protocol_id stringclasses 263
values | section_number stringlengths 1 12 | title stringlengths 1 1.88k | content stringlengths 0 866k | merged_titles listlengths 0 491 |
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NCT04691115 | 3.1.1 | Part A | 3.1.1. Part A Part A will comprise a single-ascending dose, sequential-group design incorporating a single-group, 2-period crossover arm incorporating a food-effect evaluation. Overall, 48 subjects will be studied in 6 groups (Groups A1 to A6), with each group consisting of 8 subjects. Potential subjects will be screen... | [
"Groups A1, A2, and A4 to A6",
"Group A3",
"Additional Groups (Groups A7 to A9)",
"Sentinel Dosing"
] |
NCT04691115 | 3.1.2 | Part B | 3.1.2. Part B Part B will comprise a multiple-ascending dose, sequential-group design. Overall, it is planned for 24 subjects to be studied in 3 groups (Groups B1 to B3), with each group Covance Study: 8417263 Protocol Reference: 1476-291-001 consisting of 8 subjects. Part B may start following review of the safety and... | [] |
NCT04691115 | 3.2 | Study Start and End of Study Definitions | 3.2. Study Start and End of Study Definitions The start of the study is defined as the date the first subject signs an Informed Consent Form (ICF). The point of enrolment occurs at the time of subject number allocation. The end of the study is defined as the date of the last subject's last assessment (scheduled or unsc... | [] |
NCT04691115 | 3.3 | Additional Groups | 3.3. Additional Groups Following review of the safety, tolerability, and PK data, additional dose groups (where systemic exposure is not expected to exceed that stated in the dose escalation stopping criteria [Section 3.7]) may be added to the study. There will be no further dose escalation in these additional groups i... | [] |
NCT04691115 | 3.4 | Discussion of Study Design, Including the Choice of Control Groups | 3.4. Discussion of Study Design, Including the Choice of Control Groups For both parts of the study, a sequential-group, ascending-dose design has been chosen for safety reasons as AM1476 is in the early stages of clinical development, with Part A of the study being the first time it will be administered to humans. Ora... | [] |
NCT04691115 | 34.1 | Dose Interval | 34.1. Dose Interval Following thorough review of all available non-clinical data (pharmacological and toxicological), dosing at each dose level in Part A will be such that 2 subjects (1 AM1476 and 1 placebo) will be dosed at least 24 hours before the remaining 6 subjects. After dosing the first 2 subjects on a separate... | [
"351, Starting Dose of 1 mg",
"3.6. Dose Escalation",
"4. SELECTION OF STUDY POPULATION",
"4.1. Inclusion Criteria",
"4.2. Exclusion Criteria",
"4.3. Rescreening of Subjects",
"4.4. Subject Number and Identification",
"4.5. Subject Withdrawal and Replacement",
"4.6. Study Termination",
"5. STUDY T... |
NCT04691115 | T2 | Analytical Methodology | T2 Analytical Methodology Plasma and urine concentrations of AM1476 will be determined using validated analytical procedures. Specifics of the analytical methods will be provided in separate documents.  Adverse event definitions, assignment of severity and causality, and procedures for reporting... | [
"7.2.3. Vital Signs",
"7.2.4. Electrocardiograms",
"7.2.4.1. 12-lead Electrocardiograms",
"7.2.4.2. Telemetry",
"8. SAMPLE SIZE AND DATA ANALYSIS",
"8.1. Determination of Sample Size",
"8.4. Safety Analysis",
"8.5. Interim Analysis",
"9. REFERENCES",
"10. APPENDICES",
"Appendix 1: Adverse Event ... |
NCT04705415 | 1 | Synopsis | 1. Synopsis Protocol Title: A Randomized, Double-Blind, Single and Multiple Ascending Dose Study to Assess the Safety and Pharmacokinetics of ANA001 in Healthy Adults Short Title: A single ascending dose (SAD) and multiple ascending dose (MAD) PK study of ANA001 in healthy adults
Rationale: ANA001 is a new formulation... | [
"Rationale:",
"Objectives and Endpoints",
"Overall Design:",
"SAD",
"MAD",
"Number of Participants:",
"Treatment Groups and Duration:",
"SAD",
"MAD",
"Investigational Product, Dose, and Mode of Administration",
"Statistical Methods",
"Sample Size Determination:",
"Safety Analysis:",
"Pharm... |
NCT04705415 | 2 | Schedule of Activities (SoA) | 2. Schedule of Activities (SoA) Table 1 Schedule of Activities for SAD | | Screening | In-Patient | | Discharge | Followup | |-----------------------------------|-----------|------------|---|-----------|--------------| | Study Day | -30 to -2 | -1 | 1 | 2 | 7±2 | | Study Procedures | | | | | | | COVID Pre-screen inform... | [] |
NCT04705415 | 3 | Introduction | 3. Introduction Niclosamide is a chlorinated salicylanilide with anthelmintic, antiviral and anti-inflammatory activity being developed as a potential treatment for COVID-19. Niclosamide was discovered in 1958, and was approved by the Food and Drug Administration (FDA) in 1982 under New Drug Application (NDA) 018669 (B... | [] |
NCT04705415 | 3.1 | Study Rationale | 3.1. Study Rationale ANA001 is a new formulation containing 250 mg niclosamide per capsule. Although other niclosamide formulations have been studied for tapeworm infections and other potential human uses, limited systemic PK/PD data exists in the literature. To ensure proper systemic levels of niclosamide are achieved... | [] |
NCT04705415 | 3.2 | Background | 3.2. Background Niclosamide has broad in vitro antiviral activity (Fan et al[., 2019,](#page-44-1) [Andersen](#page-43-1) et al., 201[9, Jurgeit](#page-44-2) et al[., 2012,](#page-44-2) [Mazzon](#page-45-0) et al., 2019, Xu et al[., 2020,](#page-47-0) Wu et al[., 2004,](#page-46-1) Wen et al[., 2007,](#page-46-2) [Gass... | [] |
NCT04705415 | 3.2.1 | Chemical Name/Structure | 3.2.1. Chemical Name/Structure USAN: Niclosamide IUPAC: 5-Chloro-N-(2-chloro-4- nitrophenyl)-2-hydroxybenzamid Molecular formula: C13H8Cl2N2O4 Molecular weight: 327.1 g/mol | [] |
NCT04705415 | 3.2.2 | Nonclinical Studies | 3.2.2. Nonclinical Studies
Nonclinical Pharmacology In an in vitro study, Vero E6 cells were infected with a SARS-CoV-2 reporter virus. This virus has a luciferase gene engineered into its genome and when cells are infected with such a reporter virus, they express luciferase that can be quantified to measure viral rep... | [
"Nonclinical Pharmacology",
"Nonclinical Toxicology"
] |
NCT04705415 | 3.2.3 | Safety | 3.2.3. Safety Between 1971 and 1978, niclosamide was administered to 6365 patients under a US IND. Doses were up to and including 2000 mg/day for 7 days. There were 2385 evaluable patients, of which 13.3% reported side effects, all of which were mild or moderate, with none requiring treatment discontinuation. These inc... | [] |
NCT04705415 | 3.3 | Benefit/Risk Assessment | 3.3. Benefit/Risk Assessment Niclosamide is approved for dosing up to 2000 mg PO daily for 7 days. There is limited safety and PK data in humans receiving more than 2000 mg as a single dose and/or more frequently than once daily. The current SAD/MAD study is designed to explore the safety and PK of dosing up to 3000 mg... | [] |
NCT04705415 | 4 | Objectives and Endpoints | 4. Objectives and Endpoints | Objectives | Endpoints | | | |--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04705415 | 5 | Study Design | 5. Study Design | [] |
NCT04705415 | 5.1 | Overall Design | 5.1. Overall Design This is a randomized, double-blind study to be conducted in two parts: single ascending dose (SAD) and multiple ascending dose (MAD). Potential participants for each part will undergo screening procedures within 30 days of enrolment.
SAD On Day -1, eligible participants will be randomly assigned to... | [
"SAD",
"MAD"
] |
NCT04705415 | 5.2 | Participant and Study Completion | 5.2. Participant and Study Completion A minimum of 30 participants will be enrolled in the SAD part and up to 36 participants in the MAD part. At least 3 participants of each sex will be included in each cohort. | [] |
NCT04705415 | 5.3 | End of Study Definition | 5.3. End of Study Definition A participant is considered to have completed the study if he/she has completed all phases of the study including the last scheduled procedure shown in the Schedule of Activities. The end of the study is defined as the date of the last visit of the last participant in the study. | [] |
NCT04705415 | 5.4 | Scientific Rationale for Study Design | 5.4. Scientific Rationale for Study Design Sequential timing of the ascending dose cohorts will allow early stopping if serious or unanticipated safety signals are observed at any dose level. | [] |
NCT04705415 | 5.5 | Justification for Dose | 5.5. Justification for Dose Niclosamide was approved by FDA to treat tapeworms in humans and has a well understood clinical safety profile with oral administration at 2000 mg daily for up to 7 days. Furthermore, a single dose of 2000 mg reaches maximal systemic serum concentrations in humans of 0.76 μM to 18.3 μM (249 ... | [] |
NCT04705415 | 6 | Study Population | 6. Study Population Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as protocol waivers or exemptions, is not permitted. | [] |
NCT04705415 | 6.1 | Inclusion Criteria | 6.1. Inclusion Criteria Participants are eligible to be included in the study only if all of the following criteria apply: - 1. Signed the COVID and study informed consent forms as described in [Appendix 3](#page-53-0) which includes compliance with the requirements and restrictions listed in the informed consent form ... | [] |
NCT04705415 | 6.2 | Exclusion Criteria | 6.2. Exclusion Criteria Participants are excluded from the study if any of the following criteria apply: - 1. Has a history of or current clinically significant medical illness including but not limited to: cardiac arrhythmias or other cardiac disease; hematologic disease; coagulation disorders (including any abnormal ... | [] |
NCT04705415 | 6.3 | Lifestyle Restrictions | 6.3. Lifestyle Restrictions | [] |
NCT04705415 | 6.3.1 | Meals and Dietary Restrictions | 6.3.1. Meals and Dietary Restrictions 1. Participants will refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice, pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices from 3 days before the start of study treatment until after the final dose. | [] |
NCT04705415 | 6.3.2 | Caffeine, Alcohol, and Tobacco | 6.3.2. Caffeine, Alcohol, and Tobacco - 1. Participants will abstain from ingesting caffeine- or xanthine-containing products (e.g., coffee, tea, cola drinks, and chocolate) for 24 hours before the start of dosing until after collection of the final pharmacokinetic (PK) blood sample. - 2. Participants will abstain from... | [] |
NCT04705415 | 6.3.3 | Activity | 6.3.3. Activity 1. Participants will abstain from strenuous exercise for 24 hours before each blood collection for clinical laboratory tests. Participants may participate in light recreational activities during studies (e.g., watching television, reading). | [] |
NCT04705415 | 6.4 | Screen Failures | 6.4. Screen Failures Screen failures are defined as participants who consent to participate in the clinical study but are not subsequently entered into the study. A minimal set of screen failure information is required to ensure transparent reporting of screen failure participants to meet the Consolidated Standards of ... | [] |
NCT04705415 | 7 | Treatments | 7. Treatments Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or medical device(s) intended to be administered to a study participant according to the study protocol. | [] |
NCT04705415 | 7.1 | Treatments Administered | 7.1. Treatments Administered | Study Treatment Name: | ANA001 | Placebo | | | | |--------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------|-... | [] |
NCT04705415 | 7.2 | Dose Modification | 7.2. Dose Modification The dose(s) and schedule (BID or TID) in the MAD part will be determined following review of the safety and PK data from the SAD part. Total daily doses will not exceed 2000 mg. | [] |
NCT04705415 | 7.3 | Method of Treatment Assignment | 7.3. Method of Treatment Assignment Within each cohort, participants will be randomly assigned to active drug or placebo as they qualify for the study using a computer-generated randomization. | [] |
NCT04705415 | 7.4 | Blinding | 7.4. Blinding Participants will be randomly assigned to receive study treatment. Investigators will remain blinded to each participant's assigned study treatment throughout the course of the study. In order to maintain this blind, an otherwise uninvolved 3rd party (e.g., site pharmacist) will be responsible for the dis... | [] |
NCT04705415 | 7.5 | Preparation/Handling/Storage/Accountability | 7.5. Preparation/Handling/Storage/Accountability The Investigator or designee must confirm appropriate temperature conditions have been maintained during transit for all study treatment received and any discrepancies are reported and resolved before use of the study treatment. Only participants enrolled in the study ma... | [] |
NCT04705415 | 7.6 | Treatment Compliance | 7.6. Treatment Compliance Participants will receive study treatment under the direct supervision of the Investigator or designee. A hand- and mouth check will be done to ensure that the participants swallowed the drugs. | [] |
NCT04705415 | 7.7 | Concomitant Therapy | 7.7. Concomitant Therapy Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, and/or herbal supplements) that the participant is receiving at the time of enrollment or receives during the study must be recorded along with: - Reason for use - Dates of administration including start ... | [] |
NCT04705415 | 7.7.1 | Rescue Medicine | 7.7.1. Rescue Medicine No rescue medication will be provided. | [] |
NCT04705415 | 7.8 | Treatment after the End of the Study | 7.8. Treatment after the End of the Study Participants will not receive study drug (ANA001 or matching placebo) after the end of the study. | [] |
NCT04705415 | 8 | Discontinuation/Withdrawal Criteria | 8. Discontinuation/Withdrawal Criteria | [] |
NCT04705415 | 8.1 | Discontinuation of Study Treatment | 8.1. Discontinuation of Study Treatment An unexpected AE related to study drug could lead to temporary or permanent discontinuation of a participant's study treatment, as determined by the Medical Monitor or Investigator. | [] |
NCT04705415 | 8.2 | Withdrawal from the Study | 8.2. Withdrawal from the Study A participant may withdraw from the study at any time at his/her own request, or may be withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, or administrative reasons. If the participant withdraws consent for disclosure of future information, the... | [] |
NCT04705415 | 8.3 | Lost to Follow Up | 8.3. Lost to Follow Up A participant will be considered lost to follow-up if he or she 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 a required study visit: - The site must attempt t... | [] |
NCT04705415 | 9 | Study Assessments and Procedures | 9. Study Assessments and Procedures - Study procedures and their timing are summarized in the SoA. Protocol waivers or exemptions are not allowed. - Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence or awareness to determine if the participant should continue or discontinue stud... | [] |
NCT04705415 | 9.1 | Safety Assessments | 9.1. Safety Assessments Safety assessments include incidence and frequency of AEs/SAEs, study drug discontinuation due to an AE (MAD portion only), use of concomitant medications, and changes from baseline in clinical laboratory tests, vital signs, electrocardiograms (ECG), and physical examinations. | [] |
NCT04705415 | 9.1.1 | Physical Examinations | 9.1.1. Physical Examinations A complete physical examination, conducted at screening, will include, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal, and Neurological systems. Height and weight will also be measured and recorded. A brief physical examination will include, at a minimu... | [] |
NCT04705415 | 9.1.2 | Vital Signs | 9.1.2. Vital Signs Vital signs should be taken in a quiet setting without distractions (e.g., television, cell phones) and before any blood collections. Oral temperature, pulse rate, respiratory rate, and blood pressure will be assessed. Blood pressure and pulse measurements will be assessed with a completely automated... | [] |
NCT04705415 | 9.1.3 | Electrocardiograms | 9.1.3. Electrocardiograms A single ECG will be obtained for screening and at 3 hours after dosing during the SAD portion of the study and at Screening and 3 hours after dosing on Day 7 during the MAD portion. An ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals will be... | [] |
NCT04705415 | 9.1.4 | Clinical Safety Laboratory Assessments | 9.1.4. Clinical Safety Laboratory Assessments See [Appendix 2](#page-52-0) for the list of clinical laboratory tests to be performed and the SoA (Section [2\)](#page-15-0) for the timing and frequency. The Investigator must review the laboratory report, document this review, and record any clinically relevant changes (... | [] |
NCT04705415 | 9.2 | Adverse Events | 9.2. Adverse Events The definitions of an AE or SAE can be found in [Appendix](#page-57-0) 4. AE will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative). The Investigator and any designees are responsible for detecting, documenting, a... | [] |
NCT04705415 | 9.2.1 | Time Period and Frequency for Collecting AE and SAE Information | 9.2.1. Time Period and Frequency for Collecting AE and SAE Information All AEs and SAEs will be collected from the signing of the ICF until the follow-up visit at the time points specified in the SoA (Section [2\)](#page-15-0). Medical occurrences that begin before the start of study treatment but after obtaining infor... | [] |
NCT04705415 | 9.2.2 | Method of Detecting AEs and SAEs | 9.2.2. Method of Detecting AEs and SAEs Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and non-leading verbal questioning of the participant is the preferred method to inquire about AE occurrences. | [] |
NCT04705415 | 9.2.3 | Follow-up of AEs and SAEs | 9.2.3. Follow-up of AEs and SAEs After the initial AE/SAE report, the Investigator is required to proactively follow each participant at subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is otherwise explained, or the participant is lost to follow-up (as defined in Section... | [] |
NCT04705415 | 9.2.4 | Regulatory Reporting Requirements for SAEs | 9.2.4. 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 towards the safety of participants and the safety of a study treatment under clinical investigation are met. The Sponsor has a legal resp... | [] |
NCT04705415 | 9.2.5 | Pregnancy | 9.2.5. Pregnancy Details of all pregnancies in female participants and, if indicated, female partners of male participants will be collected after the start of study treatment and until 30 days after the last dose. If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of learning of the... | [] |
NCT04705415 | 9.3 | Stopping Rules in Response to SAEs or Other Events | 9.3. Stopping Rules in Response to SAEs or Other Events Dose-limiting toxicity AEs will be defined as Grade ≥3, treatment-emergent, treatment-related laboratory abnormalities (Appendix 6) or AEs per the grading system by [US Department of](#page-46-6) [Health and Human Services](#page-46-6) (CTCAE, Version 5.0)The foll... | [
"Clinical Findings:",
"Laboratory Findings:"
] |
NCT04705415 | 9.4 | Treatment of Overdose | 9.4. Treatment of Overdose For this study, any dose of ANA001 greater than 3000 mg within a 24-hour time period will be considered an overdose. In the event of an overdose, the Investigator should: - 1. Contact the Medical Monitor immediately. - 2. Closely monitor the participant for any AE/SAE and laboratory abnormali... | [] |
NCT04705415 | 9.5 | Pharmacokinetics | 9.5. Pharmacokinetics Whole blood samples of approximately 4 mL will be collected for measurement of plasma concentrations of ANA001 as specified in the SoA (Section 2). Additional samples may be collected during the study if warranted and agreed upon between the Investigator and the Sponsor. Instructions for the colle... | [] |
NCT04705415 | 9.6 | Medical Resource Utilization and Health Economics | 9.6. Medical Resource Utilization and Health Economics Not applicable. | [] |
NCT04705415 | 10 | Statistical Considerations | 10. Statistical Considerations | [] |
NCT04705415 | 10.1 | Sample Size Determination | 10.1. Sample Size Determination Sample size was not based on statistical considerations. | [] |
NCT04705415 | 10.2 | Populations for Analyses | 10.2. Populations for Analyses For purposes of analysis, the following populations are defined: | Population | Description | |-----------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------... | [] |
NCT04705415 | 10.3 | Statistical Analyses | 10.3. Statistical Analyses The statistical analysis plan will be developed and finalized before database lock and will describe the participant populations to be included in the analyses, and procedures for accounting for missing, unused, and spurious data. This section is a summary of the planned statistical analyses ... | [] |
NCT04705415 | 10.3.1 | Safety Analyses | 10.3.1. Safety Analyses All safety analyses will be performed on the Safety Population. Safety parameters will include frequency of treatment-emergent AEs (TEAEs), SAEs, study drug discontinuation due to an AE (MAD portion only), concomitant medication use, and changes from baseline in clinical laboratory results, vita... | [] |
NCT04705415 | 10.3.2 | Pharmacokinetic Analyses | 10.3.2. Pharmacokinetic Analyses The non-compartmental PK analyses will be described in the Statistical Analysis Plan finalized before database lock. Plasma concentrations of ANA001 will be summarized by dose over each scheduled sampling time using descriptive statistics. Individual plasma concentration data versus act... | [] |
NCT04705415 | 10.3.3 | Interim Analyses | 10.3.3. Interim Analyses Data from the SAD Cohorts S1 through S3 will be summarized and evaluated to determine the doses and schedule to be used in a potential 4th SAD cohort and the BID and TID MAD cohorts. The Statistical Analysis Plan will describe the planned interim analyses in greater detail. | [] |
NCT04705415 | 11 | References | 11. References Abrams G. J. et al. The treatment of human tapeworm infections with 'Yomesan'. S Afr Med J. (1963). PMID: 14010769 Ai, N. et al. Niclosamide is a Negative Allosteric Modulator of Group I Metabotropic Glutamate Receptors: Implications for Neuropathic Pain. Pharm Res. (2016). doi: 10.1007/s11095- 0162027-9... | [] |
NCT04705415 | 12 | Appendices | 12. Appendices Protocol ANA001 Page 50 of 69
Appendix 1: Abbreviations and Terms ANA ANA Therapeutics, Incorporated API Active pharmaceutical ingredient ARDS Acute respiratory distress syndrome AUC Area under curve BID Twice daily BSL Bio-safety Level CL Clearance Cmax Maximum serum concentration CoV Coronavirus COVID... | [
"Appendix 1: Abbreviations and Terms",
"Appendix 2: Clinical Laboratory Tests",
"Appendix 3: Study Governance Considerations",
"Regulatory and Ethical Considerations",
"Financial Disclosure",
"Informed Consent Process",
"Data Protection",
"Dissemination of Clinical Study Data",
"Data Quality Assuran... |
NCT04705415 | A | SAE is defined as any untoward medical occurrence that, at any dose: | A SAE is defined as any untoward medical occurrence that, at any dose:
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 the time of the event. It does not refer to an event, which hypothetically mi... | [
"a. Results in death",
"b. Is life-threatening",
"c. Requires inpatient hospitalization or prolongation of existing hospitalization",
"d. Results in persistent disability/incapacity",
"e. Is a congenital anomaly/birth defect",
"f. Other situations:",
"Recording and AE and/or SAE",
"AE and SAE Recordin... |
NCT04712669 | 1 | PROTOCOL SUMMARY | 1. PROTOCOL SUMMARY | [] |
NCT04712669 | 1.1 | Synopsis | 1.1. Synopsis
Name of Sponsor/Company: Altavant Sciences GmbH
Name of Investigational Product: Rodatristat ethyl
Name of Active Ingredient: Rodatristat ethyl
Protocol Number/Study Name: RVT-1201-2002 / ELEVATE 2
Title of Study: A Phase 2b, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Stu... | [
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"Name of Investigational Product:",
"Name of Active Ingredient:",
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"Phase of development:",
"Rationale:",
"Objectives",
"Primary Objective:",
"Secondary Objectives:",
"... |
NCT04712669 | 4 | WHO FC II or III | 4. WHO FC II or III - 5. Confirmed diagnosis of PAH and meet all the following hemodynamic criteria by means of a screening RHC completed prior to randomization: - a. mPAP of > 20 mmHg - b. 395 350 dyne•sec/cm5 - c. Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure /9('3 RI 12 PP+JLI3... | [
"Exclusion Criteria",
"Medical Conditions",
"Prior/Concomitant Therapy",
"Diagnostic Assessments",
"Lifestyle",
"Duration of Treatment and Length of Study:",
"Investigational Product, Dosage, and Mode of Administration:",
"Non-Investigational Therapies:",
"Statistical methods:",
"Sample Size Justi... |
NCT04712669 | 4 | STUDY DESIGN | 4. STUDY DESIGN | [] |
NCT04712669 | 4.1 | Overall Design | 4.1. Overall Design This study will compare the efficacy, safety, and tolerability of 2 dosing regimens of rodatristat ethyl to placebo in patients with PAH over a 24-week treatment period. Investigational product (IP) will be administered on the background of stable PAH therapy. Approximately ninety (90) patients will... | [] |
NCT04712669 | 4.2 | Number of Patients | 4.2. Number of Patients Approximately ninety (90) patients with PAH are expected to be enrolled at approximately 68 study sites in the United States, Canada, and Rest of World (ROW). | [] |
NCT04712669 | 4.3 | Treatment Assignment | 4.3. Treatment Assignment Patients will be randomized to IP according to a computer-generated allocation schedule, prepared prior to the start of the study. At the Baseline Visit, eligible patients will be randomly allocated (1:1:1) to one of the following 3 treatment groups: | Treatment ArmName | Treatment Description... | [] |
NCT04712669 | 4.4 | Dose Adjustment Criteria | 4.4. Dose Adjustment Criteria | [] |
NCT04712669 | 4.4.1 | Dose Reduction | 4.4.1. Dose Reduction All determinations of rodatristat ethyl dose reduction should be discussed with the Medical Monitor prior to implementing unless time does not allow for safety. Temporary dosage reductions or discontinuations will be allowed to manage AEs/AESIs (or other instances to be discussed with the Medical ... | [] |
NCT04712669 | 4.4.1.1 | Diarrhea | 4.4.1.1. Diarrhea In the event the patient experiences diarrhea, the dose may be reduced. The Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grading will be used to grade the severity of all AEs and serious adverse events (SAEs) of diarrhea. Management recommendations for diarrhea are based on the C... | [] |
NCT04712669 | 4.4.1.2 | Aminotransferase (Alanine aminotransferase or Aspartate Aminotransferase) Elevation | 4.4.1.2. Aminotransferase (Alanine aminotransferase or Aspartate Aminotransferase) Elevation Management recommendations for ALT or AST elevations are based on U.S. Food and Drug Administration (FDA) Guidance for Liver Toxicity. In general, all baseline or treatment-emergent ALT or AST elevations > 3X ULN should be conf... | [] |
NCT04712669 | 4.5 | Criteria for Study Termination | 4.5. Criteria for Study Termination This study (including OLE) may be temporarily suspended or prematurely terminated if there is sufficient reasonable cause. Written notification, documenting the reason for study suspension or termination, will be provided by the suspending, or terminating party, to the Investigators,... | [] |
NCT04712669 | 4.6 | Scientific Rationale for Study Design | 4.6. Scientific Rationale for Study Design The design of this study will provide efficacy, safety, and dosing information to support proof of concept. Two rodatristat ethyl doses will be studied. Patients with idiopathic PAH and other Group 1 PAH sub-types will be included in this study. Placebo-controlled randomized s... | [] |
NCT04712669 | 4.7 | Justification for Dose | 4.7. Justification for Dose The dose levels selected are based on prior pharmacodynamic (PD) observations in nonclinical models of PAH and PK, PD, safety, and tolerability data in healthy subjects receiving rodatristat ethyl for up to 14 days. Disease-modifying effects of rodatristat ethyl were demonstrated in the sema... | [] |
NCT04712669 | 4.8 | End of Study Definition | 4.8. End of Study Definition A patient is considered to have completed the study if he/she has completed 24 weeks of treatment including the Week 24 visit and the Follow-up Visit (for patients that complete the study through Week 24 but decide not to rollover to the OLE), or the last scheduled procedure shown in the Sc... | [] |
NCT04712669 | 5 | STUDY POPULATION | 5. STUDY POPULATION | [] |
NCT04712669 | 5.1 | Inclusion Criteria | 5.1. Inclusion Criteria Patients are eligible to be included in the study only if all the following criteria are met: - 1. Male and female patients must be at least 18 years of age at the time of signing the informed consent. - a. Male patients and female partners of childbearing potential must agree to use contracepti... | [] |
NCT04712669 | 5.2 | Exclusion Criteria | 5.2. Exclusion Criteria Patients are excluded from the study if any of the following criteria are met: 1. Women of childbearing potential who are pregnant, planning to become pregnant, or lactating or female/male patients unwilling to use effective contraception as defined in Section 5.4.1
Medical Conditions - 2. WHO ... | [
"Medical Conditions",
"Prior/Concomitant Therapy",
"Diagnostic Assessments",
"Lifestyle"
] |
NCT04712669 | 5.3 | Other Eligibility Criteria Considerations | 5.3. Other Eligibility Criteria Considerations To determine patient eligibility at Screening, a single repeat of certain tests such as laboratory values, vital signs, or ECGs will be allowed. To assess any potential impact on patient eligibility with regard to safety, the Investigator must refer to the rodatristat ethy... | [] |
NCT04712669 | 5.4 | Lifestyle Considerations | 5.4. Lifestyle Considerations | [] |
NCT04712669 | 5.4.1 | Contraception | 5.4.1. Contraception Female patients of childbearing potential who have a negative serum pregnancy test at Screening and a negative urine pregnancy test at the randomization visit must agree to use protocol-specified, highly effective contraception starting at Screening and for the duration of the study and for at leas... | [] |
NCT04712669 | 5.4.2 | Meals and Dietary Restrictions | 5.4.2. Meals and Dietary Restrictions | [] |
NCT04712669 | 5.4.2.1 | Tryptophan-Rich Foods | 5.4.2.1. Tryptophan-Rich Foods As tryptophan-rich foods may increase 5-HT levels and interfere with biomarker assessments, patients will be asked to abstain from the following foods for 48 hours before study visits on Day 1 and at Weeks 4, 12, and 24: - x Avocado - x Bananas - x Eggplant - x Kiwi fruit - x Tree nuts, t... | [] |
NCT04712669 | 5.4.2.2 | Food Requirements | 5.4.2.2. Food Requirements IP should be taken with food (at least a snack) at the morning and evening meals. | [] |
NCT04712669 | 5.5 | Screen Failures | 5.5. Screen Failures Screen failures are defined as patients who consent to participate in the clinical study but are not subsequently randomized into the study. After obtaining informed consent, study site personnel will enter the patient into the Interactive Response Technology (IRT), and the patient will be assigned... | [] |
NCT04712669 | 6 | INVESTIGATIONAL PRODUCT | 6. INVESTIGATIONAL PRODUCT IP is defined as any investigational medicinal product (IMP) or placebo, intended to be administered to a study patient according to the study protocol. | [] |
NCT04712669 | 6.1 | Description of IP | 6.1. Description of IP The IPs to be administered as part of this study are described in Table 3. Table 3: Investigational Products | Arm Name | 300 mg BID | 600 mg BID | Placebo | | |-------------------------|----------------------------------------------------------------------------------------|---------------------... | [] |
NCT04712669 | 6.2 | Dose Regimen | 6.2. Dose Regimen IP will be taken BID with food, approximately 12 hours apart. Each patient will receive at least 4 bottles (1 kit) of IP at each clinic visit or by mail. There is enough IP in each kit for 4 weeks of dosing, including overage. The bottles of IP given at each clinic visit or by mail should be returned ... | [] |
NCT04712669 | 6.3 | Preparation/Handling/Storage/Accountability | 6.3. Preparation/Handling/Storage/Accountability The Investigator or designee must maintain accurate records of receipt and the condition of the IP supplied for this study including dates of receipt. They must confirm appropriate temperature conditions have been maintained during transit for all IP received and any dis... | [] |
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