- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02931565
Study of IW-1701, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Type I or II Achalasia
April 8, 2021 updated by: Cyclerion Therapeutics
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Single-dose, Phase 2a Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IW-1701 in Patients With Achalasia
The objectives of this study are as follows:
In participants with primary Type I or II achalasia, following a single 5-mg dose of olinciguat (IW-1701),
- To assess the safety and tolerability
- To determine the effects on measures of esophageal function by high-resolution impedance manometry (HRIM)
- To determine the pharmacokinetic (PK) parameters
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Connecticut
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Bristol, Connecticut, United States, 06010
- Connecticut Clinical Research Foundation, Gastroenterology Institute
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Missouri
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Saint Louis, Missouri, United States, 63110
- Washington University in St. Louis - School of Medicine
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center
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Utah
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Salt Lake City, Utah, United States, 84132
- University of Utah School of Medicine, Division of Gastroenterology, Hepatology & Nutrition
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 75 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Key Inclusion Criteria:
- Patient has a diagnosis of primary Type I or II achalasia.
- Patient has no contraindications to the performance of the baseline and postdose HRIM procedures per Investigator discretion.
Key Exclusion Criteria:
- Patient has had any prior esophageal, periesophageal, or gastric surgery, or treatment with sclerosing agent.
- More than 1 pneumatic dilation procedure to a diameter of > 2 cm in their lifetime.
- Pneumatic dilation procedure to a diameter of > 2 cm within 1 year prior to randomization. Prior bougie dilation(s) or pneumatic dilation(s) ≤ 2 cm are allowed.
- Prior esophageal injection of botulinum toxin (Botox) within 6 months prior to randomization or more than 2 esophageal Botox injection procedures in their lifetime.
- Patients with malignant or premalignant esophageal lesions.
- Patient has taken any drug that can affect gastrointestinal (GI) motility in the 72 hours before check-in through discharge from the clinic.
Other inclusion and exclusion criteria specified in the protocol.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: IW-1701
Single 5-mg dose of IW-1701 administered orally
|
oral tablet
Other Names:
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PLACEBO_COMPARATOR: Placebo
Matching placebo administered orally
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oral tablet
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)
Time Frame: Deaths, SAEs, and AEs: from enrollment through end-of-trial visit Day 21 (±7 days). TEAEs: from first dose of study drug through 72 hours postdose.
|
An adverse event (AE) is any untoward medical occurrence, which does not necessarily have to have a causal relationship with study treatment.
An SAE is any AE occurring at any dose that results in any of the following outcomes: death; life-threatening: the patient was at immediate risk of death from the reaction as it occurred; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; important medical event.
Deaths and SAEs include those that occurred on or after the participant signed the informed consent at the Screening Visit through the End-of-Trial Visit.
TEAEs are defined as adverse events that occurred on/after administration of the double-blind study drug and within 72 hours after the double-blind study drug administration.
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Deaths, SAEs, and AEs: from enrollment through end-of-trial visit Day 21 (±7 days). TEAEs: from first dose of study drug through 72 hours postdose.
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Change From Baseline in Supine Bolus Flow Time (BFT)
Time Frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
|
Supine BFT defined as the median measurement from the 10 available swallows in supine position as measured by high resolution impedance manometry (HRIM), and determined by the central read (seconds; longer times=more severe achalasia).
Change=(postdose supine BFT - predose supine BFT).
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Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Change From Baseline in Upright BFT
Time Frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Upright BFT defined as the median measurement from the 5 available swallows in the upright position as measured by HRIM, and determined by the central read (seconds; longer times=more severe achalasia).
Change = (postdose upright BFT - predose upright BFT).
|
Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Change From Baseline in Supine Integrated Relaxation Pressure (IRP)
Time Frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
|
Supine IRP defined as the median measurement from the 10 available swallows in supine position as determined by the central read (mmHg; higher pressure=more severe achalasia), measured by HRIM.
Change = (postdose supine IRP - predose supine IRP).
|
Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Change From Baseline in Upright IRP
Time Frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
|
Upright IRP is defined as the median measurement from the 5 available swallows in the supine position as determined by the central read (mmHg; higher pressure=more severe achalasia), measured by HRIM.
Change = (postdose upright IRP - predose upright IRP).
|
Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Change From Baseline in 1 Minute Impedance Bolus Height (IBH)
Time Frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
|
1 minute IBH defined by the height in esophagus of 200 mL saline bolus 1 minute post-bolus as measured by HRIM and determined by the central read (cm; greater height=more severe achalasia).
Change = (postdose height 1 min IBH - predose height 1 min IBH)
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Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Change From Baseline in 2 Minute IBH
Time Frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
|
2 minute IBH defined by the height in esophagus of 200 mL saline bolus 2 minutes post-bolus as measured by HRIM and determined by the central read (cm; greater height=more severe achalasia).
Change = (postdose height 2 min IBH - predose height 2 min IBH).
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Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Change From Baseline in 5 Minute IBH
Time Frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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5 minute IBH defined by the height in esophagus of 200 mL saline bolus 5 minutes post-bolus as determined by the central read (cm; greater height=more severe achalasia).
Change = (postdose height 5 min IBH - predose height 5 min IBH).
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Day 1: predose (baseline) and 3 hours (+15 minutes) postdose
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Area Under the Plasma Concentration Time Curve From Time 0 to the Last Observation (AUClast)
Time Frame: Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).
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Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).
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Maximum Observed Plasma Concentration (Cmax)
Time Frame: Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).
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Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).
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Time of Maximum Observed Plasma Concentration (Tmax)
Time Frame: Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).
|
Day 1 predose: 0 (≤15 minutes); Day 1 postdose: 0.5 hours (±2 minutes), 1, 2, 3, 4, 5, 6, 8 hours (±5 minutes), 12, 17 hours (±15 minutes). Day 2 postdose 24 hours (±30 minutes). End of Treatment Visit: Day 21 (±7 days).
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
April 6, 2017
Primary Completion (ACTUAL)
May 1, 2018
Study Completion (ACTUAL)
May 1, 2018
Study Registration Dates
First Submitted
October 11, 2016
First Submitted That Met QC Criteria
October 12, 2016
First Posted (ESTIMATE)
October 13, 2016
Study Record Updates
Last Update Posted (ACTUAL)
May 4, 2021
Last Update Submitted That Met QC Criteria
April 8, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- C1701-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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