Healthy Volunteers
Conditions
Keywords
healthy volunteers
Brief summary
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
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.
Interventions
DRUGIW-3300
A dose of IW-3300 administered rectally (as a low-volume \[20 mL\] enema).
DRUGPlacebo
A dose of placebo administered rectally (as a low-volume \[20 mL\] enema).
Sponsors
Ironwood Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
The investigator and all other clinical research unit staff, sponsor study personnel, and the participant will remain blinded to individual participant treatment assignments throughout the study. Treatment assignments of individual participants will only be unblinded to a sponsor representative for regulatory reporting purposes or if warranted by emerging safety or tolerability issues.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (TEAEs) | From first dose of study drug through 24 hours post-Day 1 dose | 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. |
| Number of Participants With Serious TEAEs | From first dose of study drug through 24 hours post-Day 1 dose | 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. |
Countries
United States
Participant flow
Recruitment details
The study was designed to include up to 3 cohorts with 9 participants per cohort. Within each cohort, participants were randomized to receive a single dose of IW-3300 (6 participants) or placebo (3 participants). Doses to be evaluated were 100 and 300 μg. An optional 3rd cohort was planned to test an IW-3300 dose of \>100 μg but \<300 μg. Based on a blinded review of safety and tolerability data from Cohorts 1 and 2, the Dose Escalation Committee decided not to enroll the optional 3rd Cohort.
Pre-assignment details
As pre-specified by the statistical analysis plan, for the analyses reported herein, data from the 3 participants dosed with placebo in each of the 2 cohorts were pooled into a single placebo group (N=6).
Participants by arm
| Arm | Count |
|---|---|
| Placebo A dose of placebo administered rectally (as a low-volume \[20 mL\] enema) once daily for 7 days | 6 |
| 100 μg IW-3300 A 100 μg dose of IW-3300 administered rectally (as a low-volume \[20 mL\] enema) once daily for 7 days | 6 |
| 300 μg IW-3300 A 300 μg dose of IW-3300 administered rectally (as a low-volume \[20 mL\] enema) once daily for 7 days | 6 |
| Total | 18 |
Baseline characteristics
| Characteristic | Placebo | 100 μg IW-3300 | 300 μg IW-3300 | Total |
|---|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 9.52 | 47.8 years STANDARD_DEVIATION 13.5 | 49.0 years STANDARD_DEVIATION 9.3 | 44.8 years STANDARD_DEVIATION 11.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 4 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 3 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 2 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 3 / 6 | 3 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
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.
Time frame: From first dose of study drug through 24 hours post-Day 1 dose
Population: Safety Analysis Set (all participants who received any amount of study drug)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Incidence of Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| 100 μg IW-3300 | Incidence of Treatment-Emergent Adverse Events (TEAEs) | 3 Participants |
| 300 μg IW-3300 | Incidence of Treatment-Emergent Adverse Events (TEAEs) | 2 Participants |
Primary
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.
Time frame: From first dose of study drug through 24 hours post-Day 1 dose
Population: Safety Analysis Set (all participants who received any amount of study drug)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Serious TEAEs | 0 Participants |
| 100 μg IW-3300 | Number of Participants With Serious TEAEs | 0 Participants |
| 300 μg IW-3300 | Number of Participants With Serious TEAEs | 0 Participants |