Study of IW-1701, A Stimulator of Soluble Guanylate Cyclase (sGC), in Patients With Type I or II Achalasia

Phase 2TerminatedNCT02931565

Cyclerion Therapeutics9 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Achalasia

Interventions

OlinciguatDRUG

oral tablet

Matching PlaceboDRUG

oral tablet

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (5)

Connecticut Clinical Research Foundation, Gastroenterology Institute

Bristol, Connecticut, United States

Mayo Clinic

Rochester, Minnesota, United States

Washington University in St. Louis - School of Medicine

St Louis, Missouri, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Deaths, Serious Adverse Events (SAEs), and Adverse Events Resulting in Study Drug Discontinuation (ADOs)

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.

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.

Change From Baseline in Supine Bolus Flow Time (BFT)

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).

Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose

Change From Baseline in Upright BFT

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).

Time frame: Day 1: predose (baseline) and 3 hours (+15 minutes) postdose

Change From Baseline in Supine Integrated Relaxation Pressure (IRP)

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).

Data from ClinicalTrials.gov

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