...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.13	Section 9.4.4 Ultrasound (efficacy) to assess uterine fibroids Old text:	15.1.2.13 Section 9.4.4 Ultrasound (efficacy) to assess uterine fibroids Old text: […] The minimum source documentation will include printouts from the ultrasound machine showing the 3 largest fibroids. The printouts have to be labeled unambiguously, containing at least the study number, SID number, time point, and lon...	[ "New text:" ]
NCT03400943	15.1.2.14	Section 9.6.1.1 Definitions	15.1.2.14 Section 9.6.1.1 Definitions Old text: In a clinical study, an AE is any untoward medical occurrence (ie, any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation ...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.15	Section 9.6.3.1 Laboratory evaluations	15.1.2.15 Section 9.6.3.1 Laboratory evaluations A footnote was added to Laboratory evaluations of hematocrit, hemoglobin, and ferritin stating that hemoglobin, hematocrit and ferritin are also efficacy variables.	[]
NCT03400943	15.1.2.16	Section 9.6.3.3 Cervical smear	15.1.2.16 Section 9.6.3.3 Cervical smear Old text: The cervical smear should be obtained with the gynecological examination at the visits shown in Table 9—1. It may be repeated once during the screening period if the results are abnormal (this repeat is not considered rescreening). If the cervical smear is repeated at...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.17	Section 9.7.1 Iron supplementation	15.1.2.17 Section 9.7.1 Iron supplementation Old text: If causes for anemia unrelated to HMB are suspected these subjects should not be enrolled. Moderate anemia is defined as hemoglobin 10.9 g/dL (12). Iron supplementation should be offered to subjects with hemoglobin 10.9 g/dL consistent with local standards of prac...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.18	Section 9.7.3 Heavy menstrual bleeding / suspicious bleeding pattern Old text:	15.1.2.18 Section 9.7.3 Heavy menstrual bleeding / suspicious bleeding pattern Old text: […] In case of suspicious bleeding pattern (eg, continuous spotting, unusually heavy bleeding) after the start of treatment, which does not resemble the subject's natural cycle or bleeding pattern, detected from the MP or UF-DBD, t...	[ "New text:" ]
NCT03400943	15.1.2.19	Section 10.3.1 Variables	15.1.2.19 Section 10.3.1 Variables Old text: The primary efficacy variable will be calculated based on the alkaline hematin method. Secondary and other variables related to menstrual blood loss will be calculated based on the two methods, the alkaline hematin method and the menstrual pictogram, depending on the planne...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.20	Section 10.3.1.1 Primary efficacy variable	15.1.2.20 Section 10.3.1.1 Primary efficacy variable Old text: […] Subjects who discontinue treatment due to lack of efficacy, AEs, or prior to completion of treatment Week 8 of the respective treatment period will be considered not having amenorrhea. Further, based on scientific advice by FDA, subjects who did not ad...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.21	Section 10.3.1.2 Secondary efficacy variables	15.1.2.21 Section 10.3.1.2 Secondary efficacy variables Old text: The secondary efficacy variables are: - Absence of bleeding (spotting allowed) during the last 28 days of the treatment; based on the UF-DBD - Time to onset of controlled bleeding. Onset of controlled bleeding is defined by the first day, for which the ...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.22	Section 10.3.1.3 Other efficacy variables	15.1.2.22 Section 10.3.1.3 Other efficacy variables Old text: Other efficacy variables are: - Amenorrhea (yes/no), defined as MBL < 2 mL during the last 28 days of treatment (for treatment time/method not considered as primary variable) - Volume of menstrual blood loss per 28 days - Volume of menstrual blood loss per ...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.23	Section 10.3.1.6 Other safety variables	15.1.2.23 Section 10.3.1.6 Other safety variables Old text: […] - Vital signs - Change from baseline in hemoglobin, hematocrit, and ferritin - Percentage of subjects with normal hemoglobin >12 g/dL and normal hematocrit >36% - Percentage of subjects with moderate to severe anemia (ie, hemoglobin 10.9 g/dL) New text: ...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.24	Section 10.3.2.2 Efficacy analysis, Section 10.3.2.3 Secondary efficacy analysis and Section 10.3.2.4 other efficacy	15.1.2.24 Section 10.3.2.2 Efficacy analysis, Section 10.3.2.3 Secondary efficacy analysis and Section 10.3.2.4 other efficacy Old text: 10.3.2.2 Primary efficacy analysis The primary efficacy will be assessed by testing the amenorrhea (yes/no) for superiority of vilaprisan 2 mg after 12 weeks of treatment in Treatme...	[ "Old text:", "10.3.2.2 Primary efficacy analysis", "10.3.2.3 Secondary efficacy analysis", "10.3.2.4 Other efficacy", "New text:", "10.3.2.2 Efficacy analysis", "Amenorrhea (yes/no), defined as MBL <2 mL during the last 28 days of treatment", "HMB response defined as blood loss 50% reduction compared ...
NCT03400943	15.1.2.25	Section 10.3.2.5 Subgroup analysis	15.1.2.25 Section 10.3.2.5 Subgroup analysis Old text: Subgroup analyses are planned using descriptive statistics for the primary and secondary efficacy variables separately for each country (China and the US), race and ethnicity. New text: Subgroup analyses are planned using descriptive statistics for the primary an...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.26	Section 10.3.3 Missing data/drop-outs	15.1.2.26 Section 10.3.3 Missing data/drop-outs Old text: For the primary efficacy variable it is planned to collect the AH data only on days when vaginal bleeding occurred. To differentiate missing AH data and days without vaginal bleeding the bleeding intensity collected in the UF-DBD will be used. Missing bleeding ...	[ "Old text:", "New text:" ]
NCT03400943	15.1.2.27	Section 10.4 Determination of sample size	15.1.2.27 Section 10.4 Determination of sample size Old text: Assumptions for sample size calculations are based on the ASTEROID 1 study (Study 15788) with treatment duration of 12 weeks and take into account scientific advice from Health Authorities. In ASTEROID 1, amenorrhea rates (defined as MBL <2 mL during last 2...	[ "Old text:", "New text:" ]
NCT03400943	15.2	Amendment 3	15.2 Amendment 3 Amendment 3 (04 JUL 2018) Overall Rationale for the Amendment: This amendment is based on recommendations provided for ulipristal acetate on 18 May 2018 from the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) and guidance from Health Authorities regarding hep...	[ "Overall Rationale for the Amendment:" ]
NCT03400943	15.3	Amendment 4	15.3 Amendment 4 Stand-alone global amendment 4 was not integrated into the integrated version of the protocol as it explained why Bayer decided to temporarily pause enrollment and randomization, and to temporarily withdraw study treatment in already randomized patients after completion of the ongoing treatment period....	[]
NCT03400943	15.4	Amendment 5	15.4 Amendment 5 The rationale for changes in this amendment 5 and all affected sections are provided in the below'Protocol Amendment Summary of Changes Table' \| Section # andName \| Description of Major Changes \| Brief Rationale \| \|----------------------------------------------------------------------------------------...	[]
NCT03400943	15.5	Amendment 6	15.5 Amendment 6 The rationale for the HA requested changes in this amendment and all affected sections are provided in the 'Protocol Amendment Summary of Changes Table' directly before the Table of Contents in this document. A separate file with tracked changes as against the last integrated protocol version is availa...	[]
NCT03400943	16	Appendices	16. Appendices	[]
NCT03400943	16.1	Strong CYP3A4 inhibitors	16.1 Strong CYP3A4 inhibitors Table 16—1: Strong CYP3A4 inhibitors \| Substance name \| Inhibitor strength \| \|------------------\|---------------------------------------\| \| Boceprevir \| Strong \| \| Clarithromycin \| Strong \| \| Cobicistat \| Strong \| \| Conivaptan \| Strong \| \| Delavirdine \| Strong \| \| Grapefruit juice \| Depend...	[]
NCT03400943	16.2	Strong CYP3A4 inducers	16.2 Strong CYP3A4 inducers Table 16—2: Strong CYP3A4 inducers \| Substance name \| Inducer strength \| \|-----------------------------\|------------------\| \| Phenobarbital \| Strong \| \| Avasimibe \| Strong \| \| Carbamazepine \| Strong \| \| Enzalutamide \| Strong \| \| St. John's Wort (Hypericum) \| Strong \| \| Lumacaftor \| Strong \| ...	[]
NCT03453619	A	PHASE 2 STUDY TO EVALUATE THE SAFETY AND BIOLOGIC ACTIVITY OF PEGCETACOPLAN IN PATIENTS WITH IGA NEPHROPATHY, LUPUS NEPHRITIS, PRIMARY MEMBRANOUS NEPHROPATHY, OR C3 GLOMERULOPATHY (C3 GLOMERULONEPHRITIS AND DENSE DEPOSIT DISEASE)	A PHASE 2 STUDY TO EVALUATE THE SAFETY AND BIOLOGIC ACTIVITY OF PEGCETACOPLAN IN PATIENTS WITH IGA NEPHROPATHY, LUPUS NEPHRITIS, PRIMARY MEMBRANOUS NEPHROPATHY, OR C3 GLOMERULOPATHY (C3 GLOMERULONEPHRITIS AND DENSE DEPOSIT DISEASE) Phase: 2 Protocol Amendment 7 Approval Date: 07 July 2022 Confidentiality Statement Thi...	[ "Confidentiality Statement", "INVESTIGATOR AGREEMENT", "LIST OF TABLES", "PROTOCOL AMENDMENT SUMMARY OF CHANGES", "Protocol Amendment 7 (Approval date 07 July 2022)", "Overall Rationale for the Amendment:", "2. ABBREVIATIONS", "3. SYNOPSIS", "Protocol Number:", "Protocol Title:", "Version Number...

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