Overall Study Design. The overall sequence of study events is shown in Figure 1. During Screening, patients will have their SOC vasopressors titrated to an age-, size-, and disease-appropriate MAP (Appendix A, Xxxxxxxxx 2013) at the discretion of the Investigator. A minimum titration period of 2 hours, and a maximum of 48 hours, is required. The Screening MAP is calculated as the average of at least two once-hourly MAP readings during SOC vasopressor titration, and within 24 hours prior to LJPC-501 treatment initiation. In the 15 minutes prior to initiation of LJPC-501 dosing, a baseline MAP will be documented. The Baseline MAP is the average of 3 recorded MAP values documented within 15 minutes prior to initiation of LJPC-501 (ie, at approximately -15 minutes, -5 minutes, and 0 minutes or just prior to initiation of LJPC-501 administration). After obtaining informed consent from the patients’ parent(s) or legal guardian(s), assent from the patients (per institutional requirements, as age appropriate, if possible), and confirmation of eligibility, patients will begin LJPC-501 treatment at a dose rate of 5 ng/kg/min. The goal at Hour 2 of LJPC-501 administration is to increase the Baseline MAP by 25% or to decrease the sum XXX by 25%. The LJPC-501 dose will be titrated during this period according to the guidelines in Section 8.3, to achieve a MAP above baseline, but less than 90 mmHg. Throughout treatment, the LJPC-501 dose rate may be increased to a maximum rate of 40 ng/kg/min, and decreased to a minimum of 1.25 ng/kg/min. If MAP exceeds 90 mmHg, SOC vasopressors should be down-titrated first, then LJPC-501 should be down-titrated if MAP remains ≥ 90 mmHg. Any decision to increase the dose rate above 40 ng/kg/min must be made in consultation with Sponsor. With Sponsor approval, the dose rate may be increased to a maximum of 80 ng/kg/min. Unless adjustment is required for safety reasons, SOC vasopressor dosing should be decreased, but not increased, during the first 2 hours of LJPC-501 treatment (ie, up to the Hour 2 time point). MAP should not be allowed to decrease below baseline. A schedule of study procedures is shown in Table 4. Patients will be monitored for hemodynamic xxxxx xxxxx (MAP, HR) at Screening and at approximately -15, -5 and 0 minutes (or just prior to initiation of LJPC-501 dosing) to establish the Baseline MAP value. MAP should be assessed once every 5 minutes during the first 15 minutes of LJPC-501 treatment, then once every 15 minutes up to the Hour 2 tim...
Overall Study Design. The overall study design is described in the master protocol. In this cohort, all patients will receive treatment with TSR-042, bevacizumab, and niraparib (collectively referred to as “study treatment”) beginning on Cycle 1/Day 1 using the regimen detailed in Figure 1. As described in Section 5.1.6, combination treatment with TSR-042, bevacizumab, and niraparib is currently being assessed in ongoing Study 0000-00-000 (NCT03307785). If results from that study are not available at the initiation of treatment for this cohort, an interim safety analysis will be performed after a total of 12 patients are enrolled between Cohorts A and B and have completed 2 cycles of therapy. If results from Study 0000-00-000 are available and support the feasibility of the outlined starting dose regimens, the safety interim analysis will not be performed.
Overall Study Design. There are also periods between the treatments that are called washout. The washout is designed to allow your body to remove all of the drug before getting the next dose. The washout periods are about 6 days long. When you return to the clinic (Visit 1), the study drug will be administered to you and you will stay for about 8 hours after completion of dosing. During this visit, the following procedures will occur in this order:
Overall Study Design. This double-blind, randomized, placebo-controlled trial will study the safety, tolerability, and efficacy of bardoxolone methyl in qualified patients with WHO Group I CTD-PAH. Qualified patients will be randomized 1:1 to either bardoxolone methyl or placebo to be administered once daily for 24 weeks. Patients randomized to placebo will remain on placebo throughout the study and undergo sham titration. Patients randomized to bardoxolone methyl will start at 5 mg and will dose-escalate to 10 mg at Week 4, unless contraindicated clinically. Dose de-escalation is permitted during the study if indicated clinically. Please refer to Section 7.3.1 for additional details on dose escalation and dose de-escalation. All patients in the study will follow the same visit and assessment schedule. Following randomization, patients will be scheduled to be assessed in person during treatment at Weeks 1, 2, 4, 6, 8, 16, and 24 and by telephone contact on Days 3, 10, 21, 31, 38, 84, and 140. Patients will also be scheduled to be assessed at an in-person follow up visit at Week 28, four weeks after the end of treatment. Patients who complete the study and are treatment-compliant to their assigned dose will be eligible for a separate open-label extension study.
Overall Study Design. This is a Phase 2a, randomized, double‑blind, placebo-controlled, multicenter, 12-week study to evaluate the efficacy and safety of RIST4721 QD in subjects with moderate-to-severe HS. Approximately 33 subjects are planned to be enrolled (approximately 22 subjects expected in the RIST4721 group and 11 subjects in the placebo group). The study will consist of a screening period, a treatment period, and a follow-up period. Study schema is shown in Section 1.2. Subjects will be evaluated throughout the study as specified in the Schedule of Activities (SoA; Section 1.3). After signing an informed consent form (ICF), subjects will be screened for study eligibility over 4 weeks. On Day 1 (baseline visit), eligible subjects will be randomized in 2:1 ratio to receive oral study treatment for 12 weeks: • RIST4721 400 mg QD • Placebo QD All subjects who remain on study treatment through and including Week 12 will be asked to return for a follow-up visit, approximately 4 weeks after their last dose of study treatment, to assess safety and efficacy. Subjects who permanently discontinue study treatment will be followed as described in Section 7.1.
Overall Study Design. This is a Phase 3, 12-week, randomized, multicenter, double-blind, placebo-controlled, fixed dose study that will investigate the efficacy and safety of TNX-102 SL 5.6 mg (2 x 2.8 mg tablets) taken daily at bedtime for the management of military-related PTSD. This study is to be conducted at approximately 45 investigational sites in the United States. The total duration of this study over 6 visits will be approximately 13-17 weeks, with 12 weeks of treatment duration and a variable length of screening. This study will consist of a Screening visit (Visit 1, Days −35 to −8), Randomization visit (Visit 2, Day 0), telephone visit (Visit 3, Week 2) and three monthly in-clinic visits (Visits 4, 5 and 6 at Weeks 4, 8, and 12). Eligible patients who provide written informed consent to participate will have study assessments performed at Screening, including counseling regarding any required washout and instructions to refrain from use of excluded medications throughout the study. The length of the pre-randomization screening period is variable (7 to 35 days) in order to accomplish wash-out of previous medications, where appropriate, and allow for return of clinical laboratory results necessary to confirm eligibility. At Visit 2, patients will return to the site for additional baseline assessments and randomization (Day 0), when, if they meet all study randomization criteria, they will be randomly assigned in a 1:1 ratio to receive placebo or TNX- 102 SL 5.6 mg. Patients will take the study drug sublingually daily at bedtime, starting on the day that they are randomized and continuing for 12 weeks (or to early termination). A dynamic randomization procedure will be employed at Visit 2 to minimize trial-wide imbalances between the treatment groups for site, sex, current tobacco/nicotine use (yes/no) and presence (yes/no) of current Major Depressive Episode (MDE) based on the Mini International Neuropsychiatric Interview, Version 7.0.2 (M.I.N.I. 7.0.2) conducted at Visit 1. Patients who test positive for cocaine, ecstasy (MDMA), methamphetamine or other non- disclosed illicit drugs (other than marijuana) should be screen-failed. In addition, patients who meet M.I.N.I. criteria outlined in the entry criteria for alcohol/substance use disorder over the 6 months prior to Screening should be screen-failed. Patients suffering from depression are eligible for the study, provided their depression does not pose an undue risk to their well-being (e.g., suicidal risk) or warra...
Overall Study Design. This is a Phase 3, multi-center, prospective, randomized, placebo-controlled, delayed treatment, double-blind, study to evaluate the effectiveness, and safety of a single, oral dose of Solosec containing 2 grams of secnidazole in female patients with trichomoniasis. Approximately 144 patients who test positive for trichomonas on OSOM® rapid test or via wet mount assessment or have positive T. vaginalis NAAT test within 30 days of screening (and have not been treated) and fulfill other eligibility criteria at the baseline visit will be enrolled in this study. The diagnosis of T. vaginalis will be confirmed by a positive culture for T. vaginalis. The study will consist of a primary study phase (Visit 1 (baseline) to Visit 2 (Day 6-12)) and a follow-up phase (Visit 2 to Visit 3 (7-12 days post Visit 2)). During the primary phase patients will be randomly assigned in a 1:1 ratio to either Solosec or placebo. The randomization will be stratified by site and based on the clinical symptoms of trichomoniasis (present or absent). Patients will return to the clinic for the “test of cure” (TOC) visit to be conducted on Days 6-12 (Visit 2). After all Visit 2 (V2) study procedures have been completed, patients will receive the opposite treatment (placebo patients will receive Solosec and vice versa). Patients with V2 cultures that are subsequently positive for T. vaginalis will return to the clinic for Visit 3 (V3) assessments and investigator assessment of need for additional therapy (an additional Visit 4 may be scheduled at the investigator’s discretion if culture at V3 is positive). Patients with cultures that are negative at V2 will be contacted by phone and discharged from the study (no V3 required). A Schedule of Assessments is provided in Table 1.
Overall Study Design. This is a prospective cohort study comparing an ultra-low dose of 0.1 mL Magtrace® with the dual technique with Tc99 +/- blue dye for SLN detection with a non-inferiority design. There is no randomisation but instead every person is their own control, i.e., the patient will have the SLN identified with both tracer methods. This study design has already been used in several international studies and 220 persons will be included at four study sites, during 18 months. Skin staining will be documented at the first follow up at four weeks with measurements of size of staining performed and documented with a photograph if staining is present for either SPIO or blue dye. Skin staining will be followed for three years after surgery. Those with a remaining skin staining at the routine 12 months follow up will be followed by telephone interview or physical visit at 24 and 36 months. Furthermore, up to 50 persons will be included for secondary objective A, for evaluation of MRI artefacts in the operated breast at 3-6, 12, and 24 months. All MRI and corresponding mammograms will be evaluated centrally regarding artefacts and breast density.
Overall Study Design. This is a randomized, double-blind, placebo-controlled, parallel group study of the efficacy and safety of SAGE-217 in adults diagnosed with severe PPD. Participants, site staff, and sponsor personnel will be masked to treatment allocation. This study will consist of a Screening Period of up to 28 days, a 14-day double-blind Treatment Period and a Follow-up Period through Day 45. The Screening Period begins with the signing of the informed consent form (ICF); the ICF must be signed prior to beginning any screening activities. The diagnosis of depression will be determined using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) Axis I Disorders (SCID-5-CT). Participants will undergo preliminary screening procedures to determine eligibility. A full personal medical history will be taken including documentation of all major depression episodes, other Axis I disorders, and any prior PPD episodes. In addition, PPD episodes experienced by immediate female family members, including siblings, parents, and grandparents will be documented. During the study, a qualified lactation consultant will be made available upon request to participants who are breastfeeding. Psychotropic medications are permitted provided participants are on a stable dose for at least 30 days prior to Day 1 and agree to continue on a stable dose through completion of the Day 45 assessments. Initiation of new psychotropic medications that may potentially have an impact on efficacy and/or safety endpoints will not be allowed within 30 days prior to Day 1 through completion of the Day 45 assessments. On Day 1, eligible participants will be stratified based on use of antidepressant treatment (current/stable or not treated/withdrawn ≥30 days or >5 half-lives) and randomized within each stratum to one of 2 treatment groups (SAGE-217 50 mg or matching placebo) in a 1:1 ratio. Participants will self-administer investigational product (IP) once daily at approximately 8 PM with fat-containing food (eg, within 1 hour of an evening meal which contains fat, or with a fat-containing snack), on an outpatient basis, for 14 days. See Section 10.5 for examples of fat-containing snacks. As local regulations permit, IP administration will be monitored via a medication adherence monitoring platform used on smartphones to visually confirm IP ingestion. Participants will return to the study center during the treatment and follow-up periods as outlined in Table 2. Du...
Overall Study Design. This is a randomized, single-blind, placebo-controlled, QD dose study of CRV431 in presumed XXXX F2/F3 subjects. This study will consist of 3 phases: (i) Screening and Randomization; (ii) treatment; and (iii) follow up.
