A Study of Single Ascending Doses of IW-3300 in Healthy Volunteers

This is a Phase 1, single-center, randomized, double-blind, placebo-controlled, single-ascending-dose study assessing the safety, tolerability, and pharmacokinetics (PK) of IW 3300 administered rectally as a low-volume enema in healthy adult volunteers. This first-in-human study will assess participants for safety, tolerability, and PK.

The study includes up to 6 treatments: placebo and up to 5 dose levels of IW-3300 which will be determined after safety reviews of previous cohorts.

This study will enroll a maximum of 40 participants (up to 5 cohorts of 8 participants each). The 8 participants within each cohort will be randomized in a double-blind manner to receive a single dose of IW-3300 (6 participants) or placebo (2 participants), administered rectally as a low-volume [20 mL] enema. Each cohort will progress through a Screening Period, Clinic Period, and Follow-up Period. Treatment duration will be 1 day. Participants will remain in the Phase 1 unit for approximately 24 hours after dosing and will be contacted by phone for follow-up approximately 2 weeks after dosing. Total participation will be 22 to 45 days, including the Screening, Clinic, and Follow-up Periods.

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.
• Normal bowel movement frequency of formed stool at baseline (≥3 per week and ≤3 per day; average Bristol stool form scale (BSFS) score of >2 and <6).
• Body mass index (BMI) within the range 18.5 to 35.0 kg/m2 (inclusive) at the Screening Visit.
• Male subjects and female partners are willing to use double-barrier method of contraception during the study.
• If subject is ≥45 years of age, subject is compliant with colorectal cancer screening guidelines according to the American College of Gastroenterology (ACG) Clinical Guidelines: Colorectal Cancer Screening 2021.

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.
• Used a prescription medication during the 14 days before Check-in
• Used any over-the-counter medications, including laxatives, and herbal supplements during the 7 days before Check-in.
• Received a licensed or investigational vaccine during the 30 days before Check-in or is planning to receive any vaccine during the study.
• Recently received or donated blood products.
• Undergone a surgical procedure during the 30 days before Check-in, other than minor dermatologic procedures, or has a history of surgery involving the GI tract or anal canal (with the exception of endoscopic procedures, appendectomy, and cholecystectomy).
• Received any investigational drug during the 30 days or 5 half-lives of that investigational drug (whichever is longer) before the Screening Visit, or is planning to receive another investigational drug at any time during the study.
• Abnormal laboratory tests or clinically significant findings on safety tests conducted at the Screening Visit or at Check-in.
• Confirmed or suspected infection with COVID-19 at the Screening Visit or 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.
• History of alcohol or drug addiction during the year before the Screening Visit, or has a positive drug or alcohol screen at the Screening Visit or Check-in.