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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: IW-3300; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: 100 μg IW-3300; 100 μg dose of active drug (IW-3300) once daily for 7 days	Drug: IW-3300; A dose of IW-3300 administered rectally (as a low-volume [20 mL] enema).
Placebo Comparator: Cohort 1: Placebo; matching placebo once daily for 7 days	Drug: Placebo; A dose of placebo administered rectally (as a low-volume [20 mL] enema).
Experimental: Cohort 2: 300 μg IW-3300; 300 μg dose of active drug (IW-3300) once daily for 7 days	Drug: IW-3300; A dose of IW-3300 administered rectally (as a low-volume [20 mL] enema).
Placebo Comparator: Cohort 2: Placebo; matching placebo once daily for 7 days	Drug: Placebo; A dose of placebo administered rectally (as a low-volume [20 mL] enema).
Experimental: Cohort 3 (optional): Dose 3; Active drug (IW-3300) once daily for 7 days	Drug: IW-3300; A dose of IW-3300 administered rectally (as a low-volume [20 mL] enema).
Placebo Comparator: Cohort 3 (optional): Placebo; Matching placebo once daily for 7 days	Drug: Placebo; A dose of placebo administered rectally (as a low-volume [20 mL] enema).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a treatment-emergent AE (TEAE) if the AE started after initial study drug administration and within 1 day of the last dose of study drug.	From first dose of study drug through 24 hours post-Day 1 dose
Number of Participants With Serious TEAEs	A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is lifethreatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; or other situations such as important medical events that may not be immediately life threatening or result in death or hospitalization but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. An SAE was considered a treatment-emergent SAE (serious TEAE) if the SAE started after initial study drug administration and within 1 day of the last dose of study drug.	From first dose of study drug through 24 hours post-Day 1 dose

Collaborators and Investigators

• Sponsor: Ironwood Pharmaceuticals, Inc.
• Investigators: Study Director: Ironwood Study Chair, Ironwood Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2022
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): July 13, 2022

Study Registration Dates

• First Submitted: May 2, 2022
• First Submitted That Met QC Criteria: May 2, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: healthy volunteers
• Other Study ID Numbers: C3300-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No