Clinical trial NCT05188261: A Study of Single Ascending Doses of IW-3300 in Healthy Volunteers
Official title: A Phase 1 Placebo-controlled Study of the Safety and Tolerability of Rectally Administered Single Ascending Doses of IW-3300 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: healthy volunteers
Lead sponsor: Ironwood Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-12
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human study to evaluate the safety and tolerability of single ascending doses of IW-3300. The study drug will be administered rectally as a low-volume (20 mL) enema. Study participants will be randomized in a 3:1 ratio to receive a single dose of IW-3300 or placebo. Up to 5 different doses of IW-3300 will be studied. Safety reviews will be conducted before proceeding to each higher dose.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Males and female subjects of non-childbearing potential
2. Ages 18 to 60 years
3. Medically healthy with no clinically significant findings during medical evaluation including physical examination, 12-lead electrocardiogram (ECG), and clinical laboratory tests.
4. 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).
5. Body mass index (BMI) within the range 18.5 to 35.0 kg/m2 (inclusive) at the Screening Visit.
6. Male subjects and female partners are willing to use double-barrier method of contraception during the study.
7. 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:

1. Evidence or history of clinically significant acute or chronic disease, or clinically significant illness within 30 days of the Screening Visit.
2. History of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products.
3. History of any condition that would interfere with their ability to receive an enema, or has had difficulty receiving an enema in the past.
4. Recent history of anal fissure, anal abscess, complicated hemorrhoids, or presence or history of inflammatory bowel disease.
5. Used a prescription medication during the 14 days before Check-in
6. Used any over-the-counter medications, including laxatives, and herbal supplements during the 7 days before Check-in.
7. Received a licensed or investigational vaccine during the 30 days before Check-in or is planning to receive any vaccine during the study.
8. Recently received or donated blood products.
9. 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).
10. 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.
11. Abnormal laboratory tests or clinically significant findings on safety tests conducted at the Screening Visit or at Check-in.
12. Confirmed or suspected infection with COVID-19 at the Screening Visit or Check-in.
13. 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.
14. 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug through 24 hours post-Day 1 dose
measure: Number of Participants With Serious TEAEs
timeFrame: From first dose of study drug through 24 hours post-Day 1 dose
Secondary outcomes:
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD
state: Texas
Study officials:
affiliation: Ironwood Pharmaceuticals
name: Ironwood Study Chair
role: STUDY_DIRECTOR
References: