A Study of Multiple-ascending Doses of IW-3300 in Healthy Subjects

Study Overview
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Brief Summary
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This clinical study is designed as a multiple-ascending-dose, safety and tolerability study with IW-3300. The study drug will be administered as a low-volume [20 mL] enema. Study participants will be randomized in a 2:1 ratio to receive IW-3300 or placebo. Up to 3 different doses of IW-3300 will be studied. Safety reviews will be conducted before proceeding to each higher dose.

Detailed Description
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This is a Phase 1, single-center, randomized, double-blind, placebo-controlled, multiple-ascending-dose study of IW-3300 administered rectally, once-daily, for 7 days as a low-volume enema in healthy adult participants. This study will assess the effect of IW-3300 on safety and tolerability. The study includes up to 4 treatments: placebo and up to 3 dose levels of IW-3300 which will be determined after safety reviews of previous cohorts. The 9 participants within each cohort will be randomized to receive IW-3300 (6 subjects) or placebo (3 participants), administered rectally (as a low-volume [20 mL] enema). Participants in each dosing cohort will progress through 3 study periods: (1) Screening Period, (2) Clinic Period, and (3) Follow-up Period. Treatment duration will be 7 days; participants will be followed in the Phase 1 clinical research unit (CRU) for the duration of dosing, until at least 24 hours after the last dose of study drug and contacted by phone for follow-up approximately 2 weeks after the last dose. Total participant participation will be 29 to 57 days, including the Screening, Clinic, and Follow-up Periods.

Official Title
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A Phase 1 Placebo-controlled Study of the Safety and Tolerability of Rectally Administered, Multiple-ascending Doses of IW-3300 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: IW-3300
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and female subjects of non-childbearing potential Ages 18 to 60 years Medically healthy with no clinically significant findings during medical evaluation including physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory tests. Body mass index (BMI) within the range 18.5 to 35.0 kg/m^2 (inclusive) at the Screening Visit. Male subjects and female partners are willing to use double-barrier method of contraception during the study. Exclusion Criteria: Evidence or history of clinically significant acute or chronic disease, or clinically significant illness within 30 days of the Screening Visit. History of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products. History of any condition that would interfere with their ability to receive an enema, or has had difficulty receiving an enema in the past. Recent history of anal fissure, anal abscess, complicated hemorrhoids, or presence or history of inflammatory bowel disease. Abnormal laboratory tests or clinically significant findings on safety tests conducted at the Screening Visit or at Check-in. Positive serology for human immunodeficiency virus (HIV) 1, HIV 2, or hepatitis B surface antigen (HBsAg), or positive for anti-HIV 1, anti-HIV 2, or anti hepatitis C virus (HCV) antibodies at the Screening Visit.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Dose 1<br>Dose 1: active drug (IW-3300) once daily for 7 days | Drug: IW-3300<br>* A dose of IW-3300 administered rectally (as a low-volume [20 mL] enema).<br>|
| Placebo Comparator: Cohort 1: Placebo<br>Dose 1: matching placebo once daily for 7 days | Drug: Placebo<br>* A dose of placebo administered rectally (as a low-volume [20 mL] enema).<br>|
| Experimental: Cohort 2: Dose 2<br>Dose 2: active drug (IW-3300) once daily for 7 days | Drug: IW-3300<br>* A dose of IW-3300 administered rectally (as a low-volume [20 mL] enema).<br>|
| Placebo Comparator: Cohort 2: Placebo<br>Dose 2: matching placebo once daily for 7 days | Drug: Placebo<br>* A dose of placebo administered rectally (as a low-volume [20 mL] enema).<br>|
| Experimental: Cohort 3 (optional): Dose 3<br>Dose 3: active drug (IW-3300) once daily for 7 days | Drug: IW-3300<br>* A dose of IW-3300 administered rectally (as a low-volume [20 mL] enema).<br>|
| Placebo Comparator: Cohort 3 (optional): Placebo<br>Dose 3: matching placebo once daily for 7 days | Drug: Placebo<br>* A dose of placebo administered rectally (as a low-volume [20 mL] enema).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) |  | From study drug administration through last dose (up to 7 days) plus 1 calendar day | 
| Incidence of Treatment-Emergent Serious Adverse Events (TESAEs) |  | From study drug administration through last dose (up to 7 days) plus 1 calendar day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers