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NCT05673889
6.4.2
Blinding of Site Personnel
6.4.2. Blinding of Site Personnel Investigators and other site staff will be unblinded to participants' assigned study intervention.
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NCT05673889
6.4.3
Blinding of the Sponsor
6.4.3. Blinding of the Sponsor Sponsor staff will be unblinded to participants' assigned study intervention.
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NCT05673889
6.5
Study Intervention Compliance
6.5. Study Intervention Compliance When participants are dosed at the site, they will receive study intervention directly from the investigator or designee, under medical supervision. The date and time of each dose administered in the clinic will be recorded in the source documents and recorded in the CRF. The dose of ...
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NCT05673889
6.6
Dose Modification
6.6. Dose Modification No dose modification is anticipated.
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NCT05673889
6.7
Continued Access to Study Intervention After the End of the Study
6.7. Continued Access to Study Intervention After the End of the Study No intervention will be provided to study participants at the end of their study participation.
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NCT05673889
6.8
Treatment of Overdose
6.8. Treatment of Overdose For this study, any dose of ARV-471 greater than 200 mg or dabigatran etexilate (as mesylate) greater than 75 mg within a 24-hour time period will be considered an overdose. An accidental overdose of dabigatran may lead to increased risk of bleeding. In the event of hemorrhagic complications,...
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NCT05673889
6.9
Prior and Concomitant Therapy
6.9. Prior and Concomitant Therapy Use of prescription or nonprescription medications, including vitamins, dietary and herbal supplements, grapefruit/grapefruit containing products, and Seville orange/Seville orange containing products are prohibited in this study. A washout of 7 days or 5 half-lives (whichever is long...
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NCT05673889
6.9.1
Rescue Medicine
6.9.1. Rescue Medicine There is no rescue therapy to reverse the AEs observed with ARV-471. For dabigatran, the specific reversal agent (idarucizumab) is available. Standard medical supportive care must be provided to manage the AEs.
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NCT05673889
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL
7. DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT DISCONTINUATION/WITHDRAWAL
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NCT05673889
7.1
Discontinuation of Study Intervention
7.1. Discontinuation of Study Intervention It may be necessary for a participant to permanently discontinue study intervention. Reasons for permanent discontinuation of study intervention include the following: - AE requiring discontinuation at the discretion of investigator - Positive COVID-19 test If study interventi...
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NCT05673889
7.1.1
Liver Injury
7.1.1. Liver Injury Reasons for permanent discontinuation of study intervention due to potential liver injury are described in [Appendix 6.](#page-93-0)
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NCT05673889
7.1.2
ECG Changes
7.1.2. ECG Changes A participant who meets either bulleted criterion based on the average of triplicate ECG readings will be withdrawn from the study intervention. - QTcF >500 ms. - Change from baseline: QTcF >60 ms and QTcF >450 ms. If a clinically significant finding is identified (including, but not limited to, chan...
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NCT05673889
7.1.3
Potential Cases of Acute Kidney Injury
7.1.3. Potential Cases of Acute Kidney Injury Abnormal values in SCr concurrent with presence or absence of increase in BUN that meet the criteria below, in the absence of other causes of kidney injury, are considered potential cases of acute kidney injury and should be considered important medical events. An increase ...
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NCT05673889
7.1.4
COVID-19
7.1.4. COVID-19 If a participant has COVID-19 during the study, this should be reported as an AE or SAE (as appropriate) and appropriate medical intervention provided.
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NCT05673889
7.2
Participant Discontinuation/Withdrawal From the Study
7.2. Participant Discontinuation/Withdrawal From the Study A participant may withdraw from the study at any time at their own request. Reasons for discontinuation from the study include the following: - Unacceptable toxicity; - Significant protocol violation; - Lost to follow-up; - Refused further study procedures; - S...
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NCT05673889
7.2.1
Withdrawal of Consent
7.2.1. Withdrawal of Consent Participants who request to discontinue receipt of study intervention will remain in the study and must continue to be followed for protocol-specified follow-up procedures. The only exception to this is when a participant specifically withdraws consent for any further contact with them or p...
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NCT05673889
7.3
Lost to Follow-up
7.3. Lost to Follow-up A participant will be considered lost to follow-up if the participant repeatedly fails to return for scheduled visits and is unable to be contacted by the study site. The following actions must be taken if a participant fails to return to the clinic for/attend a required study visit: - • The site...
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NCT05673889
8
STUDY ASSESSMENTS AND PROCEDURES
8. STUDY ASSESSMENTS AND PROCEDURES
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NCT05673889
8.1
Administrative and Screening Procedures
8.1. Administrative and Screening Procedures The investigator (or an appropriate delegate at the investigator site) must obtain a signed and dated ICD before performing any study-specific procedures. Study procedures and their timing are summarized in the [SoA.](#page-16-0) Protocol waivers or exemptions are not allowe...
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NCT05673889
8.1.1
Baseline Procedures
8.1.1. Baseline Procedures The following procedures will be completed: - Obtain written informed consent. - Review Inclusion and Exclusion criteria. - Confirm proper contraception is being used. - Demographics (race, age, gender and ethnicity). - Obtain medical history, including but not limited to history of prior dru...
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NCT05673889
8.2
Efficacy Assessments
8.2. Efficacy Assessments Not applicable.
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NCT05673889
8.3
Safety Assessments
8.3. Safety Assessments Planned time points for all safety assessments are provided in the [SoA.](#page-16-0) Unscheduled safety measurements may be obtained at any time during the study to assess any perceived safety issues.
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NCT05673889
8.3.1
Physical Examinations
8.3.1. Physical Examinations Physical examinations are to be performed at the nominal timepoints specified in the [SoA.](#page-16-0) Additional physical examinations will be permitted, as necessary, to ensure appropriate collection of safety data. A full physical examination without genitourinary evaluation will includ...
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NCT05673889
8.3.2
Vital Signs
8.3.2. Vital Signs
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NCT05673889
8.3.2.1
Blood Pressure and Pulse Rate
8.3.2.1. Blood Pressure and Pulse Rate Supine BP will be measured with the participant's arm supported at the level of the heart, and recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm (preferably the dominant arm) will be used throughout the study. Participants should be instructed not t...
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NCT05673889
8.3.3
Electrocardiograms
8.3.3. Electrocardiograms Standard 12-lead ECGs utilizing limb leads (with a 10-second rhythm strip) should be collected at times specified in the [SoA](#page-16-0) section of this protocol using an ECG machine that automatically calculates the HR and measures PR interval, QT interval, QTcF, and QRS complex. Alternativ...
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NCT05673889
8.3.4
Clinical Safety Laboratory Assessments
8.3.4. Clinical Safety Laboratory Assessments See [Appendix 2](#page-80-0) for the list of clinical safety laboratory tests to be performed and the [SoA](#page-16-0) for the timing and frequency. All protocol-required laboratory assessments, as defined in [Appendix 2,](#page-80-0) must be conducted in accordance with t...
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NCT05673889
8.3.5
COVID-19 Related Measures
8.3.5. COVID-19 Related Measures Participants will undergo COVID-19 related measures per local procedures.
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NCT05673889
8.4
Adverse Events, Serious Adverse Events, and Other Safety Reporting
8.4. Adverse Events, Serious Adverse Events, and Other Safety Reporting The definitions of an AE and an SAE can be found in [Appendix 3](#page-81-0). AEs may arise from symptoms or other complaints reported to the investigator by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's leg...
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NCT05673889
8.4.1
Time Period and Frequency for Collecting AE and SAE Information
8.4.1. Time Period and Frequency for Collecting AE and SAE Information The time period for actively eliciting and collecting AEs and SAEs ("active collection period") for each participant begins from the time the participant provides informed consent, which is obtained before undergoing any study-related procedure and/...
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NCT05673889
8.4.1.1
Reporting SAEs to Pfizer Safety
8.4.1.1. Reporting SAEs to Pfizer Safety All SAEs occurring in a participant during the active collection period as described in Section [8.4.1](#page-57-2) are reported to Pfizer Safety on the CT SAE Report Form immediately upon awareness and under no circumstance should this exceed 24 hours, as indicated in [Appendix...
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NCT05673889
8.4.1.2
Recording Nonserious AEs and SAEs on the CRF
8.4.1.2. Recording Nonserious AEs and SAEs on the CRF All nonserious AEs and SAEs occurring in a participant during the active collection period, which begins after obtaining informed consent as described in [Section 8.4.1,](#page-57-2) will be recorded on the AE section of the CRF. The investigator is to record on the...
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NCT05673889
8.4.2
Method of Detecting AEs and SAEs
8.4.2. Method of Detecting AEs and SAEs The method of recording, evaluating, and assessing causality of AEs and SAEs and the procedures for completing and transmitting SAE reports are provided in [Appendix 3.](#page-81-0) Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and nonleading...
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NCT05673889
8.4.3
Follow-Up of AEs and SAEs
8.4.3. Follow-Up of AEs and SAEs After the initial AE or SAE report, the investigator is required to proactively follow each participant at subsequent visits/contacts. For each event, the investigator must pursue and obtain adequate information until resolution, stabilization, the event is otherwise explained, or the p...
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NCT05673889
8.4.4
Regulatory Reporting Requirements for SAEs
8.4.4. Regulatory Reporting Requirements for SAEs Prompt notification by the investigator to the sponsor of an SAE is essential so that legal obligations and ethical responsibilities toward the safety of participants and the safety of a study intervention under clinical investigation are met. The sponsor has a legal re...
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NCT05673889
8.4.5
Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and Occupational Exposure
8.4.5. Environmental Exposure, Exposure During Pregnancy or Breastfeeding, and Occupational Exposure Environmental exposure, occurs when a person not enrolled in the study as a participant receives unplanned direct contact with or exposure to the study intervention. Such exposure may or may not lead to the occurrence o...
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NCT05673889
8.4.5.1
Exposure During Pregnancy
8.4.5.1. Exposure During Pregnancy An EDP occurs if: - A female participant is found to be pregnant while receiving or after discontinuing study intervention. - A male participant who is receiving or has discontinued study intervention inseminates a female partner. - A female nonparticipant is found to be pregnant whil...
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NCT05673889
8.4.5.2
Exposure During Breastfeeding
8.4.5.2. Exposure During Breastfeeding An EDB occurs if: - A female participant is found to be breastfeeding while receiving or after discontinuing study intervention. - A female nonparticipant is found to be breastfeeding while being exposed or having been exposed to study intervention (ie, environmental exposure). An...
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NCT05673889
8.4.5.3
Occupational Exposure
8.4.5.3. Occupational Exposure The investigator must report any instance of occupational exposure to Pfizer Safety within 24 hours of the investigator's awareness using the CT SAE Report Form regardless of whether there is an associated SAE. Since the information about the occupational exposure does not pertain to a pa...
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NCT05673889
8.4.6
Cardiovascular and Death Events
8.4.6. Cardiovascular and Death Events Not applicable.
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NCT05673889
8.4.7
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs or SAEs
8.4.7. Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as AEs or SAEs Not applicable.
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NCT05673889
8.4.8
Adverse Events of Special Interest
8.4.8. Adverse Events of Special Interest AESIs are examined as part of routine safety data review procedures throughout the clinical trial and as part of signal detection processes. Should an aggregate analysis indicate that these prespecified events occur more frequently than expected, eg, based on epidemiological da...
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NCT05673889
8.4.8.1
Lack of Efficacy
8.4.8.1. Lack of Efficacy This section is not applicable because efficacy is not expected in the study population.
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NCT05673889
8.4.9
Medical Device Deficiencies
8.4.9. Medical Device Deficiencies Not applicable.
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NCT05673889
8.4.10
Medication Errors
8.4.10. Medication Errors Medication errors may result from the administration or consumption of the study intervention by the wrong participant, or at the wrong time, or at the wrong dosage strength. Medication errors are recorded and reported as follows: | Recorded on theMedicationError Pageof the CRF | Recorded on t...
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NCT05673889
8.5
Pharmacokinetics
8.5. Pharmacokinetics Blood sample collection for measurements of plasma concentration of dabigatran (total) is detailed in Section 8.5.1. CCI evaluation of dabigatran etexilateCCI Plasma samples may be used for For PK collections, the actual times may change, but the number of samples will remain the same. All efforts...
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NCT05673889
8.5.1
Pharmacokinetics for total dabigatran
8.5.1. Pharmacokinetics for total dabigatran Blood samples of approximately 4 mL, to provide approximately 1.5 to 1.8 mL plasma, will be collected for measurement of plasma concentrations of total dabigatran (sum of unconjugated and conjugated dabigatran) as specified in the [SoA.](#page-16-0) Instructions for the coll...
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NCT05673889
8.6
Genetics
8.6. Genetics
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NCT05673889
8.6.1
Specified Genetics
8.6.1. Specified Genetics Specified genetic analyses are not evaluated in this study.
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NCT05673889
8.6.2
Retained Research Samples for Genetics
8.6.2. Retained Research Samples for Genetics A 4 mL blood sample optimized for DNA isolation Prep D1 will be collected according to the [SoA,](#page-16-0) as local regulations and IRBs/ECs allow. Retained Research Samples may be used for research related to the study intervention(s). Genes and other analytes (eg, prot...
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NCT05673889
8.7
Biomarkers
8.7. Biomarkers Biomarkers are not evaluated in this study.
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NCT05673889
8.7.1
Retained Research Samples for Biomarkers
8.7.1. Retained Research Samples for Biomarkers These Retained Research Samples will be collected in this study: • 10 mL whole blood (Prep B2 optimized for serum). Retained Research Samples will be collected as local regulations and IRB/ECs allow according to the [SoA.](#page-16-0) Retained Research Samples may be used...
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NCT05673889
8.8
Immunogenicity Assessments
8.8. Immunogenicity Assessments Immunogenicity assessments are not included in this study.
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NCT05673889
8.9
Health Economics
8.9. Health Economics Health economics/medical resource utilization and health economics parameters are not evaluated in this study.
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NCT05673889
9
STATISTICAL CONSIDERATIONS
9. STATISTICAL CONSIDERATIONS Detailed methodology for summary and statistical analyses of the data collected in this study is outlined here and further detailed in the SAP, which will be maintained by the sponsor. The SAP may modify what is outlined in the protocol where appropriate; however, any major modifications o...
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NCT05673889
9.1
Statistical Hypotheses
9.1. Statistical Hypotheses No statistical hypothesis will be tested in this study.
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NCT05673889
9.2
Analysis Sets
9.2. Analysis Sets For purposes of analysis, the following analysis sets are defined: | ParticipantAnalysis | Description | |----------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------...
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NCT05673889
9.3
Statistical Analyses
9.3. Statistical Analyses The SAP will be developed and finalized before any analyses are performed and will describe the analyses and procedures for accounting for missing, unused, and spurious data. This section is a summary of the planned statistical analyses of the primary and secondary endpoints.
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NCT05673889
9.3.1
Pharmacokinetic Analysis
9.3.1. Pharmacokinetic Analysis The plasma PK parameters for total dabigatran will be derived (as data permit and as appropriate) from the concentration time profiles as detailed in [Table 5](#page-67-2) for CCI and treatment. Actual PK sampling times will be used in derivation of PK parameters. In the case that actual...
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NCT05673889
9.3.2
Statistical Methods for PK Data
9.3.2. Statistical Methods for PK Data Natural log transformed parameters (AUCinf [if data permit], AUClast, and Cmax) of total dabigatran (sum of unconjugated or glucuronide-conjugated dabigatran) will be analyzed using a mixed effect model with treatment as a fixed effect and participant as a random effect. Estimates...
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NCT05673889
9.3.3
Safety Analyses
9.3.3. Safety Analyses All safety analyses will be performed on the safety population. . AEs, ECGs, BP, pulse rate, and safety laboratory data will be reviewed and summarized on an ongoing basis during the study to evaluate the safety of participants. Any clinical laboratory, ECG, BP, and pulse rate abnormalities of po...
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NCT05673889
9.3.3.1
Electrocardiogram Analyses
9.3.3.1. Electrocardiogram Analyses Changes from baseline for the ECG parameters HR, QTcF, PR interval, and QRS complex will be summarized by treatment and time. The frequency of uncorrected QT values above 500 ms will be tabulated. The number (%) of participants with maximum postdose QTcF values and maximum increases ...
[ "Safety QTcF Assessment" ]
NCT05673889
9.3.4
Other Analyses
9.3.4. Other Analyses Pharmacogenomic or biomarker data from Retained Research Samples may be collected during or after the trial and retained for future analyses; the results of such analyses are not planned to be included in the CSR.
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NCT05673889
9.4
Interim Analyses
9.4. Interim Analyses No interim analysis will be conducted for this study. As this is an open-label study, the sponsor may conduct unblinded reviews of the data during the course of the study for the purpose of safety assessment, facilitating PK/PD modeling, and/or supporting clinical development.
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NCT05673889
9.5
Sample Size Determination
9.5. Sample Size Determination A sample size of 24 participants will provide 90% confidence intervals for the difference between treatments of CCI and of CCI on the natural logarithmic scale for AUCinf and Cmax respectively with 80% coverage probability. The following table presents the width of 90% confidence interval...
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NCT05673889
10
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
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NCT05673889
10.1
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations
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NCT05673889
10.1.1
Regulatory and Ethical Considerations
10.1.1. Regulatory and Ethical Considerations This study will be conducted in accordance with the protocol and with the following: - Consensus ethical principles derived from international guidelines, including the Declaration of Helsinki and CIOMS International Ethical Guidelines; - Applicable ICH GCP guidelines; - Ap...
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NCT05673889
10.1.1.1
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
10.1.1.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable regulatory authority in any area of the world, or if the investigator is aware of any new information that might influence the evaluation of th...
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NCT05673889
10.1.2
Financial Disclosure
10.1.2. Financial Disclosure Not applicable.
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NCT05673889
10.1.3
Informed Consent Process
10.1.3. Informed Consent Process The investigator or the investigator's representative will explain the nature of the study, including the risks and benefits, to the participant and answer all questions regarding the study. The participant should be given sufficient time and opportunity to ask questions and to decide w...
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NCT05673889
10.1.4
Data Protection
10.1.4. Data Protection All parties will comply with all applicable laws, including laws regarding the implementation of organizational and technical measures to ensure protection of participant data. Participants' personal data will be stored at the study site in encrypted electronic and/or paper form and will be pass...
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NCT05673889
10.1.5
Committees Structure
10.1.5. Committees Structure
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NCT05673889
10.1.5.1
Data Monitoring Committee
10.1.5.1. Data Monitoring Committee This study will not use an E-DMC.
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NCT05673889
10.1.6
Dissemination of Clinical Study Data
10.1.6. Dissemination of Clinical Study Data Pfizer fulfills its commitment to publicly disclose clinical study results through posting the results of studies on [www.clinicaltrials.gov](http://www.clinicaltrials.gov/) (ClinicalTrials.gov), the EudraCT/CTIS, and/or [www.pfizer.com,](http://www.pfizer.com/) and other pu...
[ "[www.clinicaltrials.gov](http://www.clinicaltrials.gov/)", "EudraCT/CTIS", "[www.pfizer.com](http://www.pfizer.com/)", "Documents within marketing applications", "Data sharing" ]
NCT05673889
10.1.7
Data Quality Assurance
10.1.7. Data Quality Assurance All participant data relating to the study will be recorded on printed or electronic CRF unless transmitted to the sponsor or designee electronically (eg, laboratory data). The investigator is responsible for verifying that data entries are accurate and correct by physically or electronic...
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NCT05673889
10.1.8
Source Documents
10.1.8. Source Documents Source documents provide evidence for the existence of the participant and substantiate the integrity of the data collected. Source documents are filed at the investigator site. Data reported on the CRF or entered in the eCRF that are from source documents must be consistent with the source doc...
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NCT05673889
10.1.9
Study and Site Start and Closure
10.1.9. Study and Site Start and Closure The study start date is the date on which the clinical study will be open for recruitment of participants. The first act of recruitment is the date of the first participant's first visit and will be the study start date. The sponsor designee reserves the right to close the study...
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NCT05673889
10.1.10
Publication Policy
10.1.10. Publication Policy For multicenter trials, the primary publication will be a joint publication developed by the investigator and Pfizer reporting the primary endpoint(s) of the study covering all study sites. The investigator agrees to refer to the primary publication in any subsequent publications. Pfizer wil...
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NCT05673889
10.1.11
Sponsor's Medically Qualified Individual
10.1.11. Sponsor's Medically Qualified Individual ![](page79Picture3.jpeg) To facilitate access to their investigator and the sponsor's MQI for study related- medical questions or problems from nonstudy healthcare professionals, participants are provided with an ECC at the time of informed consent. The ECC contains, at...
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NCT05673889
10.1.12
Transfer of Obligations Statement
10.1.12. Transfer of Obligations Statement ![](page79Picture7.jpeg) For the purposes of this protocol, "sponsor" refers to Pfizer.
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NCT05673889
10.2
Appendix 2: Clinical Laboratory Tests
10.2. Appendix 2: Clinical Laboratory Tests The following safety laboratory tests will be performed at times defined in the [SoA](#page-16-0) section of this protocol. Additional laboratory results may be reported on these samples as a result of the method of analysis or the type of analyzer used by the clinical labora...
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NCT05673889
10.3
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting
10.3. Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-Up, and Reporting
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NCT05673889
10.3.1
Definition of AE
10.3.1. Definition of AE AE Definition - An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. - Note: An AE can therefore be any unfavorable and unintended sign (includ...
[ "AE Definition", "Events Meeting the AE Definition", "Events NOT Meeting the AE Definition" ]
NCT05673889
10.3.2
Definition of an SAE
10.3.2. Definition of an SAE An SAE is defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria listed below: a. Results in death b. Is life-threatening The term "life-threatening" in the definition of "serious" refers to an event in which the participant was at risk of death at...
[ "a. Results in death", "b. Is life-threatening", "c. Requires inpatient hospitalization or prolongation of existing hospitalization", "d. Results in persistent or significant disability/incapacity", "e. Is a congenital anomaly/birth defect", "f. Is a suspected transmission via a Pfizer product of an infec...
NCT05673889
10.3.3
Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active Collection Period
10.3.3. Recording/Reporting and Follow-Up of AEs and/or SAEs During the Active Collection Period AE and SAE Recording/Reporting The table below summarizes the requirements for recording AEs on the CRF and for reporting SAEs on the CT SAE Report Form to Pfizer Safety throughout the active collection period. These requi...
[ "AE and SAE Recording/Reporting", "Assessment of Intensity", "Assessment of Causality", "Follow-Up of AEs and SAEs" ]
NCT05673889
10.3.4
Reporting of SAEs
10.3.4. Reporting of SAEs SAE Reporting to Pfizer Safety via an Electronic DCT - The primary mechanism for reporting an SAE to Pfizer Safety will be the electronic DCT. - If the electronic system is unavailable, then the site will use the paper SAE DCT (see next section) to report the event within 24 hours. - The site...
[ "SAE Reporting to Pfizer Safety via an Electronic DCT", "SAE Reporting to Pfizer Safety via the CT SAE Report Form" ]
NCT05673889
10.4
Appendix 4: Contraceptive and Barrier Guidance
10.4. Appendix 4: Contraceptive and Barrier Guidance
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NCT05673889
10.4.1
Male Participant Reproductive Inclusion Criteria
10.4.1. Male Participant Reproductive Inclusion Criteria Male participants are eligible to participate if they agree to the following requirements during the intervention period and for at least 90 days after the last dose of study intervention, which corresponds to the time needed to eliminate reproductive safety risk...
[ "PLUS either:" ]
NCT05673889
10.4.2
Female Participant Reproductive Inclusion Criteria
10.4.2. Female Participant Reproductive Inclusion Criteria The criteria below are part of Inclusion Criterion 1 (Age and Sex; [Section 5.1\)](#page-38-2) and specify the reproductive requirements for including female participants. Refer to [Section 10.4.4](#page-89-0) for a complete list of contraceptive methods permit...
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NCT05673889
10.4.3
Woman of Childbearing Potential
10.4.3. Woman of Childbearing Potential A woman is considered fertile following menarche and until becoming postmenopausal unless permanently sterile (see below). If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be confirmed before the first dose of study intervention, ad...
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NCT05673889
10.4.4
Contraception Methods
10.4.4. Contraception Methods Contraceptive use by men or women should be consistent with local availability/regulations regarding the use of contraceptive methods for those participating in clinical trials. The following contraceptive methods are appropriate for this study: Highly Effective Methods That Have Low User...
[ "Highly Effective Methods That Have Low User Dependency", "Highly Effective Methods That Are User Dependent" ]
NCT05673889
10.5
Appendix 5: Genetics
10.5. Appendix 5: Genetics Use/Analysis of DNA - Genetic variation may impact a participant's response to study intervention, susceptibility to, and severity and progression of disease. Therefore, where local regulations and IRBs/ECs allow, a blood sample will be collected for DNA analysis. - The scope of the genetic ...
[ "Use/Analysis of DNA" ]
NCT05673889
10.6
Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments Potential Cases of Drug-Induced Liver Injury
10.6. Appendix 6: Liver Safety: Suggested Actions and Follow-Up Assessments Potential Cases of Drug-Induced Liver Injury Humans exposed to a drug who show no sign of liver injury (as determined by elevations in transaminases) are termed "tolerators," while those who show transient liver injury but adapt are termed "ada...
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NCT05673889
10.7
Appendix 7: Kidney Safety: Monitoring Guidelines
10.7. Appendix 7: Kidney Safety: Monitoring Guidelines
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NCT05673889
10.7.1
Laboratory Assessment of Change in Kidney Function and Detection of Kidney Injury
10.7.1. Laboratory Assessment of Change in Kidney Function and Detection of Kidney Injury Standard kidney safety monitoring requires assessment of baseline and postbaseline serum creatinine (Scr measurement to estimate glomerular filtration rate [Scr-based eGFR] or creatinine clearance [eCrCl]). Baseline and postbaseli...
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NCT05673889
10.7.2
Age-Specific Kidney Function Calculation Recommendations
10.7.2. Age-Specific Kidney Function Calculation Recommendations
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NCT05673889
10.7.2.1
Adults (18 Years and Above)—2021 CKD-EPI Equations
10.7.2.1. Adults (18 Years and Above)—2021 CKD-EPI Equations | 2021 CKDEPIScr Only | Scr(mg/dL) | Scys(mg/L) | Recommended eGFR Equation | |-----------------------------------------|----------------|----------------|---------------------------------------------------------------| | Female | if ≤0.7 | N/A | eGFR = 143 ×...
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NCT05673889
10.7.3
Adverse Event Grading for Kidney Safety Laboratory Abnormalities
10.7.3. Adverse Event Grading for Kidney Safety Laboratory Abnormalities AE grading for decline in kidney function (ie, eGFR or eCrCl) will be according to KDIGO criteria.
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NCT05673889
10.8
Appendix 8: ECG Findings of Potential Clinical Concern
10.8. Appendix 8: ECG Findings of Potential Clinical Concern ECG Findings That May Qualify as AEs - Marked sinus bradycardia (rate 280 ms. - New prolongation of QTcF to >480 ms (absolute) or by ≥60 ms from baseline. - New-onset atrial flutter or fibrillation, with controlled ventricular response rate: ie, rate 30 seco...
[ "ECG Findings That May Qualify as AEs", "ECG Findings That May Qualify as SAEs", "ECG Findings That Qualify as SAEs" ]